The Cerebellum and Language: Special Issue, Folia Phoniatrica Et Logopaedica 2007

The Cerebellum and Language

Guest Editor

Philippe Paquier, Brussels/Antwerp

10 figures and 13 tables, 2007

Basel • Freiburg • Paris • London • New York • Bangalore • Bangkok • Singapore • Tokyo • Sydney

S. Karger Medical and Scientific Publishers Basel • Freiburg • Paris • London New York • Bangalore • Bangkok Singapore • Tokyo • Sydney

Disclaimer The statements, options and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the journal is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.

Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center (see ‘General Information’). © Copyright 2007 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland) Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel ISBN 978–3–8055–8329–9

Vol. 59, No. 4, 2007

Contents

Editorial 163 The Cerebellum and Language Paquier, P.F. (Brussels/Antwerp)

165 The Cerebellum and Language: The Story So Far De Smet, H.J.; Baillieux, H. (Brussels); De Deyn, P.P. (Antwerp); Mariën, P.; Paquier, P. (Brussels/Antwerp) 171 The Unnoticed Contributions of the Cerebellum to Language Walter, N.; Joanette, Y. (Montréal, Que.) 177 Cerebellum and Reading Vlachos, F. (Volos); Papathanasiou, I. (Patras); Andreou, G. (Volos) 184 Language Disorders Subsequent to Left Cerebellar Lesions: A Case for

Bilateral Cerebellar Involvement in Language? Murdoch, B.E.; Whelan, B.-M. (Brisbane) 190 The Impact of a Cerebellar Tumour on Language Function in Childhood Docking, K.M.; Murdoch, B.E.; Suppiah, R. (Brisbane) 201 Language and Social Communication in Children with Cerebellar

Dysgenesis Tavano, A. (Pordenone); Fabbro, F. (Pordenone/Udine); Borgatti, R. (Lecco) 210 Cerebellar Involvement in Motor Speech Planning: Some Further Evidence

from Foreign Accent Syndrome Mariën, P. (Antwerp); Verhoeven, J. (London)

218 Author and Subject Index

© 2007 S. Karger AG, Basel Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/fpl_issues

Editorial Folia Phoniatr Logop 2007;59:163–164 DOI: 10.1159/000102926

The Cerebellum and Language Philippe F. Paquier Department of Neurology, Erasme Hospital, Université Libre de Bruxelles, and Department of Linguistics, Vrije Universiteit Brussel, Brussels, and Unit of Neurosciences, Universiteit Antwerpen, Antwerp, Belgium

Traditional neurological tenets posit that the cerebellum coordinates skilled voluntary movements and controls motor tone, posture and gate. However, anatomical, clinical and neuroimaging studies conducted over the past decades have shown that the cerebellum is implicated in several higher cognitive functions, such as language, memory, executive functions, visuospatial skills, thought modulation and emotional regulation of behaviour [1]. The purpose of this special issue is to provide speech/language therapists with recent insights into the contribution of the cerebellum to language functioning. It was felt that a better understanding of the language-related clinical pictures associated with cerebellar damage and of their possible underlying pathogenic mechanisms would be profitable to all speech/language practitioners confronted with cerebellar patients. To gain further insights into the nature of a person’s neurologically based language disorder should allow the practitioner to improve the quality of the rehabilitation programme. This will in the first place be of benefit to the patients themselves and ultimately result in the improvement of their health-related quality of life. The basis for this special issue was laid at the 26th World Congress of the IALP, Brisbane, August 29 to September 2, 2004. There, several members of the Aphasia Committee graciously agreed to work during the intercongress period on the role of the cerebellum in language processes. Their commitment to publish their findings resulted in this collection of excellent papers on a difficult

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0163$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

yet fascinating field of research. It is my pleasure to introduce the fruits of their labours. Based on a methodical review of the literature, De Smet et al. [2] show that the cerebellum is involved in a variety of linguistic functions. In this introductory overview, they summarize a number of hypotheses put forward to explain the nature of the cerebellar contribution to language. In their review of the literature on the functional neuroimaging of language, Walter and Joanette [3] systematically describe the unreported cerebellar activations associated with language tasks. They conclude that the full integration of the cerebellum in the language network is still to come. Vlachos et al. [4], in turn, review the role of the cerebellum in written language and suggest that cerebellar dysfunctions might be a cause of developmental dyslexia. Investigating the language profiles of a group of individuals with left cerebellar lesions, Murdoch and Whelan [5] discuss the role of the left as well as right cerebellar hemisphere in the regulation of language functions. Their conclusion is that their findings challenge the notion of a lateralized linguistic cerebellum. Docking et al. [6] report high-level language deficits in children with cerebellar lesions. They highlight the importance of longitudinal follow-up and assessment, particularly given the long-lasting difficulties in thinking flexibility and problem solving.

Prof. Dr. Philippe F. Paquier Service de Neurologie, ULB – Hôpital Erasme 808 route de Lennik BE–1070 Bruxelles (Belgium) Tel. +32 2 555 34 29, Fax +32 2 555 39 42, E-Mail [email protected]

Tavano et al. [7] present longitudinal data on the development of language and social communication skills in children with congenital malformations of the cerebellum. Their findings point to a specific role for the cerebellum in modulating linguistic and other cognitive abilities. Finally, Mariën and Verhoeven [8] document a new patient with foreign accent syndrome. Based on phonetic, neurobehavioural and neuroimaging data, they assume that foreign accent syndrome may result from the disruption of a close functional interplay between supra- and infratentorial brain areas concerned with motor speech planning. Being convinced that these most interesting papers will be appreciated at their true value by Folia’s readership, it only remains for me to thank the experts who willingly accepted to review the submitted manuscripts:

Marijke Van Mourik, PhD Walcheren Hospital, The Netherlands Helena Leheckova, PhD University of Helsinki, Finland Manfredi Ventura, MD Free University of Brussels (ULB-CTR), Belgium John Van Borsel, PhD University of Ghent, Belgium Peter Mariën, PhD Free University of Brussels (VUB), Belgium Sebastiaan Engelborghs, MD, PhD University of Antwerp, Belgium (2 manuscripts). Enjoy your reading!

References 1 Paquier P, Mariën P: A synthesis of the role of the cerebellum in cognition. Aphasiology 2005;19:3–19. 2 De Smet HJ, Baillieux H, De Deyn PP, Mariën P, Paquier P: The cerebellum and language: the story so far. Folia Phoniatr Logop 2007;59:165–170. 3 Walter N, Joanette Y: The unnoticed contributions of the cerebellum to language. Folia Phoniatr Logop 2007;59:171–176.

164

4 Vlachos F, Papathanasiou I, Andreou G: Cerebellum and reading. Folia Phoniatr Logop 2007;59:177–183. 5 Murdoch BE, Whelan BM: Language disorders subsequent to left cerebellar lesions: a case for bilateral cerebellar involvement in language? Folia Phoniatr Logop 2007;59: 184–189. 6 Docking KM, Murdoch BE, Suppiah R: The impact of a cerebellar tumour on language function in childhood. Folia Phoniatr Logop 2007;59:190–200.

Folia Phoniatr Logop 2007;59:163–164

7 Tavano A, Fabbro F, Borgatti R: Language and social communication in children with cerebellar dysgenesis. Folia Phoniatr Logop 2007;59:201–209. 8 Mariën P, Verhoeven J: Cerebellar involvement in motor speech planning: some further evidence from foreign accent syndrome. Folia Phoniatr Logop 2007;59:210–217.

Paquier

Folia Phoniatr Logop 2007;59:165–170 DOI: 10.1159/000102927

The Cerebellum and Language: The Story So Far Hyo Jung De Smet a Hanne Baillieux a Peter P. De Deyn c, d Peter Mariën a, c, d Philippe Paquier a, b, e a Department of Linguistics, Vrije Universiteit Brussel, and b Department of Neurology, Hôpital Universitaire Erasme ULB, Brussels; c Department of Neurology, ZNA-Middelheim Hospital, d Laboratory of Neurochemistry and Behavior, Born-Bunge Institute, and e Unit of Neurosciences, Universiteit Antwerpen, Antwerp, Belgium

Key Words Cerebellum, language
Linguistic functions
Linguistic abilities

Abstract Background: The cerebellum was traditionally considered to be exclusively involved in the coordination of voluntary movement, gait, posture, balance and motor speech. However, this view was challenged by recent neuroanatomical, neuroimaging and clinical findings, providing preliminary evidence of a cerebellar contribution to linguistic functioning. Aim: To discuss the role of the cerebellum in a variety of linguistic functions and to explore the underlying mechanisms. Methods: A literature search was conducted via electronic databases. Exclusion criteria were: disorders following congenital cerebellar lesions, motor speech disorders, cognitive deficits outside the language sphere, neuropsychiatric disorders and insufficient information on the cerebellar role in language. Abstracts were not included. In addition, only adult subjects were taken into consideration. Results: A variety of linguistic disorders were found to occur following acquired cerebellar lesions: (1) impaired phonological and semantic fluency; (2) agrammatism (at morphological

H.J.D.S. and H.B., the first two authors, contributed equally to the manuscript.

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0165$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

and sentence level); (3) naming and word finding difficulties; (4) cerebellar-induced aphasia; (5) reading difficulties; (6) writing problems, and (7) higher-level language deficits, including disturbed listening comprehension, impaired language proficiency and metalinguistic ability. Several hypotheses have been suggested to explain the nature of the cerebellar contribution to language. However, findings are not univocal. Conclusion: The cerebellum appears to be involved in a variety of linguistic functions. However, the precise nature of this contribution is not clear yet. Linguistic, neuroimaging, neuroanatomical and neuropsychological studies should be combined in order to disentangle the specific contribution of the cerebellum to linguistic processing. Copyright © 2007 S. Karger AG, Basel

Introduction

At the beginning of the 19th century, neurophysiologists such as Luigi Rolando, Joseph Babinski and MarieJean-Pierre Flourens observed staggering gait, balancing problems and clumsiness following cerebellar ablation in animals [1]. A decade later, Holmes [2–4] described abnormal and scanning speech with an indistinct articulation in patients with cerebellar lesions in his famous ‘croonian lectures’. As a result, the role of the cerebellum was defined as the coordinator of voluntary movement,

Prof. Dr. Philippe F. Paquier Service de Neurologie, Hôpital Universitaire Erasme 808 route de Lennik BE–1070 Anderlecht (Belgium) Tel. +32 2 555 34 29, Fax +32 2 555 39 42, E-Mail [email protected]

gait, posture, balance and motor speech. In accordance with this view, patients with cerebellar lesions should present with exclusively motor symptoms or motor speech disorders with intact linguistic abilities. However, results from recent neuroanatomical, neuroimaging and clinical studies challenged these beliefs about cerebellar functioning. Neuroanatomical studies showed neuronal pathways linking the cerebellum with autonomic, limbic and associative regions of the supratentorial cortex [5]. More specifically, cortical areas send information to the cerebellum via the basilar pons [6], and deep cerebellar nuclei send information back to prefrontal areas through dentatothalamic pathways [7]. This bidirectional circuit connects the cerebellum with cerebral areas concerned with, for instance, higher linguistic functioning. The existence of a reciprocal functional connectivity was further demonstrated by functional neuroimaging studies showing cerebellar activation during a variety of linguistic tasks which required no motor response [8]. Finally, due to the development of more sensitive neurolinguistic tests, clinicians were more capable of identifying subtle but significant linguistic disturbances in patients with cerebellar lesions. These studies created a renewed interest in the specific role of the cerebellum and elicited numerous case reports showing cerebellar involvement in a broad spectrum of linguistic functions. The aim of this paper is to explore the role of the cerebellum in a variety of linguistic functions and to discuss the nature of the cerebellar contribution.

Methods Relevant English literature on language disorders following acquired cerebellar damage was identified through searches of electronic databases (Medline, PsycINFO, Current Contents, Web of Science) using a combination of the key word ‘cerebellum’ and ‘language’, ‘linguistic functions’ and ‘linguistic abilities’. This review exclusively focused on the cerebellar involvement in linguistic processing. Consequently, literature on the role of the cerebellum in motor speech production or cognitive functioning was excluded. Other exclusion criteria were: (a) disorders following congenital cerebellar lesions; (b) cerebellar lesions in children; (c) neuropsychiatric disorders; (d) reports with insufficient information on the cerebellar role in language, and (e) abstracts. The articles dated from 1988 [8]1 to June 2006. Because of the introductory nature of this review, not all cited reports are exhaustively described. 1

The publication of Petersen et al. [8] may be considered the seminal functional neuroimaging study on the involvement of the cerebellum in linguistic processing.

166

Folia Phoniatr Logop 2007;59:165–170

Results and Discussion

Our literature search disclosed 508 references on cerebellum and language, of which 83 remained after applying the aforementioned exclusion criteria. However, not all 83 articles are discussed in this introductory review because on second inspection it appeared that they partially overlapped, focused on theoretical considerations, or provided information that was beyond the scope of this introduction (e.g. language and humor, language and emotion). Word Generation and Production Preliminary evidence in support of the assumptions of Leiner et al. [9] about a possible cerebellar involvement in linguistic functions was provided by positron emission tomography (PET) activation studies which demonstrated that, in addition to Broca’s area, the contralateral cerebellar hemisphere was active during the generation of semantically related verbs in response to visually presented nouns [8, 10]. These studies showed that this activation was not related to the motor verbal response but to cognitive word association. Notwithstanding variations on the original task design, subsequent studies have consistently reported activation of the right lateral cerebellum during word generation tasks [11–14]. In addition, Hubrich et al. [15] recently compared a left- and righthanded volunteer with functional magnetic resonance imaging (fMRI) while performing a silent verbal fluency task. In the right-handed subject, regions of activation included the left frontoparietal cortex and the right cerebellar hemisphere, while in the left-handed subject the opposite pattern of crossed cerebral-cerebellar activation was observed. The authors concluded that cerebellar activation is contralateral to the activation of the cerebral cortex, even under conditions of different language dominance. Schlösser et al. [16] and Gourovitch et al. [17] had reached similar conclusions in previous studies. Clinical studies of patients with cerebellar lesions confirmed the implication of the cerebellum in word production. Fiez et al. [18] described a 41-year-old, right-handed patient who presented with semantic retrieval deficits, despite high-level conversational skills, after a vascular lesion of the right cerebellar hemisphere. Furthermore, Leggio et al. [19] compared patients with left and right cerebellar lesions with controls using cluster analysis. Their results showed that cerebellar damage specifically affects the phonemic rule performances while sparing semantic rules. In addition, lateralization was not observed since reduced verbal fluency was noted in patients with either left or right cerebellar lesions [20, 21]. De Smet /Baillieux /De Deyn /Mariën / Paquier

Naming and Word Finding Difficulties Schmahmann and Sherman [22] identified the ‘cerebellar cognitive-affective syndrome’, which may include subtle language difficulties, such as agrammatism and mild anomia, without the presence of aphasia. Other studies briefly reported naming or word finding difficulties in patients with cerebellar lesions [20, 23–26]. In addition, using PET Grönholm et al. [27] found cerebellar activation in 10 right-handed subjects during naming of newly learned objects and suggested that retrieval efforts incorporate semantic and phonological processes related to the ventral prefrontal cortex and the cerebellum. Grammatical Disorders Silveri et al. [28] were the first to document an association between focal damage of the right cerebellum and transient expressive agrammatism, characterized by omission of free-standing grammatical morphemes, omission of auxiliaries and clitics, and substitutions of bound grammatical morphemes. A single photon emission computed tomography (SPECT) scan showed a relative hypoperfusion in the entire left cerebral hemisphere, more stable and consistent in the left posterior temporal region. The authors interpreted their patient’s selective speech production impairment as a ‘peripheral’ disorder and hypothesized that agrammatism may be the result of the patient’s adaptation to a deficit lying outside the mental linguistic system. Since then, other instances of cerebellar patients displaying expressive and/or receptive agrammatism, frequently associated with more extensive linguistic impairments, have been reported [24, 25, 29– 33]. Strelnikov et al. [34] investigated brain mechanisms underlying syntactically correct perception of phrases with syntagmatic splitting using PET in 12 right-handed subjects. Activation was seen in the right dorsolateral prefrontal cortex and medial posterior area of the right cerebellum. According to the authors, right cerebellar activation was related to assessment of time intervals necessary for different sensorimotor and cognitive activities [35, 36], to estimation of phonetic and semantic borders of syntagmata, or to maintenance of the phrase structure in working memory during processing [37]. Other imaging studies on syntactic processing provided additional evidence for ipsilateral cerebellocerebral connectivity [38–40]. However, Stowe et al. [41] investigated sentence comprehension using PET in 16 healthy subjects who had to read syntactically unambiguous and ambiguous sentences. The ambiguous sentences activated four areas more than the unambiguous ones, namely the left inferior and the left superior frontal gyri, the right basal ganThe Cerebellum and Language: The Story So Far

glia and the right posterior dorsal cerebellum. The authors suggested that the cerebellum may play an ‘active’ role itself as an error detector and that failure in comprehension of ambiguous sentences may occur if errors are not detected efficiently. Aphasia-Like Pictures The co-occurrence of linguistic impairments affecting phonological, lexicosemantic and syntactic abilities to different degrees gave rise to the notion of cerebellarinduced language disorders resembling aphasic syndromes [25, 29, 31, 32, 42]. Mariën et al. [29, 31] described a 73-year-old, right-handed patient who presented with an aphasia-like picture after an ischemic lesion in the right cerebellar hemisphere. Their patient’s language disorder was characterized by a marked dissociation between imposed and spontaneous language, severe diminution of speech initiation, and effortful and fragmented attempts to formulate ideas. In addition, word finding difficulties, marked expressive and receptive agrammatism, and reading and writing deficits were also present. Mariën et al. [29, 31] explicitly labeled their patient’s language disorder a cerebellar-induced ‘aphasia’. SPECT studies revealed a significant hypoperfusion in the right cerebellum and in the left frontoparietal region. At follow-up, changes in perfusional patterns paralleled the alterations in the neurolinguistic profile. Aphasia-like alterations following right cerebellar damage are considered to result from a loss of excitatory impulses through cerebello-ponto-thalamo-cortical pathways [29]. Reading Difficulties Although reading difficulties may occur following cerebellar damage, they have only been scarcely described (reading problems after cerebellar lesions will be discussed in more detail later in this issue). Moretti et al. [43] investigated cerebellar involvement in reading in patients compared to right-handed controls. Cerebellar patients demonstrated a lower degree of accuracy in reading words and sentences. Patients made errors both at letter and word levels. The authors suggested that the acquired dyslexia may be related either to an imperfect oculomotor control (nystagmus) or a disruption of cerebellar-encephalic projections connecting the cerebellum to supratentorial areas implicated in language as well as in attentional and alerting processes. Reading comprehension of words, sentences or a short story may also be disturbed [25, 32]. Fulbright et al. [44] investigated cerebellar activation during reading using fMRI in 42 right-handed healthy controls. Task requirements were orthographic Folia Phoniatr Logop 2007;59:165–170

167

processing, phonological assembly and semantic processing. Both phonological assembly and semantic processing activated the right cerebellar hemisphere. Furthermore, semantic processing required increased cognitive processing, which resulted in activation in the inferior vermis and right deep nuclear region. The authors suggested that the cerebellum contributes to cognitive processes specific to reading via connections with frontal, temporal and parietal areas engaged in reading. Writing Difficulties With respect to writing deficits, Silveri et al. [45, 46] described two patients with spatial dysgraphia, characterized by segmented and dysmetric writing movements. The authors hypothesized that a discoordination between the planning of the graphic motor patterns generated by supratentorial structures and peripheral, proprioceptive afferences during ongoing writing movements may cause spatial dysgraphia. The functional pathway responsible for the peripheral control of writing might include the left cerebellum and the controlateral supratentorial structures. Fabbro et al. [25, 32] reported impaired dictation of words and sentences and impaired copying; however they did not analyze these writing deficits. Higher-Level Language Deficits Recently, Cook et al. [20] investigated general and higher-level language skills, including language proficiency and metalinguistic abilities, in five patients with left cerebellar lesions (cf. study by Whelan and Murdoch [21]). All patients presented with difficulties in definition tests and recreating sentences tasks, figurative language tests, word association tasks, antonym/synonym generation and interpreting semantic absurdities. The test results indicated that left cerebellar lesions may affect the ability to efficiently manipulate semantic elements at multiword levels of language production, and to interpret and generate semantically constrained output. The authors suggested that cerebellar-cerebral output supports the regulation of lexical-semantic operations and the organization of complex language output, and that both the left and right cerebellar hemisphere may be involved in the regulation of language functioning. Although SPECT was not performed, Cook et al. [20] stated that their findings provide support for the hypothesis of ipsilateral diaschisis, or alternatively, crossed diaschisis via left-right intracerebellar neural mechanisms, since all patients had left cerebellar lesions resulting in higher-level language deficits [20]. Xiang et al. [47] performed an fMRI study in 6 right-handed subjects during semantic discrimina168

Folia Phoniatr Logop 2007;59:165–170

tion tasks without overt articulation. Subjects were asked to indicate which one of the target words was more semantically related to the probe word in three different conditions. Activation was found in left frontal regions and the right cerebellum. In addition, a parallelism was demonstrated between cerebellar activation and task difficulty. Based on their results, the authors suggested that the amount of cerebellar-induced activity should be directly related to the sensory requirements of a particular computation and that the cerebellum is more likely to fulfil a support function. Consequently, cerebellar activity should increase as the level of difficulty of a particular task increases. In summary, the role of the cerebellum is not limited to motor functions but appears to be involved in a broad spectrum of linguistic functions, such as verbal fluency, word retrieval, syntax, reading, writing and metalinguistic abilities. The possible underlying mechanism of the cerebellar role in language is discussed in the next paragraphs. The Nature of the Cerebellar Contribution to Language The precise nature of the cerebellar involvement in linguistic processing is not yet clear. In the literature, three major hypotheses have been suggested: (1) cerebellocerebral diaschisis; (2) timing hypothesis, and (3) a direct cerebellar contribution. Cerebellocerebral Diaschisis The phenomenon of cerebellocerebral diaschisis has frequently been suggested as a possible functional substrate of linguistic deficits in patients with cerebellar lesions [29, 37, 42]. Cerebellocerebral diaschisis reflects the metabolic impact of a cerebellar lesion on a distant, but anatomically and functionally connected, supratentorial region [37]. Due to the lack of excitatory impulses through cerebello-ponto-thalamo-cerebral pathways, cortical blood flow will be disturbed and specific cortical areas will not be working properly [37], thus resulting in linguistic disturbances. Mariën et al. [29] described a patient with cerebellar-induced aphasia and attributed the specific language symptoms to a focal left frontoparietal hypoperfusion as revealed by SPECT scan. Several studies and case reports showed similar observations of reduced cerebral blood flow in the anatomoclinically suspected cortical regions [29, 30, 37, 42]. However, studies have indicated that the cerebellar influence on language is not necessarily lateralized [19, 20, 32]. Both left and right cerebellar lesions may cause linguistic disturbances, De Smet /Baillieux /De Deyn /Mariën / Paquier

suggesting that both crossed and ipsilateral cerebellocerebral connections might be implicated in language. However, such findings are not univocal. For instance, Gasparini et al. [24] were not able to detect any supratentorial blood flow alterations in the suspected cortical regions in their patient with agrammatism following a right cerebellar stroke. Timing Hypothesis A second possible explanation for the cerebellar involvement in linguistic functioning refers to the timing hypothesis. It states that the cerebellum has no direct influence on linguistic processes but plays an important role in the timing or modulation of linguistic functions represented on a supratentorial level [28, 46, 48]. Patients with cerebellar damage will experience great difficulty in temporal modulation, required for several linguistic processes, such as phonological processing, sentence construction and comprehension and application of syntactic rules. According to this hypothesis, cerebellar damage will not influence language per se, but an intact cerebellum is essential for a correct execution of linguistic tasks. Evidence for this view is found in a case report by Silveri et al. [28], who ascribed the agrammatism of their patient to a delay in the processes underlying sentence construction. More specifically, the online application of syntactic rules may be slowed, causing the representation of morphemes to decay from working memory. As a result, sentence integration will be disturbed. Direct Cerebellar Influence A final hypothesis regarding the nature of cerebellar involvement in language assumes that the cerebellum has a direct and specific influence on language processing [49, 50]. Possible evidence for this view rests upon neuroanatomical data [49, 51, 52]. The cerebellum receives topographically organized projections from cortical association areas involved in higher linguistic functioning through the feedforward loop of the cortico-ponto-cerebellar system [49, 51, 52]. In return, the dentate nucleus projects to the prefrontal cortex, posterior parietal areas and the superior temporal sulcus via cerebello-thalamocortical pathways [49, 51, 52]. These projections might transfer a feedback on the information the cerebellum receives from supratentorial areas involved in linguistic processing [51]. According to this view, the cerebellum does not act as a sole modulator of linguistic functions but is actively involved in the organization, construction and execution of linguistic processes.

The Cerebellum and Language: The Story So Far

Conclusion

During the last two decades, new insights into the cerebellar contribution to linguistic functioning have substantially redefined the role of the cerebellum. Neuroanatomical studies have shown reciprocal connections linking the cerebellum with cortical areas crucially involved in high-level linguistic functioning. In addition, current neuroimaging techniques have consistently revealed cerebellar activation during a variety of linguistic tasks, and thorough clinical investigations of patients with cerebellar damage have disclosed a broad spectrum of linguistic symptoms. These results led to the clinical awareness of a modulating role of the cerebellum in various language processes. Today, clinicians recognize this cerebellar involvement, and patients with cerebellar lesions are examined with sensitive neurolinguistic tests to identify possible language disturbances. However, many questions still remain unanswered. The precise influence on linguistic processing and the specific nature of the cerebellar involvement are not yet fully understood. Results from neuroanatomical studies, neuroimaging techniques and neurolinguistic investigations should be combined in order to disentangle the mysteries of this impressive structure at the bottom of the brain.

Acknowledgments This study was supported by grant G.0209.05 of Fonds voor Wetenschappelijk Onderzoek Vlaanderen, by Onderzoeksraad Vrije Universiteit Brussel, by Nationale Vereniging tot Steun aan Gehandicapte Personen, by Stichting Integratie Gehandicapten, and by Deloitte Belgium.

References

1 Fine EJ, Ionita CC, Lohr L: The history of the development of the cerebellar examination. Semin Neurol 2002;22:375–384. 2 Holmes G: A form of familial degeneration of the cerebellum. Brain 1907;30:466–480. 3 Holmes G: The symptoms of acute cerebellar injuries due to gunshot injuries. Brain 1917; 40:401–534. 4 Holmes G: The cerebellum: the croonian lectures on the clinical symptoms of cerebellar diseases and their interpretation. Brain 1922; 44:522–591. 5 Schmahmann JD: Disorders of the cerebellum: ataxia, dysmetria of thought and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2004; 16: 367–378. 6 Schmahmann JD, Pandya DN: The cerebrocerebellar system. Int Rev Neurobiol 1997;41: 31–60.

Folia Phoniatr Logop 2007;59:165–170

169

7 Middleton FA, Strick PL: Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science 1994;266:458–461. 8 Petersen SE, Fox PT, Posner MI, Mintun MA, Raichle ME: Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature 1988;331:585–589. 9 Leiner HC, Leiner AL, Dow RS: Does the cerebellum contribute to mental skills? Behav Neurosci 1986;100:443–454. 10 Petersen SE, Fox PT, Posner MI, Mintun MA, Raichle ME: Positron emission tomographic studies of the processing of single words. J Cogn Neurosci 1989;1:153–170. 11 Raichle ME, Fiez JA, Videen TO, MacLeod AM, Pardo JV: Practice-related changes in human brain functional anatomy during nonmotor learning. Cereb Cortex 1994; 4: 8– 26. 12 Martin A, Haxby JV, Lalonde FM, Wiggs CL, Ungerleider LG: Discrete cortical regions associated with knowledge of color and knowledge of action. Science 1995;270:102–105. 13 Grabowski TJ, Frank RJ, Brown CK, Damasio H, Boles-Ponto LL: Reliability of PET activation across statistical methods, subject groups, and sample sizes. Hum Brain Mapp 1996; 4: 23–46. 14 Papathanassiou D, Etard O, Mellet E, Zago L, Mazoyer B, Tzourio-Mazoyer N: A common language network for comprehension and production: a contribution to the definition of language epicenters with PET. NeuroImage 2000;11:347–357. 15 Hubrich-Ungureanu P, Kaemmerer N, Henn FA, Braus DF: Lateralized organization of the cerebellum in a silent verbal fluency task: a functional magnetic resonance imaging study in healthy volunteers. Neurosci Lett 2002;319: 91–94. 16 Schlösser R, Hutchinson M, Joseffer S, Rusinek H, Saarimaki A, Stevenson J, Dewey SL, Brodie JD: Functional magnetic resonance imaging of human brain activity in a verbal fluency task. J Neurol Neurosurg Psychiatry 1998;64:492–498. 17 Gourovitch ML, Kirby BS, Goldberg TE, Weinberger DR, Gold JM, Esposito G, Van Horn JD, Faith Berman K: A comparison of rCBF patterns during letter and semantic fluency. Neuropsychology 2000;14:353–360. 18 Fiez JA, Peterson SE, Cheney MK, Raichle ME: Impaired non-motor learning and error detection associated with cerebellar damage: a single case study. Brain 1992;115:155–178. 19 Leggio MG, Silveri MC, Petrosini L, Molinari M: Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study. J Neurol Neurosurg Psychiatry 2000; 69:102–106. 20 Cook M, Murdoch B, Cahill L, Whelan B: Higher-level language deficits resulting from left primary cerebellar lesions. Aphasiology 2004;18:771–784. 21 Whelan B-M, Murdoch BE: Unravelling subcortical linguistic substrates: comparison of

170

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

thalamic versus cerebellar cognitive-linguistic regulation mechanisms. Aphasiology 2005;19:1097–1106. Schmahmann JD, Sherman JC: The cerebellar cognitive affective syndrome. Brain 1998; 121:561–579. Chafetz MD, Friedman AL, Kevorkian G, Levy K: The cerebellum and cognitive function: implications for rehabilitation. Arch Phys Med Rehabil 1996;77:1303–1308. Gasparini M, Di Piero V, Ciccarelli O, Cacioppo MM, Pantano P, Lenzi GL: Linguistic impairment after right cerebellar stroke: a case report. Eur J Neurol 1999;6:353–356. Fabbro F, Moretti R, Bava A: Language impairments in patients with cerebellar lesions. J Neurolinguistics 2000;13:173–188. Paulus KS, Magnano I, Galistu P, D’Onofrio M, Satta W, Aiello I: Pure post-stroke cerebellar cognitive affective syndrome: a case report. Neurol Sci 2004;25:220–224. Grönholm P, Rinne JO, Vorobyev V, Laine M: Naming of newly learned objects: a PET activation study. Cogn Brain Res 2005; 25: 359– 371. Silveri MC, Leggio MG, Molinari M: The cerebellum contributes to linguistic production: a case of agrammatic speech following a right cerebellar lesion. Brain 1994;121:2175–2187. Mariën P, Saerens J, Nanhoe R, Moens E, Nagels G, Pickut B, Dierckx RA, De Deyn PP: Cerebellar induced aphasia: case report of cerebellar induced prefrontal aphasic language phenomena supported by SPECT findings. J Neurol Sci 1996;144:34–43. Zettin M, Cappa SF, D’Amico A, Rago R, Perino C, Perani D, Fazio F: Agrammatic speech production after a right cerebellar haemorrhage. Neurocase 1997;3:375–380. Mariën P, Engelborghs S, Pickut B, De Deyn PP: Aphasia following cerebellar damage: fact or fallacy? J Neurolinguistics 2000; 13: 145– 171. Fabbro F, Tavano A, Corti S, Bresolin N, De Fabritiis P, Borgatti R: Long-term neuropsychological deficits after cerebellar infarctions in two young adult twins. Neuropsychologia 2004;42:536–545. Justus T: The cerebellum and English grammatical morphology: evidence from production, comprehension, and grammaticality judgments. J Cogn Neurosci 2004; 16: 1115– 1130. Strelnikov KN, Vorobyev VA, Chernigovskaya TV, Medvedev SV: Prosodic clues to syntactic processing – a PET and ERP study. NeuroImage 2006;29:1127–1134. Ivry RB, Richardson TC: Temporal control and coordination: the multiple timer model. Brain Cogn 2002;48:117–132. Salman MS: The cerebellum: it’s about time! But timing is not everything – New insight into the role of the cerebellum in timing motor and cognitive tasks. J Child Neurol 2002; 17:1–9. Mariën P, Engelborghs S, Fabbro F, De Deyn PP: The lateralized linguistic cerebellum: a

Folia Phoniatr Logop 2007;59:165–170

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

review and new hypothesis. Brain Lang 2001; 79:580–600. Dogil G, Ackermann H, Grodd W, Haider H, Kamp H, Mayer J, Riecker A, Wildgruber D: The speaking brain: a tutorial introduction to fMRI experiments in the production of speech, prosody and syntax. J Neurolinguistics 2002;15:59–90. Peck KK, Wierenga CE, Bacon Moore A, Maher LM, Gopinath K, Gaiefsky M, Briggs RW, Crosson B: Comparison of baseline conditions to investigate syntactic production using functional magnetic resonance imaging. NeuroImage 2004;23:104–110. Strelnikov KS, Vorob’ev VA, Rudas MS, Chernigovskaya TV, Medvedev SV: A PET study of the brain mechanisms underlying perception of phrases with syntagmatic splitting. Hum Physiol 2004;30:255–261. Stowe LA, Paans AMJ, Wijers AA, Zwarts F: Activations of ‘motor’ and other non-language structures during sentence comprehension. Brain Lang 2004;89:290–299. Hassid EI: A case of language dysfunction associated with cerebellar infarction. J Neurol Rehabil 1995;9:157–160. Moretti R, Bava A, Torre P, Antonello RM, Cazzato G: Reading errors in patients with cerebellar vermis lesions. J Neurol 2002; 249: 461–468. Fulbright RK, Jenner AR, Einer Menel W, Pugh KR, Shaywitz BA, Shaywitz SE, Frost JS, Skudlarski P, Constable RT, Lacadie CM, Marchione KE, Core JC: The cerebellum’s role in reading: a functional MR imaging study. AJNR Am J Neuroradiol 1999; 20: 1925–1930. Silveri MC, Misciagna S, Leggio MG, Molinari M: Spatial dysgraphia and cerebellar lesion: a case report. Neurology 1997;48:1529– 1532. Silveri MC, Misciagna S, Leggio MG, Molinari M: Cerebellar spatial dysgraphia: further evidence. J Neurol 1999;246:312–313. Xiang H, Lin C, Ma X, Zhang Z, Bower JM, Weng X, Gao J: Involvement of the cerebellum in semantic discrimination: an fMRI study. Hum Brain Mapp 2003;18:208–214. Keele SW, Ivry R: Does the cerebellum provide a common computation for diverse tasks? A timing hypothesis. Ann NY Acad Sci 1991;608:179–211. Leiner HC, Leiner AL, Dow RS: The human cerebro-cerebellar system: its computing, cognitive and language skills. Behav Brain Res 1991;24:113–128. Schatz J, Hale S, Myerson J: Cerebellar contribution to linguistic processing efficiency revealed by focal damage. J Int Neuropsychol Soc 1998;4:491–501. Daum I, Ackermann H: Cerebellar contributions to cognition. Behav Brain Res 1995; 67: 201–210. Leiner HC, Leiner AL, Dow RS: Cognitive and language functions of the human cerebellum. Trends Neurosci 1993;16:444–447.

De Smet /Baillieux /De Deyn /Mariën / Paquier

Folia Phoniatr Logop 2007;59:171–176 DOI: 10.1159/000102928

The Unnoticed Contributions of the Cerebellum to Language Nathalie Walter a Yves Joanette a, b a

Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, and b Faculté de Médecine, Université de Montréal, Montréal, Que., Canada

Key Words Cerebellum
Language
Literature review, cerebellum
Neuroimaging

Abstract Background: In addition to its well-known role in motor processing, the cerebellum has been shown to contribute to a number of nonmotor cognitive abilities. However, despite (1) the acknowledged demonstration of the motor, perceptual and cognitive contributions of the cerebellum and (2) the growing number of neuroimaging studies allowing for the exploration of the neurobiological bases of language abilities, only a small number of neuroimaging studies focus on the cerebellar contribution to language. Aims: To look for unreported cerebellar activations in the neuroimaging literature for language, in order to systematically describe the unreported or otherwise unnoticed cerebellar activations associated with language tasks. Methods: A recent review paper by Démonet et al. [Physiol Rev 2005; 85: 49–95] was used as a base in order to investigate the literature on the neuroimaging of language abilities. Results: Of the 450 papers cited in this review, 100 articles were directly related to single-word processing, of which only 34 reported cerebellum activations. Conclusion: The full integration of the cerebellum in the network allowing for language and communication is still to come, as very few neuroimaging studies do report cerebellar activations underlying the processing of words. Copyright © 2007 S. Karger AG, Basel

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0171$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

Introduction

For almost two centuries, the cerebellum was mainly recognized for its contribution to motor processing. According to human clinical data and animal behavioral data, the integrity of the cerebellum has been demonstrated to be crucial for the coordination of ballistic movements and for the postural adjustments necessary for their execution. Some 200 years of studies are available in the literature. For example, as early as 1809, Rolando [1] measured the impact of cerebellectomies and concluded that they result in motor deficits without sensory alterations. Several years later, Flourens [2] specified that cerebellar lesions cause uncoordinated movements rather than palsy. The motor regulation function of the cerebellum took into account notions such as balance [3] and the tonic action on the motor centers [4]. Between 1897 and 1939, clinical descriptions of motor and postural cerebellar syndrome [5–7] established the cerebellum as a structure essential for balance, posture, motor programming, and the implementation and temporal organization of movements. Since then, numerous studies have confirmed and extended the motor role of the cerebellum. For example, Ito [8] showed that the cerebellum contributes to motor learning and the automatization of gesture. However, a number of studies have gradually begun to suggest that the cerebellar contribution to certain nonmotor cognitive fields should be broadened. Based on both neural evi-

Nathalie Walter, PhD Centre de Recherche, Institut Universitaire de Gériatrie de Montréal 4565 Queen-Mary Montréal (QC) H3W 1W5 (Canada) Tel. +1 514 340 3540, Fax +1 514 340 3548, E-Mail [email protected]

dence and information processing theory, Leiner et al. [9] showed that the newest part of the cerebellum (in particular the dentate nucleus) might interact with the frontal association cortex to allow for the skilled manipulation of information or ideas. Furthermore, some patients with cerebellar lesions were found to be impaired on both motor and perceptual tasks requiring accurate timing [10]. This observation led these authors to suggest that the lateral regions of the cerebellum are critical for the accurate functioning of an internal timing system. After it was recognized that cerebellar activation can be seen during motor imagery [11], Ryding et al. [12] reported regional activations in inferolateral parts of the cerebellum on both sides, using silent counting tasks. Parallel to the study of these cognitive tasks, other studies focused specifically on language processing. According to Leiner et al. [13], the cerebellum, with its contributions to mental and language functions, could serve as an adaptive mechanism whose signals enable the frontal cortex to execute learned procedures optimally. In the absence of such cerebellar signals, the frontal cortex would perform this processing less rapidly and fluently. In fact, it has been suggested that cerebellar functional expansion to nonmotor functions is a consequence of specific cerebellar structural changes during hominid evolution that may have been a prerequisite for the evolution of human language [14]. It is in this context that many studies have indicated that the cerebellum may be involved in language processing, from the processing of words to that of sentences. For example, Silveri et al. [15] reported a case of agrammatic speech following a right cerebellar lesion. The authors hypothesized that the cerebellum provides the temporal interplay among the neural structures underlying the processes responsible for sentence production. Clearly, the idea that the cerebellum only contributes to motor functions is now an artifact from the past. Habas [16] summarized a number of relevant arguments in support of the effective contribution of the cerebellum to nonmotor abilities, such as language processes. The author emphasized the presence of many cerebellar loops integrated with cerebral structures, such as the associative frontal cortex (including Broca’s area, in the inferior frontal cortex) and the limbic system. Some cerebellar stimulations or lesions do not even have a motor impact at all, in particular when they affect lateral regions of the cerebellum. Conversely, psychological or psychiatric deficits have been observed with cerebellar alterations. Many imaging studies showed cerebellar activation with nonmotor processing, in well-known procedures involving cerebellar capabilities [16]. 172

Folia Phoniatr Logop 2007;59:171–176

In summary, it is now clear that the cerebellum contributes to a number of motor, perceptual and even cognitive processing and abilities. Although the number of studies that specifically focus on the cerebellar contribution to language is still limited, there is a growing amount of neuroimaging data looking at the neurobiological bases of language abilities that could be used to describe the nature and pattern of cerebellar activation in individuals engaged in language tasks. It is our belief that the cerebellum probably makes many unnoticed contributions to language that are hidden in the neuroimaging literature. The goal of this study was to undertake a systematic review of the literature in order to find out whether or not such unnoticed, or undiscussed, contributions can be found in the literature. In so doing, it is hoped that this systematic review will contribute to the wealth of data from which a more precise understanding of the nature of the cerebellar contribution to language will emerge.

Methodology for the Literature Review

In order to systematically explore the literature on the neuroimaging of language abilities, we decided to use the most recent and most exhaustive review paper on that issue. Though the reviews by Bookheimer [17] and Gernsbacher and Kaschak [18] are notably complete and well thought out, we chose the more recent review paper by Démonet et al. [19]. With its 450 cited papers, this review includes the essence of the current neuroimaging literature on language abilities. Since cerebellar activations were not specifically reported in the Démonet et al. [19] paper, we re-examined all papers cited by Démonet et al. that reported neuroimaging data on language abilities in normal participants, limiting ourselves to the word level processing. These papers essentially used either PET or fMRI to explore the patterns of activation. The systematic analysis of these papers allowed us to tackle the following questions: whether or not the entire brain was scanned, including the cerebellum; methods (subjects, tasks, imaging device and experimental design); reported brain activations, and cerebellar activations.

Main Findings

In the review written by Démonet et al. [19], 100 of the articles reported on (excluding reviews and book chapters) were directly related to single-word processing, essentially using PET or fMRI. However, only 34 of these Walter/Joanette

Table 1. Summary of cerebellar activation, when present, related to word processing in articles cited by Démonet et al. [19] Study

Tasks

Cerebral activations

Tasks involving auditory materials (auditory input, according to Démonet et al.) [20] Categorization or sequence interpretation on word Frontal and temporal areas and sounds sequences [21] Vocal and nonvocal listening Temporal and parietal areas [22] Word and nonword passive listening Frontal and temporal areas [23] Pseudoword reading and rhythm judgment Frontal and temporal areas, supramarginal gyrus [24] Word listening and repetition Frontal and temporal areas, subcortical structures [25] Word listening Frontal, temporal and parietal areas

Cerebellar activation Bilateral activation Not reported Bilateral activation Bilateral activation Right activation Bilateral activation

Tasks involving visual materials (visual input, according to Démonet et al.) [26] Word and drawing naming Frontal, temporal and parietal areas [27] Word and pseudoword reading Frontal, temporal and parietal areas [28] Reading aloud Frontal, temporal and parietal areas [29] Text comprehension Frontal, temporal and parietal areas [30] Kana-to-kanji transcription and oral reading Frontal, temporal and parietal areas [31] Word and pseudoword reading Frontal, temporal and parietal areas [32] Silent reading and reading aloud Frontal and parietal areas [33] Visually presented word naming Frontal, temporal and parietal areas [34] Written word pronunciation and lexical decision Frontal, temporal and parietal areas [35] Reading aloud Temporal, parietal and occipital areas

Bilateral activation Bilateral activation Bilateral activation Not reported With medial occipital areas Right activation Right activation Bilateral activation Bilateral activation Not reported

Tasks asking for semantic processing (semantics, according to Démonet et al.) [26] Word and drawing naming Frontal, temporal and parietal areas [36] Addition Frontal and temporal areas [37] Silent reading Frontal, temporal and parietal areas, thalamus [38] Word generation Frontal and temporal areas [39] Working memory for faces Frontal, temporal and parietal areas [40] Word and sentence comprehension Frontal, temporal and parietal areas, brain stem [41] Viewing drawings and verb generation Frontal, temporal and parietal areas [42] Lexical decision on words Frontal, temporal and parietal areas [43] Drawing identification and naming Frontal, temporal, occipital and parietal areas [44] Semantic decision Frontal, temporal and parietal areas [45] Lexical decision on nouns and verbs Frontal, temporal and parietal areas [46] Sentence generation Frontal and parietal areas [47] Same/different decision Frontal, temporal, occipital and parietal areas

Bilateral activation Right activation Bilateral activation Right activation Right activation Bilateral activation Right activation Bilateral activation Bilateral activation, essentially right Left activation Right activation Right activation Right activation

Tasks involving verbal production (speech output, according to Démonet et al.) [48] Naming Frontal, temporal and parietal areas, thalamus [49] Recitation of months Frontal, temporal and parietal areas [50] Word stem completion Frontal and occipital areas

Right activation Right activation Bilateral activation

Tasks involving special written stimuli (written output, according to Démonet et al.) [51] Kana writing names of pictures Frontal and parietal areas [52] Kana-to-kanji transcription Frontal and parietal areas [53] Kana-to-kanji transcription Frontal and parietal areas

Bilateral activation Not reported Not reported

papers mentioned the cerebellum in their results (table 1). There are many potential explanations of the absence of any reports regarding possible cerebellar activations in the 66 other papers. First, a number of studies did not scan the entire brain and thus excluded the cerebellar structures, probably for reasons of economy (quicker scanning, less costly) and/or because no cerebellar activation was expected. Some studies reported a small number of slices to highlight activation in explicit brain areas. Other papers, sometimes similar in terms of methodology (tasks, design, etc.), varied depending on whether

they did or did not report activations located in cerebellar structures. One can ask whether these papers referred to language tasks, which supposedly do not require the cerebellum – a claim that is debatable, in our view – or whether the authors were, more or less deliberately, unaware of possible cerebellar activations. The small proportion of papers reporting the presence of cerebellar activation (34/100) was somewhat surprising but it certainly confirmed the limited interest in the possible cerebellar contribution to word processing.

The Unnoticed Contributions of the Cerebellum to Language

Folia Phoniatr Logop 2007;59:171–176

173

Démonet et al. [19] divided the word processing paragraph into five distinct sections. Since the different studies looking at the neuroimaging of word processing made use of very different theoretical frameworks, Démonet et al. [19] did not organize the systematic review according to the underlying cognitive organization but rather based on a pragmatic partition of word processing: auditory input, visual input, semantics, speech output and written output. Such levels range from word perception to word production, with the intermediate levels corresponding to semantic representations and processes. Table 1 shows the cerebellar activation patterns, when reported, for the 35 studies that did include the cerebellum in the scanning protocol. The following paragraphs represent a summary of the converging data to be found in table 1. Auditory Input Only six studies using auditory input tasks gathered activation data from the cerebellum. Of these six studies, one did not report any data from the slices including the cerebellum. From the other five papers, it appears that a bilateral activation of the cerebellum was present in most of them (four out of five), while the last one reported only right cerebellar activation. If these parcellar data are representative of the unreported patterns in the rest of the studies, this would mean that cerebellar activation is present in most auditory input processing tasks and that most of the time it is bilateral. For example, Thierry et al. [20] reported activation in bilateral cerebellar structures during semantic tasks (categorization task and sequence interpretation task). This study compared semantic processing of spoken words to the equivalent processing of environmental sounds, after controlling for low-level perceptual differences. Word processing enhanced activation in left anterior and posterior superior temporal regions, while environmental sounds enhanced activation in a right posterior superior temporal region. Moreover, Thierry et al. [20] mentioned that the conjunction of words and sounds, relative to the noise baselines, activated regions of the bilateral cerebellum, while semantic decisions increased activation in the left cerebellum for words only. However, the authors did not propose any hypothesis regarding the cerebellar contribution to this auditory input task. Visual Input Among the studies which used visual input tasks, ten included the cerebellum in the neuroimaging data. Two of these ten studies did not report any data from the cerebellum. Of the other eight papers, six mentioned a bilat174

Folia Phoniatr Logop 2007;59:171–176

eral activation of cerebellar structures, and two reported an activation of the right side of the cerebellum. It seems difficult to account for the differences between bilateral or right unilateral activations on the basis of the nature of the required processing. For example, Moore and Price [26] investigated word and object processing during naming and viewing tasks. In terms of cerebral activation, the authors reported the involvement of three distinct regions in the left ventral occipitotemporal cortex (including the fusiform gyrus), the left superior temporal gyrus and the left supramarginal gyrus. In addition, they highlighted activation localized in the right midline cerebellum for the common effects of word and object naming, in the left anterior cerebellum for word-specific naming and in the right midline cerebellum for object-specific naming. Interestingly, this paper did contain a discussion of the cerebellar activations. Thus, Moore and Price [26] noticed that several regions of the cerebellum were differentially affected by task and stimulus type. They presented the distinct activations of the cerebellum in relation to the characteristics of the experimental procedure, but they concluded that ‘it is not clear at this stage what the significance of these findings is in relation to the segregation of function within the cerebellum’ [26, p. 190]. Semantics In spite of an extensive literature on the neuroimaging of semantic processing, only thirteen studies gathered activation data from the cerebellum. Unlike the studies focusing on auditory or visual input, all thirteen reported activation in cerebellum: six papers reported right cerebellar activation, two highlighted left activation and the five others bilateral activation. For example, Dehaene et al. [36] looked at mathematical intuition abilities, which may depend on linguistic competence or on visuospatial representations. They showed that there was a left cerebellar activation in the condition in which subjects had to estimate the result and select the closest number. The authors made no hypothesis regarding this activation. On the other hand, Hagoort et al. [37] included the cerebellum in their region of interest, for a PET study on silent reading and reading aloud of words and pseudowords. They considered the motor function of the cerebellum in language, affirming that this area (especially the left and medial parts) is engaged in the preparation and execution of articulation. However, none of the other studies reporting similar activation proposed this kind of motor explanation for their data. Thus, the reasons for these cerebellar activations accompanying the semantic processing of words remain to be discovered. Walter/Joanette

Speech Output and Written Output Although one might have expected to find more studies involving the cerebellum for such motor-related abilities, only six in the review of Démonet et al. [19] included the cerebellum in their scanning procedure: three related to speech output and the other three to written output. Furthermore, two of the three studies based on a written output task totally ignored the possible contribution of the cerebellum. Of the three studies looking at speech output, two reported right cerebellar activation and the other one bilateral activation of the cerebellum. For a speech output task, for example, Etard et al. [48] used PET to investigate lexical and semantic retrieval in normal volunteers by comparing picture confrontation naming and verb generation related to the same pictures. Naming and verb generation produced two distinct patterns: verb generation showed specific involvement of Broca’s and Wernicke’s areas, whereas naming specifically relied on the primary visual areas, the right fusiform and parahippocampal gyri and the left anterior temporal region. Their results also showed an activation of the right cerebellum during the verb generation task as compared to rest, which was significantly greater than during the naming task as compared to rest. The authors associated this activation of the cerebellum with the rehearsal system of verbal working memory. An example of a result for a written output task is provided by the study by Katanoda et al. [51]. These authors wanted to identify the regions crucial for the processing of writing, using fMRI. Three conditions were used, which differentially engaged visual, linguistic and/or motor functions: (1) writing names of pictures with the right index finger; (2) naming pictures silently, and (3) visually cued finger tapping. The results showed a complex pattern of brain activations, mostly in the right cerebellum. The authors suggested that the right cerebellar activation highlighted the necessity of more complex movements in the writing condition than in the tapping condition. In fact, they concluded that ‘the right cerebellar activation represents the difference in the complexity of the finger movements, although the possibility exists that the region is associated with a certain linguistic function’ [51, p. 41].

Concluding Remarks

The goal of our systematic review of literature was to explore the possibility that activations of the cerebellum could have been overlooked in the vast literature on the neuroimaging of language. The use of a recent and reThe Unnoticed Contributions of the Cerebellum to Language

spected published review [19] ensured the representativeness and thoroughness of the reported cerebral and cerebellar activations. Given the small proportion of studies acquiring data at the level of the cerebellum, the first conclusion has to do with the inclusion of the cerebellum in future neuroimaging studies of the bases of language processing. Though the methodological choice not to include the cerebellum in scanning appears at first glance to be totally legitimate in some cases, it expresses a more profound tautological malaise in some of the neuroimaging literature. Indeed, many studies include brain components that are a posteriori presumed to be activated and thus do not acquire data in areas which may unexpectedly make a contribution, such as the cerebellum. However, considering that approximately 34% of the studies reviewed did include the cerebellum in their scanning, one could say that the integration of the cerebellum into the network of central nervous system structures sustaining language is slowly consolidating. It is to be hoped that the cerebellum will be systematically included in future studies in order to gain a more precise idea of its effective contribution to language processing. At this point, and based on this literature review, its exact role is not yet perceivable. This approach should be extended to all components of cognition, given the importance of the anatomical links between the cerebellum and the rest of the brain, which suggest that the cerebellum is indeed a structure that contributes to the most complex cognitive processing.

References

1 Rolando L: Saggio sopra la vera struttura del cervello dell’uomo e degli animali, e sopra le funzioni del sistema nervoso. Sassari, 1809. 2 Flourens P: Détermination des propriétés du système nerveux. Mémoires lus à l’Académie des Sciences de l’Institut, 1822. 3 Magendie F: Mémoire sur les fonctions de quelques parties du système nerveux. J Physiol Exp Pathol 1824;4:399–407. 4 Luciani L: Il cervelletto. Nuovi studi di fisiologia normale e patologica. Florence, Le Monnier, 1891. 5 Thomas A: Le cervelet. Etude anatomique, clinique et physiologique. Paris, Steinheil, 1897. 6 Babinski J: De l’asynergie cérébelleuse. Rev Neurol 1899;7:806–816. 7 Holmes G: The cerebellum of man. Brain 1939;62:1–30. 8 Ito M: The Cerebellum and Neural Control. New York, Raven Press, 1984. 9 Leiner HC, Leiner AL, Dow RS: Does the cerebellum contribute to mental skills? Behav Neurosci 1986;100:443–454.

Folia Phoniatr Logop 2007;59:171–176

175

10 Ivry RB, Keele SW, Diener HC: Dissociation of the lateral and medial cerebellum in movement timing and movement execution. Exp Brain Res 1988;73:167–180. 11 Decety J, Sjoholm H, Ryding E, Stenberg G, Ingvar DH: The cerebellum participates in mental activity: tomographic measurements of regional cerebral blood flow. Brain Res 1990;535:313–317. 12 Ryding E, Decety J, Sjöholm H, Stenberg G, Ingvat DH: Motor imagery activates the cerebellum regionally: a SPECT rCBF study with 99mTc-HMPAO. Brain Res Cogn Brain Res 1993;1:94–99. 13 Leiner HC, Leiner AL, Dow RS: Cerebrocerebellar learning loops in apes and humans. Ital J Neurol Sci 1987;8:425–436. 14 Leiner HC, Leiner AL, Dow RS: Cognitive and language functions of the human cerebellum. Trends Neurosci 1993;16:444–447. 15 Silveri MC, Leggio MG, Molinari M: The cerebellum contributes to linguistic production: a case of agrammatic speech following a right cerebellar lesion. Neurology 1994;44: 2047–2050, comments 2001–2005. 16 Habas C: Le cervelet: de la coordination motrice aux fonctions cognitives. Rev Neurol 2001;157:1471–1497. 17 Bookheimer S: Functional MRI of language: new approaches to understanding the cortical organization of semantic processing. Ann Rev Neurosci 2002;25:151–188. 18 Gernsbacher MA, Kaschak MP: Neuroimaging studies of language production and comprehension. Annu Rev Psychol 2003; 54: 91– 114. 19 Démonet JF, Thierry G, Cardebat D: Renewal of the neurophysiology of language: functional neuroimaging. Physiol Rev 2005; 85: 49–95. 20 Thierry G, Giraud AL, Price C: Hemispheric dissociation in access to the human semantic system. Neuron 2003;38:499–506. 21 Belin P, Zatorre RJ, Lafaille P, Ahad P, Pike B: Voice-selective areas in human auditory cortex. Nature 2000;403:309–312. 22 Majerus S, Collette F, Van der Linden M, Peigneux P, Laureys S, Delfiore G, Degueldre C, Luxen A, Salmon E: A PET investigation of lexicality and phonotactic frequency in oral language processing. Cogn Neuropsychol 2002;19:343–360. 23 Paulesu E, Frith CD, Frackowiak RS: The neural correlates of the verbal component of working memory. Nature 1993; 362: 342– 345. 24 Wise RJ: Language systems in normal and aphasic human subjects: functional imaging studies and inferences from animal studies. Br Med Bull 2003;65:95–119. 25 Price CJ, Wise RJ, Warburton EA, Moore CJ, Howard D, Patterson K, Frackowiak RS, Friston KJ: Hearing and saying: the functional neuro-anatomy of auditory word processing. Brain 1996;119:919–931.

176

26 Moore CJ, Price CJ: Three distinct ventral occipitotemporal regions for reading and object naming. Neuroimage 1999;10:181–192. 27 Brunswick N, McCrory E, Price CJ, Frith CD, Frith U: Explicit and implicit processing of words and pseudowords by adult developmental dyslexics: a search for Wernicke’s Wortschatz? Brain 1999;122:1901–1917. 28 Herbster AN, Mintun MA, Nebes RD, Becker JT: Regional cerebral blood flow during word and nonword reading. Hum Brain Mapp 1997;5:84–92. 29 McCandliss BD, Cohen L, Dehaene S: The visual word form area: expertise for reading in the fusiform gyrus. Trends Cogn Sci 2003; 7:293–299. 30 Nakamura K, Honda M, Okada T, Hanakawa T, Toma K, Fukuyama H, Konishi J, Shibasaki H: Participation of the left posterior inferior temporal cortex in writing and mental recall of kanji orthography: a functional MRI study. Brain 2000;123:954–967. 31 Paulesu E, McCrory E, Fazio F, Menoncello L, Brunswick N, Cappa SF, Cotelli M, Cossu G, Corte F, Lorusso M, Pesenti S, Gallagher A, Perani D, Price C, Frith CD, Frith U: A cultural effect on brain function. Nat Neurosci 2000;3:91–96. 32 Price CJ, Friston KJ: Cognitive conjunction: a new approach to brain activation experiments. Neuroimage 1997;5:261–270. 33 Price CJ, Moore CJ, Frackowiak RS: The effect of varying stimulus rate and duration on brain activity during reading. Neuroimage 1996;3:40–52. 34 Rumsey JM, Horwitz B, Donohue BC, Nace K, Maisog JM, Andreason P: Phonological and orthographic components of word recognition: a PET-rCBF study. Brain 1997;120: 739–759. 35 Sakurai Y, Momose T, Iwata M, Sudo Y, Ohtomo K, Kanazawa I: Different cortical activity in reading of Kanji words, Kana words and Kana nonwords. Cogn Brain Res 2000;9:111–115. 36 Dehaene S, Spelke E, Pinel P, Stanescu R, Tsivkin S: Sources of mathematical thinking, behavioral and brain-imaging evidence. Science 1999;284:970–974. 37 Hagoort P, Indefrey P, Brown C, Herzog H, Steinmetz H, Seitz RJ: The neural circuitry involved in the reading of German words and pseudowords: a PET study. J Cogn Neurosci 1999;11:383–398. 38 Buckner RL, Koutstaal W, Schacter DL, Rosen BR: Functional MRI evidence for a role of frontal and inferior temporal cortex in amodal components of priming. Brain 2000;123:620–640. 39 Furey ML, Pietrini P, Haxby JV, Alexander GE, Lee HC, VanMeter J, Grady CL, Shetty U, Rapoport SI, Schapiro MB, Freo U: Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory. Proc Nat Acad Sci USA 1997;94:6512–6516.

Folia Phoniatr Logop 2007;59:171–176

40 Giraud AL, Truy E, Frackowiak RS, Gregoire MC, Pujol JF, Collet L: Differential recruitment of the speech processing system in healthy subjects and rehabilitated cochlear implant patients. Brain 2000; 123: 1391– 1402. 41 Hamzei F, Rijntjes M, Dettmers C, Glauche V, Weiller C, Büchel C: The human action recognition system and its relationship to Broca’s area: an fMRI study. Neuroimage 2003;19:637–644. 42 Kiehl KA, Liddle PF, Smith AM, Mendrek A, Forster BB, Hare RD: Neural pathways involved in the processing of concrete and abstract words. Hum Brain Mapp 1999; 7:225– 233. 43 Martin A, Wiggs CL, Ungerleider LG, Haxby JV: Neural correlates of category-specific knowledge. Nature 1996;379:649–652. 44 Mummery CJ, Patterson K, Hodges JR, Price CJ: Functional neuroanatomy of the semantic system: divisible by what? J Cogn Neurosci 1998;10:766–777. 45 Perani D, Cappa SF, Schnur T, Tettamanti M, Collina S, Rosa MM, Fazio F: The neural correlates of verb and noun processing: a PET study. Brain 1999;122:2337–2344. 46 Ruby P, Decety J: Effect of subjective perspective taking during simulation of action: a PET investigation of agency. Nat Neurosci 2001;4:546–550. 47 Vandenberghe R, Price C, Wise R, Josephs O, Frackowiak RS: Functional anatomy of a common semantic system for words and pictures. Nature 1996;383:254–256. 48 Etard O, Mellet E, Papathanassiou D, Benali K, Houde O, Mazoyer B, Tzourio-Mazoyer N: Picture naming without Broca’s and Wernicke’s area. Neuroreport 2000;11:617–622. 49 Ackermann H, Wildgruber D, Daum I, Grodd W: Does the cerebellum contribute to cognitive aspects of speech production? A functional magnetic resonance imaging (fMRI) study in humans. Neurosci Lett 1998; 247:187–190. 50 Desmond JE, Gabrieli JD, Glover GH: Dissociation of frontal and cerebellar activity in a cognitive task: evidence for a distinction between selection and search. Neuroimage 1998;7:368–376. 51 Katanoda K, Yoshikawa K, Sugishita M: A functional MRI study on the neural substrates for writing. Hum Brain Mapp 2001; 13:34–42. 52 Matsuo K, Kato C, Ozawa F, Takehara Y, Isoda H, Isogai S, Moriya T, Sakahara H, Okada T, Nakai T: Ideographic characters call for extra processing to correspond with phonemes. Neuroreport 2001;12:2227–2230. 53 Matsuo K, Kato C, Tanaka S, Sugio T, Matsuzawa M, Inui T, Moriya T, Glover GH, Nakai T: Visual language and handwriting movement: functional magnetic resonance imaging at 3 tesla during generation of ideographic characters. Brain Res Bull 2001; 55: 549–554.

Walter/Joanette

Folia Phoniatr Logop 2007;59:177–183 DOI: 10.1159/000102929

Cerebellum and Reading Filippos Vlachos a Ilias Papathanasiou b Georgia Andreou a a

University of Thessaly, Volos, and b Technological Educational Institute of Patras, Patras, Greece

Key Words Cerebellum
Reading
Reading difficulties

Abstract Background: Traditionally, the cerebellum has been considered to control coordinated movement. However, in recent years it has been argued that it contributes to higher cognitive functions. Objectives: This review aims to present recent evidence concerning the role of the cerebellum and discusses how it can contribute to reading. Method: The procedure used involves findings coming from three quite different areas, lesion, anatomic and functional imaging studies. Results: These studies indicate a link between cerebellum and reading and its relationship with specific reading difficulties. Conclusions: Our review provides evidence which is in accordance with the recently established role of the cerebellum as a regulator of mental functions and supports theoretical models suggesting that cerebellar deficits might be a cause of developmental dyslexia. Copyright © 2007 S. Karger AG, Basel

Reading – the process of extracting meanings from print – involves both visual-perceptual and linguistic faculties. This complex neurocognitive activity involves multimodal component operations and requires the use of widely distributed areas of the brain. In brief outline, reading must begin with sensing of visual stimuli and processing of information through the pathway of the retina, lateral geniculate nuclei and primary visual cortex [1]. At some stage, visual information is probably made

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0177$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

available to neuronal systems that apply learned, language-specific rules to convert symbolic images into component representations of language [2] and that perhaps evolved for processing of spoken language. Readingrelated cognition is accompanied by high activation of left-hemisphere cortical regions, including some areas known to be important in language processing [3, 4]. However, learning to read may also depend on other implicit learning processes, which allow acquiring and executing new motor, perceptual and cognitive skills. Thus, those processes lead to automatization of the mechanisms reading is based on, such as phonological processing and the ability to automatize elementary articulatory and auditory skills which are perhaps mediated partly by the cerebellum [5, 6], and on feedback between these mechanisms. A simple example of feedback is that eye movements during reading must be appropriately regulated by previous progress along a line of text or through a word; hence, fine sensorimotor coordination must also be involved [7, 8]. A deficit in reading ability might stem from diverse disruptions to the range of neural systems used in reading, from simple sensory impairments to impairments in complex cognitive processes, particularly those related to language. Researchers have used neuropsychological, psychophysical, event-related potential and functional brain imaging methods to study differences between individuals with reading difficulties (dyslexia) and controls during a wide variety of sensory [9, 3, 10], cognitive [11] and behavioral [5, 6] tasks aiming at localizing brain areas involved in the reading process.

Dr. Ilias Papathanasiou Department of Speech and Language Therapy, TEI Patras 1, Megalou Alexandrou Street GR–26334 Patras (Greece) Tel. +30 2610 369 160, Fax +30 2610 369 167, E-Mail [email protected]

Hemispere

Vermis Anterior lobe

Primary fissure Posterior lobe Horizontal fissure

Posterior fissure

Flocculus

Flocculonodular lobe Nodulus

Fig. 1. The regions, lobes and main fissures of the cerebellum.

The goal of this review is to summarize and evaluate recent neurobiological evidence, which puts the relation between cerebellum and reading process on a new basis. With the advent of more sophisticated neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), numerous diverse functions are now at least partially attributed to the cerebellum. What was once thought to be primarily a motor/sensory integration region is now proving to be involved in many diverse functions. The cerebellum may participate in reading processes, traditionally considered a cerebral cortex domain.

Anatomy and Function of the Cerebellum

The cerebellum is a complex structure which plays an important role in sending and receiving messages (nerve signals) necessary for the production of muscle movements and coordination. There are both afferent (input) and efferent (output) pathways in the cerebellum. The cerebellum is located in the posterior fossa of the skull, dorsal to the pons and medulla, from which it is separated by the aqueduct of Sylvius and the fourth ventricle. Certain terms are used to identify regions of the cerebellum. At the basic level, it is divided into 3 distinct areas: the vermis (the region in and near the midline) and the paravermis (also called the intermediate zone), while the reminder of the cerebellum is referred to as the ‘hemispheres’. The cerebellar surface is folded to form long, transverse convolutions called ‘folia’, separated by paral178

Folia Phoniatr Logop 2007;59:177–183

lel ‘sulci’. The surface is divided into ‘lobes’ or ‘lobules’ by a number of fissures and sulci, most of which are transversely oriented. The ‘primary fissure’ separates the ‘anterior’ and ‘posterior lobes’ of the cerebellum. The anterior lobe is everything rostral to the primary fissure, while the posterior lobe is everything between the primary fissure and the ‘posterolateral fissure’. The posterolateral fissure separates the posterior and ‘flocculonodular lobe’. The flocculonodular lobe is a small component that lies at the rostral edge of the inferior surface. In fact, each lobe consists of a vermal and hemispheric component. In the midsagittal view of the cerebellum, the vermis is divided into 10 lobules (I–X). Lobules I–V are part of the anterior lobe, VI–IX are part of the posterior lobe, and X is part of the flocculonodular lobe. The 3 lobes have different functions: the anterior lobe and parts of the posterior lobe (the vermis and paravermis) form the spinocerebellum, a region that plays a role in the control of proximal muscles, posture and locomotion such as walking. The cerebellar hemispheres (part of the posterior lobe) are collectively known as the cerebrocerebellum (or the pontocerebellum); they receive signals from the cerebral cortex and aid in the initiation, coordination and timing of movements. The cerebrocerebellum is also thought to play a role in cognition and affective state (fig. 1). Three main theories address the function of the cerebellum. One claims that it functions as a regulator of the ‘timing of movements’. This emerged from studies of patients whose timed movements are disrupted [12]. The second theory claims that the cerebellum operates as a learning machine, encoding information as does a computer. This was first proposed by Marr and Albus in the early 1970s [13]. The third, the ‘Tensor Network Theory’, provides a mathematical model of transformation of sensory (covariant) space-time coordinates into motor (contravariant) coordinates by cerebellar neuronal networks [14, 15]. Like many controversies in the physical sciences, there is evidence supporting the above hypotheses. Studies of motor learning in the vestibulo-ocular reflex and eyeblink conditioning demonstrate that the timing and amplitude of learned movements are encoded by the cerebellum [16]. Many synaptic plasticity mechanisms have been found throughout the cerebellum. The Marr-Albus model mostly attributes motor learning to a single plasticity mechanism: the long-term depression of parallel fiber synapses. The Tensor Network Theory of sensorimotor transformations by the cerebellum has also been experimentally supported [17, 18].

Vlachos /Papathanasiou /Andreou

During recent years clinical, experimental and functional neuroimaging studies have demonstrated that the cerebellum is involved in multiple different functions from arousal to sensorimotor function and higher-order processing. Preliminary evidence suggests that there is a topographic arrangement of these functions within the cerebellum. The evolving understanding of this broader role of the cerebellum has been facilitated and substantiated by new insights into the cerebellar connections with other brain regions. Given the uniformity of the cerebellar cortical architecture, the connectional specificity of the cerebrocerebellar pathways confers on the cerebellum the ability to modulate the wide array of behaviors attributed to it [19–22].

Anatomical Research

Morphological neuroimaging studies, mainly using MRI, have compared brains from (mainly adult) dyslexics to those of normal controls. The anatomomorphological correlations in dyslexia started with the postmortem observations of Galaburda et al. [23, 24], who reported more symmetric plana temporale in dyslexic subjects. The analysis of the cortical pathology demonstrated the presence of a diffuse pattern of cortical scars, dyslaminations and ectopias. A morphological postmortem anatomical study is also available for the cerebellum, based on the same specimens from the Orton Society Brain Bank used by Galaburda et al.; in their study, Finch et al. [25] identified a significantly larger mean cellular area in the medial posterior and in the anterior lobe of the cerebellar cortex for the dyslexic subjects. Leonard et al. [26], using MRI, reported 4 anatomical measures that differentiate their phonological dyslexic subjects from the reading-disabled and control subjects: (i) marked rightward cerebral asymmetry; (ii) marked leftward asymmetry of the anterior lobe of the cerebellum; (iii) combined leftward asymmetry of the planum temporale and posterior ascending ramus of the sylvian fissure, and (iv) large duplication of Heschl’s gyrus on the left. Eckert et al. [27], also using MRI, found significant morphological cerebral alterations in dyslexic children, such as smaller right anterior cerebellar lobes, pars triangularis of the inferior frontal gyrus bilaterally and overall brain volume. All these areas showed significant correlations with reading, spelling and language measures. Finally, in an MRI morphometric study on the cerebellum, Rae et al. [28] found that, although normal controls had a larger right hemispheric cerebellar cortical surface, the Cerebellum and Reading

cerebellar hemispheres in the dyslexic subjects were symmetric. The degree of cerebellar symmetry was correlated with the severity of dyslexics’ phonological decoding deficit. Those with a more symmetric cerebellum made more errors on a nonsense word reading measure of phonological decoding ability. Anatomical studies also found biochemical differences between dyslexic men and controls in the left temporoparietal lobe and right cerebellum [28]. These metabolic abnormalities showed that the cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction. Brown et al. [29], using a voxel-based morphometric analysis, compared the MR images of 16 men with dyslexia with those of 14 control subjects. They found evidence of decreases in grey matter in dyslexic subjects, most notably in the left temporal lobe and bilaterally in the temporoparieto-occipital juncture, but also in the frontal lobe, caudate, thalamus and cerebellum. In a recent voxel-based morphometric study, Brambati et al. [30] observed significant reductions of grey matter volume in areas of the brain associated with language and reading processing in people with a family history of dyslexia in comparison with controls who had no reading problems. Significant grey matter reductions were located bilaterally in the planum temporale, inferior temporal cortex, cerebellar nuclei, and in the left superior and inferior temporal regions. Overall, structural MRI studies of dyslexic children and adults have demonstrated differences compared to controls in a variety of brain regions, including the inferior frontal gyrus, cerebellum, insula, caudate, corpus callosum, left temporal lobe and thalamus. Of course, all these studies also found differences between controls and dyslexics in many other areas besides the cerebellum, but the cerebellum is one of the most consistent locations for structural differences between dyslexic and control participants in imaging studies [27]. Taken together, the MRI morphometric studies published so far on dyslexia reveal complex and variable anatomical patterns: these may be relevant for dyslexia as a neurological syndrome and the distribution of the underlying pathology, but perhaps less informative on which morphometric abnormality is truly relevant for the core neuropsychological syndrome of dyslexia, i.e. the deficit in the phonological component of language.

Folia Phoniatr Logop 2007;59:177–183

179

Cerebellar Lesion Studies

In humans, studies of cerebellar lesions show deficits in error detection, language, attentional control and problem-solving [19]. In lesion studies, infarcts of the right cerebellum have resulted in impaired linguistic processing manifested as agrammatism or impaired error detection and learning of a verb generation task [31, 32]. Studies of children with cerebellar tumors demonstrate a critical role of the right cerebellar hemisphere in linguistic performance [33, 34]. For example, small samples of children with right cerebellar tumors exhibited poor verbal and literacy performance, in contrast to children with left cerebellar tumors and spatial deficits [34]. Akshoomoff et al. [35] reported poor verbal fluency and naming performance in a patient with cerebellar degenerative disorder. To test the hypothesis of cerebellar involvement in the reading process – justified by its emergent role in language and cognition – Moretti et al. [36] studied 10 patients with cerebellar vermis/paravermis lesions using reading tests, and they compared the results with those produced by 10 normal volunteers. The data obtained demonstrate an increased number of reading mistakes in the patient group, resulting from a possible alteration of the diffuse connection system from the cerebellum to different cerebrocortical and subcortical structures. According to the researchers it is plausible that some cerebellar structures (right cerebellar hemisphere and portions of the vermis) control language processing by integrating their activity with the so-called ‘frontal lobe system’, disrupting therefore, in consequence of pathological lesions, some linguistic procedure, such as reading [37]. They conclude, therefore, that acquired dyslexia may also be considered as a consequence of selective impairment of the vermis/paravermis region. Action and perception are strongly coupled in the act of reading, and visual perception is tightly bound to attention and to activation of brain regions necessary for action preparation. Acquired dyslexia cases, described by Moretti et al. [38], may be due to oculomotor alteration, or more subtly to the intimate cerebellar-encephalic projections, connecting the cerebellum to the attentive and alerting process and to language systems. In this way the cerebellum may participate in the reading process, traditionally considered a cerebral cortex domain.

180

Folia Phoniatr Logop 2007;59:177–183

Functional Neuroimaging Studies

Functional neuroimaging studies used first PET and then fMRI to observe the brain in function, especially during the act of reading. Such studies demonstrate that a widespread set of brain regions is engaged during reading tasks [39]. One of the first studies involving reading and functional neuroimaging was conducted by Petersen et al. [40]. The authors used a PET technique to determine orthographic effects in 8 right-handed individuals. They used 4 types of stimulus: real words (single common nouns), pseudowords (letter strings that obey the rules of English orthography), unpronounceable consonant letter strings and false letters, and they identified the activation of the lateral extrastriate cortex in the 4 groups of stimuli. Words and pseudowords produced activation of the medial extrastriate cortex on the left. Comparing the activation in the passive presentation of real words and pseudowords, the activation of the left frontal cortex was verified during the silent reading of real words, suggesting that the prefrontal area on the left could be involved in the semantic processing of words. During reading tasks, fMRI demonstrated an activation of the left occipital and temporal cortex, the left frontal operculum, bilateral motor, supplementary motor cortex and also cerebellum [41]. Fulbright et al. [42] designed an fMRI study to determine whether cerebellar activation occurs during cognitive tasks that differentially engage the component processes of word identification in reading. After studying 42 neurologically normal adults they found that specific regions of the cerebellar hemispheres (part of the posterior lobe) activate in response to phonological and semantic tasks. More specifically, during phonologic assembly, cerebellar activation was observed in the middle and posterior aspects of the posterior superior fissure and adjacent simple lobule (lobule VI) and semilunar lobule (which occupies the posterior third of the upper surface of the hemispheres) bilaterally and in posterior aspects of the simple lobule, superior semilunar lobule and inferior semilunar lobule bilaterally. Semantic processing, however, resulted in activation in the deep nuclear region on the right and in the inferior vermis, in addition to posterior areas which were active during phonologic assembly, including the simple, superior semilunar and inferior semilunar lobules. Researchers concluded that the cerebellum is engaged during reading and is differentially activated in response to phonologic and semantic tasks. These results indicate that the cerebellum contributes to the cognitive processes integral to reading. Vlachos /Papathanasiou /Andreou

In a very recent study [43], fMRI was used to investigate the patterns of cerebral activation in lexical and phonological reading in 13 healthy women with a formal educational level longer than 11 years. Participants were submitted to a silent reading task containing 3 types of stimulus: real words (irregular and foreign words), nonwords and illegitimate graphic stimuli. An increased number of activated voxels was identified by fMRI in the word reading (lexical processing) rather than in the nonword reading (phonological processing) task. Activation was greater for word reading than for nonwords in the following areas: superior, middle and inferior frontal gyri, and bilateral superior temporal gyrus, right cerebellum and the left precentral gyrus, as indicated by fMRI. In the reading of nonwords, the activation was predominant in the right cerebellum and in the left superior temporal gyrus. In this study, the right cerebellar hemisphere was activated in both the word and nonword reading tasks in more than half the subjects, suggesting the participation of the cerebellum in reading, engaged not only in the ability of phonologic assembly but also in semantic processing. Additional evidence for cerebellar contribution to reading process comes from another recent study which investigated whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements [44]. Early blind and normal sighted subjects were studied with MRI during Braille reading, tactile discrimination of nonsense dots, dots forming symbols and finger tapping. The results showed that parts of cerebellar activation during Braille reading in blind subjects (i.e. within lobules IV, V and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. However, additional cerebellar activation during Braille reading within bilateral semilunar lobule (which occupies the posterior third of the upper surface of the hemispheres) may be due to language processes or inner speech similar to those found during text reading in normal sighted subjects. Because of the reason that intersubject variability and subtle differences in experimental design can lead to variable results in studies of cognitive processes such as reading, Turkeltaub et al. [45] conducted a meta-analysis from 11 PET studies of the functional neuroanatomy of single-word reading. Regions of significant concordance were identified in bilateral motor and superior temporal cortices, left fusiform gyrus and the cerebellum. These meta-analytic results were validated by comparison with new fMRI data on aloud word reading in normal adult

subjects. Excellent correspondence between the 2 statistical maps was observed, with fMRI maxima lying close to all meta-analysis peaks and statistical values at the peaks identified by the 2 techniques correlating strongly. This close correspondence between PET meta-analysis and fMRI results also demonstrates the validity of using fMRI for the study of language tasks involving overt speech responses. Despite this constant evidence, functional imaging studies alone are not able to provide answers as to the functional significance of the cerebellum for reading process. Although they show involvement of specific brain areas in reading tasks, they cannot determine their relevance; however, they may serve to generate hypotheses regarding the type and location of computations in the cerebellum.

Cerebellum and Reading

Folia Phoniatr Logop 2007;59:177–183

Conclusions

Clinical and anatomic data as well as functional imaging studies have given rise to new ideas about cerebellar function, particularly stressing the importance of cerebrocerebellar interactions for a variety of cognitive functions, including language [21, 46]. Although some authors still hold that these ‘language’ deficits in cerebellar patients are confined to the motor aspects of language, e.g. the lack of motor coordination of the muscles required for phonation, many linguistic deficits reported after cerebellar lesions, e.g. dysprosodia, agrammatism, anomia or reduced verbal fluency, can scarcely be explained solely as a result of limited motor coordination [46, 47]. By combining fMRI with hierarchically organized reading tasks, Fulbright et al. [42] showed that the cerebellum activates during reading tasks and it becomes more active as cognitive demands increase. They also identified neuroanatomic foci in the cerebellum that were differentially engaged in phonologic assembly (posterior superior fissure and adjacent simple and superior semilunar lobules in the middle part of the cerebellum) and lexical-semantic processing (the right deep nuclear region and the inferior vermis), indicating that in addition to motor function, the cerebellum is involved in cognitive processes that are integral to word identification in reading. The results for cerebellum involvement in reading are consistent with an emerging research literature that shows that the cerebellum activates during learning and not just motor function – the circuits of the cerebellum that are activated during the learning phase differ from 181

those activated during the automatic phase following practice and learning [48, 49]. The study by Nicolson et al. [48] showed that dyslexic participants demonstrated less PET activation in the right cerebellar anterior lobe when they performed learned finger movement sequences. The reduced activation volume could be related to reduced anterior lobe size. These findings are consistent with Fawcett and Nicolson’s cerebellar deficit hypothesis, which attributes the cognitive and motor problems exhibited by individuals with dyslexia to disrupted cerebellar pathways and/or primary cerebellar impairment [5, 50]. Lately, there has been great debate about this theory, with some researchers [51] remaining skeptical in front of the contradicting data and others [52, 53] challenging the idea that a cerebellar lesion or dysfunction could be the main cause of developmental dyslexia, while offering possible explanations concerning other, mainly cerebral, brain areas [5]. Lesion studies support this idea and demonstrate verbal, linguistic and naming deficits in children with cerebellar tumors [33, 34], reading errors in adults with vermal lesions [36] and olivopontocerebellar atrophy [38], and depressed cerebellar activation in dyslexic compared to control adults when performing reading and phonological tasks [54]. Based on the aforementioned studies and on the known anatomic pathways between the cerebral cortex and the cerebellum [19, 55], we postulate that the cerebellum might play a part in word identification in reading. A growing body of evidence based on anatomic research, lesion studies and functional imaging research indicates that the cerebellum is involved in language and reading tasks and other cognitive processes. Anatomically, the

cerebellum has more neurons than the cerebrum and has an input-to-output axon ratio of 40:1 [56]. The cerebellum is a widely connected region, having physiologic links with all of the major divisions of the central nervous system [19]. These anatomic links, especially those to regions in the frontal, temporal and parietal lobes that are engaged in reading, may be a reason for part of the cerebellar activity during the process of reading. Therefore, possible anomalies or lesions in those links may produce harmful effects on the function of the cerebellum by disrupting some linguistic procedure such as reading. We conclude that the studies have revealed interesting evidence of cerebellar abnormalities in dyslexic brains. Although the slight discrepancy between studies could reflect the different methods used (neuropathology vs. in vivo imaging), it might also mirror the heterogeneity of conditions such as developmental dyslexia, which does not have consistent diagnostic criteria. We believe that the evidence reviewed here in conjunction with other behavioral and neurophysiological evidence provides important information that will lead to a better understanding of the underlying causes of dyslexia. The several neurofunctional systems implicated in the reading process and the anatomic variability within the dyslexic population may justify the widely distributed morphologic differences found in dyslexia. If a heterogeneous neurobiological substrate is indicative of diverse deficits in dyslexia, further studies in which subpopulations are identified through finer neurofunctional testing might determine the nature of neuroanatomic variability in reading disorders.

References 1 Kandel E, Schwartz J, Jessell T: Principles of Neural Science. New York, McGraw-Hill, 2000. 2 Castles A, Coltheart M: Varieties of developmental dyslexia. Cognition 1993; 47: 149– 180. 3 Eden G, Zeffiro T: Neural systems affected in developmental dyslexia revealed by functional neuroimaging. Neuron 1998; 21: 279– 282. 4 Pugh K, Mencl W, Jenner A, Katz L, Frost S, Lee J, Shaywitz S, Shaywitz B: Functional neuroimaging studies of reading and reading disability (developmental dyslexia). Ment Retard Dev Disabil Res Rev 2000; 6: 207–213.

182

5 Nicolson R, Fawcett A, Dean P: Developmental dyslexia: the cerebellar deficit hypothesis. Trends Neurosci 2001;24:508–511. 6 Rae C, Harasty J, Dzentrowskyj T, Talcott J, Simpson J, Blamire A, Richardson A, Stein J: Cerebellar morphology in developmental dyslexia. Neuropsychologia 2002; 4: 1285– 1292. 7 Stein J, Richardson A, Fowler M: Monocular occlusion can improve binocular control and reading in dyslexics. Brain 2000; 123: 164– 170. 8 Velay J, Daffaure V, Giraud K, Habib M: Interhemispheric sensorimotor integration in pointing movements: a study on dyslexic adults. Neuropsychologia 2002;40:827–834.

Folia Phoniatr Logop 2007;59:177–183

9 Habib M: The neurological basis of developmental dyslexia: an overview and working hypothesis. Brain 2000;123:2373–2399. 10 Stein J, Walsh V: To see but not to read: the magnocellular theory of dyslexia. Trends Neurosci 1997;20:147–152. 11 Snowling M: Dyslexia. A Cognitive Developmental Perspective. Oxford, Blackwell, 1987. 12 Ivry R, Keele S, Diener H: Dissociation of the lateral and medial cerebellum in movement timing and movement execution. Exp Brain Res 1988;73:167–180. 13 Marr D: A theory of the cerebellar cortex. J Physiol 1969;202:437–470.

Vlachos /Papathanasiou /Andreou

14 Pellionisz A, Llinás R: Tensorial approach to the geometry of brain function: cerebellar coordination via a metric tensor. Neuroscience 1980;5:1125–1136. 15 Pellionisz A, Llinás R: Tensor network theory of the metaorganization of functional geometries in the CNS. Neuroscience 1985;16: 245–273. 16 Boyden E, Katoh A, Raymond J: Cerebellumdependent learning: the role of multiple plasticity mechanisms. Annu Rev Neurosci 2004;2:581–609. 17 Pellionisz A, Llinás R: Space-time representation in the brain: the cerebellum as a predictive space-time metric tensor. Neuroscience 1982;7:2949–2970. 18 Gielen C, van Zuylen E: Coordination of arm muscles during flexion and suspiration: application of the tensor analysis approach. Neuroscience 1986;17:527–539. 19 Schmahmann J: The cerebrocerebellar system: anatomic substrates of the cerebellar contribution to cognition and emotion. Int Rev Psychiatry 2001;13:247–260. 20 Bloom R, Ferrand C: Neuromotor speech disorders; in Ferrand CT, Bloom RL (eds): Introduction to Organic and Neurogenic Disorders of Communication. Current Scope of Practice. Boston, Allyn & Bacon, 1997, pp 166–192. 21 Fiez J, Raichle M: Linguistic processing. Int Rev Neurobiol 1997;41:233–254. 22 Ackermann H, Wildgruber D, Daum I, Grodd W: Does the cerebellum contribute to cognitive aspects of speech production? A functional magnetic resonance imaging (fMRI) study in humans. Neurosci Lett 1998; 247:187–190. 23 Galaburda A, Sanides F, Geschwind N: Human brain: cytoarchitectonic left-right asymmetries in the temporal speech region. Arch Neurol 1978;35:812–817. 24 Galaburda A, Sherman G, Rosen G, Aboitiz F, Geschwind N: Developmental dyslexia: four consecutive patients with cortical anomalies. Ann Neurol 1985;18:222–233. 25 Finch A, Nicolson R, Fawcett A: Evidence for a neuroanatomical difference within the olivo-cerebellar pathway of adults with dyslexia. Cortex 2002;38:529–539. 26 Leonard C, Eckert M, Lombardino L, Oakland T, Kranzler J, Mohr C, King W, Freeman A: Anatomical risk factors for phonological dyslexia. Cereb Cortex 2001;11:148–157. 27 Eckert M, Leonard C, Richards T, Aylward E, Thomson J, Berninger V: Anatomical correlates of dyslexia: frontal and cerebellar findings. Brain 2003;126:482–494.

Cerebellum and Reading

28 Rae C, Lee M, Dixon R, Blamire A, Thompson C, Styles P, Talcott J, Richardson A, Stein J: Metabolic abnormalities in developmental dyslexia detected by H-1 magnetic resonance spectroscopy. Lancet 1998;351:1849–1852. 29 Brown W, Eliez S, Menon V, Rumsey J, White C, Reiss A: Preliminary evidence of widespread morphological variations of the brain in dyslexia. Neurology 2001;56:781–783. 30 Brambati S, Termine C, Ruffino M, Stella G, Fazio F, Cappa S, Perani D: Regional reductions of grey matter volume in familial dyslexia. Neurology 2004;63:742–745. 31 Fiez J, Petersen S, Cheney M, Raichle M: Impaired non-motor learning and error detection associated with cerebellar damage: a single case study. Brain 1992;115:155–178. 32 Silveri MC, Leggio MG, Molinari M: The cerebellum contributes to linguistic production: a case of agrammatic speech following a right cerebellar lesion. Neurology 1994;44: 2047–2050. 33 Riva D, Giorgi C: The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours. Brain 2000;123:1051–1061. 34 Scott R, Stoodley C, Anslow P, Stein J, Sugden E, Mitchell C: Lateralized cognitive deficits in children following cerebellar lesions. Dev Med Child Neurol 2001;43:685–691. 35 Akshoomoff N, Courchesne E, Press G, Iraqui V: Contribution of the cerebellum to neuropsychological functioning: evidence from a case of cerebellar degenerative disorder. Neuropsychologia 1992;30:315–328. 36 Moretti R, Bava A, Torre P, Antonello R, Gazzato G: Reading errors in patients with cerebellar vermis lesions. J Neurol 2002;249: 461–468. 37 Fabbro F, Moretti R, Bava A: Language impairments in patients with cerebellar lesions. J Neurolinguistics 2000;13:173–188. 38 Moretti R, Torre P, Antonello R, Carraro M, Zambito-Marsala S, Ukmar M: Peculiar aspects of reading and writing performances in patients with olivopontocerebellar atrophy. Percept Mot Skills 2002;94:677–694. 39 Klingberg T, Hedehus M, Temple E, Gabrieli J, Moseley M: Microstructure of temporoparietal white matter as a basis for reading ability: evidence from diffusion tensor magnetic resonance imaging. Neuron 2000; 25: 493–500. 40 Petersen S, Fox P, Posner M, Mintun M, Raichle M: Positron emission tomographic studies of the cortical anatomy of singleword processing. Nature 1998;331:585–589. 41 Fiez J, Petersen S: Neuroimaging studies of word reading. Proc Natl Acad Sci USA 1998; 95:914–921.

42 Fulbright R, Jenner A, Mencl W, Pugh K, Shaywitz B, Shaywitz SE, Frost SJ, Skudlarski P, Constable RT, Lacadie CM, Marchione KE, Gore JC: The cerebellum’s role in reading: a functional MR imaging study. Am J Neuroradiol 1999;20:1925–1930. 43 Senaha M, Martin M, Amaro E, Campi C, Caramelli P: Patterns of cerebral activation during lexical and phonological reading in Portuguese. Braz J Med Biol Res 2005; 38: 1847–1856. 44 Gizewski E, Timmann D, Forsting M: Specific cerebellar activation during Braille reading in blind subjects. Hum Brain Mapp 2004;22:229–235. 45 Turkeltaub P, Eden G, Jones K, Zeffiro T: Meta-analysis of the functional neuroanatomy of single-word reading: method and validation. Neuroimage 2002;16:765–780. 46 Molinari M, Leggio M, Solida A, Ciorra R, Misciagna S, Silveri MC, Petrosini L: Cerebellum and procedural learning: evidence from focal cerebellar lesion. Brain 1997;120: 1753–1763. 47 Schmahmann J, Sherman J: Cerebellar cognitive affective syndrome. Int Rev Neurobiol 1997;41:433–440. 48 Nicolson R, Fawcett A, Berry E, Jenkins I, Dean P, Brooks D: Association of abnormal cerebellar activation with motor learning difficulties in dyslexic adults. Lancet 1999; 353:1662–1667. 49 Poldrack R, Gabrieli J: Characterizing the neural mechanisms of skill learning and repetition priming: evidence from mirror reading. Brain 2001;124:67–82. 50 Nicolson R, Fawcett A: Automaticity: a new framework for dyslexia research? Cognition 1990;35:159–182. 51 Beaton A: Dyslexia and the cerebellar deficit hypothesis. Cortex 2002;38:479–490. 52 Ivry R, Justus T: A neural instantiation of the motor theory of speech perception. Trends Neurosci 2001;24:513–515. 53 Zeffiro T, Eden G: The cerebellum and dyslexia: perpetrator or innocent bystander? Trends Neurosci 2001;2:512–513. 54 Brunswick N, McCrory E, Price C, Frith C, Frith U: Explicit and implicit processing of words and pseudowords by adult developmental dyslexics. Brain 1999; 122: 1901– 1917. 55 Middleton F, Strick P: Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science 1994; 266:458–461. 56 Carpenter M: Core Text of Neuroanatomy, ed 4. Baltimore, Williams & Wilkins, 1991.

Folia Phoniatr Logop 2007;59:177–183

183

Folia Phoniatr Logop 2007;59:184–189 DOI: 10.1159/000102930

Language Disorders Subsequent to Left Cerebellar Lesions: A Case for Bilateral Cerebellar Involvement in Language? Bruce E. Murdoch Brooke-Mai Whelan Motor Speech and Neurogenic Language Disorders Research Centre, The University of Queensland, Brisbane, Australia

Key Words Left cerebellar lesion
Cerebellum, language
Diaschisis

Abstract Background: Crossed cerebello-cerebral diaschisis, reflecting a functional depression of supratentorial language areas due to reduced input via cerebello-cortical pathways, may represent the neuropathological mechanism responsible for language deficits associated with cerebellar pathology. Although it has been proposed that language is lateralized to the right cerebellar hemisphere, recent clinical and neuroimaging studies suggest that the cerebellum may bilaterally influence the regulation of language, with the left cerebellar hemisphere also contributing to the mediation of language via ipsilateral cerebello-cortical pathways. Aims: The aim of the study was to determine the effect of left primary cerebellar lesions on general as well as higher-level language function. Methods and Procedures: Linguistic profiles of a group of ten individuals with left primary cerebellar lesions were compared with those of a group of non-neurologically impaired controls matched for age, gender and level of education. Outcomes and Results: The findings confirmed that higher-level language deficits may result from left primary cerebellar lesions possibly as a consequence of ipsilateral cerebral diaschisis. Conclusions: The results challenge the notion of a right lateralized cerebellum and support a role for the left as well as the right cerebellar hemisphere in the regulation of language function. Copyright © 2007 S. Karger AG, Basel

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0184$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

Introduction

Investigation of a possible role for the cerebellum in the mediation of cognitive processes, including language, has historically been overshadowed by research interest in cerebellar coordination of motor control [1]. Recent advances in our understanding of the neuroanatomy of the cerebellum combined with evidence from functional neuroimaging, neurophysiological and neuropsychological research, has, however, extended our view of the cerebellum from that of a simple coordinator of autonomic and somatic motor function. Rather, it is now more widely accepted that the cerebellum, and in particular the right cerebellar hemisphere, participates in the modulation of cognitive functioning, especially of those parts of the brain to which it is reciprocally connected [2]. Indeed, the discovery of major reciprocal neural pathways between the cerebellum and the frontal areas of the language-dominant hemisphere, including Broca’s area and the supplementary motor area, was a major impetus in the development of the concept of cerebellar involvement in non-motor linguistic processes. During the past decade, numerous studies have identified the presence of disturbed language processing in association with primary lesions of various aetiologies involving the right cerebellar hemisphere (for reviews see [2, 3]). Marien et al. [2] proposed the concept of a ‘lateralized linguistic cerebellum’. Based on a comprehensive review of the literature, they noted that the right cerebellar

Prof. Bruce E. Murdoch School of Health and Rehabilitation Sciences The University of Queensland Brisbane, Qld. 4072 (Australia) E-Mail [email protected]

hemisphere was implicated in several aspects of language processing including semantic and phonological word retrieval as well as syntactic and dynamic processing. Although the concept of ‘crossed aphasia’ in relation to cortical-based language disorders is well documented, to date only 2 studies have reported the occurrence of language problems in right-handed individuals in association with left cerebellar hemisphere lesions [4, 5]. Fabbro et al. [5] documented the case of a 59-year-old, righthanded woman with fluent spontaneous speech, morphosyntactic errors, poor grammatical comprehension and poor mental arithmetic skills subsequent to surgery for removal of a left cerebellar astrocytoma. Similarly, Cook et al. [4] outlined the linguistic profiles of 5 individuals with left primary cerebellar lesions of vascular origin. All 5 of their participants demonstrated deficits on measures of word fluency, sentence construction within a set context, producing word definitions and producing multiple definitions for the same words. Cook et al. [4] also reported deficits for several of their participants on measures of understanding figurative language, forming word associations, identifying and correcting semantic absurdities and producing synonyms and antonyms. Collectively, the findings of Cook et al. [4] and Fabbro et al. [5] highlight the need for further investigation of language disorders associated with left cerebellar lesions in order to further elucidate the extent and nature of language lateralization in the cerebellum. It has been proposed that crossed cerebral diaschisis, reflecting a functional depression of supratentorial language areas due to reduced input via cerebello-cortical pathways, may represent the neuropathological mechanism responsible for language deficits associated with cerebellar pathology [2, 6, 7]. Studies based on neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography and magnetic resonance imaging have consistently revealed regions of contralateral cortical hypoperfusion in relation to the orientation of the cerebellar lesion [8, 9], a phenomenon called crossed cerebello-cerebral diaschisis. Neurophysiologically, this form of diaschisis translates as the functional deactivation of a disconnected contralateral cerebral region, as a consequence of impeded excitatory neural transmission via cerebello-thalamocortical pathways [6]. Reports of ipsilateral cortical diaschisis subsequent to cerebellar lesions [8] support a possible left cerebellar hemisphere contribution to the mediation of linguistic processes, presumably via ipsilateral cerebellar-basal ganglia-cortical pathways [10].

Previously, linguistic functioning in individuals with cerebellar lesions has largely been investigated using tests derived from neuropsychological test batteries, predominantly incorporating verbal fluency measures and more general language assessments such as confrontation naming [8, 11, 12]. Unfortunately it has been reported that assessments of general language function often fail to identify or adequately characterize the nature of language pathology resulting from cerebellar lesions [13]. Rather, based on the findings of Cook et al. [4], it would appear that linguistic disturbances subsequent to cerebellar lesions may be more accurately detected and characterized by higher-level assessments that evaluate the proficiency of more complex language processes beyond single word hierarchies. Consequently, the aim of the present study was to determine the effect of left primary cerebellar lesions on language function in a group of participants with cerebrovascular lesions using a comprehensive battery of general as well as higher-level linguistic measures.

Language Disorders following Left Cerebellar Stroke

Folia Phoniatr Logop 2007;59:184–189

Methods Subjects Ten patients (8 male and 2 female) with left primary cerebellar lesions of ischaemic or haemorrhagic vascular origin served as experimental subjects in this research (mean age = 53.60 8 14.43 years; mean level of education = 10.90 8 3.96 years). All subjects were at least 3 months after stroke at the time of assessment, native speakers of English and right-hand-dominant. Each of the patients presented with a negative history for previous stroke, speech and/or language impairment or coexisting neurological disease. Biographical details are outlined in table 1. A group of 10 non-neurologically impaired adults served as age- and educationmatched controls (mean age = 51.90 8 14.72 years; mean level of education = 14.20 8 3.58 years). All control subjects were righthanded, native speakers of English, with no reported history of neurological insult/disease or substance abuse. Procedure Both the experimental and control subjects underwent a single testing session involving the administration of both general and high-level language batteries (table 2). All testing was conducted in a quiet distraction-free environment according to the standardized testing instructions from the manual of each assessment.

Results

A series of independent samples t tests failed to reveal any significant differences between the cerebellar stroke and normal control cohorts on the variables of age and education; however, significantly (p ^ 0.05) lower scores were achieved by the cerebellar stroke group on a number 185

Table 1. Biographical summary of left primary cerebellar lesion patients

Patient Gender

Age Education Lesion Time years years side after CVA

CT/MRI results left cerebellar infarct and associated hydrocephalus due to left vertebral artery dissection left cerebellar infarct and hydrocephalus left cerebellar haemorrhagic infarct complicated by hydrocephalus; significant subacute haemorrhage centred on postero-medial aspect of left cerebellar hemisphere and involvement of the vermis left cerebellar haematoma producing effacement of 4th ventricle and acute hydrocephalus with tonsillar herniation left PICA territory infarct with occlusion of vessel on angiogram and small focus of hyperdensity in genu of corpus callosum changes in left medulla oblongata and left cerebellum consistent with acute infarction left cerebellar wedge-shaped hypodensity, probably infarct, some associated distortion of 4th ventricle, mild hydrocephalus hypodensity in left cerebellar hemisphere, subacute infarct in region of PICA, ? pontine stroke acute pontine infarct in left basilar perforating vessel left cerebellar infarct

1

M

35

15

L

4 months

2 3

M M

69 68

8 8

L L

6 months 41 months

4

M

51

15

L

9 months

5

M

55

15

L

9 months

6

M

73

11

L

23 months

7

F

39

10

L

17 years

8

M

65

3

L

41 months

9 10

M F

43 38

10 14

L L

10 months 9 months

CVA = Cerebrovascular accident; PICA = posterior-inferior cerebellar artery.

of language variables. Within the general language battery, significantly lower scores were observed on the total score of the Neurosensory Centre Comprehensive Examination for Aphasia (NCCEA) and the word fluency subtest of this assessment (table 3). In relation to higher-level language functions, significantly lower scores were evident on the total scores of the Test of Language Competence – Expanded (TLC-E) and the Word Test – Revised (TWT-R), including performance on the ambiguous sentences, recreating sentences, figurative language, antonyms, definitions and multiple definitions subtests of these assessments (table 4).

Discussion

The findings of the present study support the hypothesis that primary left cerebellar hemisphere lesions may disrupt language processing, particularly in the area of complex or high-level language skills, including phonemic fluency, sentence formulation and lexical-semantic manipulation tasks. Such tasks, involving the manipulation of novel situations, lexical-semantic operations, the development of language strategies and the organization and monitoring of responses, have been hypothesized to demand frontal lobe support in their manipulation [18]. 186

Folia Phoniatr Logop 2007;59:184–189

Frontal lobe hypoperfusion, therefore, provides one plausible explanation for the language disorders observed in association with primary left cerebellar lesions in the present study, functioning of the left cortical language centres being implicated as a consequence of ipsilateral cortical diaschisis. Ipsilateral cerebellar-cerebral diaschisis is a reported consequence of cerebellar lesions [8]. Beldarrain et al. [8] investigated the relationship between neuropsychological deficits (including language) and SPECT scan perfusion patterns in the cerebral hemispheres subsequent to cerebellar lesions. Of the 19 participants in their study who underwent a SPECT scan, 6 showed contralateral diaschisis and 7 ipsilateral diaschisis. The remaining 6 participants showed no evidence of diaschisis. As an alternative to the ipsilateral cortical diaschisis hypothesis, left cerebellar lesions as evidenced by the present cohort of participants may impact on language function by causing contralateral diaschisis in the right cerebral hemisphere (i.e. crossed cerebello-cerebral diaschisis involving damage to the left cerebellar hemisphere leading to reduced functioning of the right cerebral hemisphere). In support of this suggestion, patients with cerebellar lesions have been reported to have lowered metabolism in the contralateral frontal and parietal lobes on SPECT [19]. Further, a number of the abnormal language features exhibited by the participants with left cerebellar Murdoch/Whelan

Table 2. Language assessment battery

Battery 1: general language – Neurosensory Centre Comprehensive Examination for Aphasia [14] – Boston Naming Test [15] Battery 2: high-level linguistics – Test of Language Competence – Expanded [16] Subtests a Ambiguous sentences [e.g. providing 2 essential meanings for ambiguous sentences (e.g. ‘Right then and there the man drew a gun’)] b Making inferences (e.g. utilizing causal relationships or chains in short paragraphs to make logical inferences) c Recreating sentences [e.g. formulating grammatically complete sentences utilizing key semantic elements within defined contexts (e.g. defined context = ‘at the ice-cream store’; key semantic elements = ‘some’, ‘and’, ‘get’)] d Figurative language [e.g. interpreting metaphorical expressions (e.g. ‘There is rough sailing ahead for us’) and correlating structurally related metaphors (e.g. ‘We will be facing a hard road’) according to shared meanings] e Remembering word pairs (e.g. recalling paired word associates) – The Word Test – Revised [17] a Associations [e.g. identifying semantically unrelated words within a group of 4 spoken words (e.g. ‘knee’, ‘shoulder’, ‘bracelet’, ‘ankle’) and providing an explanation for the selected word in relation to the category of semantically related words (e.g. ‘The rest are parts of the body’)] b Synonym generation [e.g. generation of synonyms for verbally presented stimuli (e.g. ‘afraid’ = ‘scared’)] c Semantic absurdities [e.g. identifying and repairing semantic incongruities (e.g. ‘My grandfather is the youngest person in my family’ = ‘My grandfather is the oldest person in my family’)] d Antonym generation [e.g. generating antonyms for verbally presented stimuli (e.g. ‘alive’ = ‘dead’)] e Definitions [e.g. identify and describe critical semantic features of specified words (e.g. ‘house’ = ‘person’ + ‘lives’)] f Multiple definitions [e.g. provision of 2 distinct meanings for series of spoken homophonic words (e.g. ‘down’ = ‘position’/‘feathers’/‘feeling’)]

lesions in the present study are similar to those noted in cases of right cerebral lesions. For example, one of the most commonly described language deficits in association with right cerebral hemisphere damage is the misinterpretation of figurative/non-literal language [20]. Similar to participants in the present study, adults with right cerebral hemisphere damage often do not appreciate abstract meanings of words and phrases. A comparison of the language profiles of participants with demonstrated right cortical lesions with those of persons with left cerLanguage Disorders following Left Cerebellar Stroke

Table 3. Comparison of general language performance between the cerebellar stroke and normal control group

Assessment variable

Left cerebellar stroke (n = 10)

Normal control (n = 10)

NCCEA TOT VN TNR TNL SR REPD REVD WF SC TT ORNAME ORSENT RNM RSM VGN WN WD WC ARTIC BNT

540.05821.07 15.7080.95 15.9080.32 15.6081.27 17.4083.44 9.2082.10 6.9082.13 28.5088.91 24.8080.63 161.0083.09 19.8080.63 15.8080.63 10.0080.00 17.0080.00 7.6081.27 21.7084.83 10.0583.70 11.5080.71 99.4082.32 52.2084.97

571.15813.47 165.0080.00 16.0080.00 16.0080.00 18.3082.21 10.2081.93 7.7082.00 50.0086.62 24.5081.58 162.1081.91 20.0080.00 16.0080.00 10.0080.00 16.9080.32 8.0080.00 23.9080.32 12.7581.90 11.4080.52 100.4080.84 55.6083.06

t –3.93 –1.00 –1.00 –1.00 –0.70 –1.11 –0.87 –6.13 0.56 –0.96 –1.00 –1.00 1.00 –1.00 –1.00 –1.44 –2.05 0.36 –1.28 –1.84

p 0.00 0.34 0.34 0.34 0.50 0.82 0.40 0.00 0.58 0.35 0.33 0.33 0.34 0.34 0.34 0.18 0.06 0.72 0.22 0.08

Figures are means 8 SD. Italicized p values are statistically significant. NCCEA = Neurosensory Centre Comprehensive Examination for Aphasia; BNT = Boston Naming Test; VN = visual naming; TNR = tactile naming right; TNL = tactile naming left; SR = sentence repetition; REPD = repetition of digits; REVD = reversal of digits; WF = word fluency; SC = sentence construction; TT = Token Test; ORNAME = oral reading (names); ORSENT = oral reading (sentences); RNM = reading names for meaning; RSM = reading sentences for meaning; VGN = visual graphic naming; WN = writing of names; WD = writing to dictation; WC = writing (copying); ARTIC = articulation.

ebellar lesions would shed some light as to whether or not diaschisis of the right cerebral hemisphere is at least partly responsible for the observed language problems in these cases. Although the existence of either ipsilateral or contralateral cortical diaschisis was not confirmed by SPECT in the present study, the presence of high-level language problems in association with left cerebellar lesions was demonstrated, suggesting that both the left as well as the right cerebellum may be involved in the regulation of language function. Consistent with the findings of Marien et al. [13], the tests of general language function failed to adequately characterize the nature of the language disturbances exhibited by the participants with left cerebellar lesions. Models of motor control define a role for the cerebellum Folia Phoniatr Logop 2007;59:184–189

187

Table 4. Comparison of high-level language performance be-

tween the cerebellar stroke and normal control group Assessment variable

Left cerebellar CVA (n = 10)

TLCETOT 148.10819.85 AMBSENT 30.5085.68 MINF 28.5083.63 RS 60.7088.82 FIGLANG 28.4086.65 RWP 8.2584.17 TWTTOT 71.90816.68 ASSOC 12.7082.50 SYN 12.4083.06 SEMAB 12.1082.89 ANT 12.8081.55 DEF 11.6083.13 MULDEF 13.5081.51

Normal control (n = 10) 170.1089.54 34.9082.23 29.8084.59 71.7084.95 33.7082.75 12.1089.07 84.7082.75 13.4081.27 14.3080.95 14.0081.05 14.1080.88 14.3080.82 14.6080.52

t –3.28 –2.28 –0.70 –3.44 –2.33 –1.19 –2.40 –0.79 –1.87 –1.96 –2.31 –2.64 –2.18

p 0.01 0.04 0.49 0.00 0.03 0.25 0.04 0.44 0.08 0.08 0.04 0.03 0.04

Figures are means 8 SD. Italicized p values are statistically significant. CVA = Cerebrovascular accident; TLCETOT = Total score on Test of Language Competence – Expanded; AMBSENT = ambiguous sentences; MINF = making inferences; RS = recreating sentences; FIGLANG = figurative language; RWP = remembering word pairs; TWTTOT = total score on the Word Test – Revised; ASSOC = associations; SYN = synonyms; SEMAB = semantic absurdities; ANT = antonyms; DEF = definitions; MULDEF = multiple definitions.

in the refinement and coordination of movement [21]. Akin to these models, it has also been postulated that cerebellar contribution to cognition would be high-level in nature [13, 22]. Although in relation to the cognitive domain of language the role of the cerebellum remains irresolute, Cook at al. [4] proposed that cerebellar lesions may evoke a form of linguistic incoordination or crudity, potentially manifesting as higher-level language deficits. The findings of the present study concur with this suggestion, the evident high-level language disorders providing further evidence that the cerebellum may indeed be responsible for regulating, refining and coordinating language. For example, as a group the participants with left cerebellar lesions performed significantly below the control group on the phonemic fluency task of the NCCEA, consistent with the findings of previous studies [8, 13, 22]. These findings confirm that left cerebellar lesions may impact on phonetically based strategic word searches, hypothetically undertaken within the left dorsolateral frontal cortex [23]. Likewise, the results of the TWT-R, an assessment of expressive vocabulary and semantics, indicated that the participants with left cerebellar lesions as a group exhib188

Folia Phoniatr Logop 2007;59:184–189

ited deficiencies in tasks that required identification and/ or sentential description of the critical semantic features of specified words, including words with more than 1 meaning. For example, when asked to define the word ‘window’ (required critical semantic elements: ‘look out’/ ‘see through’/‘open’/‘close’) on the definitions subtest, 1 case responded, ‘something that lets air in’. When asked to provide 2 meanings for the word ‘change’ (required definition references: ‘alter’ and ‘coins’) on the multiple definitions subtest, 1 case’s 2 responses were stimulus-bound/inflexible (e.g. ‘to change your clothes’ and ‘change habits’). On the TLC-E, an assessment of semantics, syntax and pragmatics, the group of participants with left cerebellar lesions also exhibited problems on the recreating sentences task – this latter task requires participants to form grammatically complete sentences utilizing key semantic elements within defined contexts. For example, when asked to make a sentence with the key semantic elements: ‘actually’/‘although’/‘wrong’ within the defined context: ‘at the department store’, 1 case responded, ‘Actually wrong sizes appear correct, although they are wrong’. These findings demonstrate that the group with left cerebellar lesions had difficulty in establishing contextual plans and manipulating semantic elements at a multiword level of language production. Similarly, the group also demonstrated difficulty reversing the critical semantic dimensions of target words on the antonyms subset of the TWT-R. For example, the word ‘second’ was generated as an antonym for ‘first’. Overall these vignettes support the proposal that left cerebellar lesions primarily impact upon the ability to efficiently manipulate semantic elements at a multi-word level. Further cerebellar-cerebral output may underpin the regulation of lexical-semantic operations and the organization of complex, multi-word language output. As a group the participants with left cerebellar lesions also performed significantly below controls on the figurative language and interpretation of ambiguous sentences subtests of the TLC-E, indicative of difficulty in interpreting complex semantic information at a sentential level. These latter findings further suggest that the cerebello-cerebral pathways may also have a role in the regulation of language comprehension as well as production mechanisms. Interestingly, the pattern of language deficits exhibited by the participants with left cerebellar lesions in the present study is similar to those reported in persons with other subcortical pathologies such as Parkinson’s disease, multiple sclerosis, Huntington’s disease and non-thalamic subcortical vascular lesions [18, 24–26], suggesting that a Murdoch/Whelan

common neural substrate based on frontal lobe disconnection may underly the language deficits observed in these groups. The findings of the present study support the proposal of Cook et al. [4] that the basal ganglia, thalamus and cerebellum together may represent a symbiotic regulatory centre in relation to the mediation of complex lexico-semantic operations and language formulation which are presumably dependent on frontal lobe mechanisms. Although the effects of cerebellar lesion on language compared to those of other subcortical lesions require further investigation, if the suggestion of Cook et al. [4] is true, then frontal lobe hypoperfusion arising as a consequence of subcortical lesions, including cerebellar lesions, would appear to offer a plausible explanation for the occurrence of concomitant language disorders. The application of supplementary neuroimaging techniques such as SPECT in prospective cerebellar and other subcortical lesion studies would serve to corroborate or otherwise theories of contralateral/ipsilateral cortical diaschisis

in the frontal lobes in association with these lesions and thereby provide a better understanding of the role of the cerebellum and other subcortical structures in language.

Conclusions

The results of the present study challenge the notion of a right lateralized linguistic cerebellum and demonstrate that higher-level language impairments may result from left primary cerebellar lesions of vascular origin. Overall, the results support a role for the cerebellum in refining and modulating language presumably by way of excitatory output to the prefrontal cortex via connections with the basal ganglia and thalamus. It is proposed that cerebellar involvement in language is bilateral and that cerebellar lesions, regardless of hemispheric location, may result in language disturbances as a consequence of contralateral and ipsilateral cerebral diaschisis.

References 1 Schmahmann JD: Ataxia of thought: clinical consequences of cerebellar dysfunction on cognition and effect. Trends Cogn Sci 1998; 2:362–371. 2 Marien P, Engelborghs S, Fabbro F, De Deyn PP: The lateralized linguistic cerebellum: a review and a new hypothesis. Brain Lang 2001;79:580–600. 3 Docking K, Murdoch BE, Ward E: Cerebellar language and cognitive functions in childhood: a comparative review of the clinical research. Aphasiology 2003; 17: 1153– 1161. 4 Cook M, Murdoch BE, Cahill L, Whelan BM: Higher-level language deficits resulting from left primary cerebellar lesions. Aphasiology 2004;18:771–784. 5 Fabbro F, Moretti R, Bava A: Language impairments in patients following cerebellar lesions. J Neurolinguist 2000;13:173–188. 6 Broich K, Hartman A, Biersack H, Horn R: Crossed cerebello-cerebral diaschisis in a patient with cerebellar infarction. Neurosci Lett 1987;83:7–12. 7 Gasparini M, Di Piero, V, Ciccarelli O, Cacioppa MM, Pantano P, Lenzi GL: Linguistic impairment after right cerebellar stroke: a case report. Eur J Neurol 1999; 6:353–356. 8 Beldarrain MG, Garcia-Monco JC, Quintana JM, Llorens V, Rodeno E: Diaschisis and neuropsychological performance after cerebellar stroke. Eur Neurol 1997; 37:82–89.

Language Disorders following Left Cerebellar Stroke

9 Silveri MC, Leggio MG, Molinari M: The cerebellum contributes to linguistic production: a case of agrammatic speech following a right cerebellar lesion. Neurology 1994;44: 2047–2050. 10 Botez MI, Leveille J, Lambert R, Botez T: Single photon emission computed tomography (SPECT) in cerebellar diseases: cerebello-cerebral diaschisis. Eur Neurol 1991; 31: 401– 412. 11 Leggio MG, Silveri MC, Petrosini L, Molinari M: Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study. J Neurol Neurosurg Psychiatry 2000;69:102–106. 12 Neau JP, Arroyo-Anllo E, Bonnard V, Ingrand P, Gil R: Neuropsychological disturbances in cerebellar infarcts. Acta Neurol Scand 2000;102:363–370. 13 Marien P, Engelborghs S, Pickut BA, De Deyn PP: Aphasia following cerebellar damage: fact or fallacy? J Neurolinguist 2000;13: 145–171. 14 Spreen O, Benton AL: Neurosensory Centre Comprehensive Examination for Aphasia. Victoria, University of Victoria, 1977. 15 Kaplan E, Goodglass H, Weintraub S: Boston Naming Test. Philadelphia, Lippincott Williams & Wilkins, 1983. 16 Wiig EH, Secord W: Test of Language Competence – Expanded Edition. New York, Psychological Corporation, 1989. 17 Huisingh R, Barrett M, Zachman L, Blagden C, Orman J: The Word Test – Revised. A Test of Expressive Vocabulary and Semantics. Illinois, Linguisystems, 1990.

18 Copland DA, Chenery HJ, Murdoch BE: Persistent deficits in complex language function following dominant nonthalamic subcortical lesions. J Med Speech Lang Pathol 2000; 8:1–14. 19 Botez MI, Botez TH, Leveille J, Lambert R: Cerebello-cerebral diaschisis and the role of the cerebellum. Neurology 1990;40:173. 20 Kempler D, Van Lancker D, Marchman V, Bates E: Idiom comprehension in children and adults with unilateral brain damage. Dev Neuropsychol 1999;15:327–349. 21 Fabbro, F: Introduction to language and cerebellum. J Neurolinguist 2000;13:83–94. 22 Chafetz MD, Friedman AL, Kevorkian CG, Levy JK: The cerebellum and cognitive function: implications for rehabilitation. Arch Phys Med Rehabil 1996;77:1303–1308. 23 Pujol J, Vendrell P, Deus J, Kulisevsky J, Martin-Vilalta JL, Garcia C: Frontal lobe activation during word generation studied by functional MRI. Acta Neurol Scand 1996;93: 403–410. 24 Chenery HJ, Copland DA, Murdoch BE: Complex language function and subcortical mechanisms: evidence from Huntington’s disease and patients with non-thalamic subcortical lesions. Int J Lang Commun Disord 2002;37:459–474. 25 Lethlean JB, Murdoch BE: Language problems in multiple sclerosis. J Med Speech Lang Pathol 1993;1:45–57. 26 Lewis FM, LaPointe LL, Murdoch BE, Chenery HJ: Language impairment in Parkinson’s disease. Aphasiology 1998; 12:193–206.

Folia Phoniatr Logop 2007;59:184–189

189

Folia Phoniatr Logop 2007;59:190–200 DOI: 10.1159/000102931

The Impact of a Cerebellar Tumour on Language Function in Childhood Kimberley M. Docking a Bruce E. Murdoch a Ram Suppiah b a

University of Queensland and b Mater Children’s Hospital, Brisbane, Australia

Key Words Cerebellar tumour
Language function, children
Language ability, general, high-level

vious reports of specific impairments in high-level language and in thinking flexibility and problem solving following cerebellar hemispheric damage in childhood. Copyright © 2007 S. Karger AG, Basel

Abstract Background/Aims: Childhood-acquired cerebellar studies to date have appeared to present a concordant pattern of specific neuropsychological profiles depending on lesion site. The aim was to determine the impact of a cerebellar tumour specifically on language function in children by reporting both the general and high-level language abilities of 4 cases with differing sites of hemispheric and vermal involvement. Methods: The language abilities of 4 children (aged from 7 years 9 months to 13 years), treated with surgery and/or radiotherapy for cerebellar tumour 6 months to 3 years previously, were examined. A standardized battery of general and high-level language assessments was administered. Results: Analysis revealed intact abilities across all 4 cases on measures of general language, including receptive language, expressive language, receptive vocabulary and naming. While 2 of the 4 cases also demonstrated intact high-level language skills across all measures, the remaining 2 demonstrated specific deficits in linguistic problem solving at 6 months after treatment. Follow-up assessment of 1 case also demonstrated further decline in this area 12 months later. Conclusion: Findings of high-level language deficits in problem solving in 2 of the 4 cases examined supported pre-

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0190$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

Background

Despite greater evidence supporting the contribution of the cerebellum to the organization of cognitive and language functions in adults, an increasing body of support is highlighting similar findings in children with acquired cerebellar lesions [1, 2]. In childhood, the cerebellum possesses an intrinsic fragility due to its long neurogenesis, which exposes it to possible insults and damage [1]. Damage to cognitive organization is therefore considered all the greater when it occurs at the beginning of functional maturation and would account for why children with congenital cerebellar pathologies often present complex pictures in which cognitive deficits are associated with behavioural disturbances [1]. Reports of persistent deficits also demonstrate that the plasticity of the young brain is not powerful enough to completely compensate for early lesions [3]. Thus, damage to the cerebellum in childhood may influence a wide range of psychological processes, both as an immediate consequence and as these processes fail to develop normally later on.

Dr. Kimberley M. Docking Division of Speech Pathology University of Qld. Brisbane, Qld. 4072 (Australia) Tel. +61 7 3346 7483, Fax +61 7 3365 1877, E-Mail [email protected]

Deficits observed in frontal functions following cerebellar lesions in paediatric populations confirm the existence of connections with the frontal lobes via the thalamus [1, 4]. Studies of children with acquired cerebellar lesions also appear to support findings in adult studies, whilst furthermore appearing to present a more concordant pattern of specific neuropsychological profiles depending on lesion site [1]. In particular, involvement of the cerebellar hemispheres has been noted in the processing of cognitive functions and has been associated with patterns of side-specific cognitive dysfunctions, whereas lesions of the vermis have been related to behavioural and verbal production disturbances, including anarthric and agrammatic language disturbances [1]. Riva and Giorgi [3, 5] analyzed the specific functions of both the cerebellar hemispheres and the vermis in examining the cognitive, language and executive functions of children who had undergone surgical removal of either a cerebellar hemispheric tumour or a vermal tumour. Groups with either left or right involvement were observed to show varying degrees of reduced ability in thinking flexibility and problem solving. Results from the group of hemispheric patients also reportedly confirmed the dissociation of the circuits connecting the cerebellum to the supratentorial associative areas through the thalamus [3]. Specific high-level language deficits, global impairment, and expressive language and syntax were also acknowledged among others to be related to direct impact of cerebellar damage [6–8]. The right cerebellar hemisphere has been recently considered to maintain substantial responsibility for language processing [3, 5, 9]. Particularly, clinical manifestations resulting from damage to this specific region in children include disturbances in auditory sequential memory, alterations in verbal intelligence, decreased competence in complex language processing, significantly reduced syntactic comprehension, reduced abilities in verbal sequencing and categorical memory, and an interruption of literacy skills. Conversely, damage to the left cerebellar hemisphere has been associated with visual and spatial memory, non-verbal information processing, non-verbal intelligence and impairments in prosody [3, 5, 9–10]. The vermal region has also been specifically implicated in the occurrence of transient mutism following surgical intervention and behavioural disturbances, including a dysregulation of affect. Other areas of disturbance in children have been noted to include verbal fluency, telegraphic speech, reductions in complex language structures, impaired procedural learning and some reports of naming difficulties. The congenital cerebellar condition,

global hypoplasia of the vermis or selective hypoplasia of some vermian lobules is frequently observed in children with neurological diseases [1]. These anatomical alterations are often associated with neuropsychological or developmental disorders resembling mental insufficiency of varying severity with behavioural changes that may even mirror autism [1]. Riva and Giorgi [3, 5] reported 2 presentations: namely, post-surgical mutism and behavioural disturbances. These reports of post-surgical mutism evolved either into a classical speech disorder or a language disorder characteristic of agrammatism with intact comprehension. Behavioural disturbances presented as affective and social behavioural alterations ranging in severity from irritability to a more autistic manifestation. Evidence from childhood studies serves to indicate that the presentation of a cerebellar contribution to language and cognition in children reflects observations in adult patients. It also highlights the presence of functional cerebro-cerebellar connections early in childhood. Additionally, it has been suggested that the earlier cerebellar damage occurs during development, the greater the subsequent impact on language and cognitive function. Studies examining the role of the cerebellum in children have indicated that damage to specific areas of the cerebellum exerts impact on a distinct range of functions, indicating that functional specialization is also present at a very early age. Therefore, the aim of the present study was to examine the language abilities of 4 cases who had been treated for cerebellar tumour to identify specific areas of impairment that may present due to the impact of a disturbance to this region of the brain.

Cerebellar Tumour and Language in Children

Folia Phoniatr Logop 2007;59:190–200

Case Studies

The language abilities of 4 cases with cerebellar tumour were examined (table 1). Three males and 1 female were included, ranging in age at assessment from 7 years 9 months to 13 years of age. Three of the 4 cases were treated with surgery only, while 1 case also received radiotherapy in addition to surgery. Tumour locations within the cerebellum that were represented across the 4 cases included the right cerebellar hemisphere, left cerebellar hemisphere, midline and the vermis. The assessment battery administered to all 4 cases consisted of both general and high-level measures of language. 1 Clinical Evaluation of Language Fundamentals – 3rd edition (CELF-3). This assessment is designed to identify, diagnose and follow up general language deficits 191

Table 1. Biographical data of 4 children treated for cerebellar tumour Case Gender Age at assessment

Age at diagnosis

Time Tumour type after treatment

Tumour location

Treat- Extent ment of surgery

1 2 3 4

9;11 7;3 11;10 10;0

0;6 0;6 1;2 3;0

right cerebellar hemisphere inferior vermis, left cerebellar hemisphere cerebellar vermis cerebellar midline, left cerebellar hemisphere

S, R S S S

F M M M

10;9 7;9 13;0 13;0

ependymoma JP astrocytoma JP astrocytoma JP astrocytoma

Total radiation dosage

total 54 Gy near total – total – total –

Age and time presented in years and months. S = Surgery; R = radiotherapy; – = not applicable; JP = juvenile pilocytic.

2

3

4

5

6

in preschool, school-aged children and adolescents. It identifies children who lack the basic foundations of content and form that characterize mature language use, including knowledge of word meanings (semantics), word and sentence structure (morphology and syntax) and recall and retrieval (memory). The Hundred Pictures Naming Test (HPNT) assesses the ability to name objects in children, when presented with the line drawing of noun objects familiar to both children and adults. The Peabody Picture Vocabulary Test – 3rd edition (PPVT-3) is considered to be a highly respected assessment of receptive vocabulary and is well standardized. Each child’s ability to comprehend vocabulary items is assessed via auditory presentation and subsequent selection of an appropriate visual representation. The Test of Language Competence – Expanded Edition assesses higher-level language abilities as well as emerging metalinguistic abilities and linguistic strategy acquisition, examining the child’s ability to perceive, interpret and respond to contextual and situational demands of conversation. Both interpretative and expressive abilities are analyzed and combined to give an overall score. The Test of Word Knowledge yields information regarding semantic knowledge and lexical knowledge, whilst accommodating 2 levels of age ranges. It addresses those semantic skills that are the foundation of mature language use in thinking, learning and communicating and therefore tap into high-level abilities. The Test of Problem Solving – Elementary, Revised (TOPS-Elementary, Revised) assesses higher-level language abilities that incorporate problem solving, determining solutions, inferencing, empathizing, prediction, use of context and thinking vocabulary. Each participant is required to respond to a series of questions based on the presented stimuli.

192

Folia Phoniatr Logop 2007;59:190–200

Case 1 Case 1 was diagnosed as having a 2-cm low-grade ependymoma in the right cerebellum at the age of 9 years 11 months (fig. 1a). Case 1 presented with a 3-month history of poor balance, nausea, intermittent vomiting and dizziness. Treatment consisted of total surgical removal and an 8-week course of radiotherapy. Radiotherapy treatment consisted of 54 Gy to the cranial posterior fossa in 30 fractions using 6-MV photons via the right and left posterior oblique fields. At the age of 10 years 9 months, case 1 was assessed for this study and administered a comprehensive battery of both general and high-level language assessments. This case had not had any speech pathology assessments or intervention prior to participation in this study. An MRI conducted 6 weeks prior to language testing revealed no evidence of recurrent tumour (fig. 1b). Case 1 demonstrated intact general language abilities according to the normative data available across all general language assessments (table 2). In fact, performances on the receptive, expressive and total language components of the CELF-3, including the subtests, word classes and sentence assembly, were considered above the normal range. Receptive vocabulary skills measured by the PPVT-3 were also noted to be above the normal range. The highest normative age range available for the HPNT comparable to the age of case 1 of 10 years 9 months ranged from 7 years 1 month to 9 years 2 months (with a mean of 7 years 7 months). While the score of case 1 of 93 appears to be within the normal range compared to this age group [mean accuracy score (n = 260) = 84.11, standard deviation = 9.85 [11]], it is difficult to speculate whether performance represents intact naming skills for this participant or a mild deficit at the age of 10 years 9 months. Assessment of high-level language skills yielded reduced performance in problem solving on the TOPS-Elementary, Revised (table 3), although all remaining tests were considered within the normal range. Docking /Murdoch /Suppiah

Fig. 1. a Case 1 at diagnosis: T2-weighted axial MRI scan demonstrating a 2-cm mass in the anterior cerebellum, just to the right of the midline and adjacent to the right posterior aspect of the fourth ventricle. b Case 1

at language testing (6 months after treatment): T1-weighted axial MRI scan revealing a small cystic area just posterior to the fourth ventricle in keeping with post-surgical change. No evidence of recurrent tumour following radiotherapy treatment.

Table 2. Individual general language

assessment results (represented in standard scores) of cases 1 and 2 treated for cerebellar tumour

Tests

Case 1

CELF-3 Receptive Language Concepts and directions Word classes Semantic relationships1/sentence structure2 Expressive Language Formulated sentences Recalling sentences Sentence assembly1/word structure2 Total Language PPVT-3 HPNT (raw score/100)

Case 2

6 months after

12 months after

6 months after

118 12 14 131 120 13 12 151 120 116 93

120 11 14 15 102 9 9 11 111 105 95

106 10 12 112 96 8 9 112 101 107 95

Standard scores in italics: normal range 85–115; subtest standard score normal range = 7–13. 1 Level 2 subtest variation. 2 Level 1 subtest variation.

Cerebellar Tumour and Language in Children

Folia Phoniatr Logop 2007;59:190–200

193

Table 3. Individual high-level language assessment results (represented in standard scores) of cases 1 and 2 treated for cerebellar tumour

Tests

Case 1 6 months after

TOPS-Elementary, Revised TOWK Receptive Composite Synonyms2/word opposites3 Figurative usage2/receptive vocabulary1 Expressive Composite Word definitions Multiple contexts2/expressive vocabulary3 Total TLC-E Interpreting Intents Listening comprehension: making inferences Figurative language Expressing Intents Ambiguous sentences Oral expression: recreating sentences2/speech acts3 Total

Case 2 12 months after

6 months after

781

<551

781

109 112 122 100 10 102 105

106 122 102 97 8 112 101

115 113 143 100 9 113 108

91 8 9 97 12

100 8 12 97 12

109 13 10 100 8

72 93

72 98

123 105

TOWK = Test of Word Knowledge; TLC-E = Test of Language Competence – Expanded Edition. Standard scores in italics: normal range 85–115; subtest standard score normal range = 7–13. 1 Below normal range. 2 Level 2 subtest variation. 3 Level 1 subtest variation.

Case 1 was the only one to participate in a follow-up assessment 12 months later at the age of 11 years 9 months. Language testing at this time revealed general language abilities consistent with the initial assessment across expressive and receptive language tasks, receptive vocabulary and naming (table 2). Performance across most highlevel language measures was also consistent with the previous assessment. However, problem solving skills on the TOPS were noted to be significantly reduced at more than 2 standard deviations below the normal range (table 3). Case 2 At the age of 7 years 3 months, case 2 presented with a 4-cm juvenile pilocytic astrocytoma arising from the inferior vermis and involving the left hemisphere (fig. 2a). He also presented with obstructive hydrocephalus. Diagnosis occurred following a 4-month history of increasing intermittent headaches, nausea and vomiting. A near total surgical resection was performed leaving some residual tumour and associated oedema. Post-operatively, hydrocephalus, slight ataxia and left-sided weakness were noted. A neuropsychological assessment found average performance, with no overall difficulties prior to or follow194

Folia Phoniatr Logop 2007;59:190–200

ing surgery, despite some sequencing and attention difficulties. Case 2 was also seen by the speech pathology department while an inpatient following surgical treatment, for motor speech difficulties due to mild dysarthria. Language abilities were also assessed and reported to be intact at this time. Case 2 was discharged from this service 3 months prior to participation in this study at 3 months after treatment. Six months following treatment completion, at the age of 7 years 9 months, case 2 completed language assessments as part of this study. An MRI of the brain carried out 5 days prior to participation indicated a non-progressive residual tumour in the left side of the fourth ventricle and medial aspect of the left cerebellar hemisphere (fig. 2b). Performance on tests of general language revealed intact abilities across all domains (table 2). While case 2 performed within the normal range across most measures of high-level language, a specific disturbance to the area of problem solving was demonstrated (table 3). Case 3 Case 3 was diagnosed as having a large (6 ! 4 ! 4 cm) juvenile pilocytic astrocytoma involving the cerebellar vermis and associated hydrocephalus at the age of 11 Docking /Murdoch /Suppiah

onstrating a large complex cystic and solid mass lying within and expanding the fourth ventricle. There is cystic extension inferiorly through the foramina of Magendie into the cisterna magna, extending through the foramen magnum as far as the inferior

margin of the C1 arch. b Case 2 at language testing (6 months after treatment): post-surgical T1-weighted axial MRI scan indicating persistent non-progressive residual tumour on the left side of the fourth ventricle and medial aspect of the left cerebellar hemisphere.

years 10 months (fig. 3). A 2-month history of morning nausea and vomiting, headaches, increased clumsiness and blurred vision preceded diagnosis, with the most recent symptoms noted as unsteadiness on feet and papilloedema. A total resection and third ventriculostomy was performed. Persistent post-surgical complications included truncal ataxia, decreased coordination, right-sided high-frequency hearing difficulties and left optic atrophy with secondary left visual diplopia. Two months following surgery, case 3 was assessed by the speech pathology team at the hospital and noted to have language abilities placed within the normal range. Neuropsychological assessment conducted at both 3 and 11 months following surgery reported that an absence of concerns in academic ability was noted prior to illness. Initial performance was found to be in the average range of intellectual functioning, including cognition and memory. No difficulty was experienced returning to school. A second neuropsychological assessment 11 months following surgery also indicated performance to be in the average range of intellectual functioning, with most areas of performance considered consistent with the previous assessment or slightly improved. However, spe-

Fig. 3. Case 3 at diagnosis: sagittal view MRI scan demonstrating a 6 ! 4 ! 4 cm juvenile pilocytic astrocytoma in the cerebellar vermis.

Fig. 2. a Case 2 at diagnosis: T1-weighted sagittal MRI scan dem-

Cerebellar Tumour and Language in Children

Folia Phoniatr Logop 2007;59:190–200

195

Table 4. Individual general language assessment results (repre-

sented in standard scores) of cases 3 and 4 treated for cerebellar tumour

Table 5. Individual high-level language assessment results (represented in standard scores) of cases 3 and 4 treated for cerebellar tumour

Tests

Case 3 Case 4

Tests

CELF-3 Receptive Language Concepts and directions Word classes Semantic relationships1/sentence structure2 Expressive Language Formulated sentences Recalling sentences Sentence assembly1/word structure2 Total Language PPVT-3 HPNT (raw score/100)

114 12 10 151 106 12 11 101 110 108 97

110 10 13 121 108 13 11 101 109 110 98

Standard scores in italics: normal range 85–115; subtest standard score normal range = 7–13. 1 Level 2 subtest variation. 2 Level 1 subtest variation.

Case 3 Case 4

TOPS-Elementary, Revised 94 TOWK Receptive Composite 91 101 Synonyms1/word opposites2 Figurative usage1/receptive vocabulary2 71 Expressive Composite 97 Word definitions 9 101 Multiple contexts1/expressive vocabulary2 Total 93 TLC-E Interpreting Intents 97 Listening comprehension: making inferences 7 Figurative language 12 Expressing Intents 100 Ambiguous sentences 8 Oral expression: recreating sentences1/ 121 speech acts2 Total 98

110 97 121 71 106 11 111 101 94 8 10 118 12 141 106

cific areas of weakness were noted with some areas of relative decline from the previous assessment. These included mental arithmetic reasoning abilities and speed of information processing. At this time, the parent of case 3 also reported difficulties in his concentration, motivation, organization and task completion skills. The language abilities of case 3 were assessed for this study at the age of 13 years. Testing occurred 1 year 2 months following surgery and 3 months following the second neuropsychological testing session. Case 3 had been seen by the speech pathology team at the hospital 1 year prior to testing for the current study, at which time language abilities were reported to be within general limits. Participation in this study also revealed performance to be well within the normal range across both general assessments of language as well as higher-level language assessments (tables 4, 5).

Standard scores in italics: normal range 85–115; subtest standard score normal range = 7–13. TOWK = Test of Word Knowledge; TLC-E = Test of Language Competence – Expanded Edition. 1 Level 2 subtest variation. 2 Level 1 subtest variation.

Case 4 At the age of 10 years, case 4 was diagnosed as having a predominantly cystic 4 ! 2.3 cm juvenile pilocytic astrocytoma located in the cerebellar midline and left cerebellar hemisphere (fig. 4a). Case 4 presented with a 1-month history of nausea, vomiting and headaches, as well as papilloedema and obstructive hydrocephalus with tonsillar herniation on examination. Treatment involved a total surgical resection, in which the posterior rim of the foramen magnum was also removed to allow decompression in that area given the preoperative tonsillar herniation.

An examination of the language abilities of 4 children with cerebellar tumour revealed intact abilities across all measures of general language, including receptive language, expressive language, receptive vocabulary and naming. While 2 cases (cases 3, 4) also demonstrated intact high-level language skills across all measures, 2 of the remaining 4 cases (cases 1, 2) presented specific deficits in linguistic problem solving. These aspects of problem solving are common components of critical thinking, such as clarifying, analyzing, generating solutions, evaluating and effective thinking, with a weakness in high-

196

Folia Phoniatr Logop 2007;59:190–200

Three years following treatment at the age of 13, case 4 was administered the language assessments as part of participation in this study. A recent MRI of the brain taken 6 months prior to assessment is displayed in figure 4b. All general and higher-level language performance across all measures was noted to be well within the normal range (tables 4, 5).

Discussion of Cases

Docking /Murdoch /Suppiah

Fig. 4. a Case 4 at diagnosis: axial MRI scan revealing a 4 ! 2.3 cm juvenile pilocytic astrocytoma in the cerebellar midline and left hemisphere. b Case 4 at language testing (3 years after treatment): axial post-surgical

MRI scan of a left cerebellar and midline tumour.

level semantics and lexical retrieval key elements that underpin observed difficulties in these areas. The contribution of tumour location is considered to have a fundamental role in these observations, with other reports noting similar findings related to cerebellar hemispheric location and the vermis [3, 5, 10, 12, 13]. Despite differing laterality, both cases demonstrated hemispheric involvement: case 1 had an ependymoma treated with surgery and radiotherapy in the right cerebellar hemispheric region, while case 2 was treated with surgery for a juvenile pilocytic astrocytoma that involved the inferior vermis and the left hemisphere. Both reports by Riva and Giorgi [3, 5] which examined the cognition, language and executive functions of children who had been treated with surgery for cerebellar tumour noted that children with either right or left hemispheric involvement exhibited reduced abilities in thinking flexibility and problem solving. Riva [13] and Schatz et al. [10] also documented severe deficits in processing verbal intelligence and producing complex language structures in patients with cerebellar damage. As both cases 1 and 2 underwent total and near total tumour removal in these critical cerebellar structures, it is suggested that the observed disturbances to problem solving in these cases are related to damage to

the cerebellar structures essential for language and cognition, consistent with previous reports. A further decline in the specific area of problem solving was also noted at follow-up assessment 12 months later in the only case to be documented longitudinally (case 1). A similar pattern was unable to be supported by case 2, who did not participate in follow-up assessment. The possibility that location and surgical intervention in the area of the right cerebellar structures may have had a role in the observed high-level language findings over time was supported in a report by Scott et al. [9]. This author detected an association between damage to the right cerebellar structures and a plateauing in verbal and literacy skills in children with cerebellar tumours. Surgical removal of a tumour in the right cerebellar hemisphere was also reported by Riva and Giorgi [3, 5] to be associated with deficits in thinking flexibility and problem solving. It is also considered that a presentation of reduced problem solving ability at initial assessment followed by a pattern of decline in the profile of case 1 may highlight a structural and functional deterioration that more closely relates to recognized treatment effects associated with radiotherapy use in childhood patients [14– 16].

Cerebellar Tumour and Language in Children

Folia Phoniatr Logop 2007;59:190–200

197

Demonstrated enhanced treatment effects in the context of increased time after treatment have also been widely reported, with evidence of progressive intellectual deterioration following radiotherapy treatment for paediatric brain tumour [17–23]. Among adverse effects such as motor and sensory deficits, neuroendocrine dysfunction and second malignancies, neuropsychological and intellectual effects have been extensively documented to follow cranial radiation treatment in children in as many as 40–75% of those studied [17, 21, 24, 25]. Such sequelae have been reported to intensify with time following treatment, peaking at 3 years after [15, 23]. Surprisingly, unlike neuropsychological effects that have been related to childhood radiation treatment of brain tumour, communication disorders have generally not been commonly linked to radiotherapy [6–8, 26]. The one documented study that identified a possible connection reported language impairments inclusive of deficits in word finding, syntax and reading [8]. These discrepancies were reportedly evident only in those children who had received radiotherapy after surgery. One quarter of the cases identified with language deficits demonstrated neuropathological changes in the frontal and temporal lobes, which were noted to be directly responsible for the reductions in language performance observed. Most commonly, reports of intellectual deficits or decline have been associated with dose and volume of radiation and age at treatment (e.g. Suc et al. [25]). The severity of resulting treatment effects has been documented to escalate with increasing dose, with reports of incidence at more than 50% following dosages of 24 Gy [15, 17, 23, 27–30]. Therefore, given that case 1 received a total radiation dosage of 54 Gy, unfavourable effects on higherlevel language function are not unlikely. Thus, the progressive nature of language impairment in the area of problem solving in the report of case 1, who was administered a total radiation dosage above this reported threshold of 54 Gy, highlights the potential for detrimental effects of higher-level function. The likelihood for this case to develop more widespread difficulties in high-level language may also exist beyond the current report at both 6 and 18 months following treatment due to an upsurge in reports of neuropathological changes following radiotherapy, including radionecrosis, white matter density changes, intracerebral calcifications and atrophy, which reportedly occur from 6 months up to 20 years later following radiotherapy treatment [8, 15, 27]. Subsequent to treatment, increasing evidence of intracranial changes may escalate over time, which in turn has the opportunity to impact lan198

Folia Phoniatr Logop 2007;59:190–200

guage function to a greater extent [8, 26, 31]. The potential for even further decline is indicated by these preliminary results associated with increases in time subsequent to treatment completion reported by Hudson et al. [8]. The specific tumour location of the right cerebellar region may also have contributed to the persistent nature of problem solving disturbances, according to previous reports. As mentioned earlier, a report by Scott et al. [9] in 2001 supported an association between damage to right cerebellar structures and a plateauing in verbal and literacy skills in children with cerebellar tumours. As such, the combination of surgical intervention in this location with localized radiotherapy as mentioned above may have contributed to longitudinal findings in this case. While case 2 exhibited similar disturbances at 6 months following treatment, it is unfortunate that documentation of case 2 at a further 12 months after treatment did not occur, as it is unknown whether a further decline in function (as observed in the first case) would also have occurred subsequent to surgery alone in the language profile of this child. It must also be acknowledged that while cases 3 and 4 also had cerebellar tumours treated with surgery alone, they did not demonstrate any language deficits at 1 year 2 months and 3 years after treatment, respectively, despite large tumours in the cerebellum. A report by HoppeHirsch [32] supported these contrastive findings, stating that when surgery was restricted to the cerebellar hemisphere or vermis in their study of cognitive function, no deterioration in intellectual function was evident. Although the presence of co-occurring hydrocephalus may have contributed to findings of reduced problem solving in the second case examined, an obvious effect on language function was not demonstrated by the 2 additional cases with this feature (cases 3, 4). This is despite reports of associated language disturbances in patients with hydrocephalus [6, 17, 23, 33–37]. An additional factor contributing to the lack of findings in 2 of the 4 cases observed may lie with the possibility that present surgical intervention procedures in childhood cerebellar tumour patients have included less aggressive attempts at tumour removal, particularly in cases where the tumour is identified to be less aggressive. Findings of higher-level language deficits in problem solving in 2 of the 4 cases reported highlighted the importance of longitudinal follow-up and assessment, particularly given the large variations in language outcomes and presentation that often occur in this population. Disturbances to higher-level areas such as problem solving highlight the need for in-depth assessment of children Docking /Murdoch /Suppiah

with cerebellar tumours, certainly in light of persistent deficits in children, potential long-term deterioration of such skills and the possibility of more widespread disturbances to manifest. Larger group studies will also serve to provide greater depth of information related to the effects of cerebellar tumour location in children. Use of more sensitive measures, such as neurophysiological ones, to detect subtle areas of language dysfunction that may be masked on more traditional clinical assessments is also an important direction. The use of neurophysiological investigation in language development and in the evaluation of language outcomes has recently emerged as a highly effective means for studying the neuroelectrical correlates of language in the brains of infants and children [38]. The technique of recording event-re-

lated potentials from the scalp has been reported to be one of the few non-invasive methods currently available for the study of the underlying mechanisms in language function in children and neural-related events in children [39]. The predictive value of this investigative technique has also been consistently reported in developmental populations relating to later language development in tracking long-term language changes [38, 40]. Accordingly, the use of event-related potentials to sensitively identify changes over time in childhood populations is considered an important future aspect in accurately defining and mapping the nature of activations in language function performance following treatment for cerebellar tumour.

References 1 Riva D: Cerebellar contribution to behaviour and cognition in children. J Neuroling 2000;13:215–225. 2 Levisohn L, Cronin-Golomb A, Schmahmann JD: Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain 2000;123:1041– 1050. 3 Riva D, Giorgi C: The contribution of the cerebellum to mental and social functions in developmental age. Hum Physiol 2000; 26: 21–25. 4 Steinlin M, Styger M, Boltshauser E: Cognitive impairments in patients with congenital nonprogressive cerebellar ataxia. Neurology 1999;53:966–973. 5 Riva D, Giorgi C: The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours. Brain 2000;123:1051–1061. 6 Murdoch BE, Hudson-Tennent LJ: Differential language outcomes in children following treatment for posterior fossa tumours. Aphasiology 1994; 8:507–534. 7 Hudson LJ, Murdoch BE: Chronic language deficits in children treated for posterior fossa tumour. Aphasiology 1992;6:135–150. 8 Hudson LJ, Murdoch BE, Ozanne AE: Posterior fossa tumours in childhood: associated speech and language disorders post-surgery. Aphasiology 1989;3:1–18. 9 Scott RB, Stoodley CJ, Anslow P, Paul C, Stein JF, Sugden EM, Mitchell CM: Lateralized cognitive deficits in children following cerebellar lesions. Dev Med Child Neurol 2001;43:685–691. 10 Schatz J, Hale S, Myerson J: Cerebellar contribution to linguistic processing efficiency revealed by focal damage. J Int Neuropsychol Soc 1998;4:491–501.

Cerebellar Tumour and Language in Children

11 Fisher JP, Glenister JM: The Hundred Pictures Naming Test. Melbourne, The Australian Council for Educational Research Ltd, 1992. 12 Oki J, Takahashi S, Miyamoto A, Tachibana Y: Cerebellar hypoperfusion and developmental dysphasia in a male. Pediatr Neurol 1999;21:745–748. 13 Riva D: The cerebellar contribution to language and sequential functions: evidence from a child with cerebellitis. Cortex 1998; 34:279–287. 14 Cohen ME, Duffner PK: Brain tumors in children: principles of diagnosis and treatment; in French J, Rapin I, Pritchard JS (eds): International Review of Child Neurology. New York, Raven Press, 1984, pp 240–289. 15 Heideman RL, Packer RJ, Albright LA, Freeman CR, Rorke LB: Tumors of the central nervous system; in Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology. Philadelphia, Lippincott Company, 1993, pp 633–681. 16 Murdoch BE, Hudson LJ, Boon DL: Effects of treatment for paediatric cancer on brain structure and function; in Murdoch BE (ed): Communication Disorders in Childhood Cancer. London, Whurr Publishers, 1999, pp 21–54. 17 Danoff BF, Cowchock S, Marquette C, Mulgrew L, Kramer S: Assessment of the long-term effects of primary radiation therapy for brain tumors in children. Cancer 1982;49:1580–1586. 18 Dennis M, Spiegler BJ, Hetherington CR, Greenberg ML: Neuropsychological sequelae of the treatment of children with medulloblastoma. J Neurooncol 1996; 29:91–101. 19 Duffner PK, Cohen ME, Thomas P: Late effects of treatment on the intelligence of children with posterior fossa tumors. Cancer 1983;51:233–237.

20 Mulhern RK, Hancock J, Fairclough D, Kun L: Neuropsychological status of children treated for brain tumours: a critical review and integrative analysis. Med Pediatr Oncol 1992;20:181–191. 21 Pierre-Kahn A, Hirsch JF, Roux FX, Renier D, Sainte-Rose C: Intracranial ependymomas in childhood: survival and functional results of 47 cases. Childs Brain 1983; 10: 145–156. 22 Silverman CL, Palkes H, Talent B, Kovnar E, Clouse JW, Thomas PR: Late effects of radiotherapy on patients with cerebellar medulloblastoma. Cancer 1984; 54:825–829. 23 Silverman CL, Thomas PRM: Long-term neuropsychologic and intellectual sequelae in brain tumour patients; in Deutsch M (ed): Management of Childhood Brain Tumors. Boston, Kluwer Academic Publishers, 1990. 24 Bamford FN, Morris Jones P, Pearson D, Ribeiro GG, Shalet SM, Beardwell CG: Residual disabilities in children treated for intracranial space-occupying lesions. Cancer 1976;37:1149–1151. 25 Suc E, Kalifa C, Brauner R, Habrand JL, Terrier-Lacombe MJ, Vassal G, Lemerle J: Brain tumors under the age of three: the price of survival – a retrospective study of 20 longterm survivors. Acta Neurochir 1990; 106: 93–98. 26 Hudson LJ, Murdoch BE: Language recovery following surgery and CNS prophylaxis for the treatment of childhood medulloblastoma: a prospective study of three cases. Aphasiology 1992; 6:17–28. 27 Cohen ME, Duffner PK, Tebbi CK: Brain tumors in children: diagnosis and management; in Tebbie CK (ed): Major Topics in Pediatric and Adolescent Oncology. Boston, Hall Medical Publishers, 1982, pp 240–289.

Folia Phoniatr Logop 2007;59:190–200

199

28 Green DM: Long-Term Complications of Therapy for Cancer in Childhood and Adolescence. Baltimore, The Johns Hopkins University Press, 1989, p 171. 29 Meadows AT, Burk CD, Silber JH: Delayed consequences of therapy; in Voute PA, Barrett A, Lemerle J (eds): Cancer in Children. Clinical Management. Berlin, Springer-Verlag, 1992, pp 71–84. 30 Plowman PN: Tumours of the central nervous system; in Plowman PN, Pinkerton CR (eds): Paediatric Oncology. Clinical Practice and Controversies. London, Chapman & Hall Medical, 1992, pp 240–267. 31 Buttsworth DL, Murdoch BE, Ozanne AE: Acute lymphoblastic leukaemia: language deficits in children post-treatment. Disabil Rehabil 1993;15:67–75.

200

32 Hoppe-Hirsch E: Intellectual and psychosocial complications of posterior fossa tumor surgery and supplemental (radiation therapy/chemotherapy) treatment; in Raimondi AJ, Choux M, Di Rocco C (eds): Posterior Fossa Tumors. New York, Springer-Verlag, 1993, pp 194–200. 33 Murdoch BE, Docking KM, Ward EC: Language and phonological awareness abilities of children treated for posterior fossa tumour; in Fabbro F (ed): Neurogenic Language Disorders in Children. Oxford, Elsevier, 2004, pp 87–126. 34 Murdoch BE, Hudson LJ: Language disorders in children treated for brain tumours; in Murdoch BE (ed): Communication Disorders in Childhood Cancer. London, Whurr Publishers, 1999, pp 55–75. 35 McWhirter WR, Masel JP: Paediatric Oncology. An Illustrated Introduction. Sydney, Williams & Wilkins and Associates Pty Limited, 1987.

Folia Phoniatr Logop 2007;59:190–200

36 Van Eys J: Malignant tumors of the central nervous system; in Fernbach DJ, Vietti TJ (eds): Clinical Pediatric Oncology. St Louis, Mosby-Year Book Inc, 1991, pp 409–426. 37 Wilson CB: Diagnosis and surgical treatment of childhood brain tumors. Cancer 1975;35:950–956. 38 Molfese DL, Molfese VJ, Espy KA: The predictive use of event-related potentials in language development and the treatment of language disorders. Dev Neuropsychol 1999;16: 373–377. 39 Mills DL, Coffey-Corina S, Neville HJ: Language comprehension and cerebral specialization from 13 to 20 months. Dev Neuropsychol 1997; 13:397–445. 40 Molfese DL, Molfese VJ, Key S, Modglin A, Kelly S, Terrell S: Reading and cognitive abilities: longitudinal studies of brain and behaviour changes in young children. Ann Dyslex 2002;52:99–119.

Docking /Murdoch /Suppiah

Folia Phoniatr Logop 2007;59:201–209 DOI: 10.1159/000102932

Language and Social Communication in Children with Cerebellar Dysgenesis Alessandro Tavano a Franco Fabbro a, c Renato Borgatti b a

Neurolinguistics Unit, San Vito al Tagliamento, Pordenone, b Department of Neurorehabilitation, Scientific Institute E. Medea, Bosisio Parini, Lecco, and c Faculty of Education, University of Udine, Udine, Italy

Key Words Cerebellar malformation
Language
Procedural memory
Social communication
Neurodevelopment

with cerebellar malformations supports a key role of the cerebellum in language acquisition and affect regulation as distinguished functional domains. Copyright © 2007 S. Karger AG, Basel

Abstract Objective: Acquired cerebellar lesions in children and adults may determine deficits of executive functions, visuoperceptual skills, expressive language and modulation of affect; a complex pattern termed ‘cerebellar cognitive affective syndrome’. However, the long-term sequelae of malformative cerebellar lesions have yet to be systematically investigated, particularly in children. The purpose of this study was to present preliminary longitudinal data on the development of language and social communication skills in children with congenital malformations confined to the cerebellum. Patients and Methods: Five children (3 males, 2 females) with cerebellar malformations confined to the cerebellum were selected. Three patients presented with cerebellar hypoplasia involving the vermis and the hemispheres, while the remaining 2 had a malformation affecting only the cerebellar hemispheres. Neurobehavioral and language development were traced through access to available clinical data. Results: In the patients with cerebellar vermis malformation, language and social communicative skills were affected to a variable extent: 1 patient did not present with social disturbances during development. Those with hemispheric cerebellar lesions presented with selective linguistic impairments. Conclusions: The neurobehavioral profile of children

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0201$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

Introduction

In recent years an interest in a specific cerebellar contribution to language has raised following clinical reports of subtle agrammatic symptoms, which seem to be present especially after an acquired lesion to the right cerebellar hemisphere in adults [1–4]. The main types of reported error are omissions of free-standing grammatical morphemes (e.g. clitic pronouns) and, in the case of verbs, substitution of tensed inflections with infinitive endings. These findings have been interpreted in at least 4 different ways: as a problem with online coupling of stem forms and morphological markings in verbal working memory [4, 5]; as a phonological planning deficit which may impact on the selection of unstressed function words and word stems [6, 7]; as a reduced access to morphophonemic or morphosyntactic representations [8, 9], and as an instance of an inability of the damaged cerebellum to maintain a smooth and fine-tuned organization of the different components of language processing [10]. However, besides morphosyntactic errors, adults with acquired cerebellar damage have also evidenced selective semantic deficits, such as verb-to-noun or antonym-to-

Renato Borgatti, MD Neurorehabilitation Unit 1 Scientific Institute Eugenio Medea Bosisio Parini IT–23842 Posisio Parini, Lecco (Italy) Tel. +39 031 877 811, Fax +39 031 877 499, E-Mail [email protected]

noun generation [11–13]. It follows that theories of cerebellar involvement in language should be expanded to explain both morphosyntactic and lexical access deficits. Moreover, if adult patients mainly display expressive language difficulties, children with acquired tumor or vascular lesions show receptive disorders as well [14–16]. In particular, while it appears that right cerebellar hemispheric lesions specifically impact on grammatical abilities, a lesion to either cerebellar hemisphere may give rise to semantic comprehension deficits [14, 16]. Overall, these results suggest the need to clarify the profile of language abilities after cerebellar lesions [17, 18]. This is especially so for children, as the early onset of a cerebellar lesion may influence the acquisition of different aspects of language. To this end, an interesting case is provided by patients with congenital malformative cerebellar lesions. Very few studies were conducted on this clinical population [19]. Chedda et al. [19] studied 8 patients (6 children and 2 adults) with cerebellar agenesis: as for children, 2 cases had near complete agenesis, 2 cases marked hypoplasia of 1 cerebellar hemisphere (1 left, 1 right), and 2 cases lacked both posterior hemispheres. One adult had vermal agenesis, the other showed agenesis of the right posterior cerebellar hemisphere. The study documents the presence of important neuropsychological deficits affecting executive functions and visuospatial abilities. All cases showed marked prosodic difficulties, while only some children presented with expressive language difficulties, specifically involving overgeneralization of regular past tense forms. These patients also showed autistic-like behaviors and difficulty understanding social cues. Thus, language abilities in children and adults with cerebellar malformations appear to be relatively more preserved than executive, visuospatial and, above all, social and affective functions. In a very recent investigation conducted at our research unit, we traced cognitive, linguistic and social development in 27 children and adults with congenital cerebellar lesions [Tavano et al., unpublished data] and found that impairments of executive functions (e.g. attention) and visuoperceptual skills characterize the group’s longterm outcome to a greater extent than language disabilities, which on average are mildly impaired. However, our data allowed 2 further observations: (1) when language abilities could be properly tested, evidence was found of both receptive and expressive deficits, especially at an early age; (2) patients who presented with language impairments also had communication difficulties due to social interaction failure. With regard to the former point, since malformative lesions impact on early functional de202

Folia Phoniatr Logop 2007;59:201–209

velopment, it is possible to envisage a role for the cerebellum in the acquisition of language comprehension and expression [20]. With regard to the latter point, most of the patients in our study showed marked psychopathological disorders such as anxiety, depression and autistic traits, which appear to have persistently impacted on social communication. Such traits were present at first evaluation and usually maintained clinical relevance also at follow-ups. The need thus arises to distinguish between language and socioaffective skill development in congenital malformative lesions. This seems to be especially important when malformations affect the cerebellar vermis, since vermal lesions have been associated with autisticlike behavior [21]. Investigations of behavioral sequelae of tumoral cerebellar lesions in children documented the presence of disturbances in affect regulation, but the association with linguistic impairments is not clear [14]. Children who underwent excision of vermal medulloblastoma showed 2 different postsurgical sequelae: transient mutism without behavioral or neuropsychological abnormalities and mutism evolving into speech and language disorders with behavioral and neuropsychological impairments, too. Children with behavioral impairments had the inferior vermis excised, while in the other cases the entire vermis was lesioned. These findings suggest the need for further investigations into the role of the cerebellar vermis in social and affective behavior and language development. In this perspective, it is important to study the neurodevelopmental profile of children with congenital malformations confined to the cerebellum, and in particular those with a vermal lesion. In this work we compared the individual profiles of 5 children with different functional profiles, 3 of whom had dysgenetic lesions involving the vermis and the cerebellar hemispheres, while the remaining 2 had aplastic lesions of both cerebellar hemispheres. We aimed at: (1) distinguishing the contribution of the cerebellum to language and social behavior; (2) clarifying the influence of the cerebellum on language abilities in children by comparing the outcomes of congenital malformative lesions with the data on acquired lesions available in the literature.

Materials and Methods Subjects We selected 5 children out of a larger group of 27 patients (4 adults, 23 children) with congenital lesions confined to the cerebellum, referred to the Neurorehabilitation Department of the Eugenio Medea Institute (Bosisio Parini, Lecco, Italy) in the 2001– 2003 time period. The study was run by retrospectively selecting

Tavano /Fabbro /Borgatti

all the patients with malformative lesions confined to the cerebellum. A total number of 155 patients were found. Further, the following exclusion criteria were applied: (1) radiological picture or medical history consistent with a diagnosis of acquired lesions due to pre-perinatal suffering; (2) progressive cerebellar pathology, and (3) malformations affecting other cerebral structures besides the cerebellum. Other exclusion criteria were syndromic pictures known to be associated with secondary cortical suffering (e.g. Joubert syndrome, Arnold-Chiari syndrome) and the presence of epileptic fits or febrile convulsions in the patients’ clinical history. The selection process yielded 27 patients. For these patients MRI scans were acquired with a 0.5- or 1.5-tesla MRI equipment, protonic density and T1-, T2-weighted spin-echo sequences, through axial and coronal sections, 4 or 5 mm thick. All the MRI scans were reviewed by a neuroradiologist blind to the patients’ identity and clinical data according to the Atlas of Schmahmann et al. [22]. Neuroradiological data allowed a classification of cerebellar malformations according to ontogenetic anatomical criteria: type I, complete cerebellar agenesis (1 patient); type II, vermal agenesis (complete or partial; 5 patients); type III, hypoplasia involving the vermis and both hemispheres (17 patients), and type IV, malformations involving only the cerebellar hemispheres (1 or both; 4 patients) [23]. Among these, 5 children were chosen; 3 of them (2 males, 1 female) were considered as a representative sample of the variable spectrum of disorders evidenced by patients with type III malformation amenable to testing (8 patients in the group study; patients 1, 2 and 3 of the present study) and 2 of them (2 females) as a representative sample of the disorders manifested by patients with type IV malformation (4 patients in the group study; patients 4 and 5 of the present study). Patients with type III malformation who were not amenable to testing (9 out of 17) were not included. Developmental Assessment Developmental milestones were recorded using the items of the Griffiths Mental Development Scale as indicators [24]. Detailed neurological examinations were performed including an evaluation of cerebellar functions on the basis of the International Cooperative Ataxia Rating Scale [25]. Cognitive, Linguistic and Behavioral Assessments Intellectual profile: Wechsler Preschool and Primary Scale of Intelligence [26]; Wechsler Intelligence Scale for Children – Revised (WISC-R, [27]); Griffiths Mental Developmental Scales – Revised [24]; Stanford-Binet Scale – Revised [28]. T Attention and memory: Wisconsin Card Sorting Test [29]; Continuous Performance Test [30]; Wide Range Assessment of Memory and Learning [31]; Rey Complex Figure Test, B [32]; Corsi Span [33]. T Perceptual, visuospatial and graphic abilities: Test of VisualPerceptual Skills (nonmotor) – Revised [34]; Rey Complex Figure Test, A [32]. T

Repetition: word/nonword repetition [37]; sentence repetition [38]. T Production: naming [37]; semantic fluency [37]; The Nest Story [39, 40]; spontaneous language sample [35]. T

Behavioral and Psychiatric Evaluation All the patients received a standard clinical psychiatric assessment. Neuropsychiatric observations were performed by a child neuropsychiatrist (R.B.) based on observations of free motherchild and peer social interaction, according to the DSM-IV indications [41]. The psychopathological diagnoses were formulated in line with DSM-IV criteria. Social communication was therefore assessed on the basis of neuropsychiatric observations.

Results

All the patients with a malformation affecting both the vermis and the hemispheres showed mild to moderate early developmental deficits. Case 1 presented with a worse cognitive profile but preserved motor abilities. As for cases 4 and 5, who had a malformation affecting both cerebellar hemispheres, they initially presented with cognitive and affective development within normal limits (table 1). At present, a standard neurological examination of cerebellar functions evidences dysdiadochokinesis in all cases; cases 1, 2, 4 and 5 present with mild generalized hypotonia, case 3 shows mild ataxia, while case 2 has intentional tremors and speech dyspraxia. Clinical behavioral assessments have been run according to DSM-IV criteria [41]. Four out of 5 patients show signs of psychopathological behavior, however mild. Case 1 is characterized by marked difficulties in communication and expression of emotions, which suggest a diagnosis of atypical autism, while case 2 shows free anxiety and obsessive traits. Cases 4 and 5 all present emotional lability and depressive symptoms. Case 3 shows no psychopathological signs (table 2).

Case Descriptions

Case 1

Speech and Language Children aged 4.00–12.00 years were assessed with the Batteria di valutazione del linguaggio (Language Assessment Battery) [35], which includes the following subtests. T Comprehension: phonemic discrimination (Same/Different Test, Figure Detection Test [35]); semantic comprehension [35]; Token Test (21 items) [35]; grammatical comprehension [36].

Neurobehavioral Development Case 1 first came to our hospital at 9 years of age. The neurological examination revealed mild hypotonia and dysdiadochokinesis as well as a general delay in motor abilities. At MRI he showed a moderate enlargement of the 4th ventricle (mega cisterna magna) with diffuse moderate atrophy of the cerebellar vermis. The cerebellar hemispheres were nearly normal (coronal section, T1-weighted; fig. 1A). The EEG evidenced the presence of paroxysmal abnormalities in nonrapid eye movement sleep in anterior and central posterior regions.

Language in Cerebellar Dysgenesis

Folia Phoniatr Logop 2007;59:201–209

203

Table 1. Age at the first and last evaluations and general developmental milestones

Subject

Gender

Age1

Age2

Motor

Cognition Affect

Language

1 2 3 4 5

M F M F F

9 11.07 2.01 4.05 4.05

10.5 14 10.10 7.05 7.05

MI MI MI MI MI

MO MI MI N N

MO MI MI MI MI

MO MI N N N

MI = Mild impairment; MO = moderate impairment; N = no impairment. 1 First evaluation. 2 Last available evaluation.

Table 2. Cerebellar signs at neurological examination and psychiatric diagnosis

Subject

1 2 3 4 5

Neurological examination

Psychopathological signs

HT

DD

A

T

D

+ + – + +

+ + + + +

– – + – –

– + – – –

– +++ + – –

markedly impaired social interaction, atypical autism anxiety, compulsive traits – mild depressive symptoms mild depressive symptoms

HT = Hypotonia; DD = dysdiadochokinesis; A =ataxia; T = intentional tremors; D = dysarthria. +++ = Severe deficit; ++ = moderate deficit; + = mild deficit; – = no deficit. Deficits were evaluated as severe, moderate or mild according to the International Cooperative Ataxia Rating Scale.

On the Stanford-Binet Scale (form L-M) he scored a mental age of 4.06 years, thereby qualifying for a diagnosis of moderate mental retardation [full-scale IQ (FIQ) = 50]. His cognitive profile did not change after a year’s treatment [WISC-R: FIQ !49, verbal IQ (VIQ) !51, performance IQ (PIQ) !49]. A psychomotor evaluation evidenced a severe impairment in fine and gross motor skills, including spatial and temporal organization. The child did not collaborate in completing all the tasks which make up the psychomotor profile, tended to speak about himself using 3rd person pronouns and to play presymbolic games which could grant him sensorimotor pleasurable experiences, with subsequent excitement stereotypes. The child might gradually engage in playing games with the clinician but tended to make lists of all objects at hand and explore the environment without planning. Emotional and social interaction impairments were evident in his relationship with adults, while peer relationships were absent. Verbal initiative was extremely reduced. Eye contact could be established but was usually brief and initiated by a caring adult. When required to join a conversation, he tended to enact postural readjustments which allowed him to keep distance from the speaking adult. Such behaviors were substantially maintained at follow-ups. Language At the first language evaluation (age 9.00 years), he showed a strong tendency to do better on semantic than phonological or morphosyntactic tasks. On the Language Assessment Battery

204

Folia Phoniatr Logop 2007;59:201–209

[35] he scored within normal limits in a semantic comprehension test which required him to choose among 4 plates the one that pictured the meaning of a name he was given (z score = –0.58). Naming of action verbs was at ceiling, although the test only required naming of 5 actions. His score on a lengthier object naming test was also within normal limits (z score = –0.87). However, semantic fluency was extremely reduced (3 names of animals, 2 names of objects). The Token Test scores were several standard deviations below the mean for his age, evidencing problems in verbal working memory (color names were often misplaced in remembering the relevant ordered sequence), which can possibly be attributed to a deficit in executive functions that could also account for the fluency impairment. Morphosyntactic and phonological abilities were significantly more impaired than naming abilities. Grammatical comprehension was severely impaired, the scores being appropriate for children aged 4.06 years. The patient showed comprehension problems with all types of sentence, from simple SVO active constructions to passive negatives, the latter being the most difficult for him. Word repetition was almost within normal limits but nonword repetition showed phonemic elision and simplification. Sentence repetition was also severely impaired (5 correct out of 14). One major source of difficulty was function word repetition (pronouns, conjunctions, complementizers). For example, if the original sentence was ‘Io non penso che tu debba farlo’ (I do not think you should do it), the patient repeated it as ‘Io non penso non farlo’ (I do not

Tavano /Fabbro /Borgatti

Fig. 1. A MRI, coronal section, of a moder-

ate enlargement of the 4th ventricle (mega cisterna magna) with diffuse moderate atrophy of the cerebellar vermis. Cerebellar hemispheres are nearly normal (patient 1). B MRI, sagittal section, shows a diffuse cerebellar hypoplasia involving both the vermis and the hemispheres (patient 2). C MRI, sagittal section, of a marked hypoplasia confined to the cerebellar vermis associated with hypoplasia of the superior cerebellar peduncles (patient 3). D MRI, coronal section, shows a malformation of cortical development of the hemispheres that appear partially torqued and rotated. The malformation is more evident on the right side (patient 4).

A

B

C

D

think not do it). Notice that this also results in a simplification of the underlying syntactic structure. After a year of language rehabilitation the patient showed nonsignificant improvements on the Token Test, grammatical comprehension, sentence repetition and semantic fluency tasks, while he obtained significantly lower scores on both naming and semantic comprehension. Word and nonword repetition were within normal limits. The language profile of case 1 can be seen in 2 different, yet complementary, perspectives. First, his language abilities showed a sharp performance distinction between lexical semantic knowledge and phonemic, morphosyntactic abilities. Lexical knowledge was preserved in both production and comprehension, while access to syntactic abilities was impaired. Although a particular drop could be identified in the use of function words, the grammatical comprehension test evidenced problems also with bound morphology, which was consistent in both testing sessions. Second, language development shows a generally negative trend, with marginal learning of morphosyntactic abilities at the expenses of previously acquired lexicosemantic abilities; thus, a tendency towards a plateauing of language abilities can be foreseen.

ebellar hypoplasia involving both the vermis and the hemispheres (fig. 1B). Motor and affective development was mildly delayed. At present her affective development is within normal limits, although she shows anxiety, obsessive traits and mild depression. Cognitive as well as linguistic abilities were also delayed (first words at 24 months, scanned words and syllable inversion were reported to have lasted up to the age of 10 years). She now presents with borderline cognitive abilities (WISC-R: FIQ = 81, VIQ = 96, PIQ = 69). Her performance abilities are significantly lower than her verbal skills. This profile is primarily due to deficient visuoperceptual processes (block design = 1) and executive (attentional and planning) deficits (Continuous Performance Test overall index = 15.11, WCST mean performance at 8th percentile), besides problems in praxic abilities. Her visuospatial memory is deficient (Corsi Test appropriate for 8 years of age), while her verbal short-term memory is age-appropriate (digit span = 8).

Neurobehavioral Development Case 2 first came to our hospital when she was 11.07 years old. The neurological examination showed mild hypotonia, dysmetria, dysdiadochokinesis and intentional tremors, as well as a general delay in motor abilities. Her voice was scanned, and the speech was low and effortful. At MRI she showed a diffuse cer-

Language Her language development showed a positive trend, with minor speech problems due to speech dyspraxia. Her performance on the Language Assessment Battery [35] shows ceiling scores for all subtests. Interestingly though, her spontaneous production shows evidence of excessive use of phrase repetition (often the verb phrase or a discursive marker) with strategic intent, as if trying to limit the effort of producing fluent speech. This habit is likely to be secondary to her slowness in processing language, in both spoken and reading/writing modes (her reading/writing accuracy is normal, but she scores significantly below normal limits as far as reading time is concerned).

Language in Cerebellar Dysgenesis

Folia Phoniatr Logop 2007;59:201–209

Case 2

205

Case 3 Neurobehavioral Development Case 3 was first seen when he was 2.01 years old. At the first neurological examination he showed a markedly ataxic gait and had problems in coordinating eye movements when following quickly moving objects. Later on ataxia became milder but balance was still impaired. He showed dysdiadochokinesis as well as a general delay in motor abilities. At MRI a marked hypoplasia confined to the cerebellar vermis was associated with hypoplasia of superior cerebellar peduncles (fig. 1C). A recent cognitive assessment shows a harmonic borderline profile (WISC-R: FIQ = 71, VIQ = 72, PIQ = 76). Both his verbal and spatial memory abilities are highly deficient (digit span = 3; Wide Range Assessment of Memory and Learning general memory score = 70, qualifying for the 2nd percentile), along with his visuoperceptual abilities (Rey figure copy and memory appropriate for 5-year-olds). However, the patient’s severer impairments lie within the attentional domain (Continuous Performance Test = 15.11). From a behavioral viewpoint, case 3 has always shown adequate collaboration with adults, displayed symbolic abilities and has been keen on playing games and engaging in conversational interaction. His emotional development was within normal limits, with no signs of psychopathological behavior. Language Initially his language development was delayed: at 3 years of age he was able to say some words with strictly referential value, but 2-word utterances were absent. However, he gradually recovered and did not require language therapy. Only a recent language assessment (10.10 years) was made available for this study. At the Language Assessment Battery [35] the patient scored within normal limits on the grammatical comprehension test, and word and nonword repetition tests, while his lower scores on semantic comprehension (22 correct items out of 32; adequate for 9-year-olds) might suggest an impairment of lexical semantic skills: however, a qualitative inspection shows errors only on low-frequency abstract names. Semantic fluency was normal. Overall, then, lexical semantic deficits are circumscribed to low-frequency abstract words and may therefore be more dependent on limited environmental input than on specific lexical failures. Memory limits do not impact on his morphosyntactic abilities, which have been acquired to an age-appropriate extent.

Cases 4 and 5

Language At the age of 5.07 both children were administered the Language Assessment Battery [35]. The results show significant problems in semantic comprehension and grammatical comprehension tests, on which both scored 2 standard deviations below the mean for their age. Sentence, word and nonword repetition were normal. Such a pattern of impaired comprehension with normal expression is highly unusual. Narrative speech shows differences between the 2 girls: while case 4 tends to speak less and use correct, although referentially vague, sentences, case 5 is descriptively more accurate but tends to omit function words such as verb auxiliaries. At 7 years of age their language was well within normal limits, with the exception of grammatical comprehension (scores appropriate for the age of 5.06 years). Interestingly, both patients showed problems with sentences whose comprehension either requires an increased verbal working memory load (negative active and passive sentences) or an intact processing of morphological information which is crucial for comprehension (number/gender marking for nouns and tense/aspect marking for verbs). It must be stressed that the sentences carrying such morphological features are usually acquired by the age of 4 years. We can hypothesize that both patients had difficulties in acquiring morphological information in a procedural, effortless way and possibly relied on declarative knowledge of grammar which is heavily taxed in cognitively (e.g. attention) demanding tasks such as the grammatical comprehension test. On less demanding tests, such as those requiring the repetition of a sentence, such difficulties may go unnoticed. This would explain why formal assessments show markedly impaired comprehension but normal expression abilities.

Discussion

Neurobehavioral Development Cases 4 and 5 are 2 homozygous twin girls who were first seen at our hospital when they were 4.05 years old. At MRI they showed a malformation of cortical development of the hemispheres that appeared partially torqued and rotated. This malformation was more evident on the right side (fig. 1D). Language and motor development were mildly delayed, while cognitive and affective development was within normal limits. Cognitive development was initially within normal limits for both children. At 5.07 years of age their cognitive profile was dysharmonic (Wechsler Preschool and Primary Scale of Intelligence, case 4: FIQ = 96, VIQ = 97, PIQ = 81; case 5: FIQ = 77, VIQ = 86, PIQ = 73), with major difficulties during tasks requiring visuoperceptual and visuospatial

206

abilities (geometric design). The WISC-R scores at the age of 7 years show a major decline in cognitive abilities (case 4: FIQ = 66, VIQ = 72, PIQ = 64; case 5: FIQ = 60, VIQ = 70, PIQ = 55). For both patients the arithmetic, object assembly and picture arrangement subtests were the most difficult to perform. Regarding their emotional and social development, they show no severe psychopathological behaviors, although the patients present with emotional fragility and mild depressive symptoms. At present a standard neurological examination documents a slightly ataxic gait, balance disturbances and intentional tremors when they engage in fine praxic movements. Acquisition of reading and writing skills was unaffected.

Folia Phoniatr Logop 2007;59:201–209

This work presents preliminary data on the developmental trajectories of linguistic and social communicative impairments in 5 children with congenital malformations confined to the cerebellum. We set out to verify: (1) the contribution of the cerebellum to language and social behavior; (2) whether the outcomes of congenital malformative lesions on language development were comparable with the findings on acquired lesions available in the literature. In this discussion we will start by addressing the first issue to later expand on the second. Tavano /Fabbro /Borgatti

The social communicative behavior of case 1 is in line with a diagnosis of atypical autism in that he is not able to engage in a communicative interaction with peers or adults. His behavioral profile seems to be plateauing, and the same can be said for his linguistic abilities, which do not seem to benefit from speech therapy. In this case, then, linguistic and social communicative abilities appear to be impaired to a similar extent. Case 2 does not present with residual language disabilities, but the qualitative profile of her spontaneous speech suggests that, besides a general slowness in processing, she might be compensating for a limited access to grammar. Her behavioral profile also shows minimal psychopathological signs which might be the result of an early delay in affective and social development. Thus, the overall picture of this patient suggests a comparable development of linguistic and social affective skills. Case 3 presents with some minor lexical semantic impairment, but his grammatical skills are highly efficient notwithstanding his severe deficits in verbal memory. He also shows no psychopathological signs. Contrary to the previous 2 patients, case 3 shows initially delayed, yet sufficiently recovered, language abilities associated with a normal social communicative behavioral development. Cases 4 and 5 present with a different developmental profile: while their affective and social abilities are at present only mildly affected (minor psychopathological signs of emotional lability and mild depression), their morphosyntactic comprehension skills are severely impaired. These findings are likely to be due to the different neuroradiological profile of cases 4 and 5, with lesions involving only the cerebellar hemispheres. This provisional survey suggests that children with malformative lesions involving the vermis may suffer from social and affective disturbances which, when present, are associated with language difficulties. In such cases, both domains tend to display a similar degree of impairment, which varies from severe to very mild. Accordingly, an intervention targeting both language and social skills may show different degrees of success. Language deficits may be present at an early age even in the absence of social and affective disorders and would therefore require specific selective intervention. Malformations confined to the cerebellar hemispheres display an inverse pattern of results, sparing social and affective skills and impacting more severely on the acquisition of cognitive and language abilities. These findings are in line with results on acquired cerebellar lesions, which suggest a generally severer impairment of verbal communication (that is, language use in socially adaptive ways) following vermal lesions [1, 10, 14, 15, 42], and a

relative sparing of social abilities with respect to cognitive and linguistic skills after cerebellar hemispheric lesions [16, 17, 43]. However, the possibility that congenital vermal lesions may induce disorders in language acquisition (with minor detectable sequelae) in the absence of social and affective disorders constitutes a new finding with respect to data on acquired vermal lesions, where isolated language disorders are usually transient [14]. Our findings are limited by the fact that in our retrospective study we could not provide standard baseline scores for cognition, language and behavior but relied on available clinical data. This is a consistent drawback with respect to the generalizability of the results. However, given the rarity of the syndromic pattern and the difficulty in selecting patients amenable to evaluation, in our opinion this study has provided at least a first step towards a more complete account of the impact of cerebellar malformations on cognition, language and behavior [44]. Of course, neuronal plasticity processes may determine a reorganization of brain areas that are structurally and functionally connected to the cerebellum. For example, the application of tensor diffusion imaging techniques able to accurately detail abnormalities in white matter connections may probably enable innovative studies on this issue. Regarding the second issue that motivated this paper, case 1 presents with an interesting dissociation between lexical and morphosyntactic abilities. He also had both expressive and receptive morphosyntactic deficits, thereby suggesting the existence of a congenital impairment in the acquisition of grammatical rules. This may hold true also for cases 4 and 5, although it is not immediately manifest given their profile on language tests: their expressive abilities are within normal ranges and they fail only on the grammatical comprehension test. However, with regard to grammatical comprehension, if working memory overload could be easily advocated for negative sentences, it is not clear whether it could explain difficulties in gender, number and tense marking. It cannot be argued that they display subtle working memory deficits, such as those invoked in explaining the agrammatic speech of cerebellar patients, since their expressive abilities are intact [2–5]. We suggest that, along with case 1, and possibly case 2 (see discussion above), cases 4 and 5 present with a congenital impairment in the acquisition of grammatical rules, which can be partially compensated for by declarative memory systems. Further, cases 4 and 5 presented with diffuse lesions that were more extensive on the right side of the cerebellum, providing evidence for a major role of this structure not only in language but also specifically in the acquisition of morphosyntax, possibly

Language in Cerebellar Dysgenesis

Folia Phoniatr Logop 2007;59:201–209

207

subserving procedural memory systems [45, 46]. Case 3 presents with a different profile: his memory abilities are generally very poor, nonetheless his language delay improved, especially his grammatical abilities. Minor difficulties persist in the lexical domain. How can this case be accounted for? The available evidence on acquired lesions in children and adults suggests that lexical comprehension deficits may be present following lesions affecting either hemisphere [13, 14]. In our case, they occur in a patient with a malformation involving the vermis and superior cerebellar peduncles. We can hypothesize that in both instances associative loops connecting the cerebellum and temporoparietal (semantic memory) or frontal (search and retrieval strategies) cortices might have been affected. In any case, this points towards the need to precisely define not just the different aspects of language deficits, and particularly the grammar/lexicon distinction, but also what structures and loops within the cerebellum differentially contribute to their acquisition and normal functioning.

Overall, our data seem to at least partially confirm the common pathogenetic hypothesis, evidenced by studies on acquired cerebellar lesions, which suggests the involvement of the cerebellar vermis, together with the structures of the brain stem, the frontal lobes and the limbic system, in associative loops responsible for complex cognitive, linguistic and social behaviors [1, 42, 43]. Our data also confirm a specific role for cerebellar hemispheres in modulating cognitive and linguistic skills [43]. However, linguistic deficits in congenital cerebellar lesions tend to be severer than is the case with acquired cerebellar lesions, a likely result of impaired acquisitional processes. Finally, a comparison of linguistic and social development in congenital cerebellar lesions shows a high degree of interindividual variability, which, despite the above-mentioned general trends, suggests the need to determine, in each single case, the affected linguistic level and the associations, if any, with social disorders due to the lesioned cerebellar structure.

References 1 Schmahmann JD, Sherman JC: The cerebellar cognitive affective syndrome. Brain 1998; 121:561–579. 2 Silveri C, Leggio MG, Molinari M: The cerebellum contributes to language production: a case of agrammatic speech following a right cerebellar lesion. Neurology 1993; 44: 2047–2050. 3 Zettin M, Cappa SF, D’Amico A, Rago R, Perino C, Perani D, Fazio F: Agrammatic speech production after a right cerebellar haemorrhage. Neurocase 1997;3:375–380. 4 Silveri MC, Di Betta AM, Filippini V, Leggio MG, Molinari M: Verbal short-term storerehearsal system and the cerebellum: evidence from a patient with a right cerebellar lesion. Brain 1998;121:2175–2187. 5 Ravizza SM, McCormick AC, Schlerf JE, Justus T, Ivry RB, Fiez JA: Cerebellar damage produces selective deficits in verbal working memory. Brain 2006;129:306–320. 6 Leggio MG, Silveri MC, Petrosini L, Molinari M: Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study. J Neurol Neurosurg Psychiatry 2000;69:102–106. 7 Hubrich-Ungureanu P, Kaemmerer N, Henn FA, Braus DF: Lateralized organization of the cerebellum in a silent verbal fluency task: a functional magnetic resonance imaging study in healthy volunteers. Neurosci Lett 2002;319:91–94.

208

8 Justus T: The cerebellum and English grammatical morphology: evidence from production, comprehension, and grammaticality judgments. J Cogn Neurosci 2004; 16: 1115– 1130. 9 Justus T, Ravizza SM, Fiez AJ, Ivry RB: Reduced phonological similarity effects in patients with damage to the cerebellum. Brain Lang 2005;95:304–318. 10 Schmahmann JD: Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2004; 16: 367–378. 11 Fiez JA, Petersen SE, Cheney MK, Raichle M: Impaired non-motor learning and error detection associated with cerebellar damage. Brain 1992;115:155–168. 12 Gebhart AL, Petersen SE, Thach WT: Role of the posterolateral cerebellum in language. Ann NY Acad Sci 2002;978:318–333. 13 Fabbro F, Tavano A, Corti S, Bresolin N, De Fabritiis P, Borgatti R: Long-term neuropsychological deficits after cerebellar infarctions in two young twins. Neuropsychologia 2004;42:536–545. 14 Riva D, Giorgi C: The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumors. Brain 2000;123:1051–1061.

Folia Phoniatr Logop 2007;59:201–209

15 Levisohn L, Cronin-Golomb A, Schmahmann JD: Neuropsychological consequences of cerebellar tumor resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain 2000;123:1041– 1050. 16 Scott RB, Stoodley CJ, Anslow P, Stein JF, Sugden M, Mitchell CD: Lateralized cognitive deficits in children following cerebellar lesions. Dev Med Child Neurol 2001;43:685– 691. 17 Mariën P, Engelborghs S, Fabbro F, De Deyn PP: The lateralized linguistic cerebellum: a review and a new hypothesis. Brain Lang 2001;79:580–600. 18 Gottwald B, Wilde B, Mihajlovic Z, Mehdorn HM: Evidence for distinct cognitive deficits after focal cerebellar lesions. J Neurol Neurosurg Psychiatry 2004; 75: 1524– 1531. 19 Chedda MG, Sherman JC, Schmahmann J: Neurologic, psychiatric, and cognitive manifestations in cerebellar agenesis. Neurology 2002;58:A356. 20 Tavano A, Fabbro F, Borgatti R: Speaking without the cerebellum. Proc Int Lang Cogn Conf, Coffs Harbour, 2004. 21 Courchesne E: Neuroanatomic imaging in autism. Pediatrics 1991;87:781–790. 22 Schmahmann JD, Doyon J, McDonald D, Holmes C, Lavoie K, Hurwitz AS, et al: Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space. Neuroimage 1999;10:233–260.

Tavano /Fabbro /Borgatti

23 Altman NR, Naidich TP, Braffman BH: Posterior fossa malformations. AJNR Am J Neuroradiol 1992;13:691–724. 24 Griffiths R: The abilities of Young Children. High Wycombe, The Test Agency, 1996. 25 Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, et al: International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. J Neurol Sci 1997;145:205–211. 26 Wechsler D: Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Firenze, Organizzazioni Speciali, 1973. 27 Wechsler D: Wechsler Intelligence Scale for Children – Revised (WISC-R). Firenze, Organizzazioni Speciali, 1986. 28 Bozzo MT, Mansueto ZG: Adattamento Italiano della Scala di Intelligenza Stanford-Binet forma L-M, nella revisione Terman-Merrill (Italian version L-M form, 3rd revision). Firenze, Organizzazioni Speciali, 1993. 29 Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G: The Wisconsin Card Sorting Test. Odessa, Psychological Assessment Resources, 1993. 30 Cornoldi C, Gardinale M, Masi A, Pettenò L: Impulsività e autocontrollo. Interventi e tecniche metacognitive (Continous Performance Test). Trento, Erickson, 1996.

Language in Cerebellar Dysgenesis

31 Sheslow D, Adams W: Wide Range Assessment of Memory and Learning (WRAML). Wilmington, Jastack Associates, 1990. 32 Rey A: Reattivo della Figura Complessa. Firenze, Organizzazioni Speciali, 1959. 33 Corsi PM: Human Memory and the Medial Temporal Region of the Brain (unpublished PhD thesis). Montreal, McGill University, 1972. 34 Gardner MF: Test of Visual Perceptive Skills (Nonmotor)-Revised . Hydesville, Psychology and Educational Publications, 1996. 35 Fabbro F: Neurolinguistica e neuropsicologia dei disturbi specifici del linguaggio nel bambino: proposta di un esame del linguaggio. Saggi – Child Dev Disab 1999;25:11–23. 36 Chilosi A, Cipriani P: Test di Comprensione Grammaticale per Bambini (TCGB). Tirrenia, Del Cerro, 1995. 37 Riva D, Nichelli F, Devoti M: Una batteria di valutazione del linguaggio orale nel bambino afasico: normative italiane e considerazioni cliniche. Gior Neuropsich Età Evol 2000;20:37–50. 38 Ferrari E, De Renzi E, Faglioni P, Barbieri E: Standardizzazione di una batteria per la valutazione dei disturbi del linguaggio in età scolare. Neuropsich Infant 1981; 235–236: 145–158.

39 Paradis M: Valutazione dell’afasia bilingue. Bologna, EMS, 1999. 40 Tavano A, De Fabritiis P, Galli T, Fabbro F: Contributo alla valutazione standardizzata dell’eloquio narrativo nei bambini. Gior Neuropsich Età Evol 2005;25:48–64. 41 American Psychiatric Association: Diagnostic and Statistic Manual of Mental Disorders. DSM-IV, 4th Edition. Washington, APA, 1994. 42 Schmahmann JD: The role of the cerebellum in affect and psychosis. J Neuroling 2000;13: 189–214. 43 Schmahmann JD: Cognition, emotion and the cerebellum. Brain 2006;129:288–292. 44 Steinlin M, Styger M, Bolthauser E: Cognitive impairments in patients with congenital nonprogressive cerebellar ataxia. Neurology 1999;53:966–973. 45 Ullman MT: A neurocognitive perspective on language: the declarative/procedural model. Nat Rev Neurosci 2001;2:716–726. 46 Ullman MT, Pancheva R, Love T, Yee E, Swinney D, Hickok G: Neural correlates of lexicon and grammar: evidence from the production, reading, and judgement of inflection in aphasia. Brain Lang 2005;93:185–238.

Folia Phoniatr Logop 2007;59:201–209

209

Folia Phoniatr Logop 2007;59:210–217 DOI: 10.1159/000102933

Cerebellar Involvement in Motor Speech Planning: Some Further Evidence from Foreign Accent Syndrome Peter Mariën a Jo Verhoeven b a

Department of Neurology, ZNA Middelheim General Hospital, Antwerp, Belgium; b Department of Language and Communication Science, City University, London, UK

Key Words Foreign accent syndrome  Cerebellum  Motor speech planning

Abstract Background: Foreign accent syndrome (FAS) is a rare speech disorder that usually follows from damage to the motor speech areas of the language-dominant hemisphere. Recently, a vascular FAS patient was reported in whom a close parallelism was found between the infratentorial perfusional changes on SPECT and the regression of FAS symptoms. Based on the correlation between the near remission of a right cerebellar hypoperfusion and the near remission of FAS, it was hypothesized that the ‘linguistic cerebellum’ might be involved in the pathogenesis of motor speech planning disorders [Clin Neurol Neurosurg 2006;108:518– 522]. Aim: In this article the presumed role of the cerebellum in FAS is further investigated on the basis of an additional FAS case. Methods: Phonetic, neurobehavioral and neuroimaging data were analyzed and clinical-anatomical correlations were investigated. Results: In both patients, a close correspondence was found between the neurolinguistic findings and the functional neuroimaging data. 99mTc ECD SPECT follow-up studies demonstrated that clinical recovery of FAS symptoms was accompanied by a remission of a right

© 2007 S. Karger AG, Basel 1021–7762/07/0594–0210$23.50/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

cerebellar hypoperfusion. Conclusion: The present study, in which the data of a new FAS patient are discussed, corroborates the view that FAS may follow disruption of a close functional interplay between the supra- and infratentorial motor speech centers. Copyright © 2007 S. Karger AG, Basel

Introduction

Foreign accent syndrome (FAS) [1, 2] is a rare motor speech disorder in which articulatory distortions are perceived as a foreign accent by native speakers. Since the first descriptions in the beginning of the 20th century [3, 4], the condition has been reported in approximately 60 cases. The causative lesion for FAS mostly involves the prerolandic motor cortex (BA 4), the frontal motor association cortex (BA 6 or 44) or the striatum of the languagedominant hemisphere [5]. In only a very small number of patients a foreign accent was found after right hemisphere damage [6–8], and there have been a few cases in which FAS resulted from a psychogenic cause [6, 9–11]. Clinically as well as anatomically, FAS closely resembles apraxia of speech (AoS) (anarthria, verbal apraxia, speech apraxia), which is traditionally defined as a selective impairment of speech movements following the inProf. P. Mariën Department of Neurology, ZNA Middelheim General Hospital Lindendreef 1 BE–2020 Antwerp (Belgium) Tel. +32 3 280 3136, Fax +32 3 281 3748, E-Mail [email protected]

ability to properly and smoothly convert phonological knowledge into verbal-motor commands [12, 13]. As a result, it has been argued that FAS is a subtype of AoS [14]. Earlier terminology for AoS such as ‘ataxic aphasia’ and ‘cortical dysarthria’ [15] also suggests that AoS shares striking semiological similarities with ataxic dysarthria. Indeed, motor speech symptoms resulting from cerebellar pathology are also typically described as slow, monotonous, staccato, scanned, indistinct, remarkably irregular, jerky, explosive, slurred and labored [16, 17]. These similarities basically result from distorted articulatory planning and coordination processes: therefore, FAS, AoS and ataxic dysarthria may share a common pathophysiological mechanism. Given the recently acknowledged role of the ‘lateralized’ linguistic cerebellum in a variety of speech and language processes and the close anatomical connections between the right cerebellum and the motor speech centers of the language-dominant hemisphere, we hypothesized that in addition to the perisylvian speech regions, the right cerebellum may be crucially involved in motor speech planning disorders such as FAS and AoS [1]. During a 3-year follow-up of a FAS patient a remarkably close parallelism was found between the semiological and functional neuroimaging findings. This parallelism seemed to confirm that FAS and AoS might result, as reflected by diaschisis, from disruption of the close functional connection between the supra- and infratentorial motor speech centers. The aim of the present study is twofold: (1) to present the clinical, cognitive, structural and functional neuroimaging data of 2 FAS patients and (2) to present additional evidence to substantiate the view that the linguistic cerebellum might be involved in disrupted motor speech planning.

Case Descriptions Case V.R.M. A 53-year-old right-handed female native speaker of Dutch (V.R.M.) acutely developed major speech difficulties and a severe paresis of the right hemicorpus. On admission a few hours after the event the patient was speechless but well oriented, alert and fully cooperative. Neurological examination revealed anarthria with intact auditory-verbal comprehension, normal spelling, intact written comprehension and normal bucco-labio-lingual praxis. A moderate right hemiparesis and central facial nerve palsy were found. Tendon reflexes were brisker on the right than on the left side of the body. The right plantar response was extensor. Sensory examination was normal. On confrontation no visual field defects or spatial neglect phenomena were noticed. The med-

Cerebellar Involvement in Motor Speech Planning

ical history was unremarkable. The patient had an educational level of 14 years and worked as a technician in a medical laboratory. A computerized tomography scan of the brain on the fourth day of admission revealed an infarction in the left frontoparietal region. Two weeks after stroke, brain magnetic resonance imaging (MRI) displayed a cortical ischemic lesion in the territory of the left medial cerebral artery, involving the inferior frontal gyrus, the precentral gyrus, the anterior insular cortex, the postcentral gyrus and the supramarginal gyrus with discrete hemorrhagic conversion (fig. 1). Contrast transesophageal echocardiography revealed a patent foramen ovale with a spontaneous right-to-left shunt. A deep venous thrombosis of the lower limbs was excluded by means of venography. The day after admission speech started to recover. During the following days an oral-verbal output syndrome became apparent in which speech was slowly and hesitantly articulated. In addition, effortful articulatory struggles, particularly affecting consonant clusters, vowel and consonant lengthening, decreased stress and a general flattening of voice volume disrupted prosody and melody. As a result, syllables tended to become isochronous and of equal prominence (scanning speech). Although the articulatory distortions affected speech rather inconsistently, most errors were close phonemic target substitutions. Articulatory groping and struggling giving rise to sequential errors, and mostly unsuccessful efforts to self-correction alternated at times with ‘islands of error-free speech’. Errors significantly increased with word length and were not task-dependent. No improvement was found when the patient recited, repeated, cursed or read aloud. Apart from the articulatory deviations which resulted in a deficient speaking rate (1.96 syllables/s), analysis of 26 spontaneous speech utterances recorded in a short conversation (2 min) did not reveal any structural linguistic deficits. In addition, aphasic disturbances were formally excluded by means of standardized language tests including the Dutch version of the Aachener Aphasie Test (AAT) [18], the Boston Diagnostic Aphasia Examination [19], the Token Test [20], the Boston Naming Test (BNT) [21, 22], a phonological and semantic verbal fluency task (unpublished) and subtests of the Dutch version of the Psycholinguistic Assessments of Language Processing in Aphasia [23]. The patient herself, her direct acquaintances as well as hospital staff reported that her speech sounded odd, as if she spoke with a French or German accent. A neurolinguistic diagnosis of FAS was made and intensive speech therapy was started. As far as the phonetic characteristics of the patient’s speech are concerned, a detailed analysis revealed pronunciation problems at both the segmental and suprasegmental levels. The realization of the patient’s sound segments was mainly characterized by the relatively frequent devoicing of stops and fricatives, and frequent articulatory overshoot in that fricatives were often realized as stops. The latter was very obvious in /h/, which was consistently realized as a glottal stop. In addition, /r/ was always pronounced as a uvular fricative, whereas previous to the stroke the patient’s pronunciation of this phoneme would have been at an alveolar place of articulation. Furthermore, many of the patient’s vowels were regarded as perceptually deviant. At the suprasegmental level, her speech was characterized by a slow speech and articulation rate (1.96 and 2.80 syllables/s, respectively), the frequent use of creaky voice (jitter: 1.43%; shimmer: 12.11%) and a generally syllable-timed and isochronous speech rhythm. The patient’s implementation of intonation patterns was generally appropriate, but

Folia Phoniatr Logop 2007;59:210–217

211

Fig. 1. Brain MRI (A–F from rostral to caudal) coronal T1-weighted slices, obtained 14 days after the stroke, shows a frontoparietal lesion involving the inferior frontal gyrus, the precentral gyrus, the anterior insular cortex, the postcentral gyrus and the supramarginal gyrus of the left hemisphere.

A

B

C

D

E

F

the high number of continuation rises at phrase boundaries was clearly deviant. In addition, we observed a slight narrowing of the linguistic pitch range in comparison to the patient’s range prior to the stroke. Readministration of language tests and extensive neuropsychological investigations were carried out in the postacute phase (1 month after onset). The patient scored 30/30 on the Mini Mental State Examination [24]. The Progressive Matrices [25] revealed an IQ of 125. On the Wechsler Adult Intelligence Scale [26], she obtained a verbal IQ of 125 and a performance IQ of 110. All subtests of the Hierarchic Dementia Scale [27] scored at the maximum. The Wechsler Memory Scale-Revised [28] revealed a visual memory index 1138 and a verbal memory index of 125. On the delayed recall subtests of the Wechsler Memory Scale-Revised an index of 140 was found. The Wechsler Memory ScaleRevised concentration index was 112. Performance was normal on the Rey-Osterrieth figure, the Wisconsin Card Sorting Test [29], the Stroop Color Word Test [30], the Right-Left Orientation test, the Visual Form Discrimination Test and the Judgment of Line Orientation Test [31]. Formal assessment of handedness by means of the Edinburgh Inventory [32] showed a laterality quotient of +100. Inconsistent nonsequential substitutions of target phonemes and phonetic alterations such as prolongations and reductions of speech sounds were again observed. Articulatory deviations were less prominent, but interlocutors still perceived the patient’s speech as distinctly foreign. As structural neuroimaging was suggestive of stroke of thromboembolic origin, the patent foramen ovale was treated nonsurgically with transcatheter

212

Folia Phoniatr Logop 2007;59:210–217

closure. Pharmacological therapy with acetylsalicylic acid was started as well. After a rehabilitation period of 1 year, residual motor symptoms consisted of a right spastic hemiparesis. Complete remission of FAS was found 3 years after the stroke but very mild AoS symptoms persisted. Although the speech rate had markedly improved (from 1.96 to 3.93 syllables/s), the patient still spoke slightly hesitantly, as if she ‘wanted to keep in control over the production of sound patterns’. The articulation of consonants was near normal with the very occasional instance of overshoot in fricatives resulting in stop articulations. The inappropriate articulation of /h/ as a glottal stop in word-initial positions had disappeared completely. The /r/ phoneme was still realized as a uvular trill. As far as the articulation of vowels is concerned, there were only few mispronunciations, which seemed to be confined to the high-front area of the vowel space. The patient’s speech also showed a noticeable improvement in voice quality and intonation: creaky voice had almost disappeared completely (jitter: 0.57%; shimmer: 9.20%) and the use of intonation patterns had normalized with respect to the frequency of continuation rises. Speech rhythm was still perceived as slightly syllable-timed and isochronous. 99mTc ECD SPECT perfusion scans were acquired in the lesion and late phase of the stroke using a Trionix (Ohio, USA) Triad 3detector gamma camera equipped with high-resolution fan beam collimators. The projection data were reconstructed by filtered backprojection with a Butterworth filter (with cut-off frequency of 0.7 cyc/cm and roll-off 5) resulting in transaxial images with a pixel size of 3.56 mm. The color scale was subdivided in 16 colors,

Mariën /Verhoeven

Fig. 2. A 99mTc ECD SPECT scan of the brain in the acute phase of the stroke reveals a severe hypoperfusion in

the left frontal motor and parietal cortex as well as a secondary relative hypoperfusion in the thalamus and striatum of the left hemisphere (upper row). A relative hypoperfusion of the right hemicerebellum (crossed cerebellar diaschisis) is shown as well (lower row). B Repeat SPECT in the late phase of the stroke reveals no change of tracer uptake in the frontal motor area, parietal cortex, thalamus and striatum of the left hemisphere (upper row). Marked improvement of tracer uptake in the right cerebellum is shown (lower row).

A

B

C

D

E

F

Fig. 3. Brain MRI sagittal T2-weighted

slices obtained 3 weeks after the stroke show a hemorrhagic lesion in the left basal ganglia involving the putamen, genu and posterior limb of the internal capsule with extension to the posterior insula, the medial temporal lobe and the paraventricular white matter of the left parietal lobe.

Cerebellar Involvement in Motor Speech Planning

Folia Phoniatr Logop 2007;59:210–217

213

each representing 6.25% of the maximum activity. A baseline 99mTc ECD SPECT scan of the brain performed 33 days after the onset of neurological symptoms showed a breach of the left frontal motor cortex. A relative hypoperfusion was found in the thalamus, striatum and anterior temporal region of the left hemisphere. In addition, a relative hypoperfusion of the contralateral right cerebellum was detected as reflected by a 15% reduction of tracer uptake (fig. 2A). Repeat 99mTc ECD SPECT 3 years after the onset of neurological symptoms showed near normalization of tracer uptake in the cerebellum, whereas only mild perfusion improvement was observed in the supratentorial regions. Due to technical reasons the same color scheme could not be used when the second scan was performed (fig. 2B). Case P.L. A 61-year-old right-handed monolingual native speaker of Dutch (P.L.) acutely developed a right hemiplegia and aphasia due to a left basal ganglia hemorrhage. On admission the patient was fully alert and cooperative but could not produce comprehensible speech. He had difficulties in understanding simple auditory-verbal and written instructions. In addition to global aphasia, the neurological examination revealed a right hemiplegia, right hyperreflexia with extensor plantar response and right homonymous hemianopia. Apart from arterial hypertension, the medical history was unremarkable. The patient was professionally active as a butcher and had an educational level of 12 years. A computerized tomography scan of the brain on admission revealed a hemorrhagic lesion in the left basal ganglia that extended into the left parietotemporal region. Due to surrounding edema a slight midline shift was observed. Three weeks after the stroke, brain MRI confirmed the presence of a hemorrhagic lesion in the left basal ganglia which involved the putamen, genu and posterior limb of the internal capsule and which extended to the posterior insula, the medial temporal lobe and the paraventricular white matter of the left parietal lobe (fig. 3). An underlying vascular anomaly could not be disclosed on digital substraction angiography of the cerebral vessels. Six days after the onset of neurological symptoms global aphasia started to recover and a conduction-like aphasia associated with FAS became gradually apparent. Formal language investigations by means of the AAT, the Token Test, the BNT, a verbal fluency task and phonetic analyses of spontaneous speech samples were performed 1 and 6 months after the stroke. Although auditory-verbal comprehension rapidly improved to functional levels in the acute phase of the stroke, neurolinguistic test results at 1 month after onset still demonstrated auditory-verbal and written language comprehension deficits (table 1). Oral language investigations disclosed a fluent output disorder with severe repetition disturbances, anomia (BNT), phonematic paraphasias, numerous self-repetitions and conduites d’approches. Logorrhea and semantic retrieval deficits severely disrupted speech dynamics. A severely deficient performance was found on a verbal fluency task consisting of 1 min generation of items belonging to a particular semantic category (animals, transport, vegetables and clothes). Syntax disturbances, mainly characterized by the use of infinite verbs, omission of function words, stereotypical sentence constructions, and lexical-semantic deficits disrupted spontaneous as well as imposed speech (e.g. AAT sentence naming task = 6/30). Reading aloud words and sentences was normal. Spontaneous, dictational writing and oral spelling were severely impaired. In

214

Folia Phoniatr Logop 2007;59:210–217

Table 1. Neurolinguistic test results (AAT, BNT and verbal flu-

ency) 1 and 6 months after the onset of neurological symptoms (patient P.L.) Language tests

Results PerMax. Mean month centile 1/6

Aachener Aphasie Test Comprehension Total auditory Words Sentences Total written Words Sentences Token Test (errors) Spontaneous speech Communicative behavior Articulation and prosody Automatisms Semantic structure Phonematic structure Syntactic structure Imposed speech Total repetition Phonemes Monosyllabic words Loan and foreign words Compounds Sentences Total naming Simple nouns Color names Composed nouns Sentences Written language Reading aloud Composing Dictational writing Boston Naming Test Verbal fluency (total) Animals Means of transport Vegetables Clothes

89/102 43/50 20/28 23/22 46/52 21/26 25/26 40/31

81 SD

59/83 120 108.5 10.24 53/77 60 53.28 6.08 42/92 30 26.49 3.30 62/55 30 26.79 3.41 64/83 60 55.21 4.90 40/67 30 28.30 2.29 82/87 30 26.91 3.39 35/53 50 2.28 2.75

4/4 4/5 5/5 4/5 3/4 3/3

5 5 5 5 5 5

4.63 4.63 4.59 4.59 4.54 4.41

0.54 0.67 0.65 0.53 0.56 0.55

65/96 30/27 22/28 10/20 1/11 2/10 64/97 27/30 26/28 10/27 6/12 40/74 27/30 8/26 5/18

19/40 150 144.1 88/56 30 28.91 29/68 30 29.22 15/37 30 28.94 10/31 30 28.45 15/36 30 28.55 39/77 120 109.3 74/97 30 27.92 70/86 30 27.69 34/86 30 28.04 30/44 30 25.69 41/74 90 85.52 71/96 30 28.95 30/76 30 28.57 34/61 30 28

8.07 2.09 1.32 2.31 2.22 1.90 8.42 2.90 1.99 2.61 3.72 7.63 1.93 2.75 3.67

–/14 – –/18 –/6 –/6 –/1 –/5

60

53 57.1

3.67 10.06

addition to the aphasic symptoms, speech was also disrupted by FAS. The patient himself as well as his relatives and friends perceived his accent as distinctly foreign (North-African). At the segmental level, the patient’s articulation of consonants was characterized by occasional phoneme target substitutions, both in terms of place and manner of articulation. Hardly any errors were observed in vowel articulation. At the suprasegmental level, the patient spoke at a very high speech rate (5.61 syllables/s), often resulting in syllable omissions and consonant deletions. His voice

Mariën /Verhoeven

Fig. 4. A In addition to crossed cerebrocerebellar diaschisis affecting the contralateral right cerebellum (lower row), a 99mTc ECD SPECT scan of the brain 1 month after the onset of neurological symptoms shows a hypoperfusion in the left thalamus, the left nucleus lentiformis, the left medial and lateral temporal regions

and the left motor cortex (upper row). B Repeat SPECT performed 6 months after the stroke shows normalized perfusion in the right cerebellum but only slight improvement of perfusional deficits at the supratentorial level (upper row).

quality was noticeably harsh (jitter: 0.84%; shimmer: 15.22%). The use of intonation patterns was generally appropriate and the speaker’s pitch range was normal. His speech rhythm was syllable-timed and isochronous.

Neuropsychological functions were investigated in the postacute phase (1 month after onset of neurological symptoms). As a result of disrupted arithmetics and aphasia a defective score of 22/30 was found in the Mini Mental State Examination [24]. The Progressive Matrices [25] revealed an IQ of 117. Performance on

Cerebellar Involvement in Motor Speech Planning

Folia Phoniatr Logop 2007;59:210–217

215

the Rey-Osterrieth figure, the Right-Left Orientation Test, the Visual Form Discrimination Test and the Judgment of Line Orientation Test [31] was normal. The Edinburgh Inventory [32] showed a laterality quotient of +100. After 6 months of intensive phonological and semantic therapy, aphasic symptoms improved and FAS had resolved considerably. Formal reassessment of language functions at 6 months after the stroke disclosed near remission of auditory-verbal and written comprehension deficits. As reflected by a defective Token Test score (31 errors), comprehension disturbances for syntactically complex phrases persisted. Repetition had improved, but errors still occurred at the morphological and syntactic levels. Naming had normalized. Phonematic paraphasias, self-repetitions and conduites d’approches were sporadically observed. Groping was still present. Expressive agrammatism had only slightly improved. Agraphia persisted after 6 months. At the phonetic level, a slight improvement of speech rate was observed, which had slowed down a little (from 5.61 to 4.58 syllables/s). This caused fewer syllable omissions and consonant deletions. In addition, there was some change in voice quality: although it still sounded quite harsh at times, shimmer values had reduced from 15.22 to 9.03%. At the intonational level, the speaker’s pitch range had widened a little (from 10.88 to 19.17 semitones). Finally, there was some improvement in the speaker’s speech rhythm, which was clearly less syllable-timed. Although most improvements were not as spectacular as in the case of V.R.M., the patient’s speech sounded distinctly less foreign and was hardly ever recognized as such by hospital staff and people in his direct environment. 99mTc ECD SPECT perfusion scans were acquired 1 and 6 months after the stroke. Transaxial images with a pixel size of 3.56 mm were anatomically standardized using statistical parametric mapping and compared to a standard normal and SD image obtained from 15 normal ECD perfusion studies. Using a 31 region of interest template, the Z scores (SD) were then calculated for each region. A regional Z score of 12.0 is considered significant. In comparison to normal database findings the quantified baseline ECD SPECT studies at 1 month after onset showed a severely decreased perfusion in the left thalamus (–10.11), the left nucleus lentiformis (–6.85), the left medial (–3.62) and lateral temporal region (–5.15) and the left motor cortex (–2.11). In addition, crossed cerebrocerebellar diaschisis significantly affected the contralateral right cerebellum (–3.38) (fig. 4A). Six months after the stroke perfusion in the right cerebellum had normalized, while the perfusional deficits at the supratentorial level had only slightly improved (fig. 4B).

Discussion

Both right-handed patients developed FAS after vascular damage to the left, language-dominant hemisphere. In the first patient, FAS resulted from a vascular ischemic lesion in the frontoparietal region involving the left inferior frontal gyrus, the precentral gyrus, the anterior insular cortex, the postcentral gyrus and the supramarginal gyrus. In the lesion phase of the stroke (1 month after onset of neurological symptoms) extensive language test216

Folia Phoniatr Logop 2007;59:210–217

ing formally ruled out an accompanying aphasic or dysarthric disturbance. Three years after stroke, remission of FAS was found, but mild AoS persisted. In the second patient FAS occurred in the context of a conduction aphasia due to a hemorrhagic left basal ganglia lesion that encroached upon the paraventricular white matter of the parietal lobe, the posterior insula and medial temporal lobe. After 6 months FAS had substantially reduced, but conduction aphasia and AoS symptoms persisted. FAS is traditionally viewed as a distinct neurolinguistic entity in which the impression of a foreign accent results from segmental and suprasegmental articulatory distortions. However, extensive research in the phonetic characteristics of FAS has not been able to identify a coherent system in the speech errors nor to separate it unambiguously from AoS. On the basis of these considerations, Whiteside and Varley [14] concluded that FAS represents a subtype of AoS. Our findings corroborate this view, as residual speech symptoms in both patients were also consistent with a diagnosis of AoS. In addition, AoS and FAS are remarkably similar to ataxic speech disturbances consequent to lesions involving the superior paravermal region of the cerebellum [33, 34]. A slow and strikingly irregular articulation, a monotonous, staccato and scanned oral-verbal output as well as inconsistent misarticulations and phonetic alterations of vowel and consonant production are commonly found in AoS, FAS and ataxic dysarthria. In addition, it has been demonstrated in experimental studies [35] that voice onset time (the time interval between consonant burst and vowel onset) and production and discrimination of vowel length are affected in FAS, AoS and ataxia of speech. These obvious similarities might suggest a common pathophysiological mechanism underlying disrupted articulatory planning and deficient speech timing processes. In contrast to the long-standing belief that FAS and AoS are only produced by lesions of the anterior perisylvian speech areas, functional neuroimaging data obtained in our patients seem to indicate that the cerebellum may be crucially involved in motor speech planning disorders. A 99mTc ECD SPECT followup study in both patients showed a close parallelism between the improvement of the right cerebellar hypoperfusion and the clinical recovery of FAS symptoms. As a result of the recently acknowledged role of the linguistic cerebellum in a variety of nonmotor linguistic processes these observations seem to indicate that FAS and AoS might follow disruption of a close functional connection between the supra- and infratentorial motor speech centers which is reflected by diaschisis. In addition to a subMariën /Verhoeven

stantial amount of clinical and experimental evidence in support of a functionally lateralized linguistic cerebellum [36, 37], the present cases support the view that the cerebellum may also be crucially involved in motor speech planning disorders such as AoS and FAS. The hypothesis for a role of crossed cerebellar diaschisis in the pathogenesis of motor speech planning disorders associated with lesions in the supratentorial motor speech regions merits further prospective research on a larger number of patients. Our study also indicates that func-

tional neuroimaging might be of crucial importance to further explore the functional role of the cerebellum in cognition. Acknowledgments We are grateful to Mrs. Inge Bats (Born-Bunge Foundation, University of Antwerp) for the photographic work. This work was supported by grant G.0209.05 of the Fund for Scientific Research – Flanders.

References 1 Mariën P, Verhoeven J, Engelborghs S, Rooker S, Pickut BA, De Deyn PP: A role for the cerebellum in motor speech planning: evidence from foreign accent syndrome. Clin Neurol Neurosurg 2006;108:518–522. 2 Whitaker H: Levels of impairment in disorders of speech; in Malatesha RN, Hartlage LC (eds): Neuropsychology and Cognition. The Hague, Martinus Nijhoff, 1982, vol 1. 3 Marie P: Présentation de malades atteints d’anarthrie par lésion de l’hémisphère gauche du cerveau; in Marie P (ed): Travaux et mémoires. Paris, Masson, 1926, vol 1, pp 158–160. 4 Pick A: Über Änderungen des Sprachcharakters als Begleiterscheinung aphasischer Störungen. Z Neurol Psychiatr 1919;XLV: 230–241. 5 Dankovicova J, Gurd JM, Marshall JC, MacMahon MKC, Stuart-Smith J, Coleman JS, Slater A: Aspects of non-native pronunciation in a case of altered accent following stroke (foreign accent syndrome). Clin Linguist Phon 2001;15:195–218. 6 Critchley M: Regional ‘accent’, demotic speech and aphasia; in Livre jubilaire docteur van Bogaert . Bruxelles, L’Imprimerie des Sciences, 1962. 7 Berthier M, Ruiz A, Massone M, Starkstein SE, Leiguarda RC: Foreign accent syndrome: behavioural and anatomical findings in recovered and non-recovered patients. Aphasiology 1991;5:129–147. 8 Miller N, O’Sullivan H: What makes foreign accent syndrome foreign? (poster presentation). Int Clin Phonet Linguist Assoc, 6th Annu Conf, Nijmegen, October 13–15, 1997. 9 Reeves RR, Norton JW: Foreign accent-like syndrome during psychotic exacerbations. Neuropsychiatry Neuropsychol Behav Neurol 2001;14:135–138. 10 Van Borsel J, Janssens L, Santens P: Foreign accent syndrome: an organic disorder? J Commun Dis 2005;38:421–429.

Cerebellar Involvement in Motor Speech Planning

11 Verhoeven J, Mariën P, Engelborghs S, D’Haenen H, De Deyn PP: A foreign speech accent in a case of conversion disorder. Behav Neurol 2005;16:225–232. 12 Lebrun Y: Apraxia of speech, the history of a concept; in Square-Storer P (ed): Acquired Apraxia of Speech in Aphasic Adults. Hove, Lawrence Erlbaum, 1989, pp 3–19. 13 Rosenbek JC: Verbal apraxia; in Fabbro F (ed): Concise Encyclopedia of Language Pathology. Oxford, Pergamon, 1999. 14 Whiteside SP, Varley RA: A reconceptualisation of apraxia of speech: a synthesis of evidence. Cortex 1998;34:221–231. 15 Whitty CWM: Cortical dysarthria and dysprosody of speech. J Neurol Neurosurg Psychiatry 1964;27:507–510. 16 Holmes G: The symptoms of acute cerebellar injuries due to gunshot injuries. Brain 1917; 40:401–534. 17 Darley FL, Aronson AE, Brown JR: Differential diagnostic patterns of dysarthria. J Speech Hear Res 1969;12:246–269. 18 Graetz P, De Bleser R, Willmes K: De Akense Afasie Test. Lisse, Swets & Zeitlinger, 1992. 19 Goodglass H, Kaplan E: The Assessment of Aphasia and Related Disorders, ed 2. Philadelphia, Lea & Febiger, 1983. 20 De Renzi E, Vignolo LA: The token test: a sensitive test to detect receptive disturbances in aphasia. Brain 1962; 85:665–678. 21 Kaplan E, Goodglass H, Weintraub S: The Boston Naming Test. Philadelphia, Lea & Febiger, 1983. 22 Mariën P, Mampaey E, Vervaet A, Saerens J, De Deyn PP: Normative data for the Boston Naming Test in native Dutch-speaking Belgian elderly. Brain Lang 1998;65:447–467. 23 Bastiaanse R, Bosje M, Visch-Brink E: Psycholinguistic Assessments of Language Processing in Aphasia, Dutch ed. East Sussex, Lawrence Erlbaum Associates, 1995. 24 Folstein MF, Folstein SE, McHugh PR: Mini Mental State Examination: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–198.

25 Raven JC: Progressive Matrices. London, Lewis, 1976. 26 Stinissen J, Willems PJ, Coetsier P, Hulsman WLL: Handleiding bij de Nederlandstalige Bewerking van de Wechsler Adult Intelligence Scale (WAIS). Lisse, Swets & Zeitlinger, 1970. 27 Cole MG, Dastoor D: A new hierarchic approach to the measurement of dementia. Psychosomatics 1987;28:298–305. 28 Wechsler D: Wechsler Memory Scale-Revised. New York, Psychological Corporation, 1984. 29 Grant DA, Berg EA: Wisconsin Card Sorting Test. Odessa, Psychological Assessment Resources, 1993. 30 Lezak MD: Neuropsychological Assessment. New York, Oxford University Press, 1983. 31 Benton AL, deS Hamsher K, Varney NR, Spreen O: Contributions to Neuropsychological Assessment. A Clinical Manual. New York, Oxford University Press, 1983. 32 Oldfield RC: The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 1971;9:97–113. 33 Kertesz A: Subcortical lesions and verbal apraxia; in Rosenbek JC, McNeil MR, Aronson AE (eds): Apraxia of Speech. Physiology, Acoustics, Linguistics, Management. San Diego, College-Hill, 1984, pp 73–90. 34 Ackermann H, Vogel M, Petersen D, Poremba M: Speech deficits in ischaemic cerebellar lesions. J Neurol 1992;239:223–227. 35 Ackermann H, Hertrich I: The contribution of the cerebellum to speech processing. J Neurolinguist 2000;13:95–116. 36 Mariën P, Engelborghs S, De Deyn PP: Cerebellar neurocognition: a new avenue. Acta Neurol Belg 2001;101:96–109. 37 Mariën P, Engelborghs S, Fabbro F, De Deyn PP: The lateralised linguistic cerebellum: a review and new hypothesis. Brain Lang 2001; 79:580–600.

Folia Phoniatr Logop 2007;59:210–217

217

Author Index Vol. 59, No. 4, 2007

Andreou, G. 177 Baillieux, H. 165 Borgatti, R. 201 De Deyn, P.P. 165 De Smet, H.J. 165 Docking, K.M. 190 Fabbro, F. 201 Joanette, Y. 171 Mariën, P. 165, 210

Murdoch, B.E. 184, 190 Papathanasiou, I. 177 Paquier, P.F. 163, 165 Suppiah, R. 190 Tavano, A. 201 Verhoeven, J. 210 Vlachos, F. 177 Walter, N. 171 Whelan, B.-M. 184

Subject Index Vol. 59, No. 4, 2007

Cerebellar malformation 201 – tumour 190 Cerebellum 171, 177, 210 – language 165, 184 Diaschisis 184 Foreign accent syndrome 210 Language 171, 201 – ability, general, high-level 190 – function, children 190 Left cerebellar lesion 184

© 2007 S. Karger AG, Basel Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com

Accessible online at: www.karger.com/fpl

Linguistic abilities 165 – functions 165 Literature review, cerebellum 171 Motor speech planning 210 Neurodevelopment 201 Neuroimaging 171 Procedural memory 201 Reading 177 – difficulties 177 Social communication 201