[The cerebellum as a major player in motor disturbances related to Autistic Syndrome Disorders].
BACKGROUND
Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning. This line of study may generate new knowledge and understanding of motor symptoms associated with ASD and aims to deliver fresh perspectives for early diagnosis and therapeutic strategies against ASD.


OBJECTIVE
Despite the relative paucity of research in this area (compared to the social, linguistic, and behavioural disturbances in ASD), there is evidence that the frontostriatal motor system and/or the cerebellar motor systems may be the site of dysfunction in ASD. Indeed, the cerebellum seems to be essential in the development of basic social capabilities, communication, repetitive/restrictive behaviors, and motor and cognitive behaviors that are all impaired in ASD. Cerebellar neuropathology including cerebellar hypoplasia and reduced cerebellar Purkinje cell numbers are the most consistent neuropathologies linked to ASD. The functional state of the cerebellum and its impact on brain function in ASD is the focus of this review. This review starts by recapitulating historical findings pointing towards an implication of the cerebellum, and to a lesser extent the basal ganglia structures, in TSA. We then detail the structure/function of the cerebellum at the regional and cellular levels before describing human and animal findings indicating a role of the cerebellum and basal ganglia in ASD.
Several studies have attempted to identify the nature of the motor system dysfunction in ASD, and it became apparent that the motor fronto-striatal and cerebellar systems are major sites of dysfunction in this psychiatric illness. Anomalies in these structures have been revealed both at the anatomical and functional levels in human patients as well as in animal models. These models are obtained by manipulation of genes that are often implicated in glutamate transmission, by lesions of brain structures among which the cerebellum, by pharmacological treatment with drugs such as the Valproate or by maternal infections with bacterial membrane extracts of double stranded RNA mimicking a viral infection.


CONCLUSIONS
The "cognitive approach" has dominated ASD research for three decades and led to the design of interventional strategies, which have yielded satisfactory results. Nevertheless, new approaches and alternative hypotheses on the aetiology and diagnosis of ASD are needed. Research focused on motor rather than psychiatric symptoms may have a greater potential to elucidate the neurobiological basis of ASD.
Inserm U-1084, laboratoire de neurosciences expérimentales et cliniques, LNEC, université de Poitiers, CHU de Poitiers, bâtiment B36, 1, rue Georges-Bonnet, BP 633, TSA 51106, 86022 Poitiers cedex, France. Electronic address: mohamed.jaber@univ-poitiers.fr.
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Jaber
D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D002531:Cerebellum / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology; D006801:Humans; D007804:Language Development; D000068079:Motor Disorders / Q000503:physiopathology / Q000523:psychology*; D009069:Movement Disorders / Q000503:physiopathology / Q000523:psychology*; D011187:Posture / Q000502:physiology; D013064:Speech Disorders / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology
Ataxia; Autism; Autisme; Basal ganglia; Cerebellum; Cervelet; Diagnostic; Langage; Posture