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Open interconnected model of basal ganglia-thalamocortical circuitry and its relevance to the clinical syndrome of Huntington's disease



The early stages of Huntington's disease (HD) present with motor, cognitive, and emotional symptoms. Correspondingly, current models implicate dysfunction of the motor, associative, and limbic basal ganglia-thalamocortical circuits. Available data, however, indicate that in the early stages of the disease, striatal damage is mainly restricted to the associative striatum. Based on an open interconnected model of basal ganglia-thalamocortical organization, we provide a detailed account of the mechanisms by which associative striatal pathology may lead to the complex pattern of motor, cognitive, and emotional symptoms of early HD. According to this account, the degeneration of a direct and several indirect pathways arising from the associative striatum leads to impaired functioning of: (1) the motor circuit, resulting in chorea and bradykinesia, (2) the associative circuit, resulting in abnormal eye movements, “frontal-like” cognitive deficits and “cognitive disinhibition,” and (3) the limbic circuit, resulting in affective and psychiatric symptoms. When relevant, this analysis is aided by comparing the symptomatology of HD patients to that of patients with mild to moderate Parkinson's disease, since in the latter there is similar dysfunction of direct pathways but opposite dysfunction of indirect pathways. Finally, we suggest a potential novel treatment of HD and provide supportive evidence from a rat model of the disease. © 2001 Movement Disorder Society.