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Jose A. Obeso先生は、Movement Disorderのeditorをつとめるなど、神経学と くに大脳基底核疾患の臨床の世界的リーダーの一人です。今回、来日される機会 があり、ご子息とのセミナーをお願いしました。是非、御来聴下さい。

Parkinson’s disease (PD) is arguably the prototype of a basal ganglia disorder. It is now appreciated that the spectrum of clinical manifestations of PD goes beyond the classic motor features to involve learning and behavioral problems and also depression and other emotional symptoms. Nevertheless, the motor features continue to be the main cause of disability and the best recognized and studied component of PD clinically. Surgery for PD was revitalized in the mid-1990 along with the development of the basal ganglia model, which provided a rational basis to target the globus pallidus pars interna (GPi) first, and the subthalamic nucleus (STN) subsequently, with the aim of reducing basal ganglia output. This very basic principle was confirmed by impressive clinical improvement associated with pallidotomy, subthalamotomy and deep brain stimulation (DBS) of either target. However, surgical experience unravels some unexpected observations and findings. Among these, I like to highlight and discuss that: 1. Typical parkinsonian resting tremor is as well controlled with surgery of the STN as with surgery of the thalamic Vim nucleus (the classic target for tremor). 2. Surgery of the GPi has a drastic anti-dyskinesias (i.e. against levodopa-induced dyskinesias) effect, 3. Either pallidotomy and subthalamotomy, or both together, improves PD without any major apparent deficit. These observations force us to conceive the basal ganglia as a non-linear network based not only in firing rate activity, but in several loops called into action depending upon the task and circumstances. The nigro-striatal projection on the one hand and the subthalamo-pallidal micro-circuitry are key knots of such network.

The role of the subthalamic nucleus in cognitive and motor inhibition as revealed by Parkinson's disease patients

Ignacio Obeso Cognitive Neuroscience Information Technology (CNIT), UOC, Barcelona, Spain

Imaging studies have shown that response inhibition and conflict resolution, key executive functions essential for adaptive behaviour, are mediated by fronto-striatal circuits, with special relevance of the subthalamic nucleus (STN) as a relay station. In Parkinson´s disease (PD), overactivity of the STN and underactivation of cortical regions are pathophysiological features of PD. A series of studies were done to investigate the hypothesis that the STN is involved in inhibition of action and conflict resolution. The conditional stop signal reaction time was used. Surgical interventions (subthalamotomy and deep brain stimulation, DBS) directly altering STN functions in PD patients were used. Bilateral DBS of the STN impaired inhibition as indicated by significantly prolonged SSRTs, but had no significant effect on conflict resolution. However, subthalamotomy showed faster Go RTs and less conflict-induced slowing but at the expense of greater response selection errors. Also, PD alters not only motor inhibition but as well cognitive inhibition. The results are consistent with the proposal that the STN is involved in reactive inhibition and that the STN influences the response threshold and speed-accuracy trade-offs.