Summary The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many ...clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made.
Summary A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and ...akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
Abstract Background Deep brain stimulation (DBS) within or adjacent to the subthalamic nucleus (STN) currently represents the most common stereotactic procedure performed for Parkinson's disease. ...Better STN imaging is often regarded as a requirement for improving stereotactic targeting. But, remarkably enough, it is unclear whether there is a consensus about the optimal target. Objective and Methods To obtain an expert opinion on the site regarded optimal for 'STN stimulation', movement disorder specialists were asked to indicate their preferred position for an active contact on hardcopies of the Schaltenbrand and Wahren atlas depicting the STN in all three planes. This represented an idealized setting and it mimicked optimal imaging for direct target definition in a perfectly delineated STN. Results The suggested targets were heterogeneous, although some clustering was observed in the dorsolateral STN and subthalamic area. In particular, in the anterior-posterior direction the intended targets differed to a great extent. Most of the indicated targets are thought to also result in concomitant stimulation of structures adjacent to the STN, including the zona incerta, Fields of Forel, and/or the internal capsule. Conclusions This survey illustrates that most sites regarded as optimal for 'STN stimulation' are close to each other, but there appears to be no uniform perception of the optimal anatomical target, possibly influencing surgical results. The anatomical sweet zone for STN stimulation needs further specification since this information is likely to make MRI-based target definition less variable when applied to individual patients.
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