Chen, C.C.; (2008) Oscillatory activity in the basal ganglia - is it relevant to movement disorders therapy? Doctoral thesis , University of London.

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Abstract

Chronic high frequency stimulation of the basal ganglia can be a highly effective intervention for movement disorders in patients. In the past decade, therapeutic benefits have been seen with stimulation of the subthalamic nucleus and globus pallidus interna for Parkinson's disease (PD) and dystonia, respectively. These procedures have allowed direct recording of basal ganglia activity and have suggested that abnormal synchronisation of neurons in these nuclei may contribute to motor impairment. This thesis explores the possible correlation between synchronised activity in the basal ganglia, as evidenced by oscillations in local field potentials, and movement disorders. In Chapter 3, we demonstrate the correlation between synchronization at frequencies under 10 Hz in the globus pallidus interna and dystonic EMG. This low frequency activity is shown to be locked to neuronal activity within GPi in patients with dystonia (Chapter 4). Deep brain stimulation is thought to suppress spontaneous pathological activity in the basal ganglia. Equally, however, it must also suppress any residual physiological activity in these nuclei. In Chapter 5, we demonstrate that the basal ganglia are involved in the processing of simple limb movements in the human, by separating the effects of deep brain stimulation on pathological and physiological activities based on baseline task performance. An impairment of motor performance was seen during high frequency stimulation in those patients with the best task performance at baseline. This deleterious effect, however, should be distinguished from the effect of direct stimulation at 20 Hz in Parkinson's disease. Oscillatory activity at around 20 Hz is thought to be a core feature in Parkinson's disease. In Chapter 6, we demonstrate that the excessive synchronization imposed by stimulation of the subthalamic nucleus at 20 Hz slows movement, in those patients with the best task performance at baseline. This supports the notion that synchronization around 20 Hz may be causally linked to bradykinesia. Last, the therapeutic effectiveness of DBS therapy for patients with PD partially relies on the accurate localisation of the motor region of the subthalamic nucleus. In Chapter 7, we propose an alternative method for the localization of this region using the spontaneous pathological 20 Hz activity to be found in this nucleus. The findings of these studies provide evidence that basal ganglia oscillatory activities of differing frequencies contribute to movement disorders.

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