Oscillatory Activity in the basal ganglia of Patients with Parkinson's Disease

Parkinson’s disease (PD) is a movement disorder that is of basal ganglia origin. It is characterized by a severe loss of dopaminergic input to the striatum and symptoms such as bradykinesia, rigidity and tremor. There is growing evidence that PD is associated with pathological synchronous oscillatory activity in the basal ganglia, which primarily occurs in the 11-30 Hz range, the so-called beta band. The aim of this project was to better understand the oscillatory activity recorded from the basal ganglia of PD patients and to elucidate the significance of this activity in PD. To do this, neuronal firing and local field potentials (LFPs) were recorded from the subthalamic nucleus (STN) and globus pallidus internus (GPi) of PD patients undergoing stereotactic neurosurgery for implantation of therapeutic deep brain stimulation electrodes. Beta oscillatory LFP activity in the STN and GPi was found to be coherent with, and reflect to a certain degree, rhythmic activity in a population of local neurons. I have demonstrated for the first time that the degree of beta oscillatory firing in the STN, which is maximal in the motor portion, correlates with the patients’ benefit from dopaminergic medications, but not with baseline motor deficits. My study has also established that beta oscillatory firing in the STN does not positively correlate with the patients’ tremor scores and that during periods of tremor patients tend to have less beta oscillatory firing and increased neuronal oscillatory firing at the tremor frequency. Temporal examination of the LFPs recorded during periods of intermittent resting tremor revealed that stronger tremor is associated with increased LFP power in the low gamma range (35-55 Hz) and there is a decrease in the ratio of beta to gamma coherence. Similarly, a change in balance between oscillatory activities was observed during levodopa-induced dyskinesias. Finally, when the oscillatory activity in the GPi of PD patients was compared to that in dystonia I found that in dystonia, oscillatory LFP activity is less likely to reflect the neuronal firing. These findings indicate that beta oscillatory activity in the basal ganglia might reflect the degree of dopamine deficiency in the striatum and that the relative strength of oscillatory rhythms may play an important role in mediating the pathological features in PD.Ph