UCLA

Parkinson disease is a common neurodegenerative disorder characterized by deficits of balance, resting tremor and voluntary movement. The study of this dopamine-depleted state has come to focus upon the role of beta oscillations (12-35 Hz) as a means of explaining the movement deficits that feature prominently in the constellation of symptoms. It remains unclear what the precise role of beta oscillations is in the healthy state and why they feature so prominently in the pathophysiology of Parkinson disease. Deep brain stimulation in movement disorders affords a valuable opportunity to invasively record from cortical and subcortical structures in patients undergoing the procedure. This dissertation embarks upon an in-depth analysis of beta oscillations in the motor cortices of Parkinsonian patients undergoing deep brain stimulation and contrasts the findings in this cohort with those observed in the dopamine-intact state of essential tremor patients. The findings detailed here show that in both cohorts, transient increases in beta power (beta bursts) constitute periods of high interregional cortical synchrony and that these episodes are associated with stereotyped changes in waveform morphology. Beta bursts are furthermore characterized by high beta-phase to broadband gamma amplitude coupling. Beta bursting is preceded by increases in cortico-cortical synchrony which is proposed here to act as a driver for beta burst episodes in the motor cortex. Parkinson patients display disordered temporal patterns of beta bursting compared with essential tremor patients. Correlation between the duration of beta bursts and Unified Parkinson's Disease Rating Scale (UPDRS) scores of bradykinesia and rigidity suggests that electrophysiological dysfunction in the timing of beta bursts has direct relevance to clinical manifestations of the dopamine-depleted state. Waveform analysis shows that, when compared with Parkinson disease patients, essential tremor patients exhibit greater degrees of waveform change during bursting compared with non-burst epochs. The extent of waveform morphology change also correlates inversely with severity of bradykinesia and rigidity as measured by UPDRS scores. Analysis of movement onset in patients shows that beta oscillations are transiently suppressed at the time of movement initiation in both Parkinson disease and essential tremor cohorts. Only essential tremor patients demonstrated a significant reduction in cortico-cortical synchrony prior to movement onset. The probability of beta transients immediately following movement onset was reduced for both cohorts however this beta burst suppression occurred earlier for the essential tremor cohort and could be identified a full second prior to movement initiation. Waveform morphology during beta bursting was significantly altered during movement compared to rest and initial changes in waveform morphology occurred as early as three seconds prior to movement onset. Beta-phase to broadband gamma amplitude during bursting was reduced during movement but there was no difference between the cohorts in absolute levels of burst-associated phase-amplitude coupling. The findings presented are consistent with a model of hypersynchrony across cortico-basal ganglia loops driving disordered beta bursting in motor cortices, resulting in impairments of voluntary movement. Evidence is presented to show that burst timing pathology occurs as a direct result of synchrony abnormalities and acts to impair movement via phase-amplitude coupling and waveform morphology changes noted to occur therein. Higher burst synchrony and extended burst durations may be acting as a physiological tamponade on development and updating of movement plans. This interpretation offers a unified explanatory framework for a body of literature that has uncovered seemingly contradictory findings regarding beta oscillations and lays the groundwork for targeted therapies directed towards restoring the dopamine-intact electrophysiological features of voluntary movement.