Phase-dependent Modulation of Pathological Beta Oscillations in Parkinson’s Disease

Parkinson’s disease (PD) is a debilitating motor disorder characterized by degeneration of dopaminergic cells in the basal ganglia. This loss of dopaminergic neurons gives rise to abnormal synchronization of neuronal activity in the beta frequency range (around 20 Hz) across the cortico-basal ganglia network in parkinsonian humans and animals. Interestingly, in tremor patients the phase of ongoing peripheral oscillation can be exploited with electrical ‘phase interference’, whereby cortical stimulation on specific phase of the tremor dampens both the pathological neuronal activity and resulting symptoms. Harnessing the phase of a pathological neural activity, therefore, appears to be a promising way to find a more accurate and tailored stimulation protocols for deep brain stimulation (DBS) treatment of motor disorders. This strategy, however, has not yet been attempted for faster central nervous system oscillations, such as the exaggerated beta oscillations.
The principal aim of this study was to examine the relationship between the beta synchronisation occurring between the motor cortex and subthalamic nucleus (STN) and the power of ongoing oscillations in these brain areas. Complimentary experiments were carried out in PD patients undergoing microelectrode mapping for the implantation of DBS electrodes as well as in the 6-OHDA hemi-lesioned rat model of PD. In awake PD patients displaying beta oscillations we recorded cortical electroencephalogram (EEG) and local field potential (LFP) as well as multiunit activity from the STN. The data obtained from intraoperative recordings revealed that the power of beta oscillations in the cortex and the STN ramped up when these assemblies were at their most common phase alignment (“preferred phase”). We then tested whether this relationship could be modulated by the stimulation of the motor cortex. Utilising the 6-OHDA hemi-lesioned rat model of PD we then stimulated the cortex at approximately the same frequency as the ongoing beta oscillation while recording the electrocorticogram, the LFP and single unit activity of identified STN neurons. Concurrently, preferred phase alignment between the cortex and the STN provided the most efficient time-windows for phase interference: amplification was most effectively damped by the cortical stimulation during the onset of these periods.
These results provide further evidence that periods of coherence between nodes of the cortical-basal ganglia circuit can lead to amplification of oscillations at the same frequency. Cortical beta frequency stimulation during these periods of preferred beta phase alignment effectively disturbs the amplifying processes providing preliminary evidence of phase dependent modulation of pathophysiological oscillations in PD.