P-139 Distinct neural mechanisms of deep brain stimulation and medication on improving predictive timing functions in patients with advanced Parkinson’s disease

Background: Parkinson’s disease (PD) is characterized by motor and cognitive impairments which result from the progressive loss of dopaminergic neurons of the substantia nigra pars compacta. These symptoms may be ameliorated by subthalamic nucleus deep brain stimulation (STN-DBS), or intake of levodopa.
Objective: As suggested by previous studies, the basal ganglia play an important role in temporal prediction. We therefore expect that PD patients exhibit impairment in tasks involving such functions compared to healthy controls. Furthermore, these impairments might, at least partially, be compensated by STN-DBS or levodopa. Methods: To test these hypotheses, 12 PD patients were recruited and instructed to perform finger-tapping to synchronize with audi- tory rhythms at frequencies from 1 to 6Hz. 64-channel EEG was recorded during the task. The patients were studied in four condi- tions: with levodopa (DOPA-ON) or without (DOPA-OFF) before the surgery to implant the STN-DBS electrodes, and with STN-DBS on (DBS-ON, 130–240Hz) or off (DBS-OFF) after the surgery. A group of 12 healthy subjects, matched in age, gender, and education were recruited for the same tasks as controls. As expected, the tapping performance of controls was better than that of the patients. Performance in patients improved during DBS-ON and DOPA-ON conditions. These data were reported previously (Gulberti et al., Neuroimage Clinical, 2015). To investigate the neural mechanisms underlying these performance improvements, we re-analyzed the EEG data. The scalp signals were projected into a source space com- prising the cortical locations. Both power spectra and coupling across different brain locations were evaluated.
Results: During the task session, in both auditory and motor cortices, the spectral power in the gamma range ($75–105Hz) was generally higher in PD patients compared to controls. Furthermore, coupling across brain regions was generally reduced in patients compared to the healthy control group. The power difference between groups was largely abolished in the DOPA-ON condition, and the coupling difference was reduced in the DBS-ON condition.
Conclusion: Our data suggest that excessive, but spatially less well coupled, gamma-band activity may be induced in the cortices of PD patients while performing tasks that involve temporal coordina- tion and prediction. These altered dynamics could be improved by either suppressing such activities with levodopa or synchronizing them with STN-DBS.