Investigating deep brain stimulation-induced plasticity in Parkinson’s disease by concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG)

• Applicant: Ghazaleh Darmani, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 439417355

Deep brain stimulation (DBS) implanted in the basal ganglia (BG) can improve motor symptoms in patients with Parkinson’s disease (PD). However, the neurophysiological mechanisms underlying DBS is not fully understood. Given that the activities in the BG influence activities in other brain areas such as the motor cortex to affect movement, studying the causal mechanisms governing the effects of DBS on the BG-Cortical relationship is of great importance. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows direct investigation of cortical excitability, functional connectivity and dynamic oscillatory features of human brains before and after plasticity-based interventions. While classical TMS-EMG studies are limited to the studies of the primary motor cortex and the only readout is motor evoked potentials (MEPs) recorded from a hand muscle, TMS-EEG allows investigating of both motor and non-motor regions across multiple spatiotemporal and spectral scales due to its high temporal resolution. These advantages lead to the establishment of specific TMS-EEG markers in health and disease which are used to study the pathophysiology of brain disorders. TMS-EEG markers can also be utilized to guide treatments or to predict therapeutic outcomes. TMS evokes a sequence of positive and negative deflections which are the temporal and spatial summation of excitatory and inhibitory postsynaptic potentials; these TMS-evoked EEG potentials (TEPs) which are labeled according to their polarity and latency are highly reproducible. Previous studies showed that early component (<30ms) of TEPs of the motor area is a marker of excitation of the corticospinal and corticocortical system, while negative TEP components of motor areas (N45 and N100) have been associated with inhibitory mechanisms. The present project will take advantage of these TEP markers to investigate the effects of a single-pulse TMS-EEG to the supplementary motor area (SMA), the primary motor cortex (M1) and the posterior parietal cortex (PPC) in age-matched healthy subjects and in PD patients in DBS switch off vs. on state to provide new insights on the altered cortical state in PD. I will also use TMS-EEG methodology to study the electrophysiological mechanisms and efficacy of a recently developed protocol, which pairs DBS with repetitive motor cortical TMS at specific times, in modulating cortical plasticity in PD patients. By defining the pathological oscillatory signatures of the three targeted cortical areas, this study will provide a greater understanding of PD and how DBS changes PD pathophysiology.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Dr. Robert Chen