Mapping Motor Cortical Network Excitability and Connectivity Changes in De Novo Parkinson's Disease

Abstract Background Transcranial magnetic stimulation‐electroencephalography (TMS‐EEG) has demonstrated decreased excitability in the primary motor cortex (M1) and increased excitability in the pre‐supplementary motor area (pre‐SMA) in moderate‐advanced Parkinson's disease (PD). Objectives The aim was to investigate whether these abnormalities are evident from the early stages of the disease, their behavioral correlates, and relationship to cortico‐subcortical connections. Methods Twenty‐eight early, drug‐naive (de novo) PD patients and 28 healthy controls (HCs) underwent TMS‐EEG to record TMS‐evoked potentials (TEPs) from the primary motor cortex (M1) and the pre‐SMA, kinematic recording of finger‐tapping movements, and a 3T‐MRI (magnetic resonance imaging) scan to obtain diffusion tensor imaging (DTI) reconstruction of white matter (WM) tracts connecting M1 to the ventral lateral anterior thalamic nucleus and pre‐SMA to the anterior putamen. Results We found reduced M1 TEP P30 amplitude in de novo PD patients compared to HCs and similar pre‐SMA TEP N40 amplitude between groups. PD patients exhibited smaller amplitude and slower velocity in finger‐tapping movements and altered structural integrity in WM tracts of interest, although these changes did not correlate with TEPs. Conclusions M1 hypoexcitability is a characteristic of PD from early phases and may be a marker of the parkinsonian state. Pre‐SMA hyperexcitability is not evident in early PD and possibly emerges at later stages of the disease. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.