TMS-Evoked Potentials Unveil Occipital Network Involvement in Recently Diagnosed Patients With Parkinson’s Disease

Abstract Background: Distinguishing clinical Parkinson's disease (PD) subgroups may be achieved by observing how different networks respond to external stimuli. We aimed to compare the Trans Magnetic Stimulation (TMS) Evoked-Potential (TEP) measures obtained from stimulation of bilateral primary motor cortex (M1), dorsolateral-prefrontal cortex (DLPFC) and primary visual cortex (V1) between healthy-controls and PD subgroups. Methods: 62 PD patients (age: 69.9±7.5) and 76 healthy-controls (age: 69.25±4.3) underwent a TMS-EEG protocol. First, TEP measures were compared between groups and stimulation sites using two-way ANOVA. Then, PD patients were divided into three subgroups: Tremor Dominant (TD) (n=21, age: 68.5±6.7), Non-Tremor Dominant (NTD) (n=27, age: 69.2±6.9) and Rapid Disease Progression (RDP) (n=14, age: 72.8±9.4) and TEP measures were compared between the subgroups. Results: PD patients demonstrated lower wide-waveform adherence (wWFA) (F(1,404)=17.11, p<0.0001) and interhemispheric connectivity (IHCCONN (F(1,404)=22.02, p<0.0001) compared to controls in response to all stimulated cortices. Lower occipital IHCCONN was associated with more advanced disease stage (r=-0.37, p=0.0039). Differences between PD subgroups were found in wWFA in response to occipital stimulation. The RDP and NTD subgroups showed lower wWFA compared to TD (p=0.005). Occipital TEP measures identify patients in the RDP group with 85% accuracy (AUC-ROC=0.85, p<0.0001). Conclusions: These results demonstrate that occipital networks are involved even in the early stages of the disease, not necessarily related to cognitive deficits and hallucinations. Our results show that TEP measures can provide new insights regarding altered networks involvement in different PD subgroups. This understanding may hold implications for enhancing patient management and tailoring personalized treatment approaches.