Dissociable Physiological Biomarkers of Psychiatric Symptoms in Parkinson’s disease in the Subthalamic Nucleus: Evidence from Deep Brain Stimulation Intracranial Recordings

Psychiatric symptoms in Parkinson’s disease (PD) are highly prevalent and challenging to treat. This study maps oscillatory neural activity to diverse psychiatric symptoms in PD, using resting-state subthalamic nucleus (STN) local field potentials (LFPs) and frontal EEG in 75 PD patients undergoing deep brain stimulation (DBS). Our analysis revealed three levels of segregation: 1) Spectral: Depression was associated with increased alpha activity, apathy with elevated beta and frontal theta alongside reduced frontal beta, anxiety with decreased frontal low gamma, impulsivity with reduced low gamma and obsessive-compulsive disorders (OCD) with reduced delta activity. 2) Spatial: Depression and OCD localized to anatomical STN, apathy and impulsivity spanned both anatomical and electrophysiological STN, motor symptoms mapped to electrophysiological STN. 3) Structural connectivity: UK Biobank analyses revealed white matter pathways constraining STN oscillatory activity. These findings disentangle neurophysiological substrates of PD psychiatry, identifying symptom-specific biomarkers and informing targeted neuromodulation strategies.