Serotonergic cortico-limbic and executive network dysfunction in Parkinson’s disease impulse control disorders: a PET-fMRI study

Impulse control disorders (ICDs) affect up to 45% of Parkinson's disease (PD) patients, yet their neural mechanisms remain unclear. Using multimodal PET and resting-state fMRI in 23 PD patients (11 PDICD + , 12 PD-ICD-) and 14 healthy controls, we identified specific brain pathways underlying ICDs. PDICD+ patients showed steeper delay discounting and altered functional connectivity, including enhanced posterior parietal coupling within executive networks and disrupted salience-executive interactions. Critically, aberrant right supplementary motor area-amygdala connectivity was linked to ICD severity and decisional impulsivity. Path analysis revealed that increased SMA 5-HT₂ₐ receptor availability was associated with enhanced SMA-amygdala coupling, which in turn was positively associated with ICD symptoms. By linking serotonergic dysfunction to disrupted motor-limbic networks and impulsive behavior, this study identifies targetable pathways for managing a common non-motor complication of PD.