Impulse control disorder is linked to dyskinesia development through a cortical network in Parkinson’s disease

Impulse control disorder (ICD) constitutes a neuropsychiatric complication with consequences for quality of life, social functioning, and decision-making. In Parkinson’s disease (PD), ICD has been linked to dopaminergic dysfunction and impaired inhibitory control within frontostriatal circuits. Given that levodopa-induced dyskinesia (LID) is also associated with dopamine therapy and overlapping frontostriatal dysfunction, these conditions may share a neural mechanism whose cortical substrate remains unclear. We investigated the longitudinal relationship between baseline ICD and subsequent LID development in 464 patients with PD from the Parkinson’s Progression Markers Initiative followed for more than 4 years and categorized according to ICD status. Survival analysis showed that baseline ICD was associated with an increased LID risk independent of putaminal dopamine transporter availability after adjustment for age and sex (hazard ratio=1.3375, p = 0.0238). Threshold-free network-based statistics identified an ICD-related subnetwork with reduced morphological similarity connectivity in patients with ICD, with hub regions in the bilateral paracentral lobules and left caudal anterior cingulate cortex. Causal mediation analysis indicated that the within-module z-score of the left paracentral lobule mediated the association between ICD-related network disruption and LID development (average causal mediation effect=0.0136, 95% confidence interval = [0.0028,0.0328]), whereas no such mediation was observed for putaminal dopamine transporter availability. These findings suggest that ICD is linked to altered cortical network organization, with downstream topological vulnerability of the left paracentral lobule that may contribute to LID development. They highlight the clinical importance of incorporating ICD history into treatment planning for LID management in PD.