Microstructure predicts impulsive and compulsive behaviour following subthalamic stimulation in Parkinson’s disease

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Abstract Background Subthalamic deep brain stimulation (STN-DBS) represents an established therapeutic intervention for advanced Parkinson’s disease (PD), alleviating motor and non-motor symptoms. However, impulse control disorders (ICDs) present a complex challenge, with some patients experiencing postoperative improvements while others develop treatment induced impulsive-compulsive behaviours (ICB). The mechanisms determining these variable outcomes remain poorly understood, highlighting the need to predict postoperative ICB outcomes. Methods This prospective open-label study aimed to identify microstructural markers associated with postoperative changes in impulsive-compulsive behaviour following STN-DBS. Thirty-five patients underwent diffusion MRI and clinical evaluations preoperatively and six months postoperatively. A whole-brain voxel-wise analysis utilising diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) was conducted to explore associations between microstructural metrics and changes in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS). Results Intact microstructure in frontolimbic WM tracts, including the cingulum, insular cortex connections, and major association fibres, was associated with greater postoperative reductions in impulsive-compulsive symptoms. Conversely, intact microstructure in specific grey matter areas including paracingulate gyrus, insular cortex, and precentral gyrus were associated with lower reductions or increases in postoperative ICB. Conclusion These findings demonstrate that preoperative microstructural integrity within frontolimbic circuits and executive control networks associates with susceptibility to treatment-emergent impulsive-compulsive behaviours following STN-DBS. The convergent evidence from multiple diffusion metrics suggests that diffusion MRI may serve as a valuable tool for identifying patients at risk for developing ICB, potentially enhancing preoperative counselling and enabling targeted behavioural monitoring strategies.

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