Individualized Structural Perturbations on Normative Brain Connectome Restrict Deep Brain Stimulation Outcomes in Parkinson's Disease

Abstract Background Patients with Parkinson's disease (PD) respond to deep brain stimulation (DBS) variably. However, how brain substrates restrict DBS outcomes remains unclear. Objective In this article, we aim to identify prognostic brain signatures for explaining the response variability. Methods We retrospectively investigated a cohort of patients with PD (n = 141) between 2017 and 2022, and defined DBS outcomes as the improvement ratio of clinical motor scores. We used a deviation index to quantify individual perturbations on a reference structural covariance network acquired with preoperative T1‐weighted magnetic resonance imaging. The neurobiological perturbations of patients were represented as z scored indices based on the chronological perturbations measured on a group of normal aging adults. Results After applying stringent statistical tests ( z > 2.5) and correcting for false discoveries ( P < 0.01), we found that accelerated deviations mainly affected the prefrontal cortex, motor strip, limbic system, and cerebellum in PD. Particularly, a negative network within the accelerated deviations, expressed as “more preoperative deviations, less postoperative improvements,” could predict DBS outcomes (mean absolute error = 0.09, R 2 = 0.15). Moreover, a fusion of personal brain predictors and medical responses significantly improved traditional evaluations of DBS outcomes. Notably, the most important brain predictor, a pathway connecting the cognitive unit (prefrontal cortex) and motor control unit (cerebellum and motor strip), partially mediates DBS outcomes with the age at surgery. Conclusions Our findings suggest that individual structural perturbations on the cognitive motor control circuit are critical for modulating DBS outcomes. Interventions toward the circuit have the potential for additional clinical improvements. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.