Pallidal and subthalamic stimulations modulate inter-hemispheric interaction and asymmetry in Parkinson's disease

Substantial asymmetries of motor dysfunction are evident in patients with Parkinson's disease (PD), the mechanisms of which remain largely unexplored. This study investigated how deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) and subthalamic nucleus (STN) modulates characteristics of hemispheric lateralization in PD patients, with particular emphasis on motor asymmetries and hemispheric integration (via homotopic functional connectivity) and segregation (via hemispheric asymmetry in connectivity). Resting-state functional magnetic resonance imaging (fMRI) and Unified Parkinson's Disease Rating Scale (UPDRS) III scores were analyzed from 55 PD patients who underwent either bilateral GPi- or STN-DBS. Both targets produced significant improvements in motor function. Notably, stimulation effects on motor asymmetry depend on patients' baseline asymmetry direction (DBS OFF): STN-DBS consistently reduced asymmetry in the leftward-asymmetry patients, whereas GPi-DBS has stronger effects in rightward patients. In both cases, stimulation led to a more symmetric pattern. Beyond motor outcomes, motor gains were associated with changes in homotopic connectivity in the lateral occipital region, overlapping the extrastriate body area, suggesting a compensatory role of visual networks. These findings highlight the contribution of the visual networks to motor improvement and reveal target-dependent effects of DBS on both motor asymmetry and non-motor cognitive domains.