Changes in Functional Connectivity Relate to Modulation of Cognitive Control by Subthalamic Stimulation

Subthalamic (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients not only improves kinematic parameters of movement but also modulates cognitive control in the motor and non-motor domain, especially in situations of high conflict. The objective of this study was to investigate the relationship between DBS-induced changes in functional connectivity at rest and modulation of response- and movement inhibition by STN-DBS in a visuomotor task involving high conflict. During DBS ON and OFF conditions, we conducted a visuomotor task in 14 PD patients who previously underwent resting-state functional MRI (rs-fMRI) acquisitions DBS ON and OFF as part of a different study. In the task, participants had to move a cursor with a pen on a digital tablet either toward (automatic condition) or in the opposite direction (controlled condition) of a target. STN-DBS induced modulation of resting-state functional connectivity (RSFC) as a function of changes in behavior ON versus OFF DBS was estimated using link-wise network-based statistics. Behavioral results showed diminished reaction time adaptation and higher pen-to-target movement velocity under DBS. Reaction time reduction was associated with attenuated functional connectivity between cortical motor areas, basal ganglia, and thalamus. On the other hand, increased movement velocity ON DBS was associated with stronger pallido-thalamic connectivity. These findings suggest that decoupling of a motor cortico-basal ganglia network underlies impaired inhibitory control in PD patients undergoing subthalamic DBS and highlight the concept of functional network modulation through DBS.