Hyperdirect projections from the supplementary motor area mediate subthalamic stimulation effects on movement initiation and inhibition in Parkinson’s disease

Abstract

In Parkinson’s Disease, subthalamic deep brain stimulation improves movement initiation but can induce impulsivity. The origin of these effects remains unclear. Here, we test the hypothesis that modulation of automatic response inhibition, an underrecognized process that governs the ability to refrain from reacting, accounts for both effects. Nineteen Parkinson’s disease patients were assessed for: I) behavioral changes in a simple Go/NoGo task, ON vs. OFF deep brain stimulation, II) structural connectivity between the stimulated subthalamic region and the supplementary motor complex, and III) a previously established electroencephalographic marker of automatic response inhibition (the DMF170). Under stimulation, patients exhibited faster reaction times and increased commission errors. These changes were accompanied by an increase in DMF170 amplitude, which correlated with reaction times. Finally, behavioral changes were associated with stimulation volume overlap with fibers connecting the subthalamic nucleus to the supplementary motor complex. Our findings link improved movement initiation and increased impulsivity under stimulation of the subthalamic nucleus to a shared anatomical and functional substrate, namely the subthalamic nucleus-supplementary motor cortex loop supporting automatic response inhibition.