Stimulation of the premotor cortex enhances inter-hemispheric functional connectivity in association with upper limb motor recovery in moderate-to-severe chronic stroke

Background: Transcranial direct current stimulation (tDCS) targeting the primary motor cortex is modestly effective for promoting upper-limb motor function following stroke. The premotor cortex (PMC) represents an alternative target based on its higher likelihood of survival and dense motor-network connections. Objective: The objective of this study was to determine whether ipsilesional PMC tDCS affects motor network functional connectivity (FC) in association with reduction in motor impairment, and to determine whether this relationship is influenced by baseline motor severity. Methods: Participants with chronic stroke were randomly assigned to receive active-PMC or sham-tDCS with rehabilitation for 5-weeks. Resting-state fMRI (rs-fMRI) was acquired to characterize change in FC across motor-cortical regions. Results: Our results indicated that moderate-to-severe participants who received active-tDCS had greater increases in PMC-to-PMC inter-hemispheric FC compared to those who received sham; this increase was correlated with reduction in proximal motor impairment. There was also an increase in intra-hemispheric PMd-M1 FC across participants regardless of severity or tDCS group assignment; this increase was correlated with reduction in proximal motor impairment in only the mild participants. Conclusions: Our findings have significance for developing targeted brain-stimulation approaches. While participants with milder impairments may inherently recruit viable substrates within the ipsilesional hemisphere, stimulation of PMC may enhance inter-hemispheric FC in association with recovery in more impaired participants.