Combining brain stimulation and peripheral nerve stimulation to improve upper extremity function after severe stroke

The proposal will be the first to measure neuroplastic change and motor recovery from severe post-stroke hemiparesis in response to a novel intervention combining transcranial direct current stimulation (tDCS) and peripheral nerve stimulation (PNS) with intensive upper extremity motor training. This novel combination comprises interventions that our previous studies have already successfully applied in singularity to enhance motor recovery from severe post-stroke hemiparesis. Because tDCS and PNS modulate motor cortex plasticity, it stands to reason that they may have significant additive effects. A small-scale study in mild to moderate stroke has shown that the combination of PNS and tDCS yields improved motor function when compared to single intervention. However, there is limited generalizability of this evidence to those with severe hemiparesis, who are among the neediest of stroke populations. Our proposal will address this evidence gap by implementing a thorough investigation of the neuroplastic and motor functional effects of combined tDCS and PNS preceding intensive upper extremity motor training as a clinical intervention for subjects with severe post-stroke hemiparesis. Subjects in this study will undergo 1 of 4 stimulation conditions: 1) combined active tDCS with active PNS (“Active+Active”), 2) combined active tDCS with sham PNS (“Active+Sham”), 3) combined sham tDCS with active PNS (“Sham+Active”), or 4) combined sham tDCS with sham PNS (“Sham+Sham”). As a crucial part of the intervention, each stimulation session will be followed by intensive upper extremity motor training. Our central hypothesis is that the group receiving active tDCS and active PNS (ie, Active+Active,) will show significantly greater cortical reorganization and significantly more improved motor function post-intervention than the other 3 groups (ie, Active+Sham, Sham+Active, and Sham+Sham). Furthermore, the degree of this behaviorally-measured effect will correlate with cortical reorganization as measured by neuroimaging techniques including transcranial magnetic stimulation (TMS). The long-range goals of this work include (a) establishing evidence on maximizing restoration of upper extremity motor function for individuals with severe post-stroke hemiparesis, (b) determining the impact of this intervention on activities of daily living and quality of life, and (c) collecting solid data to plan a large-scale, federally funded study of the phenomena in question.