Functional neuroimaging as a biomarker of non-invasive brain stimulation in upper limb recovery after stroke: a systematic review and narrative discussion

Introduction: Stroke is a leading cause of adult-onset disability. Non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcutaneous vagus nerve stimulation (tVNS) are promising adjuncts to upper limb rehabilitation. The use of functional neuroimaging through task functional MRI (fMRI) or functional near-infrared spectroscopy (fNIRS) allows the visualisation of cortical activation patterns associated with stroke-related impairment and recovery. The present study comprehensively reviews the evidence base for the effects of NIBS on clinical and functional neuroimaging outcomes after stroke. Methods: Systematic searches were carried out in MEDLINE and EMBASE via Ovid. Inclusion criteria were clinical trials of adults with stroke and arm weakness undergoing NIBS, with clinical measures of arm function and neuroimaging outcome measures that included either task fMRI or task fNIRS. Two authors independently carried out study screening, risk of bias assessments, and data collection for clinical and neuroimaging outcomes pre- and post-intervention. Results: A total of 17 studies (12 rTMS, 5 tDCS), including 495 participants, met the inclusion criteria. Fifteen studies used task fMRI and four used task fNIRS. Improvements in arm-related motor activity were observed following both rTMS and tDCS. Most studies reported increased activation in ipsilesional sensorimotor areas alongside reductions in contralesional activation. Discussion: rTMS and tDCS may improve upper limb recovery in people with stroke. The increase in the laterality index towards activation of the ipsilesional hemisphere suggests that these NIBS techniques may facilitate neural reorganisation and restoration of motor networks in the affected hemisphere.