Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization

Background After stroke, increases in contralesional primary motor cortex (M1(CL)) activity and excitability have been reported. In pre-clinical studies, M1(CL) reorganization is related to the extent of ipsilesional M1 (M1(IL)) injury, but this has yet to be tested clinically. Objectives We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1(CL) reorganization and its relationship to affected hand function in humans recovering from stroke. Methods Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1(IL) was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP-)). M1(CL) reorganization was determined by TMS applied to M1(CL) at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. Results The extent of M1(CL) reorganization was related to greater lesion volume in the MEP- group, but not in the MEP+ group. Greater M1(CL) reorganization was associated with more impaired hand function in MEP- but not MEP+ participants. Absence of an MEP (MEP-), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. Conclusions In the subacute post-stroke period, stroke volume and M1(IL) output determine the extent of M1(CL) reorganization and its relationship to affected hand function, consistent with pre-clinical evidence. ClinicalTrials.gov Identifier: NCT02544503