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

Abstract

Background After stroke, increases in contralesional primary motor cortex (M1CL) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL) 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 M1CL 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 M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP−)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. Results The extent of M1CL reorganization was related to greater lesion volume in the MEP− group, but not in the MEP+ group. Greater M1CL 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 M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence. ClinicalTrials.gov Identifier: NCT02544503

Constraint-Induced Movement Therapy Modulates Neuron Recruitment and Neurotransmission Homeostasis of the Contralesional Cortex to Enhance Function Recovery after Ischemic Stroke

“…This association is crucial in determining the extent of contralateral M1 reorganization. 21 It was reported that there was a reduction in the size and volume of the ipsilesional cortical hand motor representation, along with an anterior-medial shift of the contralesional hand motor representation within the contralesional primary motor cortex. 22 The combination with cTBS over the contralesional primary motor cortex and upper limb training promoted recovery of the upper limb, reduced disability and dependence, and led to earlier discharge from the rehabilitation center in patients within 3 weeks after stroke onset.…”

“…A clinical study demonstrated that larger lesion volumes and increased severity in the corticospinal tract (CST), particularly in CST fibers originating from the lesioned primary motor cortex (M1), were associated with a more significant impairment of hand function. This association is crucial in determining the extent of contralateral M1 reorganization . It was reported that there was a reduction in the size and volume of the ipsilesional cortical hand motor representation, along with an anterior-medial shift of the contralesional hand motor representation within the contralesional primary motor cortex .…”

Self-organizing recruitment of compensatory areas maximizes residual motor performance post-stroke

“…Finally, a unilateral large-sized lesion affecting most primary and premotor areas leads to initial paralysis in the contralateral arm. However, recruitment of the contra-lesional motor cortex (Cramer et al 1997, Ward et al 2003, Bestmann et al 2010, Rehme et al 2011, Zaaimi et al 2012, Murata et al 2015, Dodd et al 2017, McPherson et al 2018, Buetefisch et al 2023) leads to some degree of recovery of function via ipsilateral projections to the reticular formation, which then projects to the spinal cord via the reticulospinal tract (Illert et al 1981; see Bradnam et al 2012 for review). Because reticular projections to the spinal cord are mostly oligosynaptic via propriospinal neurons linking multiple muscles (Peterson et al 1975, Alstermark et al 2007), they create muscle synergies in the intact nervous system (Pierrot-Deseilligny 2002).…”

Identifying biomarkers related to motor function in chronic stroke: A fNIRS and TMS study

“…Studies have highlighted MEP status (MEP+ vs. MEP−) as a promising indicator of motor outcomes. 3 Additionally, researchers have developed a predictive recovery potential (PREP) algorithm, integrating motor scores, MEP status, and MRI measurements, exhibiting strong predictive abilities for stroke patients' motor outcomes. 4 However, in a recent study, researcher found that absence of MEP does not predict poor recovery in patients with severe stroke, 5 indicating that relying solely on MEP status may not comprehensively capture the multifaceted nature of poststroke motor function recovery.…”

“…A key method to assess functional integrity of CST involves using TMS to stimulate the primary motor cortex (M1) on the affected side and observing for the induction of motor evoked potentials (MEP). Studies have highlighted MEP status (MEP+ vs. MEP−) as a promising indicator of motor outcomes 3 . Additionally, researchers have developed a predictive recovery potential (PREP) algorithm, integrating motor scores, MEP status, and MRI measurements, exhibiting strong predictive abilities for stroke patients' motor outcomes 4 .…”