The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study

Background. Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in gamma-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. Objective. To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. Methods. Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. Results. Short-interval intracortical inhibition was similar between patients and controls (P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls (P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function (P = .002 and P = .017). GABA concentration was lower within ipsilesional (P = .009) and contralesional (P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. Conclusion. These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.