Abstract 69: The Influence of Motor Cortex Inhibition on Upper Limb Recovery: A Multimodal Study

Abstract

Background: 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. The present study examined primary motor cortex (M1) inhibition in patients over the first 12 weeks after stroke, and in a cohort of age-similar healthy controls. Methods: Excitatory/inhibitory (E/I) balance was assessed from glutamate/glutamine (Glx) and gamma aminobutyric acid (GABA) concentrations from magnetic resonance spectroscopy (MRS) at 2 and 6 weeks after stroke. Threshold tracking paired-pulse transcranial magnetic stimulation (TMS) was used to assess motor cortex inhibition at 2, 6, and 12 weeks after stroke. Upper limb impairment and function were assessed with Fugl-Meyer Upper Extremity Scale and Action Research Arm Test at 2, 6, 12 and 26 weeks after stroke. Results: By 12 weeks, patients with a functionally intact corticospinal pathway as evident by the presence of MEPs in paretic upper-limb exhibited a proportional recovery such that upper limb impairment resolved by ~70% of the maximum possible (proportional recovery), whereas patients without MEPs had relatively poorer and more variable outcomes. Spectroscopy results indicated that there was an E/I in Glx:GABA ratio in both hemispheres compared to age-similar controls. Long-latency intracortical inhibition measures from TMS indicated an elevated GABA B -receptor mediated inhibition in both hemispheres during the spontaneous recovery period after stroke compared to controls. Patients with higher tonic inhibition in ipsilesional M1 tend to have a longer recovery period. Conclusion: The ability to modulate tonic inhibition levels early after stroke may have implications for upper limb recovery during the spontaneous recovery period.