Neuroplasticity in constraint-induced movement therapy

Abstract

Background: In healthy subjects, decreasing GABA facilitates motor learning[1]. Recent studies, using PET[2], TMS[3-5], and pharmacological challenges[6], have pointed indirectly to a decrease in neuronal inhibitory activity after stroke. Therefore, we hypothesize that a suppression of GABA levels post stroke might be beneficial to motor recovery during Constraint-Induced Movement Therapy (CIMT). Objective: To relate GABA changes to motor relearning after stroke through the use of j-difference edited Magnetic Resonance Spectroscopy (MRS). Methods: 21 patients (3-12 months post stroke) and 21 healthy, age-matched subjects were recruited. Patients had mild to moderate hand impairment, with at least 10° of active wrist extension, at least 10° of thumb abduction/extension, and at least 10° of extension in at least two additional digits. Patients were examined by a medical doctor and a physiotherapist prior to enrollment in the study. Patients completed two weeks of CIMT, and were scanned before and after training. For MRS a 2x2x2 cm voxel was placed on the “hand knob” (hand area located in the primary motor cortex[7]) in the affected hemisphere of the patients and in the dominant hemisphere of the healthy subjects. GABA was expressed as a ratio to Creatine (Cr). Motor function was measured using the Wolf Motor Function Test (WMFT)[8]. Results: GABA/Cr was significantly lower (p< 0.001) in patients (0.33) at baseline compared to healthy subjects (0.42). After therapy, patients showed a significant improvement in hand function (p< 0.001), which was negatively correlated with GABA/Cr changes (R=-0.57, p=0.015) – larger improvements in patients were associated with greater reductions in GABA/Cr. Results were also significant after correcting for changes in intracortical grey matter volume. Conclusion: A decrease in GABA levels appears to facilitate motor recovery after stroke. GABA, as measured non-invasively with MRS, could be a biomarker for neuronal plasticity during post stroke recovery and guide rehabilitation interventions as transcranial direct current stimulation[9].