Lower cortical gamma-aminobutyric acid level contributes to connectivity in sensory-motor inter-connected regions in progressive MS

Background: Large-scale functional abnormalities and decreased synchronization between functionally connected regions within brain networks were reported in progressive multiple sclerosis (P-MS) patients. Low concentration of gamma-aminobutyric acid (GABA) was observed in the sensorimotor cortex (SMC) of these patients and was associated with reduced motor functions of limbs. Yet, the role of GABA in modulating functional connectivity (FC) has not been investigated in MS patients. Objectives: To determine the relationship between GABA concentration in the SMC and short-term FC changes within the sensorimotor network (SMN) in P-MS patients. Methods: Combining magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rs-fMRI), we investigated the relationship between baseline GABA concentration in the left SMC and FC within SMN in P-MS patients compared to healthy controls (HCs). Additionally, we assessed the relationship between baseline GABA concentration and FC changes over a 1-year follow-up period in the patients' group only. Results: At baseline, lower GABA levels, and decreased FC levels in regions within the SMN were observed in MS patients compared to healthy controls (HCs). Overtime, an increase in FC was observed in regions within the SMN in the MS group. This increase correlated inversely with motor performance scores. Conclusions: We postulate that in P-MS patients, lower levels of GABA in the SMC contribute to decreased inhibition, and as a result, to a reactive increase of FC in inter-connected sensorimotor brain regions, thus minimizing clinical worsening.