Elevated primary motor cortex GABA in Parkinson's disease: 7T MR spectroscopy evidence

Cortical inhibitory-excitatory imbalance may contribute to motor dysfunction in Parkinson's disease (PD), but in vivo primary motor cortex (M1) neurochemistry remains incompletely characterized.

We used 7T proton MR spectroscopy to quantify γ-aminobutyric acid (GABA) and glutamate (Glu) in M1 in patients with mild-to-moderate PD and healthy controls. The inhibitory/excitatory ratio (I/E ratio, GABA/Glu) was derived as an exploratory measure. After quality control, baseline analyses included 32 patients and 28 controls. A self-paced bilateral handgrip task was conducted in a subgroup with15 patients and 14 controls.

At rest, patients with PD showed higher GABA concentrations than controls, but this did not survive FDR correction across the two primary metabolites (p_FDR = 0.06). There was no difference in Glu between the two groups. The I/E ratio was also higher in PD. Higher GABA showed nominal associations with greater MDS-UPDRS III scores, but these did not survive correction. During the motor task, Glu increased across groups, with no significant group × condition interaction for GABA, Glu. Task findings were preliminary given limited power.

Ultra-high-field MRS preliminary evidence for altered resting M1 GABAergic neurochemistry in mild-to-moderate PD. Task-related findings require validation in larger cohorts. These findings support the utility of 7T MRS for probing motor-cortical neurochemistry in PD.