Post-levodopa reduction of cerebellar Glx in Parkinson’s disease: Effect on tremor severity

Motivation: Cerebello-thalamo-cortical, particularly cerebellar, GABA, Glx may influence tremor severity in Parkinson's disease, and the impact of dopaminergic medication on cerebellar levels is current unknown. Goal(s): To measure cerebello-thalamo-cortical GABA and Glx in the OFF, and ON dopaminergic medication states in patients with PD, and ascertain the influence on tremor severity. Approach: Single-voxel J-difference edited MRS data was acquired using MEGA-semiLASER from the dentate, thalamus and motor cortex in the OFF and ON medication states. Results: Cerebellar Glx drives the tremor severity in PD, and dopaminergic medication produces a reduction in cerebellar Glx which in turn leads to an improvement in tremor severity. Impact: Cerebellar Glx drives tremor severity in PD, and dopaminergic medication mediated reduction leads to an improvement in tremor severity. These results provide the first evidence of cerebellar Glx involvement in PD, and open avenues for new therapeutic interventions.