Cerebellar GABA change during visuomotor adaptation relates to adaptation performance and cerebellar network connectivity: A Magnetic Resonance Spectroscopic Imaging study.

Abstract

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum underpinning human motor adaptation remain unknown. We used a novel Magnetic Resonance Spectroscopic Imaging (MRSI) technique to measure changes in the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA) in the human cerebellum during visuomotor adaptation. Participants used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We spatially resolved adaptation-driven GABA changes at the cerebellar nuclei and cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple right-hand movements increase GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found an increase in GABA in the left cerebellar nuclei and decrease in GABA in the right cerebellar nuclei. Early adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance: Participants showing greater GABA decrease adapted better, suggesting early GABA change is behaviourally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network: Participants showing greater decreases in GABA showed greater strength increases in cerebellar network connectivity. Results were specific to GABA, to adaptation and to the cerebellar network. This study provides first evidence for plastic changes in cerebellar neurochemistry during motor adaptation. Characterising these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate human motor adaptation. Significance StatementDespite motor adaptation being fundamental to maintaining accurate movements, its neurochemical basis remains poorly understood, perhaps because measuring neurochemicals in the human cerebellum is technically challenging. Using a novel magnetic resonance spectroscopic imaging method, this study provides evidence for GABA changes in the left and right cerebellar nuclei driven by both simple movement and motor adaptation. The adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance, and with functional connectivity change in a cerebellar network. These results show the first evidence for plastic changes in cerebellar neurochemistry during a cerebellar learning task. This provides the basis for developing therapeutic interventions that facilitate these naturally occurring changes to amplify cerebellar-dependent learning.