The Reciprocal Relationship Between Short‐ and Long‐Term Motor Learning and Neurometabolites

Skill acquisition requires practice to stimulate neuroplasticity. Changes in inhibitory and excitatory neurotransmitters, such as gamma‐aminobutyric acid (GABA) and glutamate, are believed to play a crucial role in promoting neuroplasticity. Magnetic resonance spectroscopy (MRS) at 3 T, using the MEGA‐PRESS sequence, and behavioral data were collected from 62 volunteers. Participants completed a 4‐week protocol, practicing either complex ( n  = 32) or simple ( n  = 30) bimanual tracking tasks (BTT). Neurotransmitter levels and skill levels at baseline, after 2 and 4 weeks of motor training were compared for the left and right primary sensorimotor cortex (SM1) and the left dorsal premotor cortex (PMd). Furthermore, task‐related modulations of neurotransmitter levels in the left PMd were assessed. The study yielded that baseline neurotransmitter levels in motor‐related brain regions predicted training success. Furthermore, lower GABA+ ( p  = 0.0347) and higher Glx (glutamate + glutamine compound) levels ( p  = 0.0234) in left PMd correlated with better long‐term learning of simple and complex tasks, respectively, whereas higher GABA+ in right SM1 correlated with complex task learning ( p  = 0.0064). Resting neurometabolite levels changed during the intervention: Left SM1 Glx decreased with complex training toward Week 4 ( p  = 0.0135), whereas right SM1 Glx was increased at Week 2 ( p  = 0.0043), regardless of training type. Group‐level analysis showed no task‐related neurometabolite modulation in the left PMd. However, individual baseline GABA+ and Glx modulation influenced short‐term motor learning (interaction: p  = 0.0213). These findings underscore the importance of an interplay between inhibitory and excitatory neurotransmitters during motor learning and suggest potential for future personalized approaches to optimize motor learning.