GABA and Glx Distinctively Predict Motor Learning and Retention in Young and Older Adults

Gamma-aminobutyric acid (GABA) and glutamate are fundamental in neural plasticity. Motor learning is predicted by baseline levels of these metabolites and their modulation in the sensorimotor cortex (SM1), but less is known about the metabolic activity in other areas that support learning, such as the dorsolateral prefrontal cortex (DLPFC), as well as the practice-induced metabolic modulation and age-associated differences. We investigated whether: (1) motor learning induces a differential degree of metabolic modulation in the SM1 and DLPFC, (2) learning tasks with higher difficulty levels enhance metabolic modulation as compared with those with lower difficulty levels, (3) metabolic modulation during motor learning is age dependent, and (4) training-induced metabolic modulation may have a differential effect on motor learning and retention. Young (n = 25, 12 females) and older (n = 21, 10 females) human adults completed a 6 d motor learning protocol with magnetic resonance spectroscopy scans being administered before, during, and after a low and high task complexity training condition. We observed a training-induced reduction of SM1 GABA+, regardless of age and task difficulty level, but no significant changes in DLPFC. Neither region showed a significant Glx (combined glutamate and glutamine) modulation. In addition, baseline GABA+ levels predicted learning, but this effect was region and task difficulty dependent. Age-related differences emerged in the prediction of retention, with older adults showing a beneficiary role of task-induced increase in the SM1 inhibitory tone. These results highlight the complexity of metabolic dynamics in learning and retention, showing their dependency on age, brain region, and task difficulty.