Task-related modulation of sensorimotor GABA+ levels in association with brain activity and motor performance: a multimodal MRS - fMRI study in young and older adults.

Recent studies suggest an important role of the principal inhibitory neurotransmitter GABA for motor performance in the context of aging. Nonetheless, as previous magnetic resonance spectroscopy (MRS) studies primarily reported resting-state GABA levels, much less is known about transient changes in GABA levels during motor task performance and how these relate to behavior and brain activity patterns. Therefore, we investigated GABA+ levels of left primary sensorimotor cortex (SM1) acquired before, during and after execution of a uni/bimanual action selection task in 30 (human) young (age 24.5 ± 4.1, 15 male) and 30 older adults (age 67.8 ± 4.9, 14 male). In addition to task-related MRS data, task-related fMRI data were acquired.Behavioral results indicated lower motor performance in older as opposed to young adults, particularly in complex task conditions. MRS results demonstrated lower GABA+ levels in older as compared to young adults. Furthermore, a transient task-related decrease of GABA+ levels was observed, irrespective of age. Notably, this task-induced modulation of GABA+ levels was linked to task-related brain activity patterns in SM1 such that a more profound task-induced instantaneous lowering of GABA+ was related to higher SM1 activity. Additionally, higher brain activity was related to better performance in the bimanual conditions, despite some age-related differences. Finally, the modulatory capacity of GABA+ was positively related to motor performance in older but not young adults. Together, these results underscore the importance of transient dynamical changes in neurochemical content for brain function and behavior, particularly in the context of aging.SIGNIFICANCE STATEMENTEmerging evidence designates an important role to regional GABA levels in motor control, especially in the context of aging. However, it remains unclear whether changes in GABA levels emerge when executing a motor task and how these changes relate to brain activity patterns and performance. Here, we identified a transient decrease of sensorimotor GABA+ levels during performance of an action selection task across young and older adults. Interestingly, whereas a more profound GABA+ modulation related to higher brain activity across age groups, its association with motor performance differed across age groups. Within older adults, our results highlighted a functional merit of a task-related release from inhibitory tone, i.e. lowering regional GABA+ levels, was associated with task-relevant brain activity.