Task-Related Modulation of Sensorimotor GABA1 Levels in Association with Brain Activity and Motor Performance: A Multimodal MRS–fMRI Study in Young and Older Adults

Abstract

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 GABA1 levels of left primary sensorimotor cortex (SM1) acquired before, during, and after execution of a unimanual/bimanual action selection task in 30 (human) young adults (YA; age 24.5 6 4.1, 15 male) and 30 older adults (OA; age 67.8 6 4.9, 14 male). In addition to task-related MRS data, task-related functional magnetic resonance imaging (fMRI) data were acquired. Behavioral results indicated lower motor performance in OA as opposed to YA, particularly in complex task conditions. MRS results demonstrated lower GABA1 levels in OA as compared with YA. Furthermore, a transient task-related decrease of GABA1 levels was observed, regardless of age. Notably, this task-induced modulation of GABA1 levels was linked to task-related brain activity patterns in SM1 such that a more profound task-induced instantaneous lowering of GABA1 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 GABA1 was positively related to motor performance in OA but not YA. Together, these results underscore the importance of transient dynamical changes in neurochemical content for brain function and behavior, particularly in the context of aging.