Aging and GABA

Healthy aging is associated with structural and functional alterations in the brain and declines in multiple facets of motor performance such as balance, fine motor skills and motor coordination. Inhibitory processes are essential for optimal brain function and undergo agerelated alterations that may account for these behavioral deficits. Specifically, the inability to successfully modulate corticospinal excitability has been linked to declined motor performance in older adults [1]. In this regard, a key role is played by gamma-aminobutyric acid (GABA), i.e. the main inhibitory neurotransmitter. To demonstrate the importance of GABA in human movement control, complementary neuroimaging as well as non-invasive brain stimulation techniques can be employed to unravel age-related alterations in inhibitory function. On the one hand, GABA levels can be regionally quantified in vivo using magnetic resonance spectroscopy (MRS). Multiple MRS studies point towards an age-related decline in GABA levels, correlating with degraded motor performance as well as poor cognitive functioning. In terms of measurement of age-related changes in GABA levels using MRS, a major question of interest is whether brain structure alterations need to be considered. More specifically, the identification of age-related decreases in GABA level in the brain seems to be dependent on whether loss of gray matter is considered in the quantification of GABA levels or not [2]. Besides improvements in measurement techniques, more insight into the reliability of MRS-based measures over time as well as differences in GABA levels across areas covering the cortical-subcortical territory across the lifespan is warranted. Furthermore, GABA modulation is a critical entry point for the emergence of neuroplasticity. More specifically, a reduction in GABA level is associated with training-induced motor plasticity. The question remains whether and how GABA modulation can be facilitated in the brains of older adults to promote lifelong plasticity. Alternatively, noninvasive brain stimulation techniques (such as transcranial magnetic stimulation, TMS) provide tools to study the functional status and task-related modulation of two major receptor subtypes, i.e. GABAA (fast acting ionotropic) and GABAB (slower acting metabotropic), mediating inhibition at shorter and longer time scales, respectively [3]. Motor evoked potentials (MEPs) provide a peripheral window into the Editorial