Brain GABA Levels Are Associated with Inhibitory Control Deficits in Older Adults

Abstract

Healthy aging is accompanied by motor inhibition deficits that involve a slower process of stopping a prepotent motor response (i.e., reactive inhibition) rather than a diminished ability to anticipate stopping (i.e., proactive inhibition). Some studies suggest that efficient motor inhibition is related to GABAergic function. Since age-related alterations in the GABA system have also been reported, motor inhibition impairments might be linked to GABAergic alterations in the cortico-subcortical network that mediates motor inhibition. Thirty young human adults (mean age, 23.2 years; age range, 18-34 years; 14 men) and 29 older human adults (mean age, 67.5 years; age range, 60-74 years; 13 men) performed a stop-signal task with varying levels of stop-signal probability. GABA levels were measured with magnetic resonance spectroscopy (MRS) in right inferior frontal cortex, pre-supplementary motor area (pre-SMA), left sensorimotor cortex, bilateral striatum, and occipital cortex. We found that reactive inhibition was worse in older adults compared with young adults, as indicated by longer stop-signal reaction times (SSRTs). No group differences in proactive inhibition were observed as both groups slowed down their response to a similar degree with increasing stop-signal probability. The MRS results showed that tissue-corrected GABA levels were on average lower in older as compared with young adults. Moreover, older adults with lower GABA levels in the pre-SMA were slower at stopping (i.e., had longer SSRTs). These findings suggest a role for the GABA system in reactive inhibition deficits. Inhibitory control has been shown to diminish as a consequence of aging. We investigated whether the ability to stop a prepotent motor response and the ability to prepare to stop were related to GABA levels in different regions of the network that was previously identified to mediate inhibitory control. Overall, we found lower GABA levels in older adults compared with young adults. Importantly, those older adults who were slower at stopping had less GABA in the pre-supplementary motor area, a key node of the inhibitory control network. We propose that deficits in the stop process in part depend on the integrity of the GABA system.

The trajectory of cortical GABA levels across the lifespan: An individual participant data meta-analysis of edited MRS studies

“…Marenco et al (2018) also show a decrease in GABA with aging. It is important to note that other reports (Hermans et al, 2018;Maes et al, 2018) have compared MRS of GABA between defined groups of older and younger adults rather than with continuity across the lifespan. These findings are consistent with continuous approaches, with older adults having reduced GABA.…”

“…The above paragraph reflects a large number of studies showing that GABA plays an important role in regulating cognitive function in health and disease. It is also well known that age affects cognitive processes both in development and aging, including sensory processing (Koerner and Zhang, 2018;Simmonite et al, 2019), working memory (Mok et al, 2019), motor function (Hermans et al, 2018;Maes et al, 2018;Mikkelsen et al, 2018) and many others, however the potential role of GABA has not been well-explored. Perhaps more immediately, it is not well-known how GABA changes across the lifespan.…”

Neural distinctiveness declines with age in auditory cortex and is associated with auditory GABA levels

“…Another neural factor that may be important is age-related reductions in the brain's major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). GABA levels measured using magnetic resonance spectroscopy (MRS) have been found to be reduced in older adults compared to younger adults in the occipital cortex (12)(13)(14), in frontal and parietal regions (13,15), and in supplementary motor area and sensorimotor cortex (12,13,16). Furthermore, individual differences in GABA in specific cortical regions have been associated with individual differences in some aspects of cognitive performance (13,14,17).…”

GABAergic modulation of performance in response inhibition and interference control tasks

“…Magnetic resonance spectroscopy (MRS) studies suggest higher GABA concentrations in pre-supplementary motor area (Hermans et al, 2018), basal ganglia (Haag et al, 2015;Quetscher et al, 2014) and anterior cingulate cortex (ACC) (Kühn et al, 2016) to be associated with better performance in inhibitory control tasks. However, for the ACC this effect was observed for both congruent and incongruent conditions.…”