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.SIGNIFICANCE STATEMENT 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.
Highlights
The ability to inhibit inappropriate actions is important for adaptive behavior
magnetic resonance spectroscopy (MRS) studies in young adults have shown that GABA levels in the striatum and anterior cingulate cortex are correlated with interindividual differences in go–no-go task performance (Silveri et al, 2013; Quetscher et al, 2015), suggesting that motor inhibition efficiency depends on GABAergic functioning within the corticotask (Fig. 1) was used to investigate reactive and proactive inhibition (Coxon et al, 2007; Zandbelt and Vink, 2010)
A paired t test indicated that this difference in GoRT was significant in both young adults (t(24) ϭ Ϫ12.738, p Ͻ 0.001) and older adults (t(28) ϭ Ϫ12.959, p Ͻ 0.001), which is consistent with the assumptions of the horse race model (Logan and Cowan, 1984)
Summary
The ability to inhibit inappropriate actions is important for adaptive behavior. In some situations, we need to quickly cancel an Received March 22, 2018; revised July 6, 2018; accepted July 24, 2018. A recent study (Porges et al, 2017b) reported that age-related declines in GABA levels may depend on the applied tissue correction. SMA), and subthalamic nucleus (STN) are recruited during re- imaging and TMS evidence (Coxon et al, 2006; Aron, 2011), we active inhibition (Aron and Poldrack, 2006; Aron, 2007), whereas hypothesized that reactive inhibition efficiency would correlate proactive inhibition is thought to rely more heavily on the stria- with GABA levels within the RIFC, pre-SMA, and LSM1, whereas tum (Aron, 2011; Leunissen et al, 2016). We hypothesized that lower GABA levels frontal regions of this network generate a stop command to in- would be related to worse motor inhibition (Silveri et al, 2013; tercept the planned movement that is generated in the primary Quetscher et al, 2015). It is difficult to assess cortical GABAergic functioning other than M1 with TMS, and especially subcortical regions require other techniques such as magnetic resonance spectroscopy (MRS), to probe the GABA system
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