Age-related alterations in the modulation of intracortical inhibition during stopping of actions

Abstract

We investigated the effect of age on the ability to modulate GABAA-ergic and GABAB-ergic inhibitory activity during stopping of action (reactive inhibition) and preparation to stop (proactive inhibition). Twenty-five young and twenty-nine older adults performed an anticipated response version of the stop-signal task with varying levels of stop-signal probability. Paired-pulse transcranial magnetic stimulation was applied to left primary motor cortex to assess the modulation of GABAA-mediated short-interval intracortical inhibition (SICI) during stopping and GABAB-mediated long-interval intracortical inhibition (LICI) during the anticipation of a stop-signal. At the behavioral level, reactive inhibition was affected by aging as indicated by longer stop-signal reaction times in older compared to young adults. In contrast, proactive inhibition was preserved at older age as both groups slowed down their go response to a similar degree with increasing stop-signal probability. At the neural level, the amount of SICI was higher in successful stop relative to go trials in young but not in older adults. LICI at the start of the trial was modulated as a function of stop-signal probability in both young and older adults. Our results suggest that specifically the recruitment of GABAA-mediated intracortical inhibition during stopping of action is affected by aging.

Tuning the Corticospinal System: How Distributed Brain Circuits Shape Human Actions

“…Dynamical changes in SICI have also been described in the context of action cancellation (Stinear and others 2009). Here, phasic increases in SICI (more inhibition) have been reported following the occurrence of stop signals relative to imperative Go cues (Hermans and others 2019; Lindberg and others 2016; Fig. 3C).…”

“…The contribution of this form of intra-cortical inhibition to action control has been largely studied in the context of action selection. Indeed, a number of studies has shown that the strength of SICI declines over time in selected muscles (Chowdhury and others 2019; Dupont-Hadwen and others 2019; Fujiyama and others 2011; Fujiyama and others 2012; Heise and others 2010; Heise and others 2013; Hermans and others 2019; Hummel and others 2009; Kumru and others 2008; Reynolds and Ashby 1999; see Fig. 3A), while it concomitantly increases over time in non-selected effectors (Soto and others 2010) and in task-irrelevant muscles surrounding the one involved in the action (Liepert and others 1998).…”

Alterations of hand sensorimotor function and cortical motor representations over the adult lifespan

“…Evidence from TMS studies suggests that an age-related gradual loss of inhibitory modulation is associated with a decline in sensorimotor function, such as a reduction in movement speed and impaired coordination [5,26,28,29]. Moreover, associations between the level of hand usage and short-and long-term corticospinal adaptations were observed.…”

“…Healthy aging is associated with a reduction in sensorimotor function, such as for example, a higher variability of movements [1][2][3], slower reaction times [3][4][5], impaired coordination skills [6][7][8][9], and a generally lower performance level [10] in older as compared to younger adults. Commonly, manual dexterity and force decline simultaneously, potentially at the partial expense of independence as most tasks of everyday life require an efficient and dexterous handling of objects [3,11].…”

The interaction between endogenous GABA, functional connectivity and behavioral flexibility is critically altered with advanced age

“…Experimental evidence for this association between age-related GABAergic dysfunction and declining behavior across perceptual and cognitive domains points towards stronger impact on those types of behavior that require a high level of dynamic control [e.g. [8–10]]. Lowered motor cortical GABA levels, on the other hand, are found to correlate with age-related changes in sensorimotor connectivity and diminished motor control [11].…”