Date Published: January 31, 2019
Publisher: Impact Journals
Author(s): Lize Hermans, Celine Maes, Lisa Pauwels, Koen Cuypers, Kirstin-Friederike Heise, Stephan P. Swinnen, Inge Leunissen.
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.
The ability to inhibit an intended movement is a key component of cognitive control that allows flexible behavior in everyday life. Inhibition of motor responses is mediated by activity in a cortico-basal ganglia network whose output is thought to modulate the excitability of neurons within the primary motor cortex (M1) [1–4]. Whereas the direct pathway can excite motor cortex output via the striatum, the indirect and hyperdirect basal ganglia pathways can inhibit motor cortex excitability and support the suppression of undesired actions [5,6]. In accordance with this view, transcranial magnetic stimulation (TMS) studies show a decrease in corticospinal excitability (CSE) within M1 at 100-200 ms after the presentation of a stop-signal [7–9]. Notably, this suppression in excitability is supposedly accompanied by increased activation of GABAergic interneurons in M1 [7,10,11]. Intracortical interneurons receive and integrate input from cortical and subcortical structures , and can modulate the activity of corticospinal neurons via synaptic connections.
Two older adults did not complete the TMS sessions due to high TS intensity (≥ 80 maximum stimulator output, N = 1) or high background EMG (N = 1). The SICI data of one older adult was excluded due to artifacts in the EMG data. Lastly, SICI data of one young adult was excluded due to high background EMG. Hence, a total of N = 26 of the older and N = 24 of the younger of the SICI data sets, and a total of N = 27 of the older and N = 25 of the younger LICI data sets were entered in the statistical analyses.
We investigated the effect of age on the modulation of GABAA-mediated versus GABAB-mediated neurotransmission during reactive and proactive inhibitory control. At the behavioral level, we found that reactive but not proactive inhibition was affected by aging. Results of the paired-pulse TMS measurements showed that GABAA-mediated inhibition, indicated by SICI, was higher during stopping compared to go trials in young, but not in older adults. Furthermore, GABAB-mediated inhibition, as indicated by LICI at the start of the trial, was modulated as a function of stop-signal probability in both young and older adults. These results suggest that specifically the recruitment of GABAA-ergic inhibitory activity during the successful cancellation of a prepotent motor response is altered by aging.
In summary, the current data show that older adults are able to proactively slow down their responses in anticipation of upcoming stops. Nevertheless, they demonstrate poorer performance compared to young adults when they reactively need to suppress a prepotent action. At the neural level, we find that GABAA-mediated SICI during action cancellation is modulated differently for older compared to young adults. These results reinforce the idea that measures of GABA-mediated intracortical inhibition can contribute to our understanding of age-related deficits in cancelling prepotent motor responses.