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.
Levels of GABA, the main inhibitory neurotransmitter in the brain, can be regionally quantified using magnetic resonance spectroscopy (MRS). Although GABA is crucial for efficient neuronal functioning, little is known about age-related differences in GABA levels and their relationship with age-related changes in brain structure. Here, we investigated the effect of age on GABA levels within the left sensorimotor cortex and the occipital cortex in a sample of 85 young and 85 older adults using the MEGA-PRESS sequence. Because the distribution of GABA varies across different brain tissues, various correction methods are available to account for this variation. Considering that these correction methods are highly dependent on the tissue composition of the voxel of interest, we examined differences in voxel composition between age groups and the impact of these various correction methods on the identification of age-related differences in GABA levels. Results indicated that, within both voxels of interest, older (as compared to young adults) exhibited smaller gray matter fraction accompanied by larger fraction of cerebrospinal fluid. Whereas uncorrected GABA levels were significantly lower in older as compared to young adults, this age effect was absent when GABA levels were corrected for voxel composition. These results suggest that age-related differences in GABA levels are at least partly driven by the age-related gray matter loss. However, as alterations in GABA levels might be region-specific, further research should clarify to what extent gray matter changes may account for age-related differences in GABA levels within other brain regions.
It has been established that bimanual coordination with augmented feedback (FB) versus no augmented feedback (NFB) is associated with activity in different brain regions. It is unclear however, whether this distinction remains after practice comprising both these conditions. Functional magnetic resonance imaging was used in humans to compare visual FB versus NFB conditions for a bimanual tracking task, and their differential evolution across learning. Scanning occurred before (Pre) and after 2 weeks (Post) of mixed FB and NFB training using an event-related design, allowing differentiation between the planning and execution phase of the task. Activations at the whole-brain level initially differed for FB versus NFB movements but this differentiation diminished with training for the movement execution phase. Specifically, in right dorsal premotor cortex and right dorsolateral prefrontal cortex activation increased for NFB and decreased for FB trials to converge toward the end of practice. This suggests that learning led to a decreased need to adjust the ongoing movement on the basis of FB, whereas online monitoring became more pronounced in NFB trials as discrepancies between the required and the produced motor output were detected more accurately after training, due to a generic internal reference of correctness supporting movement control under varying conditions.
The contextual interference (CI) effect is a robust phenomenon in the (motor) skill learning literature. However, CI has yielded mixed results in complex task learning. The current study addressed whether the CI effect is generalizable to bimanual skill learning, with a focus on the temporal evolution of memory processes. In contrast to previous studies, an extensive training schedule, distributed across multiple days of practice, was provided. Participants practiced three frequency ratios across three practice days following either a blocked or random practice schedule. During the acquisition phase, better overall performance for the blocked practice group was observed, but this difference diminished as practice progressed. At immediate and delayed retention, the random practice group outperformed the blocked practice group, except for the most difficult frequency ratio. Our main finding is that the random practice group showed superior performance persistence over a one week time interval in all three frequency ratios compared to the blocked practice group. This study contributes to our understanding of learning, consolidation and memory of complex motor skills, which helps optimizing training protocols in future studies and rehabilitation settings.
Physiological aging affects brain structure and function impacting morphology, connectivity, and performance. However, whether some brain connectivity metrics might reflect the age of an individual is still unclear. Here, we collected brain images from healthy participants (N = 155) ranging from 10 to 80 years to build functional (resting state) and structural (tractography) connectivity matrices, both data sets combined to obtain different connectivity features. We then calculated the brain connectome age—an age estimator resulting from a multi‐scale methodology applied to the structure–function connectome, and compared it to the chronological age (ChA). Our results were twofold. First, we found that aging widely affects the connectivity of multiple structures, such as anterior cingulate and medial prefrontal cortices, basal ganglia, thalamus, insula, cingulum, hippocampus, parahippocampus, occipital cortex, fusiform, precuneus, and temporal pole. Second, we found that the connectivity between basal ganglia and thalamus to frontal areas, also known as the fronto‐striato‐thalamic (FST) circuit, makes the major contribution to age estimation. In conclusion, our results highlight the key role played by the FST circuit in the process of healthy aging. Notably, the same methodology can be generally applied to identify the structural–functional connectivity patterns correlating to other biomarkers than ChA.
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.
Recent work in young adults has demonstrated that motor learning can modulate resting state functional connectivity. However, evidence for older adults is scarce. Here, we investigated whether learning a bimanual tracking task modulates resting state functional connectivity of both inter- and intra-hemispheric regions differentially in young and older individuals, and whether this has behavioral relevance. Both age groups learned a set of complex bimanual tracking task variants over a 2-week training period. Resting-state and task-related functional magnetic resonance imaging scans were collected before and after training. Our analyses revealed that both young and older adults reached considerable performance gains. Older adults even obtained larger training-induced improvements relative to baseline, but their overall performance levels were lower than in young adults. Short-term practice resulted in a modulation of resting state functional connectivity, leading to connectivity increases in young adults, but connectivity decreases in older adults. This pattern of age differences occurred for both inter- and intra-hemispheric connections related to the motor network. Additionally, long-term training-induced increases were observed in intra-hemispheric connectivity in the right hemisphere across both age groups. Overall, at the individual level, the long-term changes in inter-hemispheric connectivity correlated with training-induced motor improvement. Our findings confirm that short-term task practice shapes spontaneous brain activity differentially in young and older individuals. Importantly, the association between changes in resting state functional connectivity and improvements in motor performance at the individual level may be indicative of how training shapes the short-term functional reorganization of the resting state motor network for improvement of behavioral performance.
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