Lisa Pauwels

Reduced Neural Differentiation Between Feedback Conditions After Bimanual Coordination Training with and without Augmented Visual Feedback

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.

Contextual Interference in Complex Bimanual Skill Learning Leads to Better Skill Persistence

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.

Challenge to promote change: both young and older adults benefit from contextual interference

Current society has to deal with major challenges related to our constantly increasing population of older adults. Since, motor performance generally deteriorates at older age, research investigating the effects of different types of training on motor improvement is particularly important. Here, we tested the effects of contextual interference (CI) while learning a bimanual coordination task in both young and older subjects. Both age groups acquired a low and high complexity task variant following either a blocked or random practice schedule. Typical CI effects, i.e., better overall performance during acquisition but detrimental effects during retention for the blocked compared with the random groups, were found for the low complexity task variant in both age groups. With respect to the high complexity task variant, no retention differences between both practice schedules were found. However, following random practice, better skill persistence (i.e., from end of acquisition to retention) over a 1 week time interval was observed for both task complexity variants and in both age groups. The current study provides clear evidence that the effects of different practice schedules on learning a complex bimanual task are not modulated by age.

Relative cortico-subcortical shift in brain activity but preserved training-induced neural modulation in older adults during bimanual motor learning

To study age-related differences in neural activation during motor learning, functional magnetic resonance imaging scans were acquired from 25 young (mean 21.5-year old) and 18 older adults (mean 68.6-year old) while performing a bimanual coordination task before (pretest) and after (posttest) a 2-week training intervention on the task. We studied whether task-related brain activity and training-induced brain activation changes differed between age groups, particularly with respect to the hyperactivation typically observed in older adults. Findings revealed that older adults showed lower performance levels than younger adults but similar learning capability. At the cerebral level, the task-related hyperactivation in parietofrontal areas and underactivation in subcortical areas observed in older adults were not differentially modulated by the training intervention. However, brain activity related to task planning and execution decreased from pretest to posttest in temporo-parieto-frontal areas and subcortical areas in both age groups, suggesting similar processes of enhanced activation efficiency with advanced skill level. Furthermore, older adults who displayed higher activity in prefrontal regions at pretest demonstrated larger training-induced performance gains. In conclusion, in spite of prominent age-related brain activation differences during movement planning and execution, the mechanisms of learning-related reduction of brain activation appear to be similar in both groups. Importantly, cerebral activity during early learning can differentially predict the amplitude of the training-induced performance benefit between young and older adults.

Alterations in brain white matter contributing to age-related slowing of task switching performance: The role of radial diffusivity and magnetization transfer ratio

Successfully switching between tasks is critical in many daily activities. Age‐related slowing of this switching behavior has been documented extensively, but the underlying neural mechanisms remain unclear. Here, we investigated the contribution of brain white matter changes associated with myelin alterations to age‐related slowing of switching performance. Diffusion tensor imaging derived radial diffusivity (RD) and magnetization transfer imaging derived magnetization transfer ratio (MTR) were selected as myelin sensitive measures. These metrics were studied in relation to mixing cost (i.e., the increase in reaction time during task blocks that require task switching) on a local‐global switching task in young (n = 24) and older (n = 22) adults. Results showed that higher age was associated with widespread increases in RD and decreases in MTR, indicative of white matter deterioration, possibly due to demyelination. Older adults also showed a higher mixing cost, implying slowing of switching performance. Finally, mediation analyses demonstrated that decreases in MTR of the bilateral superior corona radiata contributed to the observed slowing of switching performance with increasing age. These findings provide evidence for a role of cortico‐subcortical white matter changes in task switching performance deterioration with healthy aging. Hum Brain Mapp 37:4084–4098, 2016.

Challenge to promote change: the neural basis of the contextual interference effect in young and older adults

Motor performance deteriorates with age. Hence, studying the effects of different training types on performance improvement is particularly important. Here, we investigated the neural correlates of the contextual interference (CI) effect in 32 young (YA; 16 female) and 28 older (OA; 12 female) human adults. Participants were randomly assigned to either a blocked or a random practice schedule, practiced three variations of a bimanual visuomotor task over 3 d, and were retested 6 d later. Functional magnetic resonance imaging data were acquired during the first and last training days and during retention. Although the overall performance level was lower in OA than YA, the typical CI effects were observed in both age groups, i.e., inferior performance during acquisition but superior performance during retention for random relative to blocked practice. At the neural level, blocked practice showed higher brain activity in motor-related brain regions compared with random practice across both age groups. However, although activity in these regions decreased with blocked practice in both age groups, it was either preserved (YA) or increased (OA) as a function of random practice. In contrast, random compared with blocked practice resulted in greater activations in visual processing regions across age groups. Interestingly, in OA, the more demanding random practice schedule triggered neuroplastic changes in areas of the default mode network, ultimately leading to better long-term retention. Our findings may have substantial implications for the optimization of practice schedules, and rehabilitation settings in particular. SIGNIFICANCE STATEMENT In aging societies, it is critically important to understand how motor skills can be maintained or enhanced in older adults, with the ultimate goal to prolong functional independence. Here, we demonstrated that a more challenging random as opposed to a blocked practice environment temporarily reduced performance during the acquisition phase but resulted in lasting benefits for skill retention. In older adults, learning success was critically dependent on reduction of activation in areas of the default mode network, pointing to plastic functional changes in brain regions that are vulnerable to aging effects. The random practice context led to increased economy of brain activity and better skill retention. This provides new perspectives for reversing the negative consequences of aging.

The neurochemical basis of the contextual interference effect

Efficient practice organization maximizes learning outcome. Although randomization of practice as compared to blocked practice damages training performance, it boosts retention performance, an effect called contextual interference. Motor learning modulates the GABAergic (gamma-aminobutyric acid) system within the sensorimotor cortex (SM); however, it is unclear whether different practice regimes differentially modulate this system and whether this is impacted by aging. Young and older participants were trained on 3 variations of a visuomotor task over 3 days, following either blocked or random practice schedule and retested 6 days later. Using magnetic resonance spectroscopy, SM and occipital cortex GABA+ levels were measured before and after training during the first and last training days. We found that (1) behavioral data confirmed the contextual interference effects, (2) within-day occipital cortex GABA+ levels decreased in random and increased in blocked group. This effect was more pronounced in older adults; and (3) baseline SM GABA+ levels predicted initial performance. These findings indicate a differential modulation of GABA levels across practice groups that is amplified by aging.

Age-related differences in GABA levels are driven by bulk tissue changes

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.

Age-dependent modulations of resting state connectivity following motor practice

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.

What the structural-functional connectome reveals about brain aging: The key role of the fronto-striatal-thalamic circuit and the rejuvenating impact of physical activity

Physiological ageing affects brain structure and function impacting its morphology, connectivity and performance. However, at which extent brain-connectivity metrics reflect the age of an individual and whether treatments or lifestyle factors such as physical activity influence the age-connectivity match is still unclear. Here, we assessed the level of physical activity and collected brain images from healthy participants (N=155) ranging from 10 to 80 years to build functional (resting-state) and structural (tractography) connectivity matrices that were combined as connectivity descriptors. Connectivity descriptors were used to compute a maximum likelihood age estimator that was optimized by minimizing the mean absolute error. The connectivity-based estimated age, i.e. the brain-connectome age (BCA), was compared to the chronological age (ChA). Our results were threefold. First, we showed that ageing widely affects the structural-functional connectivity of multiple structures, such as the anterior part of the default mode network, basal ganglia, thalamus, insula, cingulum, hippocampus, parahippocampus, occipital cortex, fusiform, precuneus and temporal pole. Second, our analysis showed that the structure-function connectivity between basal ganglia and thalamus to orbitofrontal and frontal areas make a major contribution to age estimation. Third, we found that high levels of physical activity reduce BCA as compared to ChA, and vice versa, low levels increment it. In conclusion, the BCA model results highlight the impact of physical activity and the key role played by the connectivity between basal ganglia and thalamus to frontal areas on the process of healthy aging. Notably, the same methodology can be generally applied both to evaluate the impact of other factors and therapies on brain ageing, and to identify the structural-functional brain connectivity correlate of other biomarkers than ChA.