Combining muscle-computer interface guided training with bihemispheric tDCS improves upper limb function in patients with chronic stroke.

Transcranial direct current stimulation (tDCS) may facilitate neuroplasticity but with a limited effect when administered while patients with stroke are at rest. Muscle-computer interface (MCI) training is a promising approach for training patients with stroke even if they cannot produce overt movements. However, using tDCS to enhance MCI training has not been investigated. We combined bihemispheric tDCS with MCI training of the paretic wrist and examined the effect of this intervention in patients with chronic stroke. A crossover, double-blind, randomized trial was conducted. Twenty-six patients with chronic stroke performed MCI wrist training for three consecutive days at home while receiving either real tDCS or sham tDCS in counterbalanced order and separated by at least 8 mo. The primary outcome measure was the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) that was measured 1 wk before training, on the first training day, on the last training day, and 1 wk after training. There was neither a significant difference in the baseline FMA-UE score between groups nor between intervention periods. Patients improved 3.9 ± 0.6 points in FMA-UE score when receiving real tDCS, and 1.0 ± 0.7 points when receiving sham tDCS (P = 0.003). In addition, patients also showed continuous improvement in their motor control of the MCI tasks over the training days. Our study showed that the training paradigm could lead to functional improvement in patients with chronic stroke. We argue that appropriate MCI training in combination with bihemispheric tDCS could be a useful adjuvant for neurorehabilitation in patients with stroke.NEW & NOTEWORTHY Bihemispheric tDCS combined with a novel MCI training for motor control of wrist extensor can improve upper limb function especially a training-specific effect on the wrist movement in patients with chronic stroke. The training regimen can be personalized with adjustments made daily to accommodate the functional change throughout the intervention. This demonstrates that bihemispheric tDCS with MCI training could complement conventional poststroke neurorehabilitation.

Frequency-dependent connectivity in large-scale resting-state brain networks during sleep.

Functional connectivity (FC) during sleep has been shown to break down as non-rapid eye movement (NREM) sleep deepens before returning to a state closer to wakefulness during rapid eye movement (REM) sleep. However, the specific spatial and temporal signatures of these fluctuations in connectivity patterns remain poorly understood. This study aimed to investigate how frequency-dependent network-level FC fluctuates during nocturnal sleep in healthy young adults using high-density electroencephalography (hdEEG). Specifically, we examined source-localized FC in resting-state networks during NREM2, NREM3 and REM sleep (sleep stages scored using a semi-automatic procedure) in the first three sleep cycles of 29 participants. Our results showed that FC within and between all resting-state networks decreased from NREM2 to NREM3 sleep in multiple frequency bands and all sleep cycles. The data also highlighted a complex modulation of connectivity patterns during the transition to REM sleep whereby delta and sigma bands hosted a persistence of the connectivity breakdown in all networks. In contrast, a reconnection occurred in the default mode and the attentional networks in frequency bands characterizing their organization during wake (i.e., alpha and beta bands, respectively). Finally, all network pairs (except the visual network) showed higher gamma-band FC during REM sleep in cycle three compared to earlier sleep cycles. Altogether, our results unravel the spatial and temporal characteristics of the well-known breakdown in connectivity observed as NREM sleep deepens. They also illustrate a complex pattern of connectivity during REM sleep that is consistent with network- and frequency-specific breakdown and reconnection processes.

Baseline GABA+ levels in areas associated with sensorimotor control predict initial and long-term motor learning progress.

Synaptic plasticity relies on the balance between excitation and inhibition in the brain. As the primary inhibitory and excitatory neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate (Glu), play critical roles in synaptic plasticity and learning. However, the role of these neurometabolites in motor learning is still unclear. Furthermore, it remains to be investigated which neurometabolite levels from the regions composing the sensorimotor network predict future learning outcome. Here, we studied the role of baseline neurometabolite levels in four task-related brain areas during different stages of motor skill learning under two different feedback (FB) conditions. Fifty-one healthy participants were trained on a bimanual motor task over 5 days while receiving either concurrent augmented visual FB (CA-VFB group, N = 25) or terminal intrinsic visual FB (TA-VFB group, N = 26) of their performance. Additionally, MRS-measured baseline GABA+ (GABA + macromolecules) and Glx (Glu + glutamine) levels were measured in the primary motor cortex (M1), primary somatosensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and medial temporal cortex (MT/V5). Behaviorally, our results revealed that the CA-VFB group outperformed the TA-VFB group during task performance in the presence of augmented VFB, while the TA-VFB group outperformed the CA-VFB group in the absence of augmented FB. Moreover, baseline M1 GABA+ levels positively predicted and DLPFC GABA+ levels negatively predicted both initial and long-term motor learning progress in the TA-VFB group. In contrast, baseline S1 GABA+ levels positively predicted initial and long-term motor learning progress in the CA-VFB group. Glx levels did not predict learning progress. Together, these findings suggest that baseline GABA+ levels predict motor learning capability, yet depending on the FB training conditions afforded to the participants.

Targeted memory reactivation during post-learning sleep does not enhance motor memory consolidation in older adults.

Targeted memory reactivation (TMR) during sleep enhances memory consolidation in young adults by modulating electrophysiological markers of neuroplasticity. Interestingly, older adults exhibit deficits in motor memory consolidation, an impairment that has been linked to age-related degradations in the same sleep features sensitive to TMR. We hypothesised that TMR would enhance consolidation in older adults via the modulation of these markers. A total of 17 older participants were trained on a motor task involving two auditory-cued sequences. During a post-learning nap, two auditory cues were played: one associated to a learned (i.e., reactivated) sequence and one control. Performance during two delayed re-tests did not differ between reactivated and non-reactivated sequences. Moreover, both associated and control sounds modulated brain responses, yet there were no consistent differences between the auditory cue types. Our results collectively demonstrate that older adults do not benefit from specific reactivation of a motor memory trace by an associated auditory cue during post-learning sleep. Based on previous research, it is possible that auditory stimulation during post-learning sleep could have boosted motor memory consolidation in a non-specific manner.

Neurological soft signs in adolescents are associated with brain structure.

Neurological soft signs (NSS) are minor deviations in motor performance. During childhood and adolescence, NSS are examined for functional motor phenotyping to describe development, to screen for comorbidities, and to identify developmental vulnerabilities. Here, we investigate underlying brain structure alterations in association with NSS in physically trained adolescents. Male adolescent athletes (n = 136, 13-16 years) underwent a standardized neurological examination including 28 tests grouped into 6 functional clusters. Non-optimal performance in at least 1 cluster was rated as NSS (NSS+ group). Participants underwent T1- and diffusion-weighted magnetic resonance imaging. Cortical volume, thickness, and local gyrification were calculated using Freesurfer. Measures of white matter microstructure (Free-water (FW), FW-corrected fractional anisotropy (FAt), axial and radial diffusivity (ADt, RDt)) were calculated using tract-based spatial statistics. General linear models with age and handedness as covariates were applied to assess differences between NSS+ and NSS- group. We found higher gyrification in a large cluster spanning the left superior frontal and parietal areas, and widespread lower FAt and higher RDt compared with the NSS- group. This study shows that NSS in adolescents are associated with brain structure alterations. Underlying mechanisms may include alterations in synaptic pruning and axon myelination, which are hallmark processes of brain maturation.

Task-Related Modulation of Sensorimotor GABA+ Levels in Association with Brain Activity and Motor Performance: A Multimodal MRS-fMRI Study in Young and Older Adults.

Recent studies suggest an important role of the principal inhibitory neurotransmitter GABA for motor performance in the context of aging. Nonetheless, as previous magnetic resonance spectroscopy (MRS) studies primarily reported resting-state GABA levels, much less is known about transient changes in GABA levels during motor task performance and how these relate to behavior and brain activity patterns. Therefore, we investigated GABA+ levels of left primary sensorimotor cortex (SM1) acquired before, during, and after execution of a unimanual/bimanual action selection task in 30 (human) young adults (YA; age 24.5 ± 4.1, 15 male) and 30 older adults (OA; age 67.8 ± 4.9, 14 male). In addition to task-related MRS data, task-related functional magnetic resonance imaging (fMRI) data were acquired. Behavioral results indicated lower motor performance in OA as opposed to YA, particularly in complex task conditions. MRS results demonstrated lower GABA+ levels in OA as compared with YA. Furthermore, a transient task-related decrease of GABA+ levels was observed, regardless of age. Notably, this task-induced modulation of GABA+ levels was linked to task-related brain activity patterns in SM1 such that a more profound task-induced instantaneous lowering of GABA+ was related to higher SM1 activity. Additionally, higher brain activity was related to better performance in the bimanual conditions, despite some age-related differences. Finally, the modulatory capacity of GABA+ was positively related to motor performance in OA but not YA. Together, these results underscore the importance of transient dynamical changes in neurochemical content for brain function and behavior, particularly in the context of aging.SIGNIFICANCE STATEMENT Emerging evidence designates an important role to regional GABA levels in motor control, especially in the context of aging. However, it remains unclear whether changes in GABA levels emerge when executing a motor task and how these changes relate to brain activity patterns and performance. Here, we identified a transient decrease of sensorimotor GABA+ levels during performance of an action selection task across young adults (YA) and older adults (OA). Interestingly, whereas a more profound GABA+ modulation related to higher brain activity across age groups, its association with motor performance differed across age groups. Within OA, our results highlighted a functional merit of a task-related release from inhibitory tone, i.e. lowering regional GABA+ levels was associated with task-relevant brain activity.

Organization of neurochemical interactions in young and older brains as revealed with a network approach: Evidence from proton magnetic resonance spectroscopy (1H-MRS).

Aging is associated with alterations in the brain including structural and metabolic changes. Previous research has focused on neurometabolite level differences associated to age in a variety of brain regions, but the relationship among metabolites across the brain has been much less studied. Investigating these relationships can reveal underlying neurometabolic processes, their interdependency, and their progress throughout the lifespan. Using 1H-MRS, we investigated the relationship among metabolite concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-Inositol (mIns) and glutamate-glutamine complex (Glx) in seven voxel locations, i.e., bilateral sensorimotor cortex, bilateral striatum, pre-supplementary motor area, right inferior frontal gyrus and occipital cortex. These measurements were performed on 59 human participants divided in two age groups: young adults (YA: 23.2 ± 4.3; 18-34 years) and older adults (OA: 67.5 ± 3.9; 61-74 years). Our results showed age-related differences in NAA, Cho, and mIns across brain regions, suggesting the presence of neurodegeneration and altered gliosis. Moreover, associative patterns among NAA, Cho and Cr were observed across the selected brain regions, which differed between young and older adults. Whereas most of metabolite concentrations were inhomogeneous across different brain regions, Cho levels were shown to be strongly related across brain regions in both age groups. Finally, we found metabolic associations between homologous brain regions (SM1 and striatum) in the OA group, with NAA showing a significant correlation between bilateral sensorimotor cortices (SM1) and mIns levels being correlated between the bilateral striata. We posit that a network perspective provides important insights regarding the potential interactions among neurochemicals underlying metabolic processes at a local and global level and their relationship with aging.

Prefronto-Striatal Structural Connectivity Mediates Adult Age Differences in Action Selection.

In complex everyday environments, action selection is critical for optimal goal-directed behavior. This refers to the process of choosing a proper action from the range of possible alternatives. The neural mechanisms underlying action selection and how these are affected by normal aging remain to be elucidated. In the present cross-sectional study, we studied processes of effector selection during a multilimb reaction time task in a lifespan sample of healthy human adults (N = 89; 20-75 years; 48 males, 41 females). Participants were instructed to react as quickly and accurately as possible to visually cued stimuli representing single-limb or combined upper and/or lower limb motions. Diffusion MRI was used to study structural connectivity between prefrontal and striatal regions as critical nodes for action selection. Behavioral findings revealed that increasing age was associated with slowing of action selection performance. At the neural level, aging had a negative impact on prefronto-striatal connectivity. Importantly, mediation analyses revealed that the negative association between action selection performance and age was mediated by prefronto-striatal connectivity, specifically the connections between left rostral medial frontal gyrus and left nucleus accumbens as well as right frontal pole and left caudate. These results highlight the potential role of prefronto-striatal white matter decline in poorer action selection performance of older adults.SIGNIFICANCE STATEMENT As a result of enhanced life expectancy, researchers have devoted increasing attention to the study of age-related alterations in cognitive and motor functions. Here we study associations between brain structure and behavior to reveal the impact of central neural white matter changes as a function of normal aging on action selection performance. We demonstrate the critical role of a reduction in prefronto-striatal structural connectivity in accounting for action selection performance deficits in healthy older adults. Preserving this cortico-subcortical pathway may be critical for behavioral flexibility and functional independence in older age.

Normal aging affects unconstrained three-dimensional reaching against gravity with reduced vertical precision and increased co-contraction: a pilot study.

Reaching for an object in space forms the basis for many activities of daily living and is important in rehabilitation after stroke and in other neurological and orthopedic conditions. It has been the object of motor control and neuroscience research for over a century, but studies often constrain movement to eliminate the effect of gravity or reduce the degrees of freedom. In some studies, aging has been shown to reduce target accuracy, with a mechanism suggested to be impaired corrective movements. We sought to explore how such changes in accuracy relate to changes in finger, shoulder and elbow movements during performance of reaching movements with the normal effects of gravity, unconstrained hand movement, and stable target locations. Three-dimensional kinematic data and electromyography were collected in 14 young (25 ± 6 years) and 10 older adults (68 ± 3 years) during second-long reaches to 3 targets aligned vertically in front of the participants. Older adults took longer to initiate a movement than the young adults and were more variable and inaccurate in their initial and final movements. Target height had greater effect on trajectory curvature variability in older than young adults, with angle variability relative to target position being greater in older adults around the time of peak speed. There were significant age-related differences in use of the multiple degrees of freedom of the upper extremity, with less variability in shoulder abduction in the older group. Muscle activation patterns were similar, except for a higher biceps-triceps co-contraction and tonic levels of some proximal muscle activation. These results show an age-related deficit in the motor planning and online correction of reaching movements against a predictable force (i.e., gravity) when it is not compensated by mechanical support.

GABA levels are differentially associated with bimanual motor performance in older as compared to young adults.

Although gamma aminobutyric acid (GABA) is of particular importance for efficient motor functioning, very little is known about the relationship between regional GABA levels and motor performance. Some studies suggest this relation to be subject to age-related differences even though literature is scarce. To clarify this matter, we employed a comprehensive approach and investigated GABA levels within young and older adults across multiple motor tasks as well as multiple brain regions. Specifically, 30 young and 30 older adults completed a task battery of three different bimanual tasks. Furthermore, GABA levels were obtained within bilateral primary sensorimotor cortex (SM1), bilateral dorsal premotor cortex, the supplementary motor area and bilateral dorsolateral prefrontal cortex (DLPFC) using magnetic resonance spectroscopy. Results indicated that older adults, as compared to their younger counterparts, performed worse on all bimanual tasks and exhibited lower GABA levels in bilateral SM1 only. Moreover, GABA levels across the motor network and DLPFC were differentially associated with performance in young as opposed to older adults on a manual dexterity and bimanual coordination task but not a finger tapping task. Specifically, whereas higher GABA levels related to better manual dexterity within older adults, higher GABA levels predicted poorer bimanual coordination performance in young adults. By determining a task-specific and age-dependent association between GABA levels across the cortical motor network and performance on distinct bimanual tasks, the current study advances insights in the role of GABA for motor performance in the context of aging.

Neurophysiological modulations in the (pre)motor-motor network underlying age-related increases in reaction time and the role of GABA levels - a bimodal TMS-MRS study.

It has been argued that age-related changes in the neurochemical and neurophysiological properties of the GABAergic system may underlie increases in reaction time (RT) in older adults. However, the role of GABA levels within the sensorimotor cortices (SMC) in mediating interhemispheric interactions (IHi) during the processing stage of a fast motor response, as well as how both properties explain interindividual differences in RT, are not yet fully understood. In this study, edited magnetic resonance spectroscopy (MRS) was combined with dual-site transcranial magnetic stimulation (dsTMS) for probing GABA+ levels in bilateral SMC and task-related neurophysiological modulations in corticospinal excitability (CSE), and primary motor cortex (M1)-M1 and dorsal premotor cortex (PMd)-M1 IHi, respectively. Both CSE and IHi were assessed during the preparatory and premotor period of a delayed choice RT task. Data were collected from 25 young (aged 18-33 years) and 28 older (aged 60-74 years) healthy adults. Our results demonstrated that older as compared to younger adults exhibited a reduced bilateral CSE suppression, as well as a reduced magnitude of long latency M1-M1 and PMd-M1 disinhibition during the preparatory period, irrespective of the direction of the IHi. Importantly, in older adults, the GABA+ levels in bilateral SMC partially accounted for task-related neurophysiological modulations as well as individual differences in RT. In contrast, in young adults, neither task-related neurophysiological modulations, nor individual differences in RT were associated with SMC GABA+ levels. In conclusion, this study contributes to a comprehensive initial understanding of how age-related differences in neurochemical properties and neurophysiological processes are related to increases in RT.

Age-related GABAergic differences in the primary sensorimotor cortex: A multimodal approach combining PET, MRS and TMS.

Healthy aging is associated with mechanistic changes in gamma-aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter in the human brain. While previous work mainly focused on magnetic resonance spectroscopy (MRS)-based GABA+ levels and transcranial magnetic stimulation (TMS)-based GABAA receptor (GABAAR) activity in the primary sensorimotor (SM1) cortex, the aim of the current study was to identify age-related differences in positron emission tomography (PET)-based GABAAR availability and its relationship with GABA+ levels (i.e. GABA with the contribution of macromolecules) and GABAAR activity. For this purpose, fifteen young (aged 20-28 years) and fifteen older (aged 65-80 years) participants were recruited. PET and MRS images were acquired using simultaneous time-of-flight PET/MR to evaluate age-related differences in GABAAR availability (distribution volume ratio with pons as reference region) and GABA+ levels. TMS was applied to identify age-related differences in GABAAR activity by measuring short-interval intracortical inhibition (SICI). Whereas GABAAR availability was significantly higher in the SM cortex of older as compared to young adults (18.5%), there were neither age-related differences in GABA+ levels nor SICI. A correlation analysis revealed no significant associations between GABAAR availability, GABAAR activity and GABA+ levels. Although the exact mechanisms need to be further elucidated, it is possible that a higher GABAAR availability in older adults is a compensatory mechanism to ensure optimal inhibitory functionality during the aging process.

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation.

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and the basal ganglia during motor learning. Our results indicate that while stimulation did not modulate motor performance nor task-related brain activity, it influenced connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence, to the best of our knowledge, that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.

Perturbation of cortical activity elicits regional and age-dependent effects on unconstrained reaching behavior: a pilot study.

Contributions from premotor and supplementary motor areas to reaching behavior in aging humans are not well understood. The objective of these experiments was to examine effects of perturbations to specific cortical areas on the control of unconstrained reaches against gravity by younger and older adults. Double-pulse transcranial magnetic stimulation (TMS) was applied to scalp locations targeting primary motor cortex (M1), dorsal premotor area (PMA), supplementary motor area (SMA), or dorsolateral prefrontal cortex (DLPFC). Stimulation was intended to perturb ongoing activity in the targeted cortical region before or after a visual cue to initiate moderately paced reaches to one of three vertical target locations. Regional effects were observed in movement amplitude both early and late in the reach. Perturbation of PMA increased reach distance before the time of peak velocity to a greater extent than all other regions. Reaches showed greater deviation from a straight-line path around the time of peak velocity and greater overall curvature with perturbation of PMA and M1 relative to SMA and DLPFC. The perturbation increased positional variability of the reach path at the time of peak velocity and the time elapsing after peak velocity. Although perturbations had stronger effects on reaches by younger subjects, this group exhibited less reach path variability at the time of peak velocity and required less time to adjust the movement trajectory thereafter. These findings support the role of PMA in visually guided reaching and suggest an age-related change in sensorimotor processing, possibly due to a loss of cortical inhibitory control.

Fiber-specific variations in anterior transcallosal white matter structure contribute to age-related differences in motor performance.

Age-related differences in bimanual motor performance have been extensively documented, but their underlying neural mechanisms remain less clear. Studies applying diffusion MRI in the aging population have revealed evidence for age-related white matter variations in the corpus callosum (CC) which are related to bimanual motor performance. However, the diffusion tensor model used in those studies is confounded by partial volume effects in voxels with complex fiber geometries which are present in up to 90% of white matter voxels, including the bilateral projections of the CC. A recently developed whole-brain analysis framework, known as fixel-based analysis (FBA), enables comprehensive statistical analyses of white matter quantitative measures in the presence of such complex fiber geometries. To investigate the contribution of age-related fiber-specific white matter variations to age-related differences in bimanual performance, a cross-sectional lifespan sample of healthy human adults (N â€‹= â€‹95; 20-75 years of age) performed a bimanual tracking task. Furthermore, diffusion MRI data were acquired and the FBA metrics associated with fiber density, cross-section, and combined fiber density and cross-section were estimated. Whole-brain FBA revealed significant negative associations between age and fiber density, cross-section, and combined metrics of multiple white matter tracts, including the bilateral projections of the CC, indicative of white matter micro- and macrostructural degradation with age. More importantly, mediation analyses demonstrated that age-related variations in the combined (fiber density and cross-section) metric of the genu, but not splenium, of the CC contributed to the observed age-related differences in bimanual coordination performance. These findings highlight the contribution of variations in interhemispheric communication between prefrontal (non-motor) cortices to age-related differences in motor performance.

Lateralized effects of post-learning transcranial direct current stimulation on motor memory consolidation in older adults: An fMRI investigation.

Previous research has consistently demonstrated that older adults have difficulties transforming recently learned movements into robust, long-lasting memories (i.e., motor memory consolidation). One potential avenue to enhance consolidation in older individuals is the administration of transcranial direct current stimulation (tDCS) to task-relevant brain regions after initial learning. Although this approach has shown promise, the underlying cerebral correlates have yet to be revealed. Moreover, it is unknown whether the effects of tDCS are lateralized, an open question with implications for rehabilitative approaches following predominantly unilateral neurological injuries. In this research, healthy older adults completed a sequential motor task before and 6 h after receiving anodal or sham stimulation to right or left primary motor cortex (M1) while functional magnetic resonance images were acquired. Unexpectedly, anodal stimulation to right M1 following left-hand sequence learning significantly hindered consolidation as compared to a sham control, whereas no differences were observed with left M1 stimulation following right-hand learning. Impaired performance following right M1 stimulation was paralleled by sustained engagement of regions known to be critical for early learning stages, including the caudate nucleus and the premotor and parietal cortices. Thus, post-learning tDCS in older adults not only exerts heterogenous effects across the two hemispheres but can also disrupt ongoing memory processing.

Skill acquisition is enhanced by reducing trial-to-trial repetition.

Developing approaches to improve motor skill learning is of considerable interest across multiple disciplines. Previous research has typically shown that repeating the same action on consecutive trials enhances short-term performance but has detrimental effects on longer term skill acquisition. However, most prior research has contrasted the effects of repetition only at the block level; in the current study we examined the effects of repeating individual trials embedded in a larger randomized block, a feature that is often overlooked when random trial orders are generated in learning tasks. With 4 days of practice, a "Minimal Repeats" group, who rarely experienced repeating stimuli on consecutive trials during training, improved to a greater extent than a "Frequent Repeats" group, who were frequently presented with repeating stimuli on consecutive trials during training. Our results extend the previous finding of the beneficial effects of random compared with blocked practice on performance, showing that reduced trial-to-trial repetition during training is favorable with regard to skill learning. This research highlights that limiting the number of repeats on consecutive trials is a simple behavioral manipulation that can enhance the process of skill learning. Data/analysis code and Supplemental Material are available at https://osf.io/p3278/.NEW & NOTEWORTHY Numerous studies have shown that performing different subtasks across consecutive blocks of trials enhances learning. We examined whether the same effect would occur on a trial-to-trial level. Our Minimal Repeats group, who primarily responded to different stimuli on consecutive trials, learned more than our Frequent Repeats group, who frequently responded to the same stimulus on consecutive trials. This shows that minimizing trial-to-trial repetition is a simple and easily applicable manipulation that can enhance learning.

Frequency-dependent functional connectivity in resting state networks.

Functional magnetic resonance imaging studies have documented the resting human brain to be functionally organized in multiple large-scale networks, called resting-state networks (RSNs). Other brain imaging techniques, such as electroencephalography (EEG) and magnetoencephalography (MEG), have been used for investigating the electrophysiological basis of RSNs. To date, it is largely unclear how neural oscillations measured with EEG and MEG are related to functional connectivity in the resting state. In addition, it remains to be elucidated whether and how the observed neural oscillations are related to the spatial distribution of the network nodes over the cortex. To address these questions, we examined frequency-dependent functional connectivity between the main nodes of several RSNs, spanning large part of the cortex. We estimated connectivity using band-limited power correlations from high-density EEG data collected in healthy participants. We observed that functional interactions within RSNs are characterized by a specific combination of neuronal oscillations in the alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-80 Hz) bands, which highly depend on the position of the network nodes. This finding may contribute to a better understanding of the mechanisms through which neural oscillations support functional connectivity in the brain.

Baseline sensorimotor GABA levels shape neuroplastic processes induced by motor learning in older adults.

Previous research in young adults has demonstrated that both motor learning and transcranial direct current stimulation (tDCS) trigger decreases in the levels of gamma-aminobutyric acid (GABA) in the sensorimotor cortex, and these decreases are linked to greater learning. Less is known about the role of GABA in motor learning in healthy older adults, a knowledge gap that is surprising given the established aging-related reductions in sensorimotor GABA. Here, we examined the effects of motor learning and subsequent tDCS on sensorimotor GABA levels and resting-state functional connectivity in the brains of healthy older participants. Thirty-six older men and women completed a motor sequence learning task before receiving anodal or sham tDCS to the sensorimotor cortex. GABA-edited magnetic resonance spectroscopy of the sensorimotor cortex and resting-state (RS) functional magnetic resonance imaging data were acquired before and after learning/stimulation. At the group level, neither learning nor anodal tDCS significantly modulated GABA levels or RS connectivity among task-relevant regions. However, changes in GABA levels from the baseline to post-learning session were significantly related to motor learning magnitude, age, and baseline GABA. Moreover, the change in functional connectivity between task-relevant regions, including bilateral motor cortices, was correlated with baseline GABA levels. These data collectively indicate that motor learning-related decreases in sensorimotor GABA levels and increases in functional connectivity are limited to those older adults with higher baseline GABA levels and who learn the most. Post-learning tDCS exerted no influence on GABA levels, functional connectivity or the relationships among these variables in older adults.

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.