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.

Frequency drift in MR spectroscopy at 3T.

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

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.

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.

Sensorimotor cortex neurometabolite levels as correlate of motor performance in normal aging: evidence from a 1H-MRS study.

Aging is associated with gradual alterations in the neurochemical characteristics of the brain, which can be assessed in-vivo with proton-magnetic resonance spectroscopy (1H-MRS). However, the impact of these age-related neurochemical changes on functional motor behavior is still poorly understood. Here, we address this knowledge gap and specifically focus on the neurochemical integrity of the left sensorimotor cortex (SM1) and the occipital lobe (OCC), as both regions are main nodes of the visuomotor network underlying bimanual control. 1H-MRS data and performance on a set of bimanual tasks were collected from a lifespan (20-75 years) sample of 86 healthy adults. Results indicated that aging was accompanied by decreased levels of N-acetylaspartate (NAA), glutamate-glutamine (Glx), creatine â€‹+ â€‹phosphocreatine (Cr) and myo-inositol (mI) in both regions, and decreased Choline (Cho) in the OCC region. Lower NAA and Glx levels in the SM1 and lower NAA levels in the OCC were related to poorer performance on a visuomotor bimanual coordination task, suggesting that NAA could serve as a potential biomarker for the integrity of the motor system supporting bimanual control. In addition, lower NAA, Glx, and mI levels in the SM1 were found to be correlates of poorer dexterous performance on a bimanual dexterity task. These findings highlight the role for 1H-MRS to study neurochemical correlates of motor performance across the adult lifespan.

Enhancing Consolidation of a New Temporal Motor Skill by Cerebellar Noninvasive Stimulation.

Cerebellar transcranial direct current stimulation (tDCS) has the potential to modulate cerebellar outputs and visuomotor adaptation. The cerebellum plays a pivotal role in the acquisition and control of skilled hand movements, especially its temporal aspects. We applied cerebellar anodal tDCS concurrently with training of a synchronization-continuation motor task. We hypothesized that anodal cerebellar tDCS will enhance motor skill acquisition. Cerebellar tDCS was applied to the right cerebellum in 31 healthy subjects in a double-blind, sham-controlled, parallel design. During synchronization, the subjects tapped the sequence in line with auditory cues. Subsequently, in continuation, the learned sequence was reproduced without auditory cuing. Motor task performance was evaluated before, during, 90 min, and 24 h after training. Anodal cerebellar tDCS, compared with sham, improved the task performance in the follow-up tests (F1,28 = 5.107, P = 0.032) of the synchronization part. This effect on retention of the skill was most likely mediated by enhanced motor consolidation. We provided first evidence that cerebellar tDCS can enhance the retention of a fine motor skill. This finding supports the promising approach of using noninvasive brain stimulation techniques to restore impaired motor functions in neurological patients, such after a stroke.

Disrupting the ipsilateral motor cortex interferes with training of a complex motor task in older adults.

Performance of unimanual movements is associated with bihemispheric activity in the motor cortex in old adults. However, the causal functional role of the ipsilateral MC (iMC) for motor control is still not completely known. Here, the behavioral consequences of interference of the iMC during training of a complex motor skill were tested. Healthy old (58-85 years) and young volunteers (22-35 years) were tested in a double-blind, cross-over, sham-controlled design. Participants attended 2 different study arms with either cathodal transcranial direct current stimulation (ctDCS) or sham concurrent with training. Motor performance was evaluated before, during, 90 min, and 24 h after training. During training, a reduced slope of performance with ctDCS relative to sham was observed in old compared with young (F = 5.8, P = 0.02), with a decrease of correctly rehearsed sequences, an effect that was evident even after 2 consecutive retraining periods without intervention. Furthermore, the older the subject, the more prominent was the disruptive effect of ctDCS (R(2) = 0.50, P = 0.01). These data provide direct evidence for a causal functional link between the iMC and motor skill acquisition in old subjects pointing toward the concept that the recruitment of iMC in old is an adaptive process in response to age-related declines in motor functions.

The aging motor system as a model for plastic changes of GABA-mediated intracortical inhibition and their behavioral relevance.

Since GABAA-mediated intracortical inhibition has been shown to underlie plastic changes throughout the lifespan from development to aging, here, the aging motor system was used as a model to analyze the interdependence of plastic alterations within the inhibitory motorcortical network and level of behavioral performance. Double-pulse transcranial magnetic stimulation (dpTMS) was used to examine inhibition by means of short-interval intracortical inhibition (SICI) of the contralateral primary motor cortex in a sample of 64 healthy right-handed human subjects covering a wide range of the adult lifespan (age range 20-88 years, mean 47.6 ± 20.7, 34 female). SICI was evaluated during resting state and in an event-related condition during movement preparation in a visually triggered simple reaction time task. In a subgroup (N = 23), manual motor performance was tested with tasks of graded dexterous demand. Weak resting-state inhibition was associated with an overall lower manual motor performance. Better event-related modulation of inhibition correlated with better performance in more demanding tasks, in which fast alternating activation of cortical representations are necessary. Declining resting-state inhibition was associated with weakened event-related modulation of inhibition. Therefore, reduced resting-state inhibition might lead to a subsequent loss of modulatory capacity, possibly reflecting malfunctioning precision in GABAAergic neurotransmission; the consequence is an inevitable decline in motor function.

Methodological considerations for behavioral studies relying on response time outcomes through online crowdsourcing platforms.

This perspective paper explores challenges associated with online crowdsourced data collection, particularly focusing on longitudinal tasks with time-sensitive outcomes like response latencies. Based on our research, we identify two significant sources of bias: technical shortcomings such as low, variable frame rates, and human factors, contributing to high attrition rates. We explored potential solutions to these problems, such as enforcing hardware acceleration and defining study-specific frame rate thresholds, as well as pre-screening participants and monitoring hardware performance and task engagement over each experimental session. With this discussion, we intend to provide recommendations on how to improve the quality and reliability of data collected via online crowdsourced platforms and emphasize the need for researchers to be cognizant of potential pitfalls in online research.

Recommendations for optimal interdisciplinary management and healthcare settings for patients with rare neurological diseases.

BACKGROUND: In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts. METHODS: An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented. RESULTS: 38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy. CONCLUSIONS: This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.

Spatial remapping in the audio-tactile ventriloquism effect: a TMS investigation on the role of the ventral intraparietal area.

Previous studies have suggested that the putative human homologue of the ventral intraparietal area (hVIP) is crucially involved in the remapping of tactile information into external spatial coordinates and in the realignment of tactile and visual maps. It is unclear, however, whether hVIP is critical for the remapping process during audio-tactile cross-modal spatial interactions. The audio-tactile ventriloquism effect, where the perceived location of a sound is shifted toward the location of a synchronous but spatially disparate tactile stimulus, was used to probe spatial interactions in audio-tactile processing. Eighteen healthy volunteers were asked to report the perceived location of brief auditory stimuli presented from three different locations (left, center, and right). Auditory stimuli were presented either alone (unimodal stimuli) or concurrently to a spatially discrepant tactile stimulus applied to the left or right index finger (bimodal stimuli), with the hands adopting either an uncrossed or a crossed posture. Single pulses of TMS were delivered over the hVIP or a control site (primary somatosensory cortex, SI) 80 msec after trial onset. TMS to the hVIP, compared with the control SI-TMS, interfered with the remapping of touch into external space, suggesting that hVIP is crucially involved in transforming spatial reference frames across audition and touch.

Modulation of training by single-session transcranial direct current stimulation to the intact motor cortex enhances motor skill acquisition of the paretic hand.

BACKGROUND AND PURPOSE: Mechanisms of skill learning are paramount components for stroke recovery. Recent noninvasive brain stimulation studies demonstrated that decreasing activity in the contralesional motor cortex might be beneficial, providing transient functional improvements after stroke. The more crucial question, however, is whether this intervention can also enhance the acquisition of complex motor tasks, yielding longer-lasting functional improvements. In the present study, we tested the capacity of cathodal transcranial direct current stimulation (tDCS) applied over the contralesional motor cortex during training to enhance the acquisition and retention of complex sequential finger movements of the paretic hand. METHOD: Twelve well-recovered chronic patients with subcortical stroke attended 2 training sessions during which either cathodal tDCS or a sham intervention were applied to the contralesional motor cortex in a double-blind, crossover design. Two different motor sequences, matched for their degree of complexity, were tested in a counterbalanced order during as well as 90 minutes and 24 hours after the intervention. Potential underlying mechanisms were evaluated with transcranial magnetic stimulation. RESULTS: tDCS facilitated the acquisition of a new motor skill compared with sham stimulation (P=0.04) yielding better task retention results. A significant correlation was observed between the tDCS-induced improvement during training and the tDCS-induced changes of intracortical inhibition (R(2)=0.63). CONCLUSIONS: These results indicate that tDCS is a promising tool to improve not only motor behavior, but also procedural learning. They further underline the potential of noninvasive brain stimulation as an adjuvant treatment for long-term recovery, at least in patients with mild functional impairment after stroke.

Effects of beta-band and gamma-band rhythmic stimulation on motor inhibition.

To investigate whether beta oscillations are causally related to motor inhibition, thirty-six participants underwent two concurrent transcranial alternating current stimulation (tACS) and electroencephalography (EEG) sessions during which either beta (20 Hz) or gamma (70 Hz) stimulation was applied while participants performed a stop-signal task. In addition, we acquired magnetic resonance images to simulate the electric field during tACS. 20 Hz stimulation targeted at the pre-supplementary motor area enhanced inhibition and increased beta oscillatory power around the time of the stop-signal in trials directly following stimulation. The increase in inhibition on stop trials followed a dose-response relationship with the strength of the individually simulated electric field. Computational modeling revealed that 20 and 70 Hz stimulation had opposite effects on the braking process. These results highlight that the effects of tACS are state-dependent and demonstrate that fronto-central beta activity is causally related to successful motor inhibition, supporting its use as a functional biomarker.

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

The flexible adjustment of ongoing behavior challenges the nervous system's dynamic control mechanisms and has shown to be specifically susceptible to age-related decline. Previous work links endogenous gamma-aminobutyric acid (GABA) with behavioral efficiency across perceptual and cognitive domains, with potentially the strongest impact on those behaviors that require a high level of dynamic control. Our analysis integrated behavior and modulation of interhemispheric phase-based connectivity during dynamic motor-state transitions with endogenous GABA concentration in adult human volunteers. We provide converging evidence for age-related differences in the preferred state of endogenous GABA concentration for more flexible behavior. We suggest that the increased interhemispheric connectivity observed in the older participants represents a compensatory neural mechanism caused by phase-entrainment in homotopic motor cortices. This mechanism appears to be most relevant in the presence of a less optimal tuning of the inhibitory tone as observed during healthy aging to uphold the required flexibility of behavioral action. Future work needs to validate the relevance of this interplay between neural connectivity and GABAergic inhibition for other domains of flexible human behavior.

The role of MRS-assessed GABA in human behavioral performance.

Understanding the neurophysiological mechanisms that drive human behavior has been a long-standing focus of cognitive neuroscience. One well-known neuro-metabolite involved in the creation of optimal behavioral repertoires is GABA, the main inhibitory neurochemical in the human brain. Converging evidence from both animal and human studies indicates that individual variations in GABAergic function are associated with behavioral performance. In humans, one increasingly used in vivo approach to measuring GABA levels is through Magnetic Resonance Spectroscopy (MRS). However, the implications of MRS measures of GABA for behavior remain poorly understood. In this respect, it is yet to be determined how GABA levels within distinct task-related brain regions of interest account for differences in behavioral performance. This review summarizes findings from cross-sectional studies that determined baseline MRS-assessed GABA levels and examined their associations with performance on various behaviors representing the perceptual, motor and cognitive domains, with a particular focus on healthy participants across the lifespan. Overall, the results indicate that MRS-assessed GABA levels play a pivotal role in various domains of behavior. Even though some converging patterns emerge, it is challenging to draw comprehensive conclusions due to differences in behavioral task paradigms, targeted brain regions of interest, implemented MRS techniques and reference compounds used. Across all studies, the effects of GABA levels on behavioral performance point to generic and partially independent functions that refer to distinctiveness, interference suppression and cognitive flexibility. On one hand, higher baseline GABA levels may support the distinctiveness of neural representations during task performance and better coping with interference and suppression of preferred response tendencies. On the other hand, lower baseline GABA levels may support a reduction of inhibition, leading to higher cognitive flexibility. These effects are task-dependent and appear to be mediated by age. Nonetheless, additional studies using emerging advanced methods are required to further clarify the role of MRS-assessed GABA in behavioral performance.

Distinct temporospatial interhemispheric interactions in the human primary and premotor cortex during movement preparation.

The preparation of a voluntary unimanual action requires sequential processing in bihemispheric motor areas. In both animals and humans, activity in the dorsal premotor cortex (PMd) ipsilateral to the moving hand has been demonstrated to precede ipsilateral primary motor cortex (M1) activity. We investigated with double-pulse transcranial magnetic stimulation how right-hemispheric motor areas (rM1, rPMd) modulate left M1 (lM1) during the preparatory period of a finger movement with the dominant right hand. We tested the hypothesis that the influence of higher order motor areas such as rPMd on lM1 (rPMd-lM1) precedes interhemispheric interactions between homologue primary motor areas (rM1-lM1). rPMd-lM1 showed modulation in the early and late phase of movement preparation, whereas the intrinsic state of inhibition between rM1-lM1 was only modulated in the late phase. The present results complement existing hierarchical models of cortical movement control by demonstrating temporospatially distinct involvement of interhemispheric interactions from PMd and M1 during movement preparation.

A First Step Toward the Operationalization of the Learned Non-Use Phenomenon: A Delphi Study.

BACKGROUND: The negative discrepancy between residual functional capacity and reduced use of the contralesional hand, frequently observed after a brain lesion, has been termed Learned Non-Use (LNU) and is thought to depend on the interaction of neuronal mechanisms during recovery and learning-dependent mechanisms. OBJECTIVE: Albeit the LNU phenomenon is generally accepted to exist, currently, no transdisciplinary definition exists. Furthermore, although therapeutic approaches are implemented in clinical practice targeting LNU, no standardized diagnostic routine is described in the available literature. Our objective was to reach consensus regarding a definition as well as synthesize knowledge about the current diagnostic procedures. METHODS: We used a structured group communication following the Delphi method among clinical and scientific experts in the field, knowledge from both, the work with patient populations and with animal models. RESULTS: Consensus was reached regarding a transdisciplinary definition of the LNU phenomenon. Furthermore, the mode and strategy of the diagnostic process, as well as the sources of information and outcome parameters relevant for the clinical decision making, were described with a wide range showing the current lack of a consistent universal diagnostic approach. CONCLUSIONS: The need for the development of a structured diagnostic procedure and its implementation into clinical practice is emphasized. Moreover, it exists a striking gap between the prevailing hypotheses regarding the mechanisms underlying the LNU phenomenon and the actual evidence. Therefore, basic research is needed to bridge between bedside and bench and eventually improve clinical decision making and further development of interventional strategies beyond the field of stroke rehabilitation.

Neurometabolic Correlates of Reactive and Proactive Motor Inhibition in Young and Older Adults: Evidence from Multiple Regional 1H-MR Spectroscopy.

Suboptimal inhibitory control is a major factor contributing to motor/cognitive deficits in older age and pathology. Here, we provide novel insights into the neurochemical biomarkers of inhibitory control in healthy young and older adults and highlight putative neurometabolic correlates of deficient inhibitory functions in normal aging. Age-related alterations in levels of glutamate-glutamine complex (Glx), N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mIns) were assessed in the right inferior frontal gyrus (RIFG), pre-supplementary motor area (preSMA), bilateral sensorimotor cortex (SM1), bilateral striatum (STR), and occipital cortex (OCC) with proton magnetic resonance spectroscopy (1H-MRS). Data were collected from 30 young (age range 18-34 years) and 29 older (age range 60-74 years) adults. Associations between age-related changes in the levels of these metabolites and performance measures or reactive/proactive inhibition were examined for each age group. Glx levels in the right striatum and preSMA were associated with more efficient proactive inhibition in young adults but were not predictive for reactive inhibition performance. Higher NAA/mIns ratios in the preSMA and RIFG and lower mIns levels in the OCC were associated with better deployment of proactive and reactive inhibition in older adults. Overall, these findings suggest that altered regional concentrations of NAA and mIns constitute potential biomarkers of suboptimal inhibitory control in aging.

Age-related differences in neural spectral power during motor learning.

We investigated how older adults preserve the capability to acquire new motor skills in the face of age-related brain alterations. We assessed neural changes associated with learning a bimanual coordination task over 4 days of practice in healthy young (n = 24) and older adults (n = 24). The electroencephalogram was recorded during task performance at the start and end of training. Motor performance improved with practice in both groups, but the amount of learning was lower in the older adults. Beta power (15-30 Hz) in sensorimotor and prefrontal cortices of older adults was reduced with training, indicative of higher neural activity. We also found a functional reorganization after training in beta and alpha (8-12 Hz) bands. Between-session changes in alpha and beta power differed between groups in several cortical areas: young adults exhibited reduced power in the beta band in sensorimotor cortices, whereas older adults displayed a smaller decrease. Our findings indicate a less flexible reorganization of neural activity accompanying learning in older adults compared with young adults.

Distinct online and offline effects of alpha and beta transcranial alternating current stimulation (tACS) on continuous bimanual performance and task-set switching.

In the present study we examined the effect of bihemispheric in-phase synchronization of motor cortical rhythms on complex bimanual coordination. Twenty young healthy volunteers received 10 Hz or 20 Hz tACS in a double-blind crossover design while performing a bimanual task-set switching paradigm. We used a bilateral high-density montage centred over the hand knob representation within the primary motor cortices to apply tACS time-locked to the switching events. Online tACS in either frequency led to faster but more erroneous switching transitions compared to trials without active stimulation. When comparing stimulation frequencies, 10 Hz stimulation resulted in higher error rates and slower switching transitions than 20 Hz stimulation. Furthermore, the stimulation frequencies showed distinct carry-over effects in trials following stimulation trains. Non-stimulated switching transitions were generally faster but continuous performance became more erroneous over time in the 20 Hz condition. We suggest that the behavioural effects of bifocal in-phase tACS are explained by online synchronization of long-range interhemispheric sensorimotor oscillations, which impacts on interhemispheric information flow and the top-down control required for flexible control of complex bimanual actions. Different stimulation frequencies may lead to distinct offline effects, which potentially accumulate over time and therefore need to be taken into account when evaluating subsequent performance.