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Purpose: Assistive devices are essential in neuropediatrics, but the database on the self-assessed use by and supply of medical aids to those affected with hereditary ataxia is small. The present work aims to examine the individual perspective of those affected by the use and supply of aids and to discuss them in the field of tension between physiological and psychosocial development and symptom progression., Methods: The research project represents a cooperation with the German Heredo-Ataxia-Society following the "patients as partners in research" approach. The data was collected via online questionnaires and focus group surveys and analyzed quantitatively and qualitatively using a mixed methodological approach., Results: Based on the present sample of affected adolescents and adults (n=47 online questionnaires, n=6 focus group surveys), a fundamentally positive assessment of the use of medical aids was evident. In contrast, for the individual evaluation of access and supply of assistive devices, four main problems were identified, some of which can be extrapolated to other diagnoses but amplified in children and adolescents due to the low prevalence of hereditary ataxia. Especially in these age groups, the lengthy process leading up to the diagnosis and the associated gap in the indication for assistive devices poses a serious problem. Moreover, there is lack of evidence for justifying prescription of age-group-specific assistive devices., Conclusion: In addition to the necessity of improvement in the care process, there are significant gaps in the knowledge about an association between self-confidence and coping with the disease, on the one hand, and the acceptance of aids, on the other, in children and adolescents with rare diseases characterized by symptom progression. In addition, there is an urgent need to improve the evidence base for specific tools, especially their importance for promoting independence according to age and developmental phase., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Tuning brain activity with non-invasive brain stimulation critically depends on optimized targeting of the brain structures of interest, especially in populations with accelerated interindividual morphological variations as they are typical in aging. Here, we explored the electric field distribution when targeting the right dorsolateral prefrontal cortex (DLPFC) using High-Definition Transcranial Alternating Current Stimulation (HD-tACS) in both young (YA) and older adults (OA). We modeled the electric field of ten datasets (OA: n=5, 63-76 y/o, 68.4±6.5 y/o; YA: n=5, 18-39 y/o, 27.4±7.5 y/o) comprising T1-and T2-weighted images using SimNIBS in combination with FreeSurfer. We simulated two montages (2x1 and 4x1) to deliver a net current of 2 mA. The simulations revealed that the peak electric field and mean electric field at the DLPFC were approximately three times stronger when using the 2x1 montage compared to the 4x1 montage. However, this increase in field strength came at the expense of focality, resulting in the spread of the electric field into the ocular area, where peak values were observed in some participants. In these cases, a viable approach to enhance the efficacy of the 2x1 montage was to individualize the current. Our simulations showed that it is possible to generate a similar electric field among participants while mitigating the spread of the electric field into the eye, thereby reducing the likelihood of phosphenes.

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., (© 2024. The Author(s).)

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., (© 2022. The Author(s).)

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B 0 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., Competing Interests: Declaration of Competing Interest Jack J. Miller would like to acknowledge the support of a Novo Nordisk Research Fellowship run in conjunction with the University of Oxford. Francisco Reyes-Madrigal has served as a speaker for Janssen (Johnson & Johnson) and AstraZeneca. Marc Thioux and Pim van Dijk were supported by The Netherlands Organization for Health Research and Development (ZonMW) and the Dorhout Mees Foundation. All other authors have no conflict of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

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.

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Inc.)

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., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

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 ( 1 H-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., (© The Author(s) 2020. Published by Oxford University Press.)

Establishing the associations between magnetic resonance spectroscopy (MRS)-assessed gamma-aminobutyric acid (GABA) levels and transcranial magnetic stimulation (TMS)-derived 'task-related' modulations in GABA A receptor-mediated inhibition and how these associations change with advancing age is a topic of interest in the field of human neuroscience. In this study, we identified the relationship between GABA levels and task-related modulations in GABA A receptor-mediated inhibition in the dominant (left) and non-dominant (right) sensorimotor (SM) cortices. GABA levels were measured using edited MRS and task-related GABA A receptor-mediated inhibition was measured using a short-interval intracortical inhibition (SICI) TMS protocol during the preparation and premotor period of a choice reaction time (CRT) task in 25 young (aged 18-33 years) and 25 older (aged 60-74 years) adults. Our results demonstrated that GABA levels in both SM voxels were lower in older adults as compared to younger adults; and higher SM GABA levels in the dominant as compared to the non-dominant SM voxel pointed to a lateralization effect, irrespective of age group. Furthermore, older adults showed decreased GABA A receptor-mediated inhibition in the preparation phase of the CRT task within the dominant primary motor cortex (M1), as compared to young adults. Finally, results from an exploratory correlation analysis pointed towards positive relationships between MRS-assessed GABA levels and TMS-derived task-related SICI measures. However, after correction for multiple comparisons none of the correlations remained significant., (Copyright © 2019. Published by Elsevier Inc.)

Aging is associated with gradual alterations in the neurochemical characteristics of the brain, which can be assessed in-vivo with proton-magnetic resonance spectroscopy ( 1 H-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. 1 H-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 ​+ ​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 1 H-MRS to study neurochemical correlates of motor performance across the adult lifespan., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

We investigated the effect of age on the ability to modulate GABA A -ergic and GABA B -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 GABA A -mediated short-interval intracortical inhibition (SICI) during stopping and GABA B -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 GABA A -mediated intracortical inhibition during stopping of action is affected by aging.

Aging is typically associated with substantial declines in motor functioning as well as robust changes in the functional organization of brain networks. Previous research has investigated the link between these 2 age-varying factors but examinations were predominantly limited to the functional organization within motor-related brain networks. Little is known about the relationship between age-related behavioral impairments and changes in functional organization at the whole brain (i.e., multiple network) level. This knowledge gap is surprising given that the decreased segregation of brain networks (i.e., increased internetwork connectivity) can be considered a hallmark of the aging process. Accordingly, we investigated the association between declines in motor performance across the adult lifespan (20-75 years) and age-related modulations of functional connectivity within and between resting state networks. Results indicated that stronger internetwork resting state connectivity observed as a function of age was significantly related to worse motor performance. Moreover, performance had a significantly stronger association with the strength of internetwork as compared with intranetwork connectivity, including connectivity within motor networks. These findings suggest that age-related declines in motor performance may be attributed to a breakdown in the functional organization of large-scale brain networks rather than simply age-related connectivity changes within motor-related networks.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Edited magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) have often been used to study the integrity of the GABAergic neurotransmission system in healthy aging. To investigate whether the measurement outcomes obtained with these 2 techniques are associated with each other in older human adults, gamma-aminobutyric acid (GABA) levels in the left sensorimotor cortex were assessed with edited MRS in 28 older (63-74 years) and 28 young adults (19-34 years). TMS at rest was then used to measure intracortical inhibition (short-interval intracortical inhibition/long-interval intracortical inhibition), intracortical facilitation, interhemispheric inhibition from left to right primary motor cortex (M1) and recruitment curves of left and right M1. Our observations showed that short-interval intracortical inhibition and long-interval intracortical inhibition in the left M1 were reduced in older adults, while GABA levels did not significantly differ between age groups. Furthermore, MRS-assessed GABA within left sensorimotor cortex was not correlated with TMS-assessed cortical excitability or inhibition. These observations suggest that healthy aging gives rise to altered inhibition at the postsynaptic receptor level, which does not seem to be associated with MRS-assessed GABA+ levels., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate a modified electrode montage with respect to its effect on tACS-dependent modulation of corticospinal excitability and discomfort caused by neurosensory side effects accompanying stimulation., Methods: In a double-blind cross-over design, the classical electrode montage for primary motor cortex (M1) stimulation (two patch electrodes over M1 and contralateral supraorbital area) was compared with an M1 centre-ring montage. Corticospinal excitability was evaluated before, during, immediately after and 15 minutes after tACS (10 min., 20 Hz vs. 30 s low-frequency transcranial random noise stimulation)., Results: Corticospinal excitability increased significantly during and immediately after tACS with the centre-ring montage. This was not the case with the classical montage or tRNS stimulation. Level of discomfort was rated on average lower with the centre-ring montage., Conclusions: In comparison to the classic montage, the M1 centre-ring montage enables a more focal stimulation of the target area and, at the same time, significantly reduces neurosensory side effects, essential for placebo-controlled study designs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Even though it has been suggested that the dorsolateral prefrontal cortex (DLPFC) and dorsal premotor cortex (PMd) are highly involved in the planning of bimanual movements, the exact nature (facilitatory or inhibitory) of their role is not well understood. Using a dual-site transcranial magnetic stimulation (TMS) paradigm, we examined the functional influence from DLPFC and PMd to the contralateral primary cortex (M1) during the preparation of a complex bimanual coordination task in which inter-hand movement frequency was manipulated. Only the left PMd showed inter-hand frequency-specific modulations in the interaction with the contralateral M1. Left PMd-right M1 interaction became facilitatory during the preparation phase when the left hand had to move faster than the right hand, while inhibitory modulation was observed when the movement frequency arrangement was reversed. Interestingly, bilateral DLPFC showed a facilitatory interaction with the contralateral M1s during the preparation period only in difficult conditions, irrespective of the inter-hand frequency ratio, suggesting a less task-specific role in the organization of complex bimanual actions. Observed task-related modulations in DLPFC-M1 and left PMd-right M1 interactions during preparation were significantly correlated with up-coming performance, predicting successful bimanual movements. These observations highlight the distinct roles of DLPFC and left PMd in the preparation of bimanual movements that require a differential contribution of each limb., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Changes in γ-aminobutyric acid (GABA) mediated synaptic transmission have been associated with age-related motor and cognitive functional decline. Since anodal transcranial direct current stimulation (atDCS) has been suggested to target cortical GABAergic inhibitory interneurons, its potential for the treatment of deficient inhibitory activity and functional decline is being increasingly discussed. Therefore, after-effects of a single session of atDCS on resting-state and event-related short-interval intracortical inhibition (SICI) as evaluated with double-pulse TMS and dexterous manual performance were examined using a sham-controlled cross-over design in a sample of older and younger participants. The atDCS effect on resting-state inhibition differed in direction, magnitude, and timing, i.e., late relative release of inhibition in the younger and early relative increase in inhibition in the older. More pronounced release of event-related inhibition after atDCS was exclusively seen in the older. Event-related modulation of inhibition prior to stimulation predicted the magnitude of atDCS-induced effects on resting-state inhibition. Specifically, older participants with high modulatory capacity showed a disinhibitory effect comparable to the younger. Beneficial effects on behavior were mainly seen in the older and in tasks requiring higher dexterity, no clear association with physiological changes was found. Differential effects of atDCS on SICI, discussed to reflect GABAergic inhibition at the level of the primary motor cortex, might be distinct in older and younger participants depending on the functional integrity of the underlying neural network. Older participants with preserved modulatory capacity, i.e., a physiologically "young" motor network, were more likely to show a disinhibitory effect of atDCS. These results favor individually tailored application of tDCS with respect to specific target groups.

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.

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.

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.

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.

Gilles de la Tourette syndrome is a neuropsychiatric disorder in which cortical disinhibition has been proposed as a pathophysiological mechanism involved in the generation of tics. Tics are typically reduced during task performance and concentration. How this task-dependent reduction of motor symptoms is represented in the brain is not yet understood. The aim of the current research was to study motorcortical excitability at rest and during the preparation of a simple motor task. Transcranial magnetic stimulation was used to examine corticospinal excitability, short-interval intracortical inhibition and intracortical facilitation in a group of 11 patients with Gilles de la Tourette syndrome and age-matched healthy controls. Parameters of cortical excitability were evaluated at rest and at six points in time during the preparation of a simple finger movement. Patients with Gilles de la Tourette syndrome displayed significantly reduced short-interval intracortical inhibition at rest, while no differences were apparent for unconditioned motor evoked potential or intracortical facilitation. During the premovement phase, significant differences between groups were seen for single pulse motor evoked potential amplitudes and short-interval intracortical inhibition. Short-interval intracortical inhibition was reduced in the early phase of movement preparation (similar to rest) followed by a transition towards more inhibition. Subsequently modulation of short-interval intracortical inhibition was comparable to controls, while corticospinal recruitment was reduced in later phases of movement preparation. The present data support the hypothesis of motorcortical disinhibition in Gilles de la Tourette syndrome at rest. During performance of a motor task, patients start from an abnormally disinhibited level of short-interval intracortical inhibition early during movement preparation with subsequent modulation of inhibitory activity similar to healthy controls. We hypothesize that while at rest, abnormal subcortical inputs from aberrant striato-thalamic afferents target the motor cortex, during motor performance, motor cortical excitability most likely underlies top-down control from higher motor areas and prefrontal cortex, which override these abnormal subcortical inputs to guarantee adequate behavioural performance.

The amount of information that can be stored in visual short-term memory is strictly limited to about four items. Therefore, memory capacity relies not only on the successful retention of relevant information but also on efficient suppression of distracting information, visual attention, and executive functions. However, completely separable neural signatures for these memory capacity-limiting factors remain to be identified. Because of its functional diversity, oscillatory brain activity may offer a utile solution. In the present study, we show that capacity-determining mechanisms, namely retention of relevant information and suppression of distracting information, are based on neural substrates independent of each other: the successful maintenance of relevant material in short-term memory is associated with cross-frequency phase synchronization between theta (rhythmical neural activity around 5 Hz) and gamma (> 50 Hz) oscillations at posterior parietal recording sites. On the other hand, electroencephalographic alpha activity (around 10 Hz) predicts memory capacity based on efficient suppression of irrelevant information in short-term memory. Moreover, repetitive transcranial magnetic stimulation at alpha frequency can modulate short-term memory capacity by influencing the ability to suppress distracting information. Taken together, the current study provides evidence for a double dissociation of brain oscillatory correlates of visual short-term memory capacity.

This article describes the method and result of an authorized German translation of the Motor Assessment Scale (MAS) - a measurement tool to scale motor function after stroke. The MAS is widely known in English speaking countries and is used as an outcome measure in clinical trials. It has been well researched regarding its psychometric characteristics. The translation is based on a methodical process according to the guidelines of the American Academy of Orthopaedic Surgeons. A synopsis was produced from two German initial translations, and an English back translation was performed to check the correctness of the content. The publication of the German version of the MAS aims to improve the outcome measurement in the area of rehabilitation after brain lesion.