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

Transcranial direct current stimulation (tDCS) may facilitate neuroplasticity but with a limited effect when administered while stroke patients are at rest. Muscle-computer interface (MCI) training is a promising approach for training stroke patients 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 chronic stroke patients. A crossover, double-blind, randomized trial was conducted. Twenty-six chronic stroke patients 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 months. The primary outcome measure was the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) which was measured one week before training, on the first training day, on the last training day, and one week after training. There was no 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). Additionally, 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 chronic stroke patients. We argue that appropriate MCI training in combination with bihemispheric tDCS could be a useful adjuvant for neurorehabilitation in stroke patients.

Accurate Prediction Equations for Ventilatory Thresholds in Cardiometabolic Disease When Gas Exchange Analysis is Unavailable: Development and Validation.

AIMS: To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains. METHODS: Cross-sectional study involving 2,868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). 'Adjusted' percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1,893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland-Altman analyses, intraclass correlation coefficients (ICC). RESULTS: HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), 'good' ICC for VT1 (0.81, 0.82) and 'excellent' for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8%-21.3%, VT2: 5.1%-16.7%), 'poor' to 'good' ICC for VT1, and 'poor' to 'excellent' for VT2, indicating inconsistencies related to specific VTs across guidelines. CONCLUSION: Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.

Equations to predict heart rate at ventilatory thresholds were developed and externally validated, offering a new perspective when a cardiopulmonary exercise test is unavailable to accurately determine the aerobic exercise intensity domains. Additionally, an adjusted range for exercise intensity prescription based on the percentage of heart rate reserve (%HRR) was provided, utilizing a large sample from eight countries. The proposed equations and the range-adjusted %HRR significantly outperformed the guideline-directed methods for determining exercise intensity, exhibiting higher accuracy, agreement, and reliability. Exercise intensity prescription based on the percentage of heart rate peak showed higher errors, raising concerns about its clinical applicability. Our study may enhance the efficacy of exercise training and physical activity advice when gas exchange analysis is unavailable, potentially leading to improved clinical outcomes, even in low-resource settings. Employing these approaches in research could facilitate more tailored and consistent interventions, introducing a contemporary perspective for studies comparing exercise intensity prescriptions.

Differences in scalp-to-cortex tissues across age groups, sexes and brain regions: Implications for neuroimaging and brain stimulation techniques.

Aging affects the scalp-to-cortex distance (SCD) and the comprising tissues. This is crucial for noninvasive neuroimaging and brain stimulation modalities as they rely on traversing from the scalp to the cortex or vice versa. The specific relationship between aging and these tissues has not been comprehensively investigated. We conducted a study on 250 younger and older adults to examine age-related differences in SCD and its constituent tissues. We identified region-specific differences in tissue thicknesses related to age and sex. Older adults exhibit larger SCD in the frontocentral regions compared to younger adults. Men exhibit greater SCD in the inferior scalp regions, while women show similar-to-greater SCD values in regions closer to the vertex compared to men. Younger adults and men have thicker soft tissue layers, whereas women and older adults exhibit thicker compact bone layers. CSF is considerably thicker in older adults, particularly in men. These findings emphasize the need to consider age, sex, and regional differences when interpreting SCD and its implications for noninvasive neuroimaging and brain stimulation.

Probing intrahemispheric interactions with a novel dual-site TMS setup.

OBJECTIVE: Using dual-site transcranial magnetic stimulation (dsTMS), the effective connectivity between the primary motor cortex (M1) and adjacent brain areas such as the dorsal premotor cortex (PMd) can be investigated. However, stimulating two brain regions in close proximity (e.g., ±2.3 cm for intrahemispheric PMd-M1) is subject to considerable spatial restrictions that potentially can be overcome by combining two standard figure-of-eight coils in a novel dsTMS setup. METHODS: After a technical evaluation of its induced electric fields, the dsTMS setup was tested in vivo (n = 23) by applying a short-interval intracortical inhibition (SICI) protocol. Additionally, the intrahemispheric PMd-M1 interaction was probed. E-field modelling was performed using SimNIBS. RESULTS: The technical evaluation yielded no major alterations of the induced electric fields due to coil overlap. In vivo, the setup reliably elicited SICI. Investigating intrahemispheric PMd-M1 interactions was feasible (inter-stimulus interval 6 ms), resulting in modulation of M1 output. CONCLUSIONS: The presented dsTMS setup provides a novel way to stimulate two adjacent brain regions with fewer technical and spatial limitations than previous attempts. SIGNIFICANCE: This dsTMS setup enables more accurate and repeatable targeting of brain regions in close proximity and can facilitate innovation in the field of effective connectivity.

Are exercise prescriptions for patients with cardiovascular disease, made by physiotherapists, in agreement with European recommendations?

AIMS: Physiotherapists often treat patients with (elevated risk for) cardiovascular disease (CVD), and should thus be able to provide evidence-based exercise advice to these patients. This study, therefore, aims to examine whether exercise prescriptions by physiotherapists to patients with CVD are in accordance with European recommendations. METHODS AND RESULTS: This prospective observational survey included forty-seven Belgian physiotherapists. The participants agreed to prescribe exercise intensity, frequency, session duration, program duration, and exercise type (endurance or strength training) for the same three patient cases. Exercise prescriptions were compared between physiotherapists and relations with their characteristics were studied. The agreement between physiotherapists' exercise prescriptions and those from European recommendations ('agreement score': based on a maximal score of 60/per case) was assessed. A wide inter-clinician variability was noticed for all exercise modalities, leading to a large variance for total peak-effort training minutes (from 461 up to 9000 over the three cases). The exercise frequency was prescribed fully out of range of the recommendations and the prescription of additional exercise modes was generally flawed. Exercise intensity and program duration were prescribed partially correct. The addition of strength exercises and session duration was prescribed correctly. This led to physiotherapist agreement scores of 25.3 ± 9.6, 23.2 ± 9.9, and 27.1 ± 10.6 (all out of 60), for cases one, two, and three, respectively. A greater agreement score was found in younger colleagues and those holding a Ph.D. CONCLUSION: Exercise prescriptions for CVD patients vary widely among physiotherapists and often disagree with European recommendations. REGISTRATION: ClinicalTrials.gov NCT05449652.

Outcome measures for electric field modeling in tES and TMS: A systematic review and large-scale modeling study.

BACKGROUND: Electric field (E-field) modeling is a potent tool to estimate the amount of transcranial magnetic and electrical stimulation (TMS and tES, respectively) that reaches the cortex and to address the variable behavioral effects observed in the field. However, outcome measures used to quantify E-fields vary considerably and a thorough comparison is missing. OBJECTIVES: This two-part study aimed to examine the different outcome measures used to report on tES and TMS induced E-fields, including volume- and surface-level gray matter, region of interest (ROI), whole brain, geometrical, structural, and percentile-based approaches. The study aimed to guide future research in informed selection of appropriate outcome measures. METHODS: Three electronic databases were searched for tES and/or TMS studies quantifying E-fields. The identified outcome measures were compared across volume- and surface-level E-field data in ten tES and TMS modalities targeting two common targets in 100 healthy individuals. RESULTS: In the systematic review, we extracted 308 outcome measures from 202 studies that adopted either a gray matter volume-level (n = 197) or surface-level (n = 111) approach. Volume-level results focused on E-field magnitude, while surface-level data encompassed E-field magnitude (n = 64) and normal/tangential E-field components (n = 47). E-fields were extracted in ROIs, such as brain structures and shapes (spheres, hexahedra and cylinders), or the whole brain. Percentiles or mean values were mostly used to quantify E-fields. Our modeling study, which involved 1,000 E-field models and > 1,000,000 extracted E-field values, revealed that different outcome measures yielded distinct E-field values, analyzed different brain regions, and did not always exhibit strong correlations in the same within-subject E-field model. CONCLUSIONS: Outcome measure selection significantly impacts the locations and intensities of extracted E-field data in both tES and TMS E-field models. The suitability of different outcome measures depends on the target region, TMS/tES modality, individual anatomy, the analyzed E-field component and the research question. To enhance the quality, rigor, and reproducibility in the E-field modeling domain, we suggest standard reporting practices across studies and provide four recommendations.

From scalp to cortex, the whole isn't greater than the sum of its parts: introducing GetTissueThickness (GTT) to assess age and sex differences in tissue thicknesses.

Noninvasive techniques to record and stimulate the brain rely on passing through the tissues in between the scalp and cortex. Currently, there is no method to obtain detailed information about these scalp-to-cortex distance (SCD) tissues. We introduce GetTissueThickness (GTT), an open-source, automated approach to quantify SCD, and unveil how tissue thicknesses differ across age groups, sexes and brain regions (n = 250). We show that men have larger SCD in lower scalp regions and women have similar-to-larger SCD in regions closer to the vertex, with aging resulting in increased SCD in fronto-central regions. Soft tissue thickness varies by sex and age, with thicker layers and greater age-related decreases in men. Compact and spongy bone thickness also differ across sexes and age groups, with thicker compact bone in women in both age groups and an age-related thickening. Older men generally have the thickest cerebrospinal fluid layer and younger women and men having similar cerebrospinal fluid layers. Aging mostly results in grey matter thinning. Concerning SCD, the whole isn't greater than the sum of its parts. GTT enables rapid quantification of the SCD tissues. The distinctive sensitivity of noninvasive recording and stimulation modalities to different tissues underscores the relevance of GTT.

Midfrontal Theta and Cognitive Control During Interlimb Coordination Across the Adult Lifespan.

Interlimb coordination is required for adequate execution of most daily life activities. Yet, aging negatively affects interlimb coordination, impacting the quality of life in older people. Therefore, disentangling the underlying age-related neural mechanisms is of utmost importance. Here, we investigated neurophysiological processes of an interlimb reaction time task, including both simple and complex coordination modes. Midfrontal theta power, measured using electroencephalography (EEG), was analyzed as a marker for cognitive control. In total, 82 healthy adults participated, with 27 younger, 26 middle-aged, and 29 older adults. On a behavioral level, reaction time increased across the adult lifespan, and error rate was higher in older adults. Notably, aging disproportionately affected reaction times in the complex coordination modes, with larger reaction time increases from simple to complex movements than in younger adults, starting already at middle age. On the neurophysiological level, EEG showed that only younger adults had significantly increased levels of midfrontal theta power during complex relative to simple coordination modes, while no significant differences were found between simple and complex movements in middle-aged and older adults. The absence of this theta power upregulation with regard to movement complexity with increasing age might reflect a premature saturation of the available mental resources.

A Systematic Review and Large-Scale tES and TMS Electric Field Modeling Study Reveals How Outcome Measure Selection Alters Results in a Person- and Montage-Specific Manner.

Background: Electric field (E-field) modeling is a potent tool to examine the cortical effects of transcranial magnetic and electrical stimulation (TMS and tES, respectively) and to address the high variability in efficacy observed in the literature. However, outcome measures used to report E-field magnitude vary considerably and have not yet been compared in detail. Objectives: The goal of this two-part study, encompassing a systematic review and modeling experiment, was to provide an overview of the different outcome measures used to report the magnitude of tES and TMS E-fields, and to conduct a direct comparison of these measures across different stimulation montages. Methods: Three electronic databases were searched for tES and/or TMS studies reporting E-field magnitude. We extracted and discussed outcome measures in studies meeting the inclusion criteria. Additionally, outcome measures were compared via models of four common tES and two TMS modalities in 100 healthy younger adults. Results: In the systematic review, we included 118 studies using 151 outcome measures related to E-field magnitude. Structural and spherical regions of interest (ROI) analyses and percentile-based whole-brain analyses were used most often. In the modeling analyses, we found that there was an average of only 6% overlap between ROI and percentile-based whole-brain analyses in the investigated volumes within the same person. The overlap between ROI and whole-brain percentiles was montage- and person-specific, with more focal montages such as 4Ã-1 and APPS-tES, and figure-of-eight TMS showing up to 73%, 60%, and 52% overlap between ROI and percentile approaches respectively. However, even in these cases, 27% or more of the analyzed volume still differed between outcome measures in every analyses. Conclusions: The choice of outcome measures meaningfully alters the interpretation of tES and TMS E-field models. Well-considered outcome measure selection is imperative for accurate interpretation of results, valid between-study comparisons, and depends on stimulation focality and study goals. We formulated four recommendations to increase the quality and rigor of E-field modeling outcome measures. With these data and recommendations, we hope to guide future studies towards informed outcome measure selection, and improve the comparability of studies.

Transcranial direct current stimulation enhances motor learning in Parkinson's disease: a randomized controlled trial.

Writing training has shown clinical benefits in Parkinson's disease (PD), albeit with limited retention and insufficient transfer effects. It is still unknown whether anodal transcranial direct current stimulation (atDCS) can boost consolidation in PD and how this interacts with medication. To investigate the effects of training + atDCS versus training + sham stimulation on consolidation of writing skills when ON and OFF medication. Second, to examine the intervention effects on cortical excitability. In this randomized sham-controlled double-blind study, patients underwent writing training (one session) with atDCS (N = 20) or sham (N = 19) over the primary motor cortex. Training was aimed at optimizing amplitude and assessed during online practice, pre- and post-training, after 24-h retention and after continued learning (second session) when ON and OFF medication (interspersed by 2 months). The primary outcome was writing amplitude at retention. Cortical excitability and inhibition were assessed pre- and post-training. Training + atDCS but not training + sham improved writing amplitudes at retention in the ON state (p = 0.017, g = 0.75). Transfer to other writing tasks was enhanced by atDCS in both medication states (g between 0.72 and 0.87). Also, training + atDCS improved continued learning. However, no online effects were found during practice and when writing with a dual task. A post-training increase in cortical inhibition was found in the training + atDCS group (p = 0.039) but not in the sham group, irrespective of medication. We showed that applying atDCS during writing training boosted most but not all consolidation outcomes in PD. We speculate that atDCS together with medication modulates motor learning consolidation via inhibitory processes ( https://osf.io/gk5q8/ , 2018-07-17).

Optimizing the Effect of tDCS on Motor Sequence Learning in the Elderly.

One of the most visible effects of aging, even in healthy, normal aging, is a decline in motor performance. The range of strategies applicable to counteract this deterioration has increased. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that can promote neuroplasticity, has recently gained attention. However, knowledge about optimized tDCS parameters in the elderly is limited. Therefore, in this study, we investigated the effect of different anodal tDCS intensities on motor sequence learning in the elderly. Over the course of four sessions, 25 healthy older adults (over 65 years old) completed the Serial Reaction Time Task (SRTT) while receiving 1, 2, or 3 mA of anodal or sham stimulation over the primary motor cortex (M1). Additionally, 24 h after stimulation, motor memory consolidation was assessed. The results confirmed that motor sequence learning in all tDCS conditions was maintained the following day. While increased anodal stimulation intensity over M1 showed longer lasting excitability enhancement in the elderly in a prior study, the combination of higher intensity stimulation with an implicit motor learning task showed no significant effect. Future research should focus on the reason behind this lack of effect and probe alternative stimulation protocols.

The influence of a single transcranial direct current stimulation session on physical fitness in healthy subjects: a systematic review.

Physical fitness is of indisputable importance for both health, and sports. Currently, the brain is being increasingly recognized as a contributor to physical fitness. Hereby, transcranial direct current stimulation (tDCS), as an ergogenic aid, has gained scientific interest. The current PRISMA-adherent review aimed to examine the effect of tDCS on the three core components of physical fitness: muscle strength, -endurance and cardiopulmonary endurance. Randomized controlled- or cross-over trials evaluating the effect of a single tDCS session (vs. sham) in healthy individuals were included. Hereby, a wide array of tDCS-related factors (e.g., tDCS montage and dose) was taken into account. Thirty-five studies (540 participants) were included. Between-study heterogeneity in factors such as age, activity level, tDCS protocol, and outcome measures was large. The capacity of tDCS to improve physical fitness varied substantially across studies. Nevertheless, muscle endurance was most susceptible to improvements following anodal tDCS (AtDCS), with 69% of studies (n = 11) investigating this core component of physical fitness reporting positive effects. The primary motor cortex and dorsolateral prefrontal cortex were targeted the most, with positive results being reported on muscle and cardiopulmonary endurance. Finally, online tDCS seemed most beneficial, and no clear relationship between tDCS and dose-related parameters seemed present. These findings can contribute to optimizing tDCS interventions during the rehabilitation of patients with a variety of (chronic) diseases such as cardiovascular disease. Therefore, future studies should focus on further unraveling the potential of AtDCS on physical fitness and, more specifically, muscle endurance in both healthy subjects and patients suffering from (chronic) diseases. This study was registered in Prospero with the registration number CRD42021258529. "To enable PROSPERO to focus on COVID-19 registrations during the 2020 pandemic, this registration record was automatically published exactly as submitted. The PROSPERO team has not checked eligibility".

Age-related changes in midfrontal theta activity during steering control: A driving simulator study.

Motor control, a ubiquitous part of driving, requires increased cognitive controlled processing in older adults relative to younger adults. However, the influence of aging on motor-related neural mechanisms in the context of driving has rarely been studied. The present study aimed to identify age-related changes in cognitive control and attention allocation during a simulated steering task, using electroencephalography. Midfrontal theta, a marker for cognitive control, and posterior alpha power, a marker for attention allocation, were measured in a total of 26 young, 25 middle-aged, and 28 older adults. By adapting driving speed, the difficulty level of this steering task was individualized for each participant. Results show age-related changes in midfrontal theta power, but not in posterior alpha power, despite similar steering accuracy across age groups. Specifically, only younger and, to a lesser extent, middle-aged adults exhibited increased theta power while driving through more demanding curved segments relative to straight segments. In contrast, theta power upregulation was absent in older adults, suggesting a saturation of cognitive resources while driving, possibly due to a limitation in resource capacity, or less automatic motor-related neural processing.

Cycling: how can we activate care-dependent older adults with a mild cognitive impairment?

PURPOSE: In residential care, 50% of older adults are sedentary in most of their time, regardless of the positive impact of physical exercise on health. This study analysed whether television images positively impact the motivation and exercise intensity of cycling exercises of older adults in residential care. METHODS: In this randomised controlled cross-over study, 10 residential older adults (mean age 85.0 ± 5.7 years) with Mild Cognitive Impairment (MCI) participated in 3 different cycling exercise interventions (TV off, TV turned on the National Geographic channel (NG) and TV with MemoRide software (Activ84Health®, Leuven, Belgium) (MR) (cybercycling)) compared with a rest condition. RESULTS: The participants cycled significantly more distance during NG compared with TVoff (p = 0.024). In comparison to the rest condition, the mean heart rate was significantly higher in all exercise conditions while the maximal heart rate was only higher during NG (p = 0.022). There was no difference in the Borg scale between the different exercise interventions. Interest and enjoyment scored significantly higher during NG (p = 0.014) and MR (p = 0.047) compared to the rest condition and in the NG versus TVoff (p = 0.018). No significant differences were observed in the emotions of the participants. CONCLUSIONS: This study has shown indications that the addition of television images may increase the exercise intensity and motivation to exercise in residential older adults with MCI. However, the overall levels of physical activity were insufficient to meet the recommendations for moderate-intense aerobic exercise according to the International Association of Gerontology and Geriatrics and Global Ageing Research Network.Implications for rehabilitationCycling in front of a television increases the exercise volume and motivation to exercise in residential (pre)frail older adults with MCICybercycling had no additional effect in comparison to television images not linked to the exercise.Even with television images (pre)frail older adults with MCI did not meet the recommendations for moderate-intense aerobic exercise for residential older adults according to the IAGG-GARN.

Aging and Complexity Effects on Hemisphere-Dependent Movement-Related Beta Desynchronization during Bimanual Motor Planning and Execution.

With aging comes degradation of bimanual movement performance. A hallmark feature of bimanual movements is movement-related beta desynchronization (MRBD), an attenuation in the amplitude of beta oscillations associated with sensorimotor activation. Here, we investigated MRBD in 39 healthy adults (20 younger and 19 older adults) in frontal, central, and parietal regions across both hemispheres, during the planning and execution of a bimanual tracking task. Task accuracy decreased with age and during more difficult conditions when both hands had to move at different relative speeds. MRBD was mostly situated in the central region, and increased in older versus younger adults during movement execution but not planning. Irrespective of age, motor planning and execution were associated with increased MRBD in the left and right hemispheres, respectively. Notably, right central MRBD during motor planning was associated with bimanual task performance, particularly in older adults. Specifically, persons who demonstrated high MRBD during motor planning performed better on the bimanual tracking task. Our results highlight the importance of lateralized MRBD during motor planning, thereby shining new light on previous research and providing a promising avenue for future interventions.

Addressing transcranial electrical stimulation variability through prospective individualized dosing of electric field strength in 300 participants across two samples: the 2-SPED approach.

Objective. Transcranial electrical stimulation (tES) is a promising method for modulating brain activity and excitability with variable results to date. To minimize electric (E-)field strength variability, we introduce the 2-sample prospective E-field dosing (2-SPED) approach, which uses E-field strengths induced by tES in a first population to individualize stimulation intensity in a second population.Approach. We performed E-field modeling of three common tES montages in 300 healthy younger adults. First, permutation analyses identified the sample size required to obtain a stable group average E-field in the primary motor cortex (M1), with stability being defined as the number of participants where all group-average E-field strengths ± standard deviation did not leave the population's 5-95 percentile range. Second, this stable group average was used to individualize tES intensity in a second independent population (n = 100). The impact of individualized versus fixed intensity tES on E-field strength variability was analyzed.Main results. In the first population, stable group average E-field strengths (V/m) in M1 were achieved at 74-85 participants, depending on the tES montage. Individualizing the stimulation intensity (mA) in the second population resulted in uniform M1 E-field strength (all p < 0.001) and significantly diminished peak cortical E-field strength variability (all p < 0.01), across all montages.Significance. 2-SPED is a feasible way to prospectively induce more uniform E-field strengths in a region of interest. Future studies might apply 2-SPED to investigate whether decreased E-field strength variability also results in decreased physiological and behavioral variability in response to tES.

Transcutaneous electrical nerve inhibition using medium frequency alternating current.

Transcutaneous medium-frequency alternating electrical current is defined as an alternating current between 1 and 10 kHz and is capable of producing an instant, reversible block. This study aims to evaluate the efficacy of sensory perception and force production of the index and middle finger after transcutaneous medium-frequency alternating electrical current stimulation of the distal median nerve. A single-center prospective interventional cohort study was conducted in adult healthy volunteers at the Jessa Hospital, Hasselt, Belgium. Two different electrodes (PALS & 3M) were placed on the distal median nerve, which was located using a Sonosite X-Porte Ultrasound transducer, with the first electrode being placed on the skin at the level of the transverse carpal ligament and the second electrode 7 cm proximally to the first electrode. The tactile sensation was evaluated with Semmes-Weinstein monofilament test and sensation of pressure/pain was evaluated with an algometer. Peak force production was assessed with an electronic dynamometer. All measurements were performed at baseline and tMFAEC stimulation frequencies of 2 and 10 kHz in a randomized manner. Statistical analysis was performed with a one-way ANOVA with repeated measures test or a Friedman rank sum test, followed by the Wilcoxon signed rank test adjusted with Bonferroni correction. A p-value < 0.05 was considered statistically significant. From 9 to 13th of April 2021, 25 healthy volunteers were included in the Jessa Hospital, Hasselt, Belgium. A statistically significant reduction in tactile sensation during 2 kHz and 10 kHz stimulation compared to baseline was observed (2.89 ± 0.22 (PALS2); 3.35 ± 0.25 (3M2) and 2.14 ± 0.12 (PALS10); 2.38 ± 0.12 (3M10) versus - 1.75 ± 0.09 (baseline), p < 0.0001). 3M electrodes showed a tendency towards the elevation of pressure pain threshold compared to baseline. No significant difference in mean peak forces of the index and middle fingers after transcutaneous medium-frequency alternating electrical current stimulation with 2 and 10 kHz was found. This study demonstrates that transcutaneous medium-frequency alternating electrical current stimulation on the distal median nerve inhibits tactile sensory nerve activity in the index and middle finger when stimulation of 2 kHz and, to a lesser extent, 10 kHz was applied. A reduction of motor nerve activity was not observed but force production measurements may be prone to error.Trial registration: clinicaltrials.gov on 01/04/2021. NCT-Number: NCT04827173.

Cerebellum and Neurorehabilitation in Emotion with a Focus on Neuromodulation.

More and more research has focused on the role of the cerebellum in emotions and social cognition. Structural cerebellar and cerebello-cerebral connectivity abnormalities have been identified in several prevalent neuropsychiatric conditions, which have in some cases even been linked to the severity of the emotional disorder.Non-invasive brain stimulation (NIBS) techniques are currently used to modulate neuronal excitability and tune the connectivity within and between neuronal networks. Targeting the cerebellum with NIBS in order to improve emotions and social behavior in neuropsychiatric conditions seems to be a very interesting and innovative approach. Several studies have already explored the effect of cerebellar vermis stimulation in patients with schizophrenia with promising results. Other neuropsychiatric disorders such as bipolar disorder (BD), obsessive-compulsive disorder (OCD), major depressive disorder, or generalized anxiety disorder (GAD) have received less attention with respect to cerebellar stimulation, although the cerebellum has been implicated in these disorders. We will address NIBS and neuropsychiatric disorders in this chapter. Future research should focus on combining cerebellar NIBS with neuroimaging to unravel the specific role of the cerebellum in emotional disorders. Such studies will be very valuable in establishing causal relationships between the structural and functional abnormalities that can be observed in these disorders, and in the search for neurophysiological biomarkers for emotions. However, it is still unclear which stimulation parameters are optimal. Moreover, an important factor to consider when applying cerebellar NIBS in order to improve emotional or other functioning is cerebellar reserve. Although the cerebellum has a wide variety of plasticity mechanisms and its structural organization intrinsically incorporates a lot of redundancy, this redundancy can be depleted. A certain amount of cerebellar reserve should be preserved to successfully apply NIBS.Systematic studies are therefore needed to clarify the optimal stimulation parameters, and methods should be developed to quantify cerebellar reserve in order to estimate the possible added value of NIBS in the rehabilitation of emotions.

Age and Interlimb Coordination Complexity Modulate Oscillatory Spectral Dynamics and Large-scale Functional Connectivity.

Interlimb coordination deteriorates as a result of aging. Due to its ubiquity in daily life, a greater understanding of the underlying neurophysiological changes is required. Here, we combined electroencephalography time-frequency spectral power and functional connectivity analyses to provide a comprehensive overview of the neural dynamics underlying the age-related deterioration of interlimb coordination involving all four limbs. Theta, alpha and beta oscillations in the frontal, central and parietal regions were analyzed in twenty younger (18-30 years) and nineteen older adults (65-78 years) during a complex interlimb reaction time task. Reaction time was significantly higher in older adults across all conditions, and the discrepancy between both age groups was largest in the most complex movement condition. Older adults demonstrated enhanced beta event-related desynchronization (i.e., the attenuation of beta power), which further increased along with task complexity and was positively linked to behavioral performance. Theta functional connectivity between frontal, central and parietal regions generally increased with movement complexity, irrespective of age group. In general, frontoparietal alpha band functional connectivity tended to be reduced in older versus younger adults, although these contrasts did not survive multiple comparison corrections. Overall, spectral results suggest that enhanced beta desynchronization in older adults reflects a successful compensatory mechanism to cope with increased difficulty during complex interlimb coordination. Functional connectivity results suggest that theta and alpha band connectivity are prone to respectively task- and age-related modulations. Future work could target these spectral and functional connectivity dynamics through noninvasive brain stimulation to potentially improve interlimb coordination in older adults.