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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 and Results: Cross-sectional study involving 2868 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 1893 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). 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., Competing Interests: Conflicts of interest: No potential conflict of interest is reported by the authors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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

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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.

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"., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bimanual coordination is an important part of everyday life and recruits a large neural network, including the cerebellum. The specific role of the cerebellum in bimanual coordination has not yet been studied in depth, although several studies indicate a differential role of the anterior and posterior cerebellum depending on the complexity of the coordination. An activation likelihood estimation (ALE) meta-analysis was used combining the data of several functional MRI studies involving bimanual coordination tasks with varying complexities to unravel the involvement of the different areas of the cerebellum in simple and complex bimanual coordination. This study confirms the general bimanual network as found by Puttemans et al. (Puttemans et al. in J Neurosci 25:4270-4278, 2005) and highlights the differences between preferred in-phase (simultaneous movements of homologous muscle groups) and anti-phase movement conditions (alternating movements of homologous muscle groups), and more complex, non-preferred bimanual movements (e.g., out-of-phase movements). Our results show a differential role for the anterior and posterior vermis in bimanual coordination, with a role for the anterior vermis in anti-phase and complex bimanual coordination, and an exclusive role for the posterior vermis in complex bimanual movements. In addition, the way complexity was manipulated also seems to play a role in the involvement of the anterior and posterior vermis. We hypothesize that the anterior vermis is involved in sequential/spatial control, while the posterior vermis is involved in temporal control of (bimanual) coordination, though other factors such as (visual) feedback and continuity of the movement also seem to have an impact. More studies are needed to unravel the specific role of the cerebellar vermis in bimanual coordination., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Creative Commons Attribution license.)

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., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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 &lt; 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 &lt; 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., (© 2022. The Author(s).)

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

Motor control of automatized and overlearned sequences, such as writing, is affected in Parkinson's disease (PD), impacting patients' daily life. Medication effects on motor performance are not only task-specific, but also variable within tasks. The nature of this variance is still unclear. This study aimed to investigate whether medication affects writing sequences differently when producing up- or downstrokes. Writing was assessed in healthy controls (HC) (N = 31) and PD (N = 32), when ON and OFF medication in a randomized order (interspersed by two months). Subjects wrote a sequential pattern with an increasing size on a digital tablet. Writing outcomes were movement vigor (amplitude and velocity), error and end-point variability, and sequence continuation, calculated separately for up- and downstrokes. Results showed that PD patients OFF-medication reduced movement vigor (amplitude) for up- and downstrokes compared to HC. Clear deficits were found for up- but not for downstroke error in PD patients in OFF, suggesting a directional bias. Dopaminergic medication improved motor vigor by increasing writing amplitude and upstroke continuation, but this occurred at the cost of the downstroke trajectory. Other writing outcomes did not improve with medication intake. In conclusion, we interpret these findings as that the impact of dopamine is complex, highly task-specific, supporting the most highly energy demanding components of a writing sequence. As medication did not regulate downstroke writing, we recommend supplementary training to address task demands that were less modulated by dopamine (registration: https://osf.io/gk5q8/ , 17 July 2018)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Frailty is an age-related decline in physical, socio-psychological and cognitive function that results in extreme vulnerability to stressors. Therefore, this study aimed to elucidate which tests have to be selected to detect frailty in a comprehensive and feasible manner in cardiovascular disease (CVD) patients based on multivariate regression and sensitivity/specificity analyses. Patients ( n = 133, mean age 78 ± 7 years) hospitalised for coronary revascularisation or heart failure (HF) were examined using the Fried and Vigorito criteria, together with some additional measurements. Moreover, to examine the association of frailty with 6-month clinical outcomes, hospitalisations and mortality up to 6 months after the initial hospital admission were examined. Some level of frailty was detected in 44% of the patients according to the Vigorito criteria and in 65% of the patients according to the Fried criteria. Frailty could best be detected by a score based on: sex, Mini Nutritional Assessment (MNA), Katz scale, timed up-and-go test (TUG), handgrip strength, Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15) and total number of medications. Frailty and specific markers of frailty were significantly associated with mortality and six-month hospitalisations. We thus can conclude that, in patients with CVD, sex, MNA, Katz scale, TUG, handgrip strength, MMSE, GDS-15 and total number of medications play a key role in detecting frailty, assessed by a new time- and cost-efficient test battery.

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., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Walking fatigability is prevalent in MS and can be measured by a percentage distance decline during a 6-min walking test. Walking is characterized by an accurate and consistent interlimb antiphase coordination pattern. A decline in coordination each minute during a 6-min walking test is observed in persons with MS (pwMS). Measuring coordination during a 6-min seated coordination task with minimized balance and strength requirements, is assumed to examine a more fundamental interlimb antiphase coordination pattern in pwMS. This research aimed to answer the following research question: How does interlimb antiphase coordination pattern change during a seated coordination task in pwMS with walking fatigability (WF), non-walking fatigability (NWF) and Healthy Controls (HC)? Methods: Thirty-five pwMS and 13 HC participated. Interlimb coordination was assessed by a seated 6-min coordination task (6MCT) with the instruction to perform antiphase lower leg movements as fast as possible. Outcomes were Phase Coordination Index (PCI) and movement parameters (amplitude, frequency). Results: Mixed models revealed a significant effect of time for the the variability of generating interlimb movements, with a difference in mean values between WF and HC. A significant group ∗ time interaction effect was found for movement amplitude, represented by a significant decrease in movement amplitude in the WF group from minute 1 to the end of the task. Conclusion: The higher variability in interlimb coordination and decrease in movement amplitude over time during the 6MCT in the WF group could be an indicator of decreased control of fundamental antiphase coordination pattern in pwMS with walking fatigability. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT04142853 (registration date: October 29, 2019) and NCT03938558 (registration date: May 6, 2019)., Competing Interests: PF was steering committee member of Neurocompass, participated to advisory board meetings of BIOGEN IDEC, and received teaching honoraria for EXCEMED and PARADIGMS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Goetschalckx, Van Geel, Meesen, Triccas, Geraerts, Moumdjian and Feys.)

Objective: To systematically review how patient characteristics and/or transcranial direct current stimulation (tDCS) parameters influence tDCS effectiveness in respect to upper limb function post-stroke., Methods: Three electronic databases were searched for sham-controlled randomised trials using the Fugl-Meyer Assessment for upper extremity as outcome measure. A meta-analysis and nine subgroup-analyses were performed to identify which tDCS parameters yielded the greatest impact on upper limb function recovery in stroke patients., Results: Eighteen high-quality studies (507 patients) were included. tDCS applied in a chronic stage yields greater results than tDCS applied in a (sub)acute stage. Additionally, patients with low baseline upper limb impairments seem to benefit more from tDCS than those with high baseline impairments. Regarding tDCS configuration, all stimulation types led to a significant improvement, but only tDCS applied during therapy, and not before therapy, yielded significant results. A positive dose-response relationship was identified for current/charge density and stimulation duration, but not for number of sessions., Conclusion: Our results demonstrate that tDCS improves upper limb function post-stroke. However, its effectiveness depends on numerous factors. Especially chronic stroke patients improved, which is promising as they are typically least amenable to recovery., Significance: The current work highlights the importance of several patient-related and protocol-related factors regarding tDCS effectiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Few studies have identified the intrahemispheric functional connectivity between the ipsilateral dorsal premotor cortex (PMd) and the primary motor hand area (M1 hand ) due to technical limitations. In this proof-of-concept study, a novel neuronavigated dsTMS set-up was employed, combining stimulation over left PMd and left M1 hand using the edge of a butterfly coil and a small cooled-coil. This arrangement was warranted because coil (over)heating and inter coil distance are limiting factors when investigating connectivity between stimulation targets in close proximity and over a longer duration. The proposed set-up was designed to deal with these limitations. Specifically, the effect of four dual-site transcranial magnetic stimulation (dsTMS) protocols on twenty-eight right-handed participants (12 males) was evaluated. These protocols differed in stimulus order, interstimulus interval and current direction induced in PMd. A structural scan with electric (E-)field modeling was obtained from seven participants prior to dsTMS, demonstrating that PMd and M1 hand were effectively stimulated. Results indicate that one protocol, in which a latero-medial current was induced in PMd 2.8 ms prior to stimulation over M1 hand , induced a sex-mediated effect. In males, significant inhibition of motor-evoked potentials was identified, whereas females demonstrated a facilitatory effect that did not survive correction for multiple comparisons. E-field simulations revealed that the E-field induced by the coil targeting PMd was maximal in PMd, with weaker E-field strengths extending to regions beyond PMd. Summarizing, the current dsTMS set-up enabled stimulating at an inter-target distance of 35 mm without any indications of coil-overheating., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Fatigue and walking difficulties are common impairments and activity limitations in persons with multiple sclerosis (PwMS). Walking fatigability (WF) can be measured by a Distance Walked Index and is defined as a decline in walking distance of 10% or more during the six-minute walking test (6MWT). However, the clinical manifestation and perceived symptoms related to fatigability are still not well documented. Forty-nine PwMS [Expanded Disability Status Scale (EDSS) ≤6] and 28 healthy controls (HC) performed a 6MWT. The perceived severity of 11 common symptoms was rated on a visual analogue scale of 0-10 before, immediately after, and 10, 20 and 30 minutes after the 6MWT by means of the symptom inventory. Short motor impairment screening tests at baseline together with other descriptive measures were performed. Twenty pwMS were categorized in the WF group and were more disabled (EDSS: 4.16 ± 1.41) than the non-walking fatigability group (n = 29, EDSS: 2.62 ± 1.94). PwMS showed exacerbations of several perceived symptoms in MS, where most symptoms returned to baseline within 10 minutes after the walking test. The WF group showed significantly more muscle weakness and gait impairment, together with balance problems, and experienced an increase in spasticity, pain and dizziness after 6MWT. Our findings showed that perceived severity of symptoms are higher in pwMS presenting WF, and increase temporally after the 6MWT. Future research with quantitative measurement during and after walking is recommended., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system with heterogeneous symptoms. Persons with MS (PwMS) show reduced walking capacity with changes in their gait pattern. It is unknown to which extent coordination deficits are present in PwMS, which can be measured by seated lower leg interlimb coordination tasks, and to which extent they are related to motor and cognitive function., Research Question: How is the control of interlimb coordination of the lower limbs characterized in PwMS compared to healthy controls (HC) during a seated rhythmical coordination task and what is the relationship between interlimb coordination, motor or cognitive function?, Methods: Rhythmical interlimb coordination was assessed during a single session in 38 PwMS and 13 HC, using a seated rhythmical coordination task, comprising of antiphase flexion-extension of the lower limbs, to metronomes at 0.75 Hz, 1.00 Hz, 1.50 Hz. Outcomes were phase coordination index (PCI), movement amplitude and movement frequency. Correlations between interlimb coordination, motor, and cognitive function were examined., Results: PwMS showed impaired walking capacity but preserved cognitive function. Mixed model analysis revealed a significant effect of group and metronome frequency for PCI, attenuated by the variability in generating knee (antiphase flexion-extension) movements. Movement amplitude was highest at metronome frequency 1.00 Hz. In PwMS significant correlations were found between PCI and cognitive function when performing the task at metronome frequencies 0.75 Hz and 1.50 Hz, as well as motor function at 1.50 Hz., Significance: PwMS had a higher variability in interlimb coordination compared to HC. The most stable interlimb antiphase coordination mode was performed at 1.00 Hz. Significant correlations support the existence of a relationship between information processing speed, as well as walking impairment, with interlimb coordination. While cognitive and motor control are always needed for interlimb coordination movements, associations are strongest in the deviant higher and lower metronome rhythms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cardiologists are more often confronted with older (>60 years) cardiovascular disease (CVD) patients. These patients have particular needs in clinical care because, for example, of frailty. However, it remains to be established what is the prevalence of frailty in different CVD's and how it relates to mortality. In this systematic review studies were included if they: (i) examined subjects (men and women) aged ≥60 years who suffered from any CVD with or without cardiac surgery, (ii.) examined the presence of frailty with a well-defined frailty tool and (iii.) reported prevalence rates of frailty. From thirty studies comprising 96.841 participants, it is found that 1. Frailty is highly common in older patients with CVD (in particular in females (approximately 1.6 times more than in males), in heart failure (up to 80 % of patients) and aortic valve disease (up to 74 % of patients)), and 2. Frailty is related to a 2.5-3.5-fold elevated mortality risk, even in patients with less severe CVD (e.g. percutaneous coronary intervention). Moreover, there is a lack of consistency on how to assess frailty as up to 20 different tools/assessment batteries are currently used. It is concluded that frailty should be assessed in all older CVD patients in a uniform manner to enhance clinical care and outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Burnout is characterized by deficiencies in attention and several components of the working memory, of which the lingering effects of impaired attention and executive functions are the most frustrating. We hypothesized that anodal transcranial direct current stimulation (atDCS) over the left dorsolateral prefrontal cortex (DLPFC) can improve the executive control of attention and possibly several other components of working memory in patients with burnout. Methods: This was a randomized double-blind sham-controlled pilot study with two groups. Patients with burnout received three weeks of daily sessions (15 sessions in total) of atDCS or sham stimulation in addition to three weekly sessions of standard behavioral therapy. The primary outcome measure was attention and the central executive of the working memory. Secondary, the effect of atDCS was measured on other components of working memory, on burnout and depression scores, and on quality of life (QoL). Results: We enrolled and randomly assigned 16 patients to a sham or real stimulation group, 15 (7 sham, 8 real) were included in the analysis. atDCS had a significant impact on attention. Post-hoc comparisons also revealed a trend towards more improvement after real tDCS for inhibition and shifting, updating and control, and encoding. Both groups improved on burnout and depression scores. Conclusion: These data provide preliminary evidence for the value of atDCS over the left DLPFC in rehabilitating attention deficits, and possibly also central executive and encoding deficits, in burnout. However, the current study has some limitations, including the sample size and heterogeneous patient population. More elaborate studies are needed to elucidate the specific impact of atDCS over the left DLPFC on burnout. Trial registration: ISRCTN.com ( ISRCTN94275121) 17/11/19., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Van Noppen P et al.)

Background . Learning processes of writing skills involve the re-engagement of previously established motor programs affected by Parkinson disease (PD). To counteract the known problems with consolidation in PD, transcranial direct current stimulation (tDCS) could be imperative to achieve a lasting regeneration of habitual motor skills. Objective . To examine tDCS-enhanced learning of writing and explore alterations in cortical excitability after stimulation in PD compared with healthy controls (HCs). Methods . Ten patients and 10 HCs received 2 training sessions combined with 20 minutes of 1-mA anodal tDCS or sham on the left primary motor cortex in a randomized crossover design. Writing skills on a tablet and paper were assessed at baseline, after training, and after 1 week of follow-up. Before and immediately after the intervention, cortical excitability and inhibition were measured during rest and activity. Results . Writing amplitude and velocity improved when practice was tDCS supplemented compared with sham in PD. Benefits were sustained at retention for trained and untrained tasks on the tablet as well as for writing on paper. No improvements were found for HCs. Reduced resting motor thresholds after tDCS indicated tDCS-enhanced cortical excitability. Additionally, increments in motor-evoked potential amplitudes correlated with improved writing in PD, whereas HCs showed the opposite pattern. Conclusion . Our results endorse the usefulness of tDCS-boosted learning in PD, at least when applied to improving writing capacity. Although further confirmatory studies are needed, these novel findings are striking because tDCS-mediated consolidation was found for learning a motor task directly affected by PD.

Background: As the prevalence of neurodegenerative diseases (such as dementia) continues to increase due to population aging, it is mandatory to understand the role of exercise for maintaining/improving brain health., Objectives: To analyse the impact of aerobic, strength and combined aerobic/strength exercise training on peripheral brain-derived neurotrophic factor (BDNF) concentrations in older adults (minimum age 60 years)., Methods: This meta-analysis adhered to PRISMA guidelines. Inclusion criteria were: (i) studies with subjects aged ≥ 60 years, (ii) completing a single exercise bout or an exercise programme, with (iii) measurements of blood BDNF in the periphery; (iv) with comparison between (a) an intervention and control group or (b) two intervention groups, or (c) pre- and post-measurements of an exercise intervention without control group. Studies with specific interest in known chronic co-morbidities or brain diseases affecting the peripheral and/or central nervous system, except for dementia, were excluded., Results: In general, peripheral blood BDNF concentrations increased significantly after a single aerobic/strength exercise bout (Z = 2.21, P = 0.03) as well as after an exercise programme (Z = 4.72, P < 0.001). However, when comparing the different types of exercise within these programmes, the increase in the peripheral BDNF concentrations was significant after strength training (Z = 2.94, P = 0.003) and combined aerobic/strength training (Z = 3.03, P = 0.002) but not after (low-to-moderate intense) aerobic exercise training (Z = 0.82, P = 0.41)., Conclusions: Based on current evidence, to increase the peripheral blood BDNF concentrations in older adults, strength training and combined aerobic/strength training is effective. More studies are needed to examine the impact of aerobic exercise training.

Despite the high prevalence and devastating outcome, only a few treatment options for cerebral ischemic stroke exist. Based on the nitric oxide (NO)-stimulating capacity of Non-pulsed Sinusoidal Electromagnetic Field (NP-SEMF) and the possible neuroprotective role of NO in ischemic stroke, we hypothesized that NP-SEMF is able to enhance survival and neurological outcome in a rat model of cerebral ischemia. The animals, in which ischemic injury was induced by occlusion of both common carotid arteries, received 20 min of NP-SEMF of either 10 or 60 Hz daily for 4 days. NP-SEMF dramatically increased survival, reduced the size of the infarcted brain area and significantly improved the neurological score of the surviving rats. Corresponding to previous reports, NP-SEMF was able to induce NO production in vitro . The importance of NO as a key signaling molecule was highlighted by inhibition of the NP-SEMF beneficial effects in the rat stroke model after blocking NO synthase (NOS). Our results indicate for the first time that NP-SEMF exposure (13.5 mT at 60 and 10 Hz) improves the survival and neurological outcome of rats subjected to cerebral ischemia and that this effect is mediated by NO, underlining the great therapeutic potential of NP-SEMF as a therapy for ischemic stroke.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can boost motor performance in Parkinson's disease (PD) when it is applied at rest. However, the potential supplementary therapeutic effect of the concurrent application of tDCS during the training of motor tasks is largely unknown. The present study examined the effects of tDCS on upper limb motor blocks during a freezing-provoking writing task (the funnel task) requiring up- and down-stroke movements at alternating amplitudes. Ten PD patients and 10 age-matched controls underwent two sessions of writing combined with 20 min of anodal or sham tDCS on the left M1 in a randomized cross-over design. The primary outcome was the number of upper limb freezing episodes during five trials of the funnel task on a touch-sensitive tablet. PD patients showed a significant reduction in freezing episodes during tDCS compared to sham. No effects of tDCS were found for the amplitude, variability and speed of the strokes outside the freezing episodes. However, patients who reported freezing episodes in daily life (N = 6) showed a beneficial effect of tDCS on stroke characteristics. These results indicate a subgroup-dependent variability in response to non-invasive brain stimulation applied during the performance of motor tasks in PD. This warrants future studies to examine tDCS as an adjuvant tool for training programs aimed to reduce motor deficits related to freezing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Force decline during strong contractions is dominated by changes in the periphery whereas during weaker contraction changes in voluntary activation become more important. We compared force decline and contributing factors in persons with multiple sclerosis (PwMS) during low and high intensity contractions., Methods: Index finger abduction force, force evoked by electrical stimulation of the ulnar nerve at rest (RTw), and during MVCs were investigated in 19 PwMS and 19 controls. Participants performed contractions in sets of six contractions (7 s-on, 3 s-off) at 25% or 80% MVC. After each set, a 5 s-MVC was performed with superimposed nerve stimulation followed by RTw. Contractions were repeated until MVC dropped below 80% of initial MVC., Results: Low compared to high intensity contractions caused a greater decline in voluntary activation and a smaller decline in RTw. Compared to controls, PwMS accomplished equal sets of contractions but showed a smaller decline in RTw. Female PwMS showed poorer voluntary activation. The number of low intensity contractions was associated with sense of fatigue in PwMS., Conclusion: Although, no difference in fatigability was observed, the mechanism contributing to force decline differed between PwMS and controls during submaximal contractions., Significance: During weak contractions, fatigue and fatigability are associated in PwMS., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)