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The use of auditory stimuli in rehabilitation to target walking has been evidenced in persons with neurological conditions. The methodologies focus on the synchronisation of persons' steps to auditory stimuli showing that the type of stimuli and tempi significantly affect the synchronisation. However, the dynamic of the interaction over time between the motor system and the auditory stimuli, i.e., when steps are aligned (termed as locking) and not aligned (termed as unlocking) to the beat of the stimuli, remains unclear. Quantifying these dynamics would assist in the development of personalised rehabilitation. Nevertheless, it is currently challenging given the variability of responses per individual over time. We propose a methodological solution to quantify the dynamics of the step-to-beat coupling over time within an experimental paradigm where healthy (n = 7) and neurological impaired (n = 6) participants walk three minutes to music and metronomes at various tempi. We applied window partitioning within the time series to account for the changing pattern. To classify data into locked and unlocked events, features of fluctuation and trend were derived on which two statistical tests (circular statistical test and slope test) were done, respectively. Based on the ground truth, the performance of our proposed method yielded high accuracy (91%), precision (90%) and recall (97%). The standard deviation of the inter-step intervals was then modelled across the label and experimental factors. The proposed method is suitable for quantifying fine-grained observation of the dynamics of auditory-motor coupling in adult healthy and neurological impaired participants, with the potential of designing personalised rehabilitation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fayyad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Many persons with multiple sclerosis (MS) are confronted with fatigue and difficulties with walking and even more so in persons with progressive subtypes of MS. Task-oriented training, and more specifically in the form of auditory-motor coupling, where persons are asked to synchronise their steps to beats in music and metronomes, is promising. However, it is currently not known whether persons with progressive MS (PwPMS) can synchronise their steps to beats in music and metronomes and if they can adapt their gait to slower and higher tempi., Methods: The study is a case control study where participants with progressive MS (PwPMS) and healthy controls (HCs) were asked to synchronise their steps during overground walking to beats in music and metronomes at five different tempi, ranging from slow (-8%, -4%), baseline (0%) and high (4%, 8%) while synchronisation, spatiotemporal parameters and gait dynamics were recorded. Mixed model analyses were performed on synchronisation outcome measures and spatiotemporal gait parameters. Additionally, a regression analysis was performed to identify clinical factors such as cognition and motor function influencing synchronisation consistency., Results: In total, 18 PwPMS (mean age = 52.4, median EDSS = 4.24) and 16 healthy controls (HCs) (mean age = 56.5) were included in the study. Results show that both groups were able to synchronise their steps to beats in music and metronomes, but highest synchronisation consistency was reached for metronome conditions compared to music conditions and for HCs compared to persons with progressive MS. Highest synchronisation consistency for persons with progressive MS was found at -4% and 0%. Additionally, more variability in inter-step-intervals and thus a more anti-persistent gait pattern was found for metronome compared to music conditions. Last, lower performance on the Timed Up & Go Test negatively impacted synchronisation consistency., Conclusion: PwPMS are able to synchronise steps to beats in music and metronomes. Overall, more consistent synchronisation is seen for metronome conditions. All participants are able to adapt their cadence to all tempi, yet, PwPMS struggle to adapt gait speed to high tempi. Noteworthy, participants walk with more random inter-step-interval fluctuations when walking to metronome compared to music conditions. Last, dynamic balance significantly impacted synchronisation consistency. These results show the potential of using auditory-motor coupling for walking related rehabilitation for PwPMS, however, tempo and auditory stimulation should be carefully considered., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Developmental coordination disorder (DCD) presents challenges in motor control. DCD affects tasks such as walking and running and is characterized by poor interlimb coordination and increased spatiotemporal variability compared to typically developing children (TDC). While auditory rhythm synchronization has shown to have benefits for gait performance in adults, its impact on children with DCD during walking and running remains unclear. This study investigated auditory-motor synchronization and interlimb coordination during walking and running in children with and without DCD. Twenty-one DCD and 23 TDC participants aged 8-12 years walked and ran to two different auditory metronomes (discrete and continuous). Synchronization consistency was the primary outcome, with interlimb coordination and spatiotemporal variability as secondary outcomes. Results showed that children with DCD exhibited significantly lower synchronization consistency than TDC, particularly during running. The metronome structure did not influence synchronization ability. Additionally, interlimb coordination differed significantly between DCD and TDC during running and was not impacted by auditory-motor synchronization. Spatiotemporal variability was higher in DCD during both walking and running than in TDC, and accentuated during running. Variability of cadence was influenced by the use of continuous metronomes, which may offer potential benefits in reducing cadence variability., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Background: Children with developmental coordination disorder (DCD) exhibit reduced interlimb coordination compared to typically developing children (TDC) during complex tasks like running, which requires dynamic postural control. However, the extent of interlimb coordination difficulties in DCD during tasks that demand minimal dynamic balance, such as self-paced and externally auditory-paced tasks, remains unclear. This study aimed to compare interlimb coordination and auditory-motor synchronization between children with DCD and TDC during a seated antiphase coordination task of the lower limbs, which has minimal postural control requirements. Methods: Twenty-one children with DCD and 22 TDC performed an antiphase knee flexion and extension task while seated, in three conditions (baseline silence, metronome discrete, and metronome continuous), for three minutes. The interlimb coordination, synchronization, and spatiotemporal movement parameters were analyzed using a mixed model analysis; Results: Children with DCD displayed less coordinated interlimb movements compared to TDC ( p = 0.0140), which was the result of the greater variability in coordinating antiphase knee flexion-extension movements ( p < 0.0001). No group differences in spatiotemporal movement parameters were observed. Children with DCD, compared to TDC, had a lower synchronization consistency to metronomes ( p = 0.0155). Discrete metronomes enhanced interlimb coordination compared to the baseline silence condition ( p = 0.0046); Conclusions: The study highlights an inferior interlimb coordination and auditory-motor synchronization in children with DCD compared to TDC. Implementing metronomes with a discrete temporal structure improved the interlimb coordination of both groups during the used fundamental seated interlimb coordination task, supporting theorical frameworks of event-based timing.

Background: A different interlimb coordination and higher variability in movement patterns is evident in children with Developmental Coordination Disorder (DCD). The impact of DCD on interlimb coordination during walking and running is unknown., Aim: To assess interlimb coordination and spatiotemporal variability during overground walking and running in children with and without DCD., Methods: Children with DCD and typically developing children (TDC), from 8 to 12 years participated. Children were equipped with portable sensors. Participants walked and ran for 3 min in an oval-path at their comfortable pace. Interlimb coordination, expressed by the phase coordination index (PCI), and spatiotemporal variability (coefficient of variance (CoV)) were collected., Results: Twenty-one children with DCD and 23 TDC participated. During walking, PCI showed similar values in both groups, but a higher spatiotemporal variability was observed in children with DCD. During running, PCI was higher (reduced coordination) in children with DCD than TDC and a higher spatiotemporal variability was shown., Conclusions and Implications: Only during running, interlimb coordination of children with DCD was lower than TDC. During both walking and running tasks, spatiotemporal variability was higher in DCD. Current results implicate that difficulties in children with DCD is more prominent when motor coordination is more challenged., What This Paper Adds: This paper adds to the literature on coordination and gait pattern in children with Developmental Coordination Disorder (DCD) through a cross-sectional analysis of interlimb coordination and variability of spatiotemporal measures of overground walking and running. Overground walking and running were performed in a large oval-path allowing the assessment of coordination and gait patterns in an ecological valid set-up. Our results indicate that during a more demanding task, namely running, children with DCD display a less coordinated running pattern, expressed by a significantly higher phase coordination index, than typically developing peers. During walking, the interlimb coordination was similar between both groups. The current result is in accordance with the hybrid model of DCD that states that motor coordination difficulties in DCD are dpendent on the interaction of the task, individual and environment. This highlights the importance of implementing running assessments in children with DCD and the need for task-oriented running training in clinical practice The study also supports previous findings that children with DCD show a higher variability in their gait pattern of both walking and running, expressed by higher coefficient of variance of spatiotemporal measures, than typically developing peers. Further understanding in the normal development of interlimb coordination during walking and running from childhood into adulthood will enhance interpretations of the phase coordination index in children with and without DCD., Competing Interests: Declaration of competing interest This study was supported by the Flemish Fund for Scientific Research (FWO Vlaanderen, 11K8622N, 1295923N) and the Special Research Fund of Hasselt University (BOF21INCENT27)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Cerebellar impairment (CI) manifests from different etiologies resulting in a heterogenic clinical presentation affecting walking and mobility. Case-reports were reviewed to provide an analytical clinical picture of persons with CI (PwCI) to differentiate cerebellar and non-cerebellar impairments and to identify interventions and assessments used to quantify impact on walking and mobility according to the International Classification of Functioning, Disability and Health (ICF)., Materials and Methods: Literature was searched in PubMed, Web Of Science and Scopus. Case-reports conducting physical rehabilitation and reporting at least one outcome measure of ataxia, gait pattern, walking or mobility were included., Results: 28 articles with a total of 38 different patients were included. Etiologies were clustered to: spinocerebellar degenerations, traumatic brain injuries, cerebellar tumors, stroke and miscellaneous. The interventions applied were activity-based, including gait and balance training. Participation based activities such as tai chi, climbing and dance-based therapy had positive outcomes on mobility. Outcomes on body function such as ataxia and gait pattern were only reported in 22% of the patients., Conclusions: A comprehensive test battery to encompass the key features of a PwCI on different levels of the ICF is needed to manage heterogeneity. Measures on body function level should be included in interventions.

Sensorimotor synchronization strategies have been frequently used for gait rehabilitation in different neurological populations. Despite these positive effects on gait, attentional processes required to dynamically attend to the auditory stimuli needs elaboration. Here, we investigate auditory attention in neurological populations compared to healthy controls quantified by EEG recordings. Literature was systematically searched in databases PubMed and Web of Science. Inclusion criteria were investigation of auditory attention quantified by EEG recordings in neurological populations in cross-sectional studies. In total, 35 studies were included, including participants with Parkinson's disease (PD), stroke, Traumatic Brain Injury (TBI), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). A meta-analysis was performed on P3 amplitude and latency separately to look at the differences between neurological populations and healthy controls in terms of P3 amplitude and latency. Overall, neurological populations showed impairments in auditory processing in terms of magnitude and delay compared to healthy controls. Consideration of individual auditory processes and thereafter selecting and/or designing the auditory structure during sensorimotor synchronization paradigms in neurological physical rehabilitation is recommended., (© 2023. The Author(s).)

Neural entrainment, defined as unidirectional synchronization of neural oscillations to an external rhythmic stimulus, is a topic of major interest in the field of neuroscience. Despite broad scientific consensus on its existence, on its pivotal role in sensory and motor processes, and on its fundamental definition, empirical research struggles in quantifying it with non-invasive electrophysiology. To this date, broadly adopted state-of-the-art methods still fail to capture the dynamic underlying the phenomenon. Here, we present event-related frequency adjustment (ERFA) as a methodological framework to induce and to measure neural entrainment in human participants, optimized for multivariate EEG datasets. By applying dynamic phase and tempo perturbations to isochronous auditory metronomes during a finger-tapping task, we analyzed adaptive changes in instantaneous frequency of entrained oscillatory components during error correction. Spatial filter design allowed us to untangle, from the multivariate EEG signal, perceptual and sensorimotor oscillatory components attuned to the stimulation frequency. Both components dynamically adjusted their frequency in response to perturbations, tracking the stimulus dynamics by slowing down and speeding up the oscillation over time. Source separation revealed that sensorimotor processing enhanced the entrained response, supporting the notion that the active engagement of the motor system plays a critical role in processing rhythmic stimuli. In the case of phase shift, motor engagement was a necessary condition to observe any response, whereas sustained tempo changes induced frequency adjustment even in the perceptual oscillatory component. Although the magnitude of the perturbations was controlled across positive and negative direction, we observed a general bias in the frequency adjustments towards positive changes, which points at the effect of intrinsic dynamics constraining neural entrainment. We conclude that our findings provide compelling evidence for neural entrainment as mechanism underlying overt sensorimotor synchronization, and highlight that our methodology offers a paradigm and a measure for quantifying its oscillatory dynamics by means of non-invasive electrophysiology, rigorously informed by the fundamental definition of entrainment., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Upper limb intention tremor in persons with multiple sclerosis (pwMS) affects the ability to perform activities of daily life and is difficult to treat. The study investigated the effect of peripheral upper limb cooling on tremor severity and functional performance in MS patients with intention tremor. In experiment 1, 17 patients underwent two 15 min cooling conditions for the forearm (cold pack and cryomanchet) and one control condition. In experiment 2, 22 patients underwent whole arm cooling for 15 min using multiple cold packs. In both experiments, patients were tested at four time points (pre- and post-0, -25 and -50 min cooling) on unilateral tasks of the Test Evaluant les Membres supérieurs des Personnes Agées (TEMPA), Fahn's tremor rating scale (FTRS), Nine Hole Peg Test (NHPT). In experiment 1, the mean FTRS ranged from 13.2 to 14.1 across conditions. A two-way ANOVA showed mainly time effects, showing that cooling the forearm significantly reduced the FTRS, the performance on the NHPT, and three out of four items of the TEMPA, mostly independent of the cooling modality. In experiment 2, the mean FTRS was 13.1. A repeated measures ANOVA showed that cooling the whole arm reduced the FTRS and time needed to execute two out of four items of the TEMPA. These effects occurred immediately after cooling lasting at least 25 min. Cooling the whole upper limb led to a clinically noticeable effect on tremor severity and improved functional performance, which was pronounced during the first half-hour after cooling.

Background and Purpose: Regular physical activity (PA) helps to reduce the severity of physical and mental symptoms and improves quality of life in people with multiple sclerosis (PwMS). Based on current evidence and expert opinion, the recent multiple sclerosis guidelines recommend at least 150 minutes/week of PA. This study presents the results of a survey analyzing whether and how PwMS met the guidelines before and during the pandemic., Methods: We developed and disseminated an international online survey between December 2020 and July 2021, investigating changes in self-reported PA type, duration, frequency, and intensity due to the COVID-19 outbreak in PwMS with differing disability levels., Results: Among respondents (n = 3810), 3725 were eligible. The proportion of those who conducted at least one activity decreased with increasing disability level at both time points (pre and during). Overall 60% of respondents met the guidelines before the pandemic (mild: 64.43%; moderate: 51.53%; severe: 39.34%; χ 2(2) = 109.13, P < 0.01); a reduction of approximately 10% occurred during the pandemic in all disability groups (mild: 54.76%; moderate: 42.47%; severe: 29.48%; χ 2(2) = 109.67, P < 0.01). Respondents with higher disability participated more in physical therapy and less in walking, cycling, and running at both time points. Most respondents reported practicing PA at a moderate intensity at both time points; frequency and duration of sessions decreased as disability level increased., Discussion and Conclusions: The percentage of those meeting the guidelines reduced with increasing disability level and during the pandemic. PA type and intensity varied widely across the disability categories. Interventions accounting for disability level are required to enable more PwMS to reap the benefits of PA.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A415 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Academy of Neurologic Physical Therapy, APTA.)

Background: The COVID-19 pandemic has led to reorganization or reduction of neurorehabilitation services for people with multiple sclerosis (PwMS). The aim of this study was to explore the changes in the organizational framework and technology usage in physiotherapy services for PwMS during the COVID-19 pandemic., Methods: This international cross-sectional survey study was designed, developed, and disseminated by RIMS European Network for Best Practice and Research in Multiple Sclerosis Rehabilitation. Physiotherapists from nine countries (Australia, Belgium, Czech Republic, Ireland, Israel, Italy, Norway, Spain, Turkey) who provided physiotherapy services to PwMS, were invited to complete an online survey to compare physiotherapy delivery to PwMS prior to and during the pandemic period., Results: The survey was completed by 215 physiotherapists. Accessibility, the average number, length and perceived effectiveness of physiotherapy sessions provided to PwMS were significantly reduced during the COVID-19 pandemic (p=0.001). Physiotherapists increased the advice of mobile apps, recorded videos for rehabilitation and exercise websites during the pandemic (p<0.001) while the use of telerehabilitation and virtual reality technology did not change., Conclusion: There was of a reduction in the number, duration and perceived effectiveness of rehabilitation sessions for people with multiple sclerosis during the COVID-19 pandemic while use of remote technologies for physiotherapy did not change. To ensure the continuity of physiotherapy for PwMS with complex healthcare needs also during pandemics, the provision of guidelines and training in telehealth technologies in professional education becomes crucial., Competing Interests: Declaration of Competing Interests The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the impact of the COVID-19 pandemic on physical activity in persons with multiple sclerosis (PwMS)., Design: Multicenter international online survey study., Setting: The survey was conducted within 11 participating countries. Each country launched the survey using online platforms from May to July 2021., Participants: This was an electronic survey study targeting PwMS (N=3725)., Intervention: Not applicable., Main Outcome Measures: The survey ascertained physical activity performance and its intensity, the nature of the activities conducted, and the use of technology to support home-based physical activity before and during the pandemic., Results: A total of 3725 respondents completed the survey. Prepandemic, the majority (83%) of respondents reported being physically active, and this decreased to 75% during the pandemic. This change was significant for moderate- and high-intensity activity (P&lt;.0001). Activities carried out in physiotherapy centers, gyms, or pools decreased the most. Walking was the most frequently performed activity prepandemic (27%) and increased during the pandemic (33%). A total of 24% of those inactive during the pandemic had no intention of changing their physical activity behavior post pandemic. A total of 58% of the respondents did not use technology to support physical activity during the pandemic. Of those who did use technology, wearables were most used (24%). Of those currently nonactive (25%) expressed a preference for an in-person format to conduct physical activity post pandemic., Conclusions: Physical activity performance, especially activities at moderate and high intensities, decreased during the pandemic in PwMS compared with prepandemic. Walking and using wearables gained popularity as ways to stay active. As we move toward an endemic COVID-19, a call for action to develop interventions focused on walking programs with specific emphasis on increasing physical activity of PwMS is proposed., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Given the prevalence of motor and cognitive functions in persons with multiple sclerosis (PwMS), we proposed that the theoretical framework of embodiment could provide a rehabilitation avenue to train these functions as one functional unit. PwMS (n = 31) and age- and gender-matched healthy controls (n = 30) underwent an embodied learning protocol. This involved learning a cognitive sequence while performing it through bodily stepping movement under three feedback conditions (melody, sound, and visual). Cognitive and movement performance was assessed by a delayed recall 15 min after undergoing the embodied learning protocol. Half of participants correctly recalled the sequence in all three conditions, while 70% of healthy controls achieved correct recall within the melody condition. Balance impairment predicted the speed of executing the sequence irrespective of learning, most apparent in the melody condition. Information processing speed predicted the speed of executing the sequence in the melody and sound conditions between participants as well as over time. Those who learned performed the sequence faster in the melody condition only and overall were faster over time. We propose how embodied learning could expand the current context of rehabilitation of cognitive and motor control in PwMS., (© 2022 New York Academy of Sciences.)

Background: The impact of the COVID-19 pandemic on physical therapy services for people with multiple sclerosis (pwMS) is unknown. Therefore, the Special Interest Group for Mobility (SIG Mobility) of the European Network for Best Practice and Research in Multiple Sclerosis Rehabilitation (RIMS) has undertaken the initiative to examine the impact of the COVID-19 outbreak on physical therapy services and physical activity participation in pwMS across Europe, Israel and Australia., Objective: To describe the impact of the COVID-19 outbreak on physical therapy practice from the perspective of the therapist., Methods: An online survey was developed and conducted from December 2020 to July 2021. The survey (50 questions), included multiple-choice questions and open-ended responses., Results: In total, 215 physical therapists (PT's) from 9 countries (Australia, Belgium, the Czech Republic, Ireland, Israel, Italy, Norway, Spain, and Turkey) participated in the study. The therapy most affected during the pandemic was aerobic training/conditioning exercises; 33.5% reported that these activities were either reduced or unavailable. In contrast, 15% of the PTs reported increased use of relaxation/mind body techniques and/or fatigue management programs during the pandemic. PTs reported a mixture of positive and negative feelings about the therapeutic sessions offered during the pandemic. Most reported positive feelings included "positive" (26.5%), and "optimistic" (24.7%). Negative feelings most frequently reported included "worried" (30.7%), and "hesitant" (20.9%). The PTs reported a 10% decrease in the use of hands-on techniques and a 10% increase in the use of oral instructions when treating moderately and severely pwMS during as compared to before the pandemic., Conclusion: The COVID-19 pandemic has affected physical therapy services in pwMS internationally in terms of content, frequency of use and format., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In a case report of a progressive multiple sclerosis with cerebellar impairments, we reported that synchronisation of steps to beats was possible only at -12% of usual walking cadence during 1 minute of walking., Objectives and Methods: Here, we investigate the effect of synchronisation using two different alignment approaches on the patient's gait pattern over 2 minutes of walking, compared to walking in silence., Results and Conclusion: This proof of concept showed that the adaptive approach was successful resulting in an improved gait pattern compared to the other conditions, providing preliminary evidence to support a full-scale intervention study.

Motor sequence learning in persons with multiple sclerosis (pwMS) and healthy controls (HC) under implicit or explicit learning conditions has not yet been investigated in a stepping task. Given the prevalent cognitive and mobility impairments in pwMS, this is important in order to understand motor learning processes and optimize rehabilitation strategies. Nineteen pwMS (the Expanded Disability Status Scale = 3.4 ± 1.2) and 18 HC performed a modified serial reaction time task by stepping as fast as possible on a stepping tile when it lit up, either with (explicit) or without (implicit) knowledge of the presence of a sequence beforehand. Motor sequence learning was studied by examining response time changes and differences between sequence and random blocks during the learning session (acquisition), 24 h later (retention), and in three dual-task (DT) conditions at baseline and retention (automaticity) using subtracting sevens, verbal fluency, and vigilance as concurrent cognitive DTs. Response times improved and were lower for the sequenced compared with the random blocks at the post- and retention tests (P's < 0.001). Response times during DT conditions improved after learning, but DT cost improved only for the subtracting sevens DT condition. No differences in learning were observed between learning conditions or groups. This study showed motor sequence learning, by acquisition and retention, in a stepping task in pwMS with motor impairments, to a similar degree as HC and regardless of learning conditions. Whether automaticity increased remains unclear., (© 2021 New York Academy of Sciences.)

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.)

Understanding rhythmic behavior in the context of coupled auditory and motor systems has been of interest to neurological rehabilitation, in particular, to facilitate walking. Recent work based on behavioral measures revealed an entrainment effect of auditory rhythms on motor rhythms. In this study, we propose a method to compute the neural component of such a process from an electroencephalographic (EEG) signal. A simple auditory-motor synchronization paradigm was used, where 28 healthy participants were instructed to synchronize their finger-tapping with a metronome. The computation of the neural outcome measure was carried out in two blocks. In the first block, we used Generalized Eigendecomposition (GED) to reduce the data dimensionality to the component which maximally entrained to the metronome frequency. The scalp topography pointed at brain activity over contralateral sensorimotor regions. In the second block, we computed instantaneous frequency from the analytic signal of the extracted component. This returned a time-varying measure of frequency fluctuations, whose standard deviation provided our " stability index " as a neural outcome measure of auditory-motor coupling. Finally, the proposed neural measure was validated by conducting a correlation analysis with a set of behavioral outcomes from the synchronization task: resultant vector length, relative phase angle, mean asynchrony, and tempo matching. Significant moderate negative correlations were found with the first three measures, suggesting that the stability index provided a quantifiable neural outcome measure of entrainment, with selectivity towards phase-correction mechanisms. We address further adoption of the proposed approach, especially with populations where sensorimotor abilities are compromised by an underlying pathological condition. The impact of using stability index can potentially be used as an outcome measure to assess rehabilitation protocols, and possibly provide further insight into neuropathological models of auditory-motor coupling., Competing Interests: The 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 Rosso, Leman and Moumdjian.)

Background: Performing a cognitive task and a motor task simultaneously is an everyday act that can lead to decreased performance on both tasks., Objective: To provide insight into the neural correlates associated with cognitive-motor dual tasking in individuals with a neurologic disorder., Method: We searched the PubMed and Web of Science databases for studies that had been published up to January 16th, 2019. Studies investigating the neural correlates of cognitive-motor dual task performance in individuals with a variety of neurologic disorders were included, independently from whether the study included healthy controls. Clinical and imaging data were abstracted for the comparison between single tasks and a dual task in the individuals with a neurologic disorder and for the comparison between the healthy controls and the individuals with a neurologic disorder., Results: Eighteen studies met the inclusion criteria. Study populations included individuals with Parkinson disease, multiple sclerosis, mild cognitive impairment, Alzheimer disease, traumatic brain injury, and stroke. Neuroimaging types used to study the neural correlates of cognitive-motor dual tasking during upper limb or gait tasks included fMRI, functional near-infrared spectroscopy, EEG, and PET., Conclusion: Despite large heterogeneity in study methodologies, some recurrent patterns were noted. Particularly, in neurologic patients, an already higher brain activation during single tasks was seen compared with healthy controls, perhaps compromising the patients' ability to further adapt brain activation with increasing load during dual tasking and resulting in reduced behavioral dual task performance., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. 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.)

Background/objective: Endurance exercise can improve memory function in persons with multiple sclerosis (pwMS), but the effects on hippocampal functioning are currently unknown. We investigated the effects of a running intervention on memory and hippocampal functional connectivity in pwMS., Methods/results: Memory and resting-state functional magnetic resonance imaging (fMRI) data were collected in a running intervention ( n  = 15) and waitlist group ( n  = 14). Visuospatial memory improvement was correlated to increased connectivity between the hippocampus and the default-mode network (DMN) in the intervention group only., Conclusion: As a result of endurance exercise, improvements in visuospatial memory may be mediated by a stronger functional embedding of the hippocampus in the DMN.

Background: Cognitive-motor interference (CMI) is measured by dual-tasking (DT), which involves motor and cognitive tasks. There is no consensus as to whether CMI is present in multiple sclerosis (MS). Objectives: We investigated the effects of 16 DT conditions by measuring motor complexity, cognitive domain, and task difficulty. Method: In total, 40 persons with MS (pwMSs) with Expanded Disease Status Scale (EDSS) 3.2 ± 1.7 and 31 age- and sex-matched healthy controls (HCs) completed 2 single walking, 8 single cognitive, and 2 complex walking tasks and 16 cognitive-motor DT. The main outcomes were mean values of gait velocity and the percentage change from single to DT (motor DT costs, mDTCs) and mean values of cognitive task accuracy and the percentage changes (cognitive DTC, cDTC). Results: Two-way analyses of variance showed the main effect of cognitive task yielded an F ratio of F (4, 268) = 72.35, p < 0.01, for mean gait velocity, and an F ratio of F (4, 304) = 17.12, p < 0.001, for mDTC, indicating that the mean velocity was significantly lower and the mDTC significantly higher for DS&#95;B (mean = 1.27, SD = 0.03, and mean = 13.52, SD = 1.28, respectively). The main effect of cognitive task yielded an F ratio of F (4, 116) = 84.32, p < 0.001, with the lowest average accuracy for DS&#95;B (mean = 43.95, SD = 3.33); no effect was found for cDTC. In pwMSs, the EDSS accounted for 28% ( F = 13.65, p = 0.001) of variance in a model predicting the highest mDTC. Conclusions: Overall, among different cognitive tasks added, the Digit Span backward was the most interfering cognitive task over gait velocity and accuracy. The effect was similar independently from the motor complexity and the group. PwMSs and HCs behaved in a similar manner at all motor complexity levels and during all cognitive task., (Copyright © 2020 Leone, Moumdjian, Patti, Vanzeir, Baert, Veldkamp, Van Wijmeersch and Feys.)

In persons with multiple sclerosis (PwMS), synchronizing walking to auditory stimuli such as to music and metronomes have been shown to be feasible, and positive clinical effects have been reported on step frequency and perception of fatigue. Yet, the dynamic interaction during the process of synchronization, such as the coupling of the steps to the beat intervals in music and metronomes, and at different tempi remain unknown. Understanding these interactions are clinically relevant, as it reflects the pattern of step intervals over time, known as gait dynamics. 28 PwMS and 29 healthy controls were instructed to walk to music and metronomes at 6 tempi (0-10% in increments of 2%). Detrended fluctuation analysis was applied to calculate the fractal statistical properties of the gait time-series to quantify gait dynamics by the outcome measure alpha. The results showed no group differences, but significantly higher alpha when walking to music compared to metronomes, and when walking to both stimuli at tempi + 8, + 10% compared to lower tempi. These observations suggest that the precision and adaptation gain differ during the coupling of the steps to beats in music compared to metronomes (continuous compared to discrete auditory structures) and at different tempi (different inter-beat-intervals).

Introduction: Fatigability, a change in performance according to tasks and circumstances, can contribute to walking limitations in daily life. Walking-related fatigability (WF) has been assessed subjectively, but current knowledge on best objective measurement methods is limited. The aim of this study was to provide an overview of objective clinical measurement methods assessing WF in different populations., Evidence Acquisition: Articles were searched in Pubmed and Web Of Science by two independent raters. Studies were included when meeting inclusion criteria of measuring WF objectively in a clinical setting, with no exclusion towards any population. Case studies and reviews were not included in the review (systematic review registration number: PROSPERO - CRD42017074121). In total, 28 articles were included. The study populations were older adults (N.=7), multiple sclerosis (N.=14), spinal muscle atrophy (N.=3), osteoarthritis (N.=3), interstitial lung diseases (N.=1), and myasthenia gravis (N.=1). Data about patient characteristics, walking task, WF formula and interpretation (cut-off values and/or psychometric properties) got extracted from included literature. Every included article got checked for quality and risk of bias., Evidence Synthesis: WF was mostly measured during longer walking test such as six-minute walking test (6MWT) and 500 or 400-m walking test, by comparing the first and last minute or lap for spatiotemporal or kinematic changes in well-defined formulas. No gold standard is however available yet given different tasks or outcome measures across study populations., Conclusions: Longer walking test were most often used, with a preference towards the 6MWT, thereby comparing the changes over the last and first part of the test. Psychometric properties need more documentation before inclusion as experimental outcome.

Background: In Persons with Multiple Sclerosis (PwMS), coupling walking to beats/pulses in short bursts is reported to be beneficial for cadence and perceived fatigue. However it is yet to be investigated if coupling and its effects can be sustained for longer durations, required for task-oriented training strategy in PwMS., Aims: To investigate if PwMS compared to healthy controls (HC) sustain synchronization for 12 min when walking to music and metronome, and its effects on perceived physical and cognitive fatigue, motivation and gait compared to walking in silence., Methods: Participants walked for 12 min in three conditions (music, metronome and silence). The tempo of the auditory conditions was individualized. Auditory-motor coupling and spatio-temporal gait parameters were measured during walking. The visual analogue scale was used for perceived fatigue, and the Likert scale for motivation., Results: 27 PwMS and 28 HC participated. All participants synchronized to both stimuli, yet PwMS synchronized better to music. Overall, participants had lower cadence, speed and stride length when over time all conditions, with an exception of HC, with increasing cadence during the music condition. PwMS perceived less cognitive fatigue, no difference in perceived physical fatigue and a higher motivation walking to music compared to metronomes and silence., Conclusion: 12 min of uninterrupted walking was possible in PwMS in all conditions, while better synchronization, low perception of cognitive fatigue and high motivation occurred with music compared to other conditions. Coupling walking to music could offer novel paradigms for motor task-oriented training in PwMS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background . Simultaneous execution of motor and cognitive tasks can result in worsened performance on one or both tasks, indicating cognitive-motor interference (CMI). A growing amount of research on CMI in persons with multiple sclerosis (pwMS) is observed. However, psychometric properties of dual-task outcomes have been scarcely reported. Objective . To investigate the between-day test-retest reliability of the motor and cognitive dual-task costs (DTCs) during multiple CMI test conditions with various task complexities in pwMS and matched healthy controls (HCs). Methods . A total of 34 pwMS (Expanded Disability Status Scale score 3.0 ± 0.8) and 31 HCs were tested and retested on 3 single cognitive, 4 single motor, and 12 cognitive-motor dual tasks. Cognitive tasks included serial subtraction by 7, titrated digit span backward, and auditory vigilance. Motor tasks were walking at self-selected speed, over obstacles, crisscross, and while carrying a water-filled cup. Outcome measures were cognitive and motor DTC, calculated as percentage change of dual-task performance compared with single-task performance. Intraclass correlations (ICCs) and Spearman correlation coefficients were calculated as appropriate. Results . For DTC motor of gait speed, ICCs ranged from 0.45 to 0.81 and Spearman correlations from 0.74 to 0.82. For DTC cognitive , ICCs ranged from -0.18 to 0.49 and Spearman correlations from -0.28 to 0.26. Reliability depended on the type of motor and cognitive task. Conclusion . Reliability of the DTC motor was, overall, good, whereas that of the DTC cognitive was poor. The "walking" and "cup" dual-task conditions were the most reliable regardless of the integrated cognitive task.

Evidence for using auditory-motor coupling in neurological rehabilitation to facilitate walking is increasing. However, the distinction between spontaneous and intended coupling and its underlying mechanisms is yet to be investigated. In this study, we include 30 persons with multiple sclerosis and 30 healthy controls (HCs) in an experiment with two sessions in which participants were asked to walk to music with various tempi, matching their preferred walking cadence (PWC) up to 10% above in incremental steps of 2%. In the first session, no instructions were given to synchronize. In the second, participants were instructed to synchronize steps to the beats. Spontaneous synchronization was possible at 0% and +2% of the PWC, and fewer persons with multiple sclerosis were able to do so compared with HCs. Instruction was needed to synchronize at above +2% tempo in all participants. In the instructed session, the +6% condition marked a cutoff for cognitively impaired persons, as they were no longer able to synchronize. Based on our findings, we constructed a model illustrating that spontaneous entrainment is limited, operating during spontaneous coupling at only 0% and +2% of the PWC, and that at a higher tempo, entrainment requires intentional synchronization, with an active cognitive control mechanism., (© 2019 New York Academy of Sciences.)

Background . Mobility dysfunctions are prevalent in persons with multiple sclerosis (PwMS), thus novel rehabilitation mechanisms are needed toward functional training. The effect of auditory cueing is well-known in Parkinson's disease, yet the application of different types of auditory stimuli at different tempi has not been investigated yet. Objectives . Investigating if PwMS, compared with healthy controls (HC), can synchronize their gait to music and metronomes at different tempi during walking and the effects of the stimuli on perceived fatigue and gait. Additionally, exploring if cognitive impairment would be a factor on the results. Methods . The experimental session consisted of 2 blocks, music and metronomes. Per block, participants walked 3 minutes per tempi, with instructions to synchronize their steps to the beat. The tempi were 0%, +2%, +4% +6%, +8%, +10% of preferred walking cadence (PWC). Results . A total of 28 PwMS and 29 HC participated. On average, participants were able to synchronize at all tempi to music and metronome. Higher synchronization was obtained for metronomes compared with music. The highest synchronization for music was found between +2% and +8% of PWC yet pwMS perceived less physical and cognitive fatigue walking to music compared with metronomes. Cognitive impaired PwMS (n = 9) were not able to synchronize at tempi higher than +6%. Conclusion . Auditory-motor coupling and synchronization was feasible in HC and PwMS with motor and cognitive impairments. PwMS walked at higher tempi than their preferred walking cadence, and lower fatigue perception with music. Coupling walking to music could be a promising functional walking training strategy.

Background: Exercise therapy studies in persons with multiple sclerosis (pwMS) primarily focused on motor outcomes in mid disease stage, while cognitive function and neural correlates were only limitedly addressed., Objectives: This pragmatic randomized controlled study investigated the effects of a remotely supervised community-located "start-to-run" program on physical and cognitive function, fatigue, quality of life, brain volume, and connectivity., Method: In all, 42 pwMS were randomized to either experimental (EXP) or waiting list control (WLC) group. The EXP group received individualized training instructions during 12 weeks (3×/week), to be performed in their community aiming to participate in a running event. Measures were physical (VO 2max , sit-to-stand test, Six-Minute Walk Test (6MWT), Multiple Sclerosis Walking Scale-12 (MSWS-12)) and cognitive function (Rao's Brief Repeatable Battery (BRB), Paced Auditory Serial Attention Test (PASAT)), fatigue (Fatigue Scale for Motor and Cognitive Function (FSMC)), quality of life (Multiple Sclerosis Impact Scale-29 (MSIS-29)), and imaging. Brain volumes and diffusion tensor imaging (DTI) were quantified using FSL-SIENA/FIRST and FSL-TBSS., Results: In all, 35 pwMS completed the trial. Interaction effects in favor of the EXP group were found for VO 2max , sit-to-stand test, MSWS-12, Spatial Recall Test, FSMC, MSIS-29, and pallidum volume. VO 2max improved by 1.5 mL/kg/min, MSWS-12 by 4, FSMC by 11, and MSIS-29 by 14 points. The Spatial Recall Test improved by more than 10%., Conclusion: Community-located run training improved aerobic capacity, functional mobility, visuospatial memory, fatigue, and quality of life and pallidum volume in pwMS.

People with multiple sclerosis (PwMS) are less physically active compared with the general population. This might also be because of the perception of temporary worsening of symptoms during physical activity. Forty-two PwMS with a mild level of disability underwent a maximal exercise test on a bicycle ergometer. Fifteen minutes before and 15 and 75 min after the maximal exercise test, the 6-minute walking test was conducted and the rate of perceived exertion was recorded. Twice before and three times after the maximal exercise test, participants rated the symptom inventory, including symptom domains of general fatigue, muscle fatigue, balance, gait pattern, muscle weakness, spasticity, pain, sensory disturbance, dizziness, and visual impairment. The visual analogue scale was used to rate the perceived symptoms from 0 (no intensity) to 10 (maximal intensity). The 6-minute walking test distance increased significantly over time, whereas the rate of perceived exertion increased temporarily after the maximal exercise test. Immediately after the maximal exercise test, significant temporary increases were found in balance, gait pattern, muscle weakness, and visual impairment. General and muscle fatigue were elevated, compared with the baseline, till 15 and 75 min after the maximal exercise test, respectively. A short-term impact of a single maximal exercise test was considered as the temporary worsening of perceived symptoms, especially (muscle) fatigue and the gait pattern, in PwMS with a mild level of disability. However, a recovery was observed after 75 min. Walking endurance was not affected by the maximal exercise test.

Background: Interdisciplinary work is needed for scientific progress, and with this review, our interest is in the scientific progress toward understanding the underlying mechanisms of auditory-motor coupling, and how this can be applied to gait rehabilitation. Specifically we look into the process of entrainment and synchronization; where entrainment is the process that governs the dynamic alignments of the auditory and motor domains based on error-prediction correction, whereas synchronization is the stable maintenance of timing during auditory-motor alignment. Methodology: A systematic literature search in databases PubMed and Web of Science were searched up to 9th of August 2017. The selection criteria for the included studies were adult populations, with a minimum of five participants, investigating walking to an auditory stimulus, with an outcome measure of entrainment, and synchronization. The review was registered in PROSPERO as CRD42017080325. Objectives: The objective of the review is to systematically describe the metrics which measure entrainment and synchronization to auditory stimuli during walking in healthy and neurological populations. Results: Sixteen articles were included. Fifty percent of the included articles had healthy controls as participants ( N = 167), 19% had neurological diseases such as Huntington's and Stroke ( N = 76), and 31% included both healthy and neurological [Parkinson's disease (PD) and Stroke] participants ( N = 101). In the included studies, six parameters were found to capture the interaction between the human movement and the auditory stimuli, these were: cadence, relative phase angle, resultant vector length, interval between the beat and the foot contact, period matching performance, and detrended fluctuation analysis. Conclusion: In this systematic review, several metrics have been identified, which measure the timing aspect of auditory-motor coupling and synchronization of auditory stimuli in healthy and neurological populations during walking. The application of these metrics may enhance the current state of the art and practice across the neurological gait rehabilitation. These metrics also have current shortcomings. Of particular pertinence is our recommendation to consider variability in data from a time-series rather than time-windowed viewpoint. We need it in view of the promising practical applications from which the studied populations may highly benefit in view of personalized medical care.

Background: Motor and cognitive symptoms are frequent in persons with neurological disorders and often require extensive long-term rehabilitation. Recently, a variety of music-based interventions have been introduced into neurological rehabilitation as training tools., Evidence Acquisition: This review aims to 1) describe and define music-based intervention modalities and content which are applied in experimental studies; and 2) describe the effects of these interventions on motor and/or cognitive symptoms in the neurological population. The databases PubMed and Web of Science were searched. Cited references of included articles where screened for potential inclusion. A systematic literature search up to 20th of June 2016 was conducted to include controlled trials and cohort studies that have used music-based interventions for ≥3 weeks in the neurological population (in- and outpatients) targeting motor and/or cognitive symptoms. No limitations to publication date was set. EVIDENCE SYNTHESISː Nineteen articles comprising thirteen randomized controlled trials (total participants Nexp=241, Nctrl=269), four controlled trials (Nexp=59, Nctrl=53) and two cohort studies (N.=27) were included. Fourteen studies were conducted in stroke, three in Parkinson's disease, and two in multiple sclerosis population. Modalities of music-based interventions were clustered into four groups: instrument-based, listening-based, rhythm-based, and multicomponent-based music interventions. Overall, studies consistently showed that music-based interventions had similar or larger effects than conventional rehabilitation on upper limb function (N.=16; fine motricity, hand and arm capacity, finger and hand tapping velocity/variability), mobility (N.=7; gait parameters), and cognition (N.=4; verbal memory and focused attention). CONCLUSIONSː Variety of modalities using music-based interventions has been identified and grouped into four clusters. Effects of interventions demonstrate an improvement in the domains assessed. Evidence is most available for improving motricity in stroke. More studies are warranted to investigate cognition as well as motor and cognition dysfunctions in combination. Instrument-based music interventions can improve fine motor dexterity and gross motor functions in stroke. Rhythm-based music interventions can improve gait parameters of velocity and cadence in stroke, Parkinson's disease and multiple sclerosis. Cognition in the domains of verbal memory and focused attention can improve after listening-based music interventions in stroke.

Cognitive-motor interference refers to dual-tasking (DT) interference (DTi) occurring when the simultaneous performance of a cognitive and a motor task leads to a percentage change in one or both tasks. Several theories exist to explain DTi in humans: the capacity-sharing, the bottleneck and the cross-talk theories. Numerous studies investigating whether a specific brain locus is associated with cognitive-motor DTi have been conducted, but not systematically reviewed. We aimed to review the evidences on brain activity associated with the cognitive-motor DT, in order to better understand the neurological basis of the CMi. Results were reported according to the technique used to assess brain activity. Twenty-three articles met the inclusion criteria. Out of them, nine studies used functional magnetic resonance imaging to show an additive, under-additive, over- additive, or a mixed activation pattern of the brain. Seven studies used near-infrared spectroscopy, and seven neurophysiological instruments. Yet a specific DT locus in the brain cannot be concluded from the overall current literature. Future studies are warranted to overcome the shortcomings identified., (Copyright © 2017 Elsevier Ltd. All rights reserved.)