Translingual neurostimulation combined with physical therapy to improve walking and balance in multiple sclerosis (NeuroMSTraLS): Study protocol for a randomized controlled trial

INTRODUCTION: Physical rehabilitation restores lost function and promotes brain plasticity in people with Multiple Sclerosis (MS). Research groups worldwide are testing the therapeutic effects of combining non-invasive neuromodulation with physical therapy (PT) to further improve functional outcomes in neurological disorders but with mixed results. Whether such devices enhance function is not clear. We present the rationale and study design for a randomized controlled trial evaluating if there is additional benefit to the synergistic pairing of translingual neurostimulation (TLNS) with PT to improve walking and balance in MS. METHODS AND ANALYSIS: A parallel group [PT + TLNS or PT + Sham], quadruple-blinded, randomized controlled trial. Participants (N = 52) with gait and balance deficits due to relapsing-remitting or progressive MS, who are between 18 and 70 years of age, will be recruited through patient registries in Newfoundland & Labrador and Saskatchewan, Canada. All participants will receive 14 weeks of PT while wearing either a TLNS or sham device. Dynamic Gait Index is the primary outcome. Secondary outcomes include fast walking speed, subjective ratings of fatigue, MS impact, and quality of life. Outcomes are assessed at baseline (Pre), after 14 weeks of therapy (Post), and 26 weeks (Follow Up). We employ multiple methods to ensure treatment fidelity including activity and device use monitoring. Primary and secondary outcomes will be analyzed using linear mixed-effect models. We will control for baseline score and site to test the effects of Time (Post vs. Follow-Up), Group and the Group x Time interaction as fixed effects. A random intercept of participant will account for the repeated measures in the Time variable. Participants must complete the Post testing to be included in the analysis. ETHICS AND DISSEMINATION: The Human Research Ethics Boards in Newfoundland & Labrador (HREB#2021.085) & Saskatchewan (HREB Bio 2578) approved the protocol. Dissemination avenues include peer-reviewed journals, conferences and patient-oriented communications

Participants’ perspectives of “NeuroSask: Active and Connect”—a virtual chronic disease management program for individuals with a neurological condition

IntroductionNeurological conditions account from more than half of Canadians requiring chronic care. Both physical activity and the development of a self-management skillset are critical components supporting individuals with chronic health conditions. “NeuroSask: Active and Connected” is a virtual chronic disease management program offering twice weekly neuro-physiotherapist directed “active” exercise sessions, followed by weekly knowledge-exchange “connect” sessions with invited guest experts. NeuroSask was launched April 2020 in response to the restricted services and supports for people with neurological conditions. The program aimed to provide seated physical activity, social interaction, and access to expertise in neurological conditions and neurorehabilitation. A program evaluation of NeuroSask was conducted to gain participants’ perspectives.MethodsAll participants registered for the NeuroSask program were invited to complete optional online surveys (SurveyMonkey) circulated by email at 3 occasions post-program launch: 10 weeks, 1 year, and 2 years. Participants could complete any one or all of the surveys, at their discretion. The number of potential respondents changed dependent on the total number of participants registered for NeuroSask at the time the survey was circulated. Questions were co-designed by multi-stakeholder team members. Descriptive statistics were used for closed-ended questions and a reflexive thematic analysis was completed with coding conducted in NVivo 12 Plus for open-ended text.ResultsResponse rates (participants/registrants) were as follows: 10-week survey 260/793, one year survey 326/1224, and 2-year survey 434/1989. 90% of participants reported being in either the age categories of 40–59 years or above 60 years. 75% of both survey respondents and program registrants were female. 70% of both survey respondents and program registrants reported a diagnosis of multiple sclerosis and 30% reported other neurological conditions. Survey respondents were from all ten Canadian provinces, with 45% reporting living outside of large cities. Respondents reported preferring online vs. in person format for this type of programming. Three main themes, and eight corresponding subthemes were identified highlighting the perceived impact and key components of the NeuroSask program: Theme 1 “together in a positive and encouraging environment” (subthemes 1a: connection, 1b: empowerment); Theme 2 “access to enthusiastic qualified leaders from home” (subthemes 2a: leader characteristics, 2b: accessibility, 2c: program logistics); Theme 3 “being able to enjoy everyday life” (subthemes 3a: symptom benefits and beyond, 3b: carry-over, 3c: keep going, please do not cancel).ConclusionNeuroSask is an example of an accessible and meaningful virtual approach to providing ongoing support for some individuals with neurological conditions. It was perceived as beneficial for fostering community and connection in a positive environment with perceived benefits extending beyond symptom management to participant reported improvements in function, daily life, and disease experience

Implementation of increased physical therapy intensity for improving walking after stroke: Walk 'n Watch protocol for a multi-site stepped-wedge cluster randomized controlled trial

Clinical practice guidelines support structured, progressive protocols for improving walking after stroke. Yet, practice is slow to change, evidenced by the little amount of walking activity in stroke rehabilitation units. Our recent study (n=75) found that a structured, progressive protocol integrated with typical daily physical therapy improved walking and quality of life measures over usual care. Research therapists progressed the intensity of exercise by using heart rate and step counters worn by the participants with stroke during therapy. To have the greatest impact, our next step is to undertake an implementation trial to change practice across stroke units where we enable the entire unit to use the protocol as part of standard of care. What is the effect of introducing structured, progressive exercise (termed the Walk 'n Watch protocol) to standard of care on the primary outcome of walking in adult participants with stroke over the hospital inpatient rehabilitation period? Secondary outcomes will be evaluated and include quality of life.Methods and sample size estimates: This national, multisite clinical trial will randomize 12 sites using a stepped-wedge design where each site will be randomized to deliver Usual Care initially for 4, 8, 12 or 16-months (three sites for each duration). Then, each site will switch to the Walk 'n Watch phase for the remaining duration of a total 20-month enrolment period. Each participant will be exposed to only one of Usual Care or Walk 'n Watch. The trial will enrol a total of 195 participants with stroke to achieve a power of 80% with a Type I error rate of 5%, allowing for 20% dropout. Participants will be medically stable adults post-stroke and able to take 5 steps with a maximum physical assistance from one therapist. The Walk 'n Watch protocol focuses on completing a minimum of 30-minutes of weight-bearing, walking-related activities (at the physical therapists' discretion) that progressively increases in intensity informed by activity trackers measuring heart rate and step number.Study outcome(s): The primary outcome will be the change in walking endurance, measured by the Six-Minute Walk Test, from Baseline (T1) to 4-weeks (T2). This change will be compared across Usual Care and Walk 'n Watch phases using a linear mixed-effects model. Additional physical, cognitive, and quality of life outcomes will be measured at T1, T2, and 12-months post-stroke (T3) by a blinded assessor. The implementation stepped-wedge cluster-randomized trial enables the protocol to be tested under real-world conditions, involving all clinicians on the unit. It will result in all sites and all clinicians on the unit to gain expertise in protocol delivery. Hence, a deliberate outcome of the trial is facilitating changes in best practice to improve outcomes for participants with stroke in the trial, and for the many participants with stroke admitted after the trial ends

Modulation of early and late event-related potentials by emotion

Although emotionally salient stimuli influence higher order information processing, the relative vulnerability of specific stages of cognitive processing to modulation by emotional input remains elusive. To test the temporal dynamics of emotional interference during executive function, we recorded event-related potentials while participants performed an effortful anticipation task with aversive emotional and neutral distracters. Participants were presented with a modified delayed Stroop task that dissociated the anticipation of an easier or more difficult task (instructional cues to attend to word versus color) from the response to the Stroop stimulus, while aversive and neutral pictures were displayed during the delay period. Our results indicated a relative decrease in the amplitude of the contingent negative variation (CNV) during aversive trials that was greater during the early anticipatory phase than during the later response preparation phase, and greater during (the more difficult) color than word trials. During the initial stage of cue processing, there was also significant interaction between emotion and anticipatory difficulty on N1 amplitude, where emotional stimuli led to significantly enhanced negativity during color cues relative to word cues. These results suggest that earlier processes of orientation and effortful anticipation may reflect executive engagement that is influenced by emotional interference while later phases of response preparation may be modulated by emotional interference regardless of anticipatory difficulty

Task-oriented exercise effects on walking and corticospinal excitability in multiple sclerosis: protocol for a randomized controlled trial

Abstract Background Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) that disrupts walking function and results in other debilitating symptoms. This study compares the effects of ‘task-oriented exercise’ against ‘generalized resistance and aerobic exercise’ and a ‘stretching control’ on walking and CNS function in people with MS (PwMS). We hypothesize that task-oriented exercise will enhance walking speed and related neural changes to a greater extent than other exercise approaches. Methods This study is a single-blinded, three-arm randomized controlled trial conducted in Saskatchewan, Canada. Eligible participants are those older than 18 years of age with a diagnosis of MS and an expanded Patient-Determined Disease Steps (PDDS) score between 3 (‘gait disability’) and 6 (‘bilateral support’). Exercise interventions are delivered for 12 weeks (3 × 60-min per week) in-person under the supervision of a qualified exercise professional. Interventions differ in exercise approach, such that task-oriented exercise involves weight-bearing, walking-specific activities, while generalized resistance and aerobic exercise uses seated machine-based resistance training of major upper and lower body muscle groups and recumbent cycling, and the stretching control exercise involves seated flexibility and relaxation activities. Participants are allocated to interventions using blocked randomization that stratifies by PDDS (mild: 3–4; moderate: 5–6). Assessments are conducted at baseline, post-intervention, and at a six-week retention time point. The primary and secondary outcome measures are the Timed 25-Foot Walk Test and corticospinal excitability for the tibialis anterior muscles determined using transcranial magnetic stimulation (TMS), respectively. Tertiary outcomes include assessments of balance, additional TMS measures, blood biomarkers of neural health and inflammation, and measures of cardiorespiratory and musculoskeletal fitness. Discussion A paradigm shift in MS healthcare towards the use of “exercise as medicine” was recently proposed to improve outcomes and alleviate the economic burden of MS. Findings will support this shift by informing the development of specialized exercise programming that targets walking and changes in corticospinal excitability in PwMS. Trial registration ClinicalTrials.gov, NCT05496881, Registered August 11, 2022. https://classic.clinicaltrials.gov/ct2/show/NCT05496881 . Protocol amendment number: 01; Issue date: August 1, 2023; Primary reason for amendment: Expand eligibility to include people with all forms of MS rather than progressive forms of MS only

Data_Sheet_1_Participants’ perspectives of “NeuroSask: Active and Connect”—a virtual chronic disease management program for individuals with a neurological condition.docx

IntroductionNeurological conditions account from more than half of Canadians requiring chronic care. Both physical activity and the development of a self-management skillset are critical components supporting individuals with chronic health conditions. “NeuroSask: Active and Connected” is a virtual chronic disease management program offering twice weekly neuro-physiotherapist directed “active” exercise sessions, followed by weekly knowledge-exchange “connect” sessions with invited guest experts. NeuroSask was launched April 2020 in response to the restricted services and supports for people with neurological conditions. The program aimed to provide seated physical activity, social interaction, and access to expertise in neurological conditions and neurorehabilitation. A program evaluation of NeuroSask was conducted to gain participants’ perspectives.MethodsAll participants registered for the NeuroSask program were invited to complete optional online surveys (SurveyMonkey) circulated by email at 3 occasions post-program launch: 10 weeks, 1 year, and 2 years. Participants could complete any one or all of the surveys, at their discretion. The number of potential respondents changed dependent on the total number of participants registered for NeuroSask at the time the survey was circulated. Questions were co-designed by multi-stakeholder team members. Descriptive statistics were used for closed-ended questions and a reflexive thematic analysis was completed with coding conducted in NVivo 12 Plus for open-ended text.ResultsResponse rates (participants/registrants) were as follows: 10-week survey 260/793, one year survey 326/1224, and 2-year survey 434/1989. 90% of participants reported being in either the age categories of 40–59 years or above 60 years. 75% of both survey respondents and program registrants were female. 70% of both survey respondents and program registrants reported a diagnosis of multiple sclerosis and 30% reported other neurological conditions. Survey respondents were from all ten Canadian provinces, with 45% reporting living outside of large cities. Respondents reported preferring online vs. in person format for this type of programming. Three main themes, and eight corresponding subthemes were identified highlighting the perceived impact and key components of the NeuroSask program: Theme 1 “together in a positive and encouraging environment” (subthemes 1a: connection, 1b: empowerment); Theme 2 “access to enthusiastic qualified leaders from home” (subthemes 2a: leader characteristics, 2b: accessibility, 2c: program logistics); Theme 3 “being able to enjoy everyday life” (subthemes 3a: symptom benefits and beyond, 3b: carry-over, 3c: keep going, please do not cancel).ConclusionNeuroSask is an example of an accessible and meaningful virtual approach to providing ongoing support for some individuals with neurological conditions. It was perceived as beneficial for fostering community and connection in a positive environment with perceived benefits extending beyond symptom management to participant reported improvements in function, daily life, and disease experience.</p

Shoot flammability of vascular plants is phylogenetically conserved and related to habitat fire-proneness and growth form

Terrestrial plants and fire have interacted for at least 420 million years. Whether recurrent fire drives plants to evolve higher flammability and what the evolutionary pattern of plant flammability is remain unclear. Here, we show that phylogeny, the susceptibility of a habitat to have recurrent fires (that is, fire-proneness) and growth form are important predictors of the shoot flammability of 194 indigenous and introduced vascular plant species (Tracheophyta) from New Zealand. The phylogenetic signal of the flammability components and the variation in flammability among phylogenetic groups (families and higher taxonomic level clades) demonstrate that shoot flammability is phylogenetically conserved. Some closely related species, such as in Dracophyllum (Ericaceae), vary in flammability, indicating that flammability exhibits evolutionary flexibility. Species in fire-prone ecosystems tend to be more flammable than species from non-fire-prone ecosystems, suggesting that fire may have an important role in the evolution of plant flammability. Growth form also influenced flammability—forbs were less flammable than grasses, trees and shrubs; by contrast, grasses had higher biomass consumption by fire than other groups. The results show that shoot flammability of plants is largely correlated with phylogenetic relatedness, and high flammability may result in parallel evolution driven by environmental factors, such as fire regime