Rationale and methodology for examining the combination of aerobic exercise and cognitive rehabilitation on new learning and memory in persons with multiple sclerosis and mobility disability: Protocol for a randomized controlled trial.

BACKGROUND: This paper describes the protocol for a Phase I/II, parallel-group, single-blind randomized controlled trial (RCT). The RCT investigates the combined effects of 12-weeks of aerobic exercise training (AET) integrated with virtual reality (VR) and cognitive rehabilitation (CR) on new learning and memory in 78 persons with multiple sclerosis (MS) who have mobility disability and objective impairments in learning and memory. METHODS: Participants will undergo baseline assessments consisting of neuropsychological testing, neuroimaging, self-report questionnaires, and cardiorespiratory fitness. Participants will then be randomized into one of two conditions using concealed allocation: aerobic cycling exercise that incorporates VR combined with CR or stretching and toning (i.e., active control; S/T) combined with CR. Participants will be masked regarding the intent of the conditions. After 7-weeks of exercise alone, the 5-week Kessler Foundation modified Story Memory Technique (KF-mSMT®) will be integrated into the training. After the 12-week training period, participants will complete the same measures as at baseline administered by treatment-blinded assessors. Primary study outcomes include new learning and memory (NLM) measured by a small battery of neuropsychological assessments that assess list learning (California Verbal Learning Test-II), prose memory (Memory Assessment Scale), visuospatial memory (Brief Visuospatial Memory Test-Revised), and everyday memory (Ecological Memory Simulations). Secondary study outcomes include neuroimaging outcomes of hippocampal structure, function, and connectivity. CONCLUSION: If successful, this trial will provide the first Class I evidence supporting the unique combination of aerobic cycling exercise with VR and CR for treating MS-related learning and memory impairments in persons with mobility disability.

Exercise as a behavioral approach to improve mood in persons with traumatic brain injury.

Mood disturbance is a common, long-term, negative consequence of traumatic brain injury (TBI) that is insufficiently addressed by most traditional treatment modalities. A large body of evidence supports the efficacy of exercise training (ET) to broadly improve mood, as measured most often by the Profile of Mood States (POMS). However, this behavioral approach is not used nearly enough in the TBI population, and when it is, mood is rarely measured. This scoping review will evaluate the use of POMS as a mood measure in TBI research and to establish a rationale for using ET as a behavioral approach to broadly improve mood in persons with TBI.

The effects of cognitive rehabilitation combined with aerobic exercise or stretching-and-toning on new learning and memory in persons with moderate-to-severe TBI: Protocol for a randomized controlled trial.

This paper describes the protocol for a Phase I/II, parallel-group, blinded randomized controlled trial that compares the effects of 12-weeks of combined learning and memory rehabilitation with either aerobic cycling exercise or stretching on cognitive, neuroimaging, and everyday life outcomes in 60 persons with moderate-to-severe traumatic brain injury (TBI) who demonstrate impairments in new learning. Briefly, participants will undergo baseline testing consisting of neuropsychological testing, neuroimaging, daily life measures, and cardiorespiratory fitness. Following baseline testing, participants will be randomized to one of 2 conditions (30 participants per condition) using concealed allocation. Participants will be masked as to the intent of the conditions. The conditions will both involve supervised administration of an enhanced, 8-week version of the Kessler Foundation modified Story Memory Technique, embedded within either 12-weeks of supervised and progressive aerobic cycling exercise training (experimental condition) or 12-weeks of supervised stretching-and-toning (active control condition). Following the 12-week intervention period, participants will complete the same measures as at baseline that will be administered by treatment-blinded assessors. The primary study outcome is new learning and memory impairment based on California Verbal Learning Test (CVLT)-III slope, the secondary outcomes include neuroimaging measures of hippocampal volume, activation, and connectivity, and the tertiary outcomes involve measures of daily living along with other cognitive outcomes. We further will collect baseline sociodemographic data for examining predictors of response heterogeneity. If successful, this trial will provide the first Class I evidence supporting combined memory rehabilitation and aerobic cycling exercise training for treating TBI-related new learning and memory impairment.

Feasibility of remotely delivered and supported aerobic walking exercise training for cognitive processing speed impairment in fully-ambulatory persons with multiple sclerosis.

PURPOSE: The current pilot, single-blind, randomized controlled trial (RCT) examined the feasibility of remotely-delivered and supported aerobic walking exercise training compared with an active control condition on cognitive processing speed (CPS) in 19 fully-ambulatory persons with multiple sclerosis (pwMS) who were pre-screened for impaired CPS. METHODS: Feasibility was assessed in the domains of process (e.g., recruitment), resource (e.g., monetary costs), management (e.g., time requirements), and scientific outcomes (i.e., treatment effect). Fully-ambulatory, but CPS-impaired pwMS were randomly assigned into either 16-weeks of home-based aerobic walking exercise or home-based stretching and range-of-motion activities. Both conditions involved delivery of informational newsletters and one-on-one, online video chats with a behavior coach. Participants across both conditions tracked their activity using highly accurate wearable motion sensors. Treatment-blinded assessors administered the Symbol Digit Modalities Test (SDMT) remotely before and after the 16-week study period. RESULTS: The study was cost-effective, accessible, and acceptable. The intervention further was safe. Adherence and compliance rates across both conditions exceeded 80%. There was an overall moderate effect for change in SDMT score between the conditions (d = 0.42). The intervention was associated with a 4.8-point improvement in SDMT scores (d = 0.70; 10% increase) compared with a 1-point improvement for the control condition (d = 0.09; 2% increase). CONCLUSIONS: This remotely-delivered and supported aerobic walking exercise training intervention was safe and feasible for fully-ambulatory, CPS-impaired pwMS. The pattern of results, including the promising effects on CPS, support the design and implementation of an appropriately-powered RCT on this approach for managing CPS impairment in a large MS sample.

Rationale and methodology for examining the acute effects of aerobic exercise combined with varying degrees of virtual reality immersion on cognition in persons with TBI.

Persons with Traumatic Brain Injury (TBI) commonly present with long-term cognitive deficits in executive function, processing speed, attention, and learning and memory. While specific cognitive rehabilitation techniques have shown significant success for deficits in individual domains, aerobic exercise training represents a promising approach for an efficient and general treatment modality that might improve many cognitive domains concurrently. Existing studies in TBI report equivocal results, however, and are hampered by methodological concerns, including small sample sizes, uncontrolled single-group designs, and the use of suboptimal exercise modalities for eliciting cognitive improvements in this population. One particularly promising modality involves the application of environmental enrichment via virtual reality (VR) during aerobic exercise in persons with TBI, but this has yet to be investigated. One approach for systematically developing an optimal aerobic exercise intervention for persons with TBI involves the examination of single bouts of aerobic exercise (i.e., acute aerobic exercise) on cognition. Acute exercise research is a necessary first step for informing the development of high-quality exercise training interventions that are more likely to induce meaningful beneficial effects. To date, such an acute exercise paradigm has yet to be conducted in persons with TBI. To that end, we propose an acute exercise study that will investigate the acute effects of aerobic exercise with incremental degrees of environmental enrichment (VR) relative to a control comparison condition on executive function (divided attention and working memory) and processing speed in 24 people with TBI.

The Effect of Chronic Exercise on Energy and Fatigue States: A Systematic Review and Meta-Analysis of Randomized Trials.

In this meta-analysis, we synthesized the results of randomized controlled trials of different exercise training interventions on participants' feelings of fatigue, energy, and vitality. The search of studies was conducted using six databases as well as several other supplementary search strategies available before December 2021. The initial search generated over 3,600 articles with 81 studies (7,050 participants) and 172 effects meeting the inclusion criteria. We analyzed the effects from the studies using a meta-analytic multivariate model and considered the potential moderating effect of multiple variables. Our analysis revealed exercise to decrease the feelings of fatigue by a small effect size (g = -0.374; 95% CI [-0.521, -0.227]), increase energy by a small-to-moderate effect size (g = 0.415; 95% CI [0.252, 0.578]), and to increase the feeling of vitality by a moderate effect size (g = 0.537; 95% CI [0.404, 0.671]). All main results remained robust after several sensitivity analyses using different statistical estimators, and consideration of outlier and influential studies. Moreover, moderator analyses revealed significant effects of exercise intensity and intervention duration on fatigue, exercise intensity, and modality on energy, and participant health, exercise intensity modality, and exercise training location on vitality. We conclude that when groups adopt a moderate intensity exercise training program while participating in a randomized trial, compared to controls, this typically results in small-to-moderate average improvements in feelings of fatigue, energy, and vitality.

Virtual reality-based distraction on pain, performance, and anxiety during and after moderate-vigorous intensity cycling.

PURPOSE: To determine whether increased visual perceptual load (PL) within an immersive virtual environment may help explain previously shown pain-relieving effects of virtual reality (VR) during high intensity cycling. METHODS: Using a within-subjects design, participants cycled at a perceptually "hard" intensity for 10 min on three separate occasions. The first session did not use VR (i.e., no perceptual load - NPL). Subsequent sessions employed VR during cycling with either a low or high perceptual load (LPL or HPL). Quadriceps pain intensity (PI) was reported by participants throughout cycling. RESULTS: Data were analyzed for 43 healthy participants (20 females, mean age 21  [SD 1.4]). For PI, ANOVA showed there were significant main effects of condition (F = 13.458, df =1.579, 66.334, p<0.001) and time (F = 113.045, df =1.618, 227.683, p<0.001). At every time point, t-tests revealed mean PI was significantly lower in the NPL than in the LPL condition (t(42)=4.737, p<0.001, d = 0.472) and HPL condition (t(42)=3.380, p = 0.002, d = 0.391). Dependent t-tests showed that more work (kilojoules) was performed during the LPL condition than the NPL (t(42)=2.992, p = 0.005) and HPL (t(42)=5.810, p<0.001) conditions. CONCLUSIONS: Compared to a traditional 10-minute bout of cycle ergometry (NPL), individuals who cycled in the LPL condition chose to exercise at a higher intensity despite greater PI. Those who cycled in the HPL condition did not change their exercise intensity, but did report higher PI, possibly, because of the greater mental effort/energy requirement.

The preliminary effects of moderate aerobic training on cognitive function in people with TBI and significant memory impairment: a proof-of-concept randomized controlled trial.

This single-blinded RCT investigated cognitive effects of aerobic exercise in persons with TBI-related memory impairment. Five participants . were randomly assigned to 12-weeks of either supervised moderate intensity aerobic cycling or an active control. Outcome measures included neuropsychological assessments and structural neuroimaging (MRI,). The exercise group demonstrated greater improvements on auditory verbal learning (RAVLT; d=1.54) and processing speed (SDMT; d=1.58). The exercise group showed larger increases in volume of the left hippocampus (d=1.49) and right thalamus (d=1.44). These pilot data suggest that 12-weeks of moderate intensity aerobic cycling may improve memory and processing speed in those with TBI-related memory impairments.

Interactive Virtual Reality Reduces Quadriceps Pain during High-Intensity Cycling.

PURPOSE: Brief, high-intensity cycling is popular because physiological benefits accrue with a short workout time, but burning pain in the quadriceps is a potential barrier to engaging in this type of exercise. Virtual reality (VR) can temporarily decrease pain, but its effect on muscle pain during high-intensity exercise is unknown. The primary purpose of this experiment was to test whether adding interactive VR (I-VR) to high-intensity cycling could reduce quadriceps pain or improve performance. METHODS: Ninety-four adults who were physically active in their leisure time and age 18 to 29 yr completed three 30-s sprint interval cycling trials at a high resistance (0.085- and 0.075-kg resistance to the flywheel per kilogram body weight for men and women, respectively). In this randomized between-subject experiment, participants cycled while wearing a head-mounted display and viewing either (i) a dynamically changing cityscape perceived as interactively cycling through a virtual city (I-VR group) or (ii) a static picture of the cityscape with instructions to mentally imagine cycling through that city (static VR/motor imagery control group). RESULTS: Sphericity-adjusted 2 × 3 (group-time) ANOVA revealed a significant group-time interaction (F = 4.568; df = 1.499, 133.301; ηp = 0.047, P = 0.021) for pain intensity. With I-VR, pain intensities were 13.3% (mean, 4.60 vs 5.31; d = 0.28) and 11.8% (mean, 5.68 vs 6.44; d = 0.27) lower at sprint trials 2 and 3, respectively. The group-time interaction (P = 0.412) was not significant for total work. CONCLUSION: Compared with a static VR/motor imagery control condition, I-VR during brief, high-intensity, fatigue-inducing leg cycling attenuates quadriceps pain intensity without reducing performance.