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Persons with stroke often have difficulty achieving target heart rate during graded exercise testing (GXT), which is known to limit test sensitivity for detecting clinically relevant cardiac conditions. A novel Recumbent Stepper 3-minute (RS 3Min) 'all out' test may increase sensitivity of stress testing after stroke.The purpose of this study was to determine the feasibility of adding a Recumbent Stepper 3Min test after a GXT among persons' post-stroke.A within-subject, non-randomized, repeated measures design.Rehabilitation research laboratory and cardiovascular stress laboratory PARTICIPANTS: Fifteen participants with chronic stroke (56.7 ± 9.6 years; 6.4 ± 4.3 years post stroke; 8 male).All participants randomly completed 1) a symptom-limited treadmill GXT; and 2) a symptom-limited RS GXT followed by a RS 3Min critical power test.Heart rate, ratings of perceived exertion, oxygen consumption, respiratory exchange ratio, and power output measured continuously during each test. Blood pressure measured every two minutes and or immediately post exercise. P value set at p0.05 from omnibus test for a significant difference among protocols.The RS 3Min test had a significantly higher rate of achieving target HR compared to the RS GXT (9/14 vs 4/14, p=0.02) and was not significantly different from the TM GXT (9/14 vs 5/14, p=0.09). Minimum power output during the RS 3Min was significantly higher than peak power output during the RS GXT (110 ± 41 W vs. 84 ± 22 W, p=0.02) with 12/15 subjects reaching a VO2 plateau.While additional studies with randomized designs are needed, a novel RS 3Min 'all out' test appears to be a promising method for enhancing test sensitivity in cardiovascular screening post-stroke, while providing a potentially valid measure of critical power. This article is protected by copyright. All rights reserved.

IntroductionLocomotor high-intensity interval training (HIIT) is a promising intervention for stroke rehabilitation that typically involves bursts of fast treadmill walking alternated with recovery periods. However, overground translation of treadmill speed gains has been somewhat limited, some important outcomes have not been tested and baseline response predictors are poorly understood. This pilot study aimed to guide future research by assessing preliminary outcomes of combined overground and treadmill HIIT.MethodsTen participants >6 months post stroke completed a multi-domain assessment battery before and after a 4-week no-intervention control phase, then again after a 4-week treatment phase involving 12 sessions of overground and treadmill HIIT. The primary analyses assessed relative changes in overground and treadmill walking speeds after HIIT, evaluated responsiveness of different outcome measures and estimated effects of baseline gait speed on treatment response.ResultsOverground and treadmill gait function both improved during the treatment phase relative to the control phase, with overground speed changes averaging 61% of treadmill speed changes (95% CI: 33-89%). Moderate or larger effect sizes were observed for measures of gait performance, balance, fitness, cognition, fatigue, perceived change and brain volume. Participants with baseline comfortable gait speed DiscussionFuture locomotor HIIT studies should consider including: 1) both overground and treadmill training; 2) measures of cognition, fatigue and brain volume, to complement typical motor & fitness assessment; and 3) baseline gait speed as a covariate.

Aerobic exercise may acutely prime the brain to be more responsive to rehabilitation, thus facilitating neurologic recovery from conditions like stroke. This aerobic priming effect could occur through multiple mechanisms, including upregulation of circulating brain-derived neurotrophic factor (BDNF), increased corticospinal excitability, and decreased intracortical inhibition. However, optimal exercise parameters for targeting these mechanisms are poorly understood. This study tested the effects of exercise intensity on acute BDNF and neurophysiological responses. Sixteen ambulatory persons >6 mo poststroke performed three different 20-min exercise protocols in random order, approximately 1 wk apart, including the following: 1) treadmill high-intensity interval training (HIT-treadmill); 2) seated-stepper HIT (HIT-stepper); and 3) treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum BDNF and transcranial magnetic stimulation measures of paretic lower limb excitability and inhibition were assessed at multiple time points during each session. Compared with MCT-treadmill, HIT-treadmill elicited significantly greater acute increases in circulating BDNF and corticospinal excitability. HIT-stepper initially showed BDNF responses similar to HIT-treadmill but was no longer significantly different from MCT-treadmill after decreasing the intensity in reaction to two hypotensive events. Additional regression analyses showed that an intensity sufficient to accumulate blood lactate appeared to be important for eliciting BDNF responses, that the interval training approach may have facilitated the corticospinal excitability increases, and that the circulating BDNF response was (negatively) related to intracortical inhibition. These findings further elucidate neurologic mechanisms of aerobic exercise and inform selection of optimal exercise-dosing parameters for enhancing acute neurologic effects. NEW & NOTEWORTHY Acute exercise-related increases in circulating BDNF and corticospinal excitability are thought to prime the brain for learning. Our data suggest that these responses can be obtained among persons with stroke using short-interval treadmill high-intensity interval training, that a vigorous aerobic intensity sufficient to generate lactate accumulation is needed to increase BDNF, that interval training facilitates increases in paretic quadriceps corticospinal excitability, and that greater BDNF response is associated with lesser intracortical inhibition response.

Objective Imagined walking has yielded insights into normal locomotor control and could improve understanding of neurologic gait dysfunction. This study evaluated brain activation during imagined walking in chronic stroke. Methods Ten persons with stroke and 10 matched controls completed a walking test battery and a magnetic resonance imaging session including imagined walking and knee extension tasks. Brain activations were compared between tasks and groups. Associations between activations and composite gait score were also calculated, while controlling for lesion load. Results Stroke and worse gait score were each associated with lesser overall brain activation during knee extension but greater overall activation during imagined walking. During imagined walking, the stroke group significantly activated the primary motor cortex lower limb region and cerebellar locomotor region. Better walking function was associated with less activation of these regions and greater activation of medial superior frontal gyrus area 9. Conclusions Compared with knee extension, imagined walking was less sensitive to stroke-related deficits in brain activation but better at revealing compensatory changes, some of which could be maladaptive. Significance The identified associations for imagined walking suggest potential neural mechanisms of locomotor adaptation after stroke, which could be useful for future intervention development and prognostication.

Background. Exercise intensity can influence functional recovery after stroke, but the mechanisms remain poorly understood. Objective. In chronic stroke, an intensity-dependent increase in circulating brain-derived neurotrophic factor (BDNF) was previously found during vigorous exercise. Using the same serum samples, this study tested acute effects of exercise intensity on other circulating molecules related to neuroplasticity, including vascular-endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF1), and cortisol, with some updated analyses involving BDNF. Methods. Using a repeated-measures design, 16 participants with chronic stroke performed 3 exercise protocols in random order: treadmill high-intensity interval training (HIT-treadmill), seated-stepper HIT (HIT-stepper), and treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum molecular changes were compared between protocols. Mediation and effect modification analyses were also performed. Results. VEGF significantly increased during HIT-treadmill, IGF1 increased during both HIT protocols and cortisol nonsignificantly decreased during each protocol. VEGF response was significantly greater for HIT-treadmill versus MCT-treadmill when controlling for baseline. Blood lactate positively mediated the effect of HIT on BDNF and cortisol. Peak treadmill speed positively mediated effects on BDNF and VEGF. Participants with comfortable gait speed ≥0.4 m/s had significantly lower VEGF and higher IGF1 responses, with a lower cortisol response during MCT-treadmill. Conclusions. BDNF and VEGF are promising serum molecules to include in future studies testing intensity-dependent mechanisms of exercise on neurologic recovery. Fast training speed and anaerobic intensity appear to be critical ingredients for eliciting these molecular responses. Serum molecular response differences between gait speed subgroups provide a possible biologic basis for previously observed differences in training responsiveness.

Supplemental material, Supplemental_Methods_and_Results for Effects of Exercise Intensity on Acute Circulating Molecular Responses Poststroke by Pierce Boyne, Colleen Meyrose, Jennifer Westover, Dustyn Whitesel, Kristal Hatter, Darcy S. Reisman, Daniel Carl, Jane C. Khoury, Myron Gerson, Brett Kissela and Kari Dunning in Neurorehabilitation and Neural Repair

Background and Purpose: Physical inactivity after stroke stymies motor recovery, perpetuates further deconditioning, and contributes to a high long-term risk of cardiac events and recurrent stroke. This study used stakeholder input to develop a cardiac rehabilitation program specific to stroke. Methods: An exploratory qualitative study was performed consisting of separate focus groups of stroke survivors, caregivers, rehabilitation clinicians, nurse practitioners along with individual physician interviews. Two experienced researchers in qualitative research methodology independently identified themes, patterns, and issues prioritized by participants. Results: Four major themes emerged: safety, individualization of the cardiac rehabilitation program, return to function and living at highest potential, and need to maintain prolonged activity. Major components identified in developing the cardiac rehabilitation program included: Individualized stroke survivor education pertaining to fall prevention, safe aerobic exercise and learning how to live well after stroke (e.g., fitness, nutrition, chronic disease management, etc.); Exercise/stress testing prior to aerobic exercise; Determine when to begin cardiac rehabilitation post stroke (e.g., readiness, needs, resources, benefit, etc.), individualize approach and timing after holistic assessment; Education/training of cardiac rehabilitation professionals regarding best care practices for stroke survivors; Interdisciplinary approach to assure safety and continuum of care; Referral programs for IADLs, driving, sexual function, etc.; Motivational interviewing to overcome barriers with inclusion of peer mentoring/coaching; Discharge to cost effective community programs or a sustainable home program. Conclusions: Addressing safety concerns along with the creation of an individualized cardiac rehabilitation program that enables stroke survivors to achieve and maintain their highest level of function long-term are fundamental components. Partnering with the major stakeholders and incorporating a coordinated interdisciplinary approach are crucial to the creation of a feasible and cost effective cardiac rehabilitation program for stroke survivors.

Introduction: Aerobic exercise (AEX) may facilitate neurologic stroke recovery. Among healthy adults, intense AEX is known to upregulate brain-derived neurotrophic factor (BDNF), a critical facilitator of neuroplasticity, motor learning and cognition. Increased blood lactate during AEX appears to be a key mechanism underlying this effect. Intense AEX also increases blood ionized calcium (Ca++). In animal studies, some of this increased Ca++ has been shown to be transported to the brain and enhance synthesis of monoamine neurotransmitters (e.g. dopamine) that are associated with neuroplasticity and motor learning. Thus, increased blood lactate and Ca++ during AEX represent potentially important biomarkers of central neurologic benefits, but neither has been previously studied in persons with stroke. Hypothesis: High intensity AEX will elicit significantly larger lactate and Ca++ responses than moderate intensity in chronic stroke. Methods: Using a crossover design, eight subjects (mean ± SD age, 57 ± 8 years; years post stroke, 8.7 ± 2.7) performed one 20 minute session each of moderate and high intensity treadmill AEX in random order. Blood lactate and Ca++ were measured at baseline and multiple time points during and after AEX. Mixed effects models were used to examine changes within and between protocols using an alpha of 0.05. Results: Blood lactate response was significantly greater for high vs moderate intensity AEX (p Conclusions: Unlike moderate intensity AEX, high intensity elicited a robust lactate response. This has promising implications for the effects of high-intensity AEX on BDNF post-stroke. Both protocols combined showed an increase in Ca++, which has promising implications for the effects of AEX on monoamine neurotransmitter synthesis after stroke.