Articulated ankle-foot-orthosis improves inter-limb propulsion symmetry during walking adaptability task post-stroke.

BACKGROUND: Community ambulation involves complex walking adaptability tasks such as stepping over obstacles or taking long steps, which require adequate propulsion generation by the trailing leg. Individuals post-stroke often have an increased reliance on their trailing nonparetic leg and favor leading with their paretic leg, which can limit mobility. Ankle-foot-orthoses are prescribed to address common deficits post-stroke such as foot drop and ankle instability. However, it is not clear if walking with an ankle-foot-orthosis improves inter-limb propulsion symmetry during adaptability tasks. This study sought to examine this hypothesis. METHODS: Individuals post-stroke (n = 9) that were previously prescribed a custom fabricated plantarflexion-stop articulated ankle-foot-orthosis participated. Participants performed steady-state walking and adaptability tasks overground with and without their orthosis. The adaptability tasks included obstacle crossing and long-step tasks, leading with both their paretic and nonparetic leg. Inter-limb propulsion symmetry was calculated using trailing limb ground-reaction-forces. FINDINGS: During the obstacle crossing task, ankle-foot-orthosis use resulted in a significant improvement in inter-limb propulsion symmetry. The orthosis also improved ankle dorsiflexion during stance, reduced knee hyperextension, increased gastrocnemius muscle activity, and increased peak paretic leg ankle plantarflexor moment. In contrast, there were no differences in propulsion symmetry during steady-state walking and taking a long-step when using the orthosis. INTERPRETATION: Plantarflexion-stop articulated ankle-foot-orthoses can improve propulsion symmetry during obstacle crossing tasks in individuals post-stroke, promoting paretic leg use and reduced reliance on the nonparetic leg.

Speed- and Endurance-Based Classifications of Community Ambulation Post-Stroke Revisited: The Importance of Location in Walking Performance Measurement.

BACKGROUND: Gait speed or 6-minute walk test are frequently used to project community ambulation abilities post-stroke by categorizing individuals as household ambulators, limited, or unlimited community ambulators. However, whether improved clinically-assessed gait outcomes truly translate into enhanced real-world community ambulation remains uncertain. OBJECTIVE: This cross-sectional study aimed to examine differences in home and community ambulation between established categories of speed- and endurance-based classification systems of community ambulation post-stroke and compare these with healthy controls. METHODS: Sixty stroke survivors and 18 healthy controls participated. Stroke survivors were categorized into low-speed, medium-speed, or high-speed groups based on speed-based classifications and into low-endurance, medium-endurance, or high-endurance groups based on the endurance-based classification. Home and community steps/day were quantified using Global Positioning System and accelerometer devices over 7 days. RESULTS: The low-speed groups exhibited fewer home and community steps/day than their medium- and high-speed counterparts (P < .05). The low-endurance group took fewer community steps/day than the high-endurance group (P < .05). Despite vast differences in clinical measures of gait speed and endurance, the medium-speed/endurance groups did not differ in their home and community steps/day from the high-speed/endurance groups, respectively. Stroke survivors took 48% fewer home steps/day and 77% fewer community steps/day than healthy controls. CONCLUSIONS: Clinical classification systems may only distinguish home ambulators from community ambulators, but not between levels of community ambulation, especially beyond certain thresholds of gait speed and endurance. Clinicians should use caution when predicting community ambulation status through clinical measures, due to the limited translation of these classification systems into the real world.

Visuospatial cognition predicts performance on an obstructed vision obstacle walking task in older adults.

Walking performance and cognitive function demonstrate strong associations in older adults, with both declining with advancing age. Walking requires the use of cognitive resources, particularly in complex environments like stepping over obstacles. A commonly implemented approach for measuring the cognitive control of walking is a dual-task walking assessment, in which walking is combined with a second task. However, dual-task assessments have shortcomings, including issues with scaling the task difficulty and controlling for task prioritization. Here we present a new assessment designed to be less susceptible to these shortcomings while still challenging cognitive control of walking: the Obstructed Vision Obstacle (OBVIO) task. During the task, participants hold a lightweight tray at waist level obstructing their view of upcoming foam blocks, which are intermittently spaced along a 10 m walkway. This forces the participants to use cognitive resources (e.g., attention and working memory) to remember the exact placement of upcoming obstacles to facilitate successful crossing. The results demonstrate that adding the obstructed vision board significantly slowed walking speed by an average of 0.26 m/s and increased the number of obstacle strikes by 8-fold in healthy older adults (n = 74). Additionally, OBVIO walking performance (a score based on both speed and number of obstacle strikes) significantly correlated with computer-based assessments of visuospatial working memory, attention, and verbal working memory. These results provide initial support that the OBVIO task is a feasible walking test that demands cognitive resources. This study lays the groundwork for using the OBVIO task in future assessment and intervention studies.

Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury.

Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (p < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (p = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (p = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n = 11), whereas others responded minimally (<0.20 L/min/%, n = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.

Sympathetic nervous system responses during complex walking tasks and community ambulation post-stroke.

Stroke survivors frequently report increased perceived challenge of walking (PCW) in complex environments, restricting their daily ambulation. PCW is conventionally measured through subjective questionnaires or, more recently, through objective quantification of sympathetic nervous system activity during walking tasks. However, how these measurements of PCW reflect daily walking activity post-stroke is unknown. We aimed to compare the subjective and objective assessments of PCW in predicting home and community ambulation. In 29 participants post-stroke, we measured PCW subjectively with the Activities-specific Balance Confidence (ABC) Scale and objectively through electrodermal activity, quantified by change in skin conductance levels (SCL) and skin conductance responses (SCR) between outdoor-complex and indoor-steady-state walking. High-PCW participants were categorized into high-change SCL (ΔSCL ≥ 1.7 µs), high-change SCR (ΔSCR ≥ 0.2 µs) and low ABC (ABC < 72%) groups, while low-PCW participants were categorized into low-change SCL (ΔSCL < 1.7 µs), low-change SCR (ΔSCR < 0.2 µs) and high-ABC (ABC ≥ 72%) groups. Number and location of daily steps were quantified with accelerometry and Global Positioning System devices. Compared to low-change SCL group, the high-change SCL group took fewer steps in home and community (p = 0.04). Neither ABC nor SCR groups differed in home or community steps/day. Objective measurement of PCW via electrodermal sensing more accurately represents home and community ambulation compared to the subjective questionnaire.

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia.

Rationale: Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses. Objectives: Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). Methods: In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures (P0.1) were evaluated. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E, APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoE knock-in rats were performed to test causality. Results: AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3/4) compared to individuals with other APOE genotypes (P = 0.048) and the other tested SNPs. Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (P = 0.004). Additionally, age was inversely related with change in P0.1 (P = 0.007). In hApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3 controls (P < 0.05). Conclusions: APOE4 genotype, sex, and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults. Addition to Knowledge Base: AIH is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative disease. Figure 5 Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, AIHH, in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.

The influence of backward versus forward locomotor training on gait speed and balance control post-stroke: Recovery or compensation?

Backward walking training has been reported to improve gait speed and balance post-stroke. However, it is not known if gains are achieved through recovery of the paretic limb or compensations from the nonparetic limb. The purpose of this study was to compare the influence of backward locomotor training (BLT) versus forward locomotor training (FLT) on gait speed and dynamic balance control, and to quantify the underlying mechanisms used to achieve any gains. Eighteen participants post chronic stroke were randomly assigned to receive 18 sessions of either FLT (n = 8) or BLT (n = 10). Pre- and post-intervention outcomes included gait speed (10-meter Walk Test) and forward propulsion (time integral of anterior-posterior ground-reaction-forces during late stance for each limb). Dynamic balance control was assessed using clinical (Functional Gait Assessment) and biomechanical (peak-to-peak range of whole-body angular-momentum in the frontal plane) measures. Balance confidence was assessed using the Activities-Specific Balance Confidence scale. While gait speed and balance confidence improved significantly within the BLT group, these improvements were associated with an increased nonparetic limb propulsion generation, suggesting use of compensatory mechanisms. Although there were no improvements in gait speed within the FLT group, paretic limb propulsion generation significantly improved post-FLT, suggesting recovery of the paretic limb. Neither training group improved in dynamic balance control, implying the need of balance specific training along with locomotor training to improve balance control post-stroke. Despite the within-group differences, there were no significant differences between the FLT and BLT groups in the achieved gains in any of the outcomes.

Recovery of walking in nonambulatory children with chronic spinal cord injuries: Case series.

The immature central nervous system is recognized as having substantial neuroplastic capacity. In this study, we explored the hypothesis that rehabilitation can exploit that potential and elicit reciprocal walking in nonambulatory children with chronic, severe (i.e., lower extremity motor score < 10/50) spinal cord injuries (SCIs). Seven male subjects (3-12 years of age) who were at least 1-year post-SCI and incapable of discrete leg movements believed to be required for walking, enrolled in activity-based locomotor training (ABLT; clinicaltrials.gov NCT00488280). Six children completed the study. Following a minimum of 49 sessions of ABLT, three of the six children achieved walking with reverse rolling walkers. Stepping development, however, was not accompanied by improvement in discrete leg movements as underscored by the persistence of synergistic movements and little change in lower extremity motor scores. Interestingly, acoustic startle responses exhibited by the three responding children suggested preserved reticulospinal inputs to circuitry below the level of injury capable of mediating leg movements. On the other hand, no indication of corticospinal integrity was obtained with transcranial magnetic stimulation evoked responses in the same individuals. These findings suggest some children who are not predicted to improve motor and locomotor function may have a reserve of adaptive plasticity that can emerge in response to rehabilitative strategies such as ABLT. Further studies are warranted to determine whether a critical need exists to re-examine rehabilitation approaches for pediatric SCI with poor prognosis for any ambulatory recovery.

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia.

Rationale: Acute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials report considerable inter-individual response variability. Objectives: Identify individual factors ( e.g. , genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). Methods: Associations of individual factors with the magnitude of AIHH (15, 1-min O 2 =9.5%, CO 2 =5% episodes) induced changes in diaphragm motor-evoked potential amplitude (MEP) and inspiratory mouth occlusion pressures (P 0.1 ) were evaluated in 17 healthy individuals (age=27±5 years) compared to Sham. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity ( BDNF, HTR 2A , TPH 2 , MAOA, NTRK 2 ) and neuronal plasticity (apolipoprotein E, APOE ) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized ( h ) ApoE knock-in rats were performed to test causality. Results: AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE 4 ( i.e., APOE 3/4 ) allele versus other APOE genotypes (p=0.048). No significant differences were observed between any other SNPs investigated, notably BDNFval/met ( all p>0.05 ). Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (p=0.004). Age was inversely related with change in P 0.1 within the limited age range studied (p=0.007). In hApoE 4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE 3 controls (p<0.05). Conclusions: APOE 4 genotype, sex and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults. ADDITION TO KNOWLEDGE BASE: Acute intermittent hypoxia (AIH) is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative diseases. Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH), in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE ), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.

The 3-Meter Backward Walk Test (3MBWT): Reliability and validity in individuals with subacute and chronic stroke.

INTRODUCTION: Backward walking (BW) is an important gait adaptation and BW speed may be an important indicator of walking function and fall risk. However, the measurement characteristics of a standardized assessment of BW post-stroke have not been fully established. OBJECTIVES: To determine intra- and interrater reliability, concurrent validity and minimal detectable change (MDC) scores for the 3-Meter Backward Walk Test (3MBWT) post-stroke. METHODS: Thirty-four individuals with subacute and 29 individuals with chronic stroke participated. Two trials of comfortable BW was measured over a total distance of 5-meters, while speed was calculated during the middle 3-meters of the walking distance. Intra and interrater reliability were determined by comparing the two trials from one rater and simultaneous assessment of two raters, respectively. Two additional trials were performed and BW speed was calculated using 3MBWT and an instrumented walkway to determine concurrent validity. Intraclass correlation coefficients (ICC) estimated reliability and validity. The MDC was calculated from the standard error of measurement. RESULTS: Excellent ICC values were obtained for the 3MBWT in the subacute (interrater: ICC2,1 = 0.99; intrarater: ICC2,1 = 0.96; validity: ICC2,1 = 0.96) and chronic (interrater: ICC2,1 = 0.99; intrarater: ICC2,1 = 0.94; validity: ICC2,1 = 0.97) groups. The MDC was 0.07 m/s (subacute) and 0.11 m/s (chronic). CONCLUSIONS: Establishment of the 3MBWT as a reliable and valid measure in assessing BW speed is an important addition to the assessment toolbox for rehabilitation post-stroke.

Spatiotemporal strategies adopted to walk at fast speed in high- and low-functioning individuals post-stroke: a cross-sectional study.

BACKGROUND: Walking at fast speed is a gait training strategy post-stroke. It is unknown how faster-than-preferred pace impacts spatiotemporal gait characteristics in survivors with different functional abilities. OBJECTIVE: To test the hypothesis that compared to high-functioning individuals, low-functioning individuals will be limited in modifying spatiotemporal gait parameters for walking at faster-than-preferred speed, and these limitations are associated with fear of falling. METHODS: Forty-two adults, 17.6 ± 14.6 months post-stroke, traversed an instrumented walkway at preferred and fast speeds. Participants were categorized to a low-functioning group (LFG) (n = 20; <0.45 m/s) and high-functioning group (HFG) (n = 22; ≥0.45 m/s). Cadence, step length, stance time and spatiotemporal asymmetry measures were calculated. The Modified Falls-efficacy Scale examined fear of falling. Multivariate and correlational analysis tested hypotheses. RESULTS: Increased speed from preferred to fast pace was significantly greater for HFG (0.27 ± 0.03 m/s) than LFG (0.10 ± 0.02 m/s) (p ≤ 0.001). Cadence gain from preferred to fast pace did not differ between groups. However, HFG exhibited greater change in paretic (∆6.1 ± 1.37 cm; p < .001) and non-paretic step lengths (∆4.5 ± 1.37 cm; p = .003) than LFG. Spatiotemporal asymmetry did not change for either group. Fear of falling had moderately positive correlation with ∆paretic step length (r = 0.43; p = .004) and ∆non-paretic step length (r = 0.32; p = .035). CONCLUSIONS: While both low- and high-functioning individuals used a step-lengthening strategy to walk at faster-than-preferred speeds, the gain in step lengths was limited in low-functioning individuals and was partially explained by falls-efficacy.

Locomotor-respiratory coupling in ambulatory adults with incomplete spinal cord injury.

STUDY DESIGN: Observational, analytical cohort study. OBJECTIVES: After incomplete spinal cord injury (iSCI), propriospinal pathways may remain intact enabling coupling between respiration and locomotion. This locomotor-respiratory coupling (LRC) may enable coordination between these two important behaviors and have implications for rehabilitation after iSCI. However, coordination between these behaviors is not well understood and it is unknown if iSCI disrupts LRC. The objective of this study was to compare LRC in ambulatory adults with iSCI to able-bodied controls. SETTING: Rehabilitation Research Center, Jacksonville, Florida, United States of America. METHODS: Adults with iSCI (4 males, 1 female) and able-bodied controls (2 males, 3 females) walked at their fastest comfortable speed for 6 min over ground, and on a treadmill with bodyweight support (10-20%) and as-needed assistance at a standardized fast speed (controls) or their fastest speed (iSCI) for 6 min. LRC was quantified as the percent of breaths that were coupled with steps at a consistent ratio during the last 4 min of each walking condition. RESULTS: Over ground, participants with iSCI demonstrated significantly more LRC than able-bodied controls (72.4 ± 6.4% vs. 59.1% ± 7.5, p = 0.016). During treadmill walking, LRC did not differ between groups (iSCI 67.5 ± 15.8% vs. controls 66.3 ± 4.0%, p > 0.05). CONCLUSIONS: Adults with iSCI demonstrated similar or greater LRC compared to able-bodied controls. This suggests that pathways subserving coordination between these behaviors remain intact in this group of individuals who walk independently after iSCI.

Feasibility of transcutaneous spinal direct current stimulation combined with locomotor training after spinal cord injury.

STUDY DESIGN: Feasibility study, consisting of random-order, cross-over study of a single intervention session, followed by a parallel-arm study of 16 sessions. OBJECTIVES: To investigate the feasibility of a novel combinatorial approach with simultaneous delivery of transcutaneous spinal direct current stimulation (tsDCS) and locomotor training (tsDCS + LT) after spinal cord injury, compared to sham stimulation and locomotor training (sham + LT), and examine preliminary effects on walking function. SETTING: Clinical research center in the southeastern United States. METHODS: Eight individuals with chronic incomplete spinal cord injury (ISCI) completed the two-part protocol. Feasibility was assessed based on safety (adverse responses), tolerability (pain, spasticity, skin integrity), and protocol achievement (session duration, intensity). Walking function was assessed with the 10 m and 6 min walk tests. RESULTS: There were no major adverse responses. Minimal reports of skin irritation and musculoskeletal pain were consistent between groups. Average training peak heart rate as percent of maximum (mean(SD); tsDCS + LT: 66 (4)%, sham + LT: 69 (10)%) and Borg ratings of perceived exertion (tsDCS + LT: 17.5 (1.2), sham + LT: 14.4 (1.8)) indicate both groups trained at high intensities. Walking speed gains exceeded the minimal clinically important difference (MCID) in three of four who received tsDCS + LT (0.18 (0.29) m/s) and one of four in sham + LT (-0.05 (0.23) m/s). Gains in walking endurance exceeded the MCID in one of four in each group (tsDCS + LT: 36.4 (69.0) m, sham + LT: 4.9 (56.9) m). CONCLUSIONS: Combinatorial tsDCS and locomotor training is safe and feasible for individuals with chronic ISCI, even those with considerable walking impairment. Study outcomes support the need to investigate the efficacy of this approach.

Enhancing Locomotor Learning With Transcutaneous Spinal Electrical Stimulation and Somatosensory Augmentation: A Pilot Randomized Controlled Trial in Older Adults.

This study investigated locomotor learning of a complex terrain walking task in older adults, when combined with two adjuvant interventions: transcutaneous spinal direct current stimulation (tsDCS) to increase lumbar spinal cord excitability, and textured shoe insoles to increase somatosensory feedback to the spinal cord. The spinal cord has a crucial contribution to control of walking, and is a novel therapeutic target for rehabilitation of older adults. The complex terrain task involved walking a 10-meter course consisting of nine obstacles and three sections of compliant (soft) walking surface. Twenty-three participants were randomly assigned to one of the following groups: sham tsDCS and smooth insoles (sham/smooth; control group), sham tsDCS and textured insoles (sham/textured), active tsDCS and smooth insoles (active/smooth), and active tsDCS and textured insoles (active/textured). The first objective was to assess the feasibility, tolerability, and safety of the interventions. The second objective was to assess preliminary efficacy for increasing locomotor learning, as defined by retention of gains in walking speed between a baseline visit of task practice, and a subsequent follow-up visit. Variability of the center of mass while walking over the course was also evaluated. The change in executive control of walking (prefrontal cortical activity) between the baseline and follow-up visits was measured with functional near infrared spectroscopy. The study results demonstrated feasibility based on enrollment and retention of participants, tolerability based on self-report, and safety based on absence of adverse events. Preliminary efficacy was supported based on trends showing larger gains in walking speed and more pronounced reductions in mediolateral center of mass variability at the follow-up visit in the groups randomized to active tsDCS or textured insoles. These data justify future larger studies to further assess dosing and efficacy of these intervention approaches. In conclusion, rehabilitation interventions that target spinal control of walking present a potential opportunity for enhancing walking function in older adults.

Acute intermittent hypercapnic-hypoxia elicits central neural respiratory motor plasticity in humans.

Acute intermittent hypoxia (AIH) elicits long-term facilitation (LTF) of respiration. Although LTF is observed when CO2 is elevated during AIH in awake humans, the influence of CO2 on corticospinal respiratory motor plasticity is unknown. Thus, we tested the hypotheses that acute intermittent hypercapnic-hypoxia (AIHH): (1) enhances cortico-phrenic neurotransmission (reflecting volitional respiratory control); and (2) elicits ventilatory LTF (reflecting automatic respiratory control). Eighteen healthy adults completed four study visits. Day 1 consisted of anthropometry and pulmonary function testing. On Days 2, 3 and 4, in a balanced alternating sequence, participants received: AIHH, poikilocapnic AIH, and normocapnic-normoxia (Sham). Protocols consisted of 15, 60 s exposures with 90 s normoxic intervals. Transcranial (TMS) and cervical (CMS) magnetic stimulation were used to induce diaphragmatic motor-evoked potentials and compound muscle action potentials, respectively. Respiratory drive was assessed via mouth occlusion pressure (P0.1 ), and minute ventilation measured at rest. Dependent variables were assessed at baseline and 30-60 min after exposures. Increases in TMS-evoked diaphragm potential amplitudes were observed following AIHH vs. Sham (+28 ± 41%, P = 0.003), but not after AIH. No changes were observed in CMS-evoked diaphragm potential amplitudes. Mouth occlusion pressure also increased after AIHH (+21 ± 34%, P = 0.033), but not after AIH. Ventilatory LTF was not observed after any treatment. We demonstrate that AIHH elicits central neural mechanisms of respiratory motor plasticity and increases resting respiratory drive in awake humans. These findings may have important implications for neurorehabilitation after spinal cord injury and other neuromuscular disorders compromising breathing. KEY POINTS: The occurrence of respiratory long-term facilitation following acute exposure to intermittent hypoxia is believed to be dependent upon CO2 regulation - mechanisms governing the critical role of CO2 have seldom been explored. We tested the hypothesis that acute intermittent hypercapnic-hypoxia (AIHH) enhances cortico-phrenic neurotransmission in awake healthy humans. The amplitude of diaphragmatic motor-evoked potentials induced by transcranial magnetic stimulation was increased after AIHH, but not the amplitude of compound muscle action potentials evoked by cervical magnetic stimulation. Mouth occlusion pressure (P0.1 , an indicator of neural respiratory drive) was also increased after AIHH, but not tidal volume or minute ventilation. Thus, moderate AIHH elicits central neural mechanisms of respiratory motor plasticity, without measurable ventilatory long-term facilitation in awake humans.

Low Risk for Persistent Back Pain Disability Is Characterized by Lower Pain Sensitivity and Higher Physical Performance.

OBJECTIVE: The STarT Back Tool (SBT) predicts risk for persistent low back pain (LBP)-related disability based on psychological distress levels. Other non-psychological factors associated with LBP, such as pain sensitivity and physical performance, may further characterize SBT-risk subgroups. The purpose of this study was to determine whether a low-risk SBT subgroup demonstrated lower pain sensitivity and/or higher physical performance compared with a medium-/high-risk SBT subgroup. METHODS: In this cross-sectional, secondary analysis, adults with LBP (N = 76) completed SBT and demographics (age, sex, race, chronicity) questionnaires. Participants underwent pain sensitivity (local and remote pressure pain thresholds, temporal summation, conditioned pain modulation) and physical performance (Back Performance Scale, walking speed, obstacle negotiation, Timed "Up & Go" [TUG], TUG Cognitive) testing. Independent samples t tests determined low- versus medium-/high-risk SBT subgroup differences. A follow-up discriminant function analysis was also conducted. RESULTS: The medium-/high-risk subgroup demonstrated a lower proportion of participants with acute pain. The low-risk subgroup demonstrated lower pain sensitivity (higher local pressure pain thresholds and higher conditioned pain modulation) and higher physical performance (superior Back Performance Scale scores, faster walking speeds, faster obstacle approach and crossing speeds, and faster TUG completion). Discriminant function analysis results supported the 2-subgroup classification and indicated strong to moderate relationships with obstacle crossing speed, chronicity, and conditioned pain modulation. CONCLUSION: Lower pain sensitivity and higher physical performance characterized the low-risk SBT subgroup and may represent additional LBP prognostic factors associated with persistent disability. Longitudinal studies are needed to confirm whether these factors can enhance SBT prediction accuracy and further direct treatment priorities. IMPACT: Sensory and physical factors contribute to SBT risk classification, suggesting additional, non-psychological factors are indicative of favorable LBP outcomes. Findings highlight the need for assessment of multiple factors to improve LBP clinical prediction. LAY SUMMARY: People at low risk for back pain disability have less sensitivity to pain and better physical performance. By measuring these factors, physical therapists could guide treatment and improve outcomes for people with back pain.

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease.

We review progress towards greater mechanistic understanding and clinical translation of a strategy to improve respiratory and non-respiratory motor function in people with neuromuscular disorders, therapeutic acute intermittent hypoxia (tAIH). In 2016 and 2020, workshops to create and update a "road map to clinical translation" were held to help guide future research and development of tAIH to restore movement in people living with chronic, incomplete spinal cord injuries. After briefly discussing the pioneering, non-targeted basic research inspiring this novel therapeutic approach, we then summarize workshop recommendations, emphasizing critical knowledge gaps, priorities for future research effort, and steps needed to accelerate progress as we evaluate the potential of tAIH for routine clinical use. Highlighted areas include: 1) greater mechanistic understanding, particularly in non-respiratory motor systems; 2) optimization of tAIH protocols to maximize benefits; 3) identification of combinatorial treatments that amplify plasticity or remove plasticity constraints, including task-specific training; 4) identification of biomarkers for individuals most/least likely to benefit from tAIH; 5) assessment of long-term tAIH safety; and 6) development of a simple, safe and effective device to administer tAIH in clinical and home settings. Finally, we update ongoing clinical trials and recent investigations of tAIH in SCI and other clinical disorders that compromise motor function, including ALS, multiple sclerosis, and stroke.

Single-session effects of acute intermittent hypoxia on breathing function after human spinal cord injury.

After spinal cord injury (SCI) respiratory complications are a leading cause of morbidity and mortality. Acute intermittent hypoxia (AIH) triggers spinal respiratory motor plasticity in rodent models, and repetitive AIH may have the potential to restore breathing capacity in those with SCI. As an initial approach to provide proof of principle for such effects, we tested single-session AIH effects on breathing function in adults with chronic SCI. 17 adults (13 males; 34.1 ± 14.5 years old; 13 motor complete SCI; >6 months post injury) completed two randomly ordered sessions, AIH versus sham. AIH consisted of 15, 1-min episodes (hypoxia: 10.3% O2; sham: 21% O2) interspersed with room air breathing (1.5 min, 21% oxygen); no attempt was made to regulate arterial CO2 levels. Blood oxygen saturation (SpO2), maximal inspiratory and expiratory pressures (MIP; MEP), forced vital capacity (FVC), and mouth occlusion pressure within 0.1 s (P0.1) were assessed. Outcomes were compared using nonparametric Wilcoxon's tests, or a 2 × 2 ANOVA. Baseline SpO2 was 97.2 ± 1.3% and was unchanged during sham experiments. During hypoxic episodes, SpO2 decreased to 84.7 ± 0.9%, and returned to baseline levels during normoxic intervals. Outcomes were unchanged from baseline post-sham. Greater increases in MIP were evident post AIH vs. sham (median values; +10.8 cmH2O vs. -2.6 cmH2O respectively, 95% confidence interval (-18.7) - (-4.3), p = .006) with a moderate Cohen's effect size (0.68). P0.1, MEP and FVC did not change post-AIH. A single AIH session increased maximal inspiratory pressure generation, but not other breathing functions in adults with SCI. Reasons may include greater spared innervation to inspiratory versus expiratory muscles or differences in the capacity for AIH-induced plasticity in inspiratory motor neuron pools. Based on our findings, the therapeutic potential of AIH on breathing capacity in people with SCI warrants further investigation.

Diaphragm Pacing and a Model for Respiratory Rehabilitation After Spinal Cord Injury.

BACKGROUND AND PURPOSE: Cervical spinal cord injury (CSCI) can cause severe respiratory impairment. Although mechanical ventilation (MV) is a lifesaving standard of care for these patients, it is associated with diaphragm atrophy and dysfunction. Diaphragm pacing (DP) is a strategy now used acutely to promote MV weaning and to combat the associated negative effects. Initial reports indicate that DP also may promote neuromuscular plasticity and lead to improvements in spontaneous diaphragm activation and respiratory function. These outcomes suggest the need for reevaluation of respiratory rehabilitation for patients with CSCI using DP and consideration of new rehabilitation models for these patients and their unique care needs. SUMMARY OF KEY POINTS: This article discusses the rationale for consideration of DP as a rehabilitative strategy, particularly when used in combination with established respiratory interventions. In addition, a model of respiratory rehabilitation and recovery (RRR) is presented, providing a framework for rehabilitation and consideration of DP as an adjuvant rehabilitation approach. The model promotes goals such as respiratory recovery and independence, and lifelong respiratory health, via interdisciplinary care, respiratory training, quantitative measurement, and use of adjuvant strategies such as DP. Application of the model is demonstrated through a description of an inpatient rehabilitation program that applies model components to patients with CSCI who require DP. RECOMMENDATIONS FOR CLINICAL PRACTICE: As DP use increases for patients with acute CSCI, so does the need and opportunity to advance rehabilitation approaches for these patients. This perspective article is a critical step in addressing this need and motivating the advancement of rehabilitation strategies for CSCI patients. (See Video Abstract, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A348).

Rehabilitation with accurate adaptability walking tasks or steady state walking: A randomized clinical trial in adults post-stroke.

OBJECTIVE: To assess changes in walking function and walking-related prefrontal cortical activity following two post-stroke rehabilitation interventions: an accurate adaptability (ACC) walking intervention and a steady state (SS) walking intervention. DESIGN: Randomized, single blind, parallel group clinical trial. SETTING: Hospital research setting. SUBJECTS: Adults with chronic post-stroke hemiparesis and walking deficits. INTERVENTIONS: ACC emphasized stepping accuracy and walking adaptability, while SS emphasized steady state, symmetrical stepping. Both included 36 sessions led by a licensed physical therapist. ACC walking tasks recruit cortical regions that increase corticospinal tract activation, while SS walking activates the corticospinal tract less intensely. MAIN MEASURES: The primary functional outcome measure was preferred steady state walking speed. Prefrontal brain activity during walking was measured with functional near infrared spectroscopy to assess executive control demands. Assessments were conducted at baseline, post-intervention (three months), and follow-up (six months). RESULTS: Thirty-eight participants were randomized to the study interventions (mean age 59.6 ± 9.1 years; mean months post-stroke 18.0 ± 10.5). Preferred walking speed increased from baseline to post-intervention by 0.13 ± 0.11 m/s in the ACC group and by 0.14 ± 0.13 m/s in the SS group. The Time × Group interaction was not statistically significant (P = 0.86). Prefrontal fNIRS during walking decreased from baseline to post-intervention, with a marginally larger effect in the ACC group (P = 0.05). CONCLUSIONS: The ACC and SS interventions produced similar changes in walking function. fNIRS suggested a potential benefit of ACC training for reducing demand on prefrontal (executive) resources during walking.