Publications

Nat Med. 2024 May;30(5):1276-1283. doi: 10.1038/s41591-024-02940-9. Epub 2024 May 20.

ABSTRACT

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARC^EX Therapy to improve arm and hand functions in people with chronic SCI. ARC^EX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARC^EX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARC^EX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARC^EX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

PMID:38769431 | PMC:PMC11108781 | DOI:10.1038/s41591-024-02940-9

Exp Physiol. 2024 Apr;109(4):576-587. doi: 10.1113/EP091531. Epub 2024 Feb 14.

ABSTRACT

Spasticity attributable to exaggerated stretch reflex pathways, particularly affecting the ankle plantar flexors, often impairs overground walking in persons with incomplete spinal cord injury. Compelling evidence from rodent models underscores how exposure to acute intermittent hypoxia (AIH) can provide a unique medium to induce spinal plasticity in key inhibitory pathways mediating stretch reflex excitability and potentially affect spasticity. In this study, we quantify the effects of a single exposure to AIH on the stretch reflex in able-bodied individuals. We hypothesized that a single sequence of AIH will increase the stretch reflex excitability of the soleus muscle during ramp-and-hold angular perturbations applied to the ankle joint while participants perform passive and volitionally matched contractions. Our results revealed that a single AIH exposure did not significantly change the stretch reflex excitability during both passive and active matching conditions. Furthermore, we found that able-bodied individuals increased their stretch reflex response from passive to active matching conditions after both sham and AIH exposures. Together, these findings suggest that a single AIH exposure might not engage inhibitory pathways sufficiently to alter stretch reflex responses in able-bodied persons. However, the generalizability of our present findings requires further examination during repetitive exposures to AIH along with potential reflex modulation during functional movements, such as overground walking.

PMID:38356241 | PMC:PMC10988685 | DOI:10.1113/EP091531

Neurotrauma Rep. 2023 Nov 6;4(1):736-750. doi: 10.1089/neur.2023.0036. eCollection 2023.

ABSTRACT

Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALK_tSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALK_tSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALK_tSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALK_tSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALK_tSTIM; Placebo + WALK_tSTIM; and tAIH + WALK_tSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O₂ with 60-sec intervals at 21% O₂) or daily placebo (fifteen 90-sec episodes at 21% O₂ with 60-sec intervals at 21% O₂) before a 45-min session of WALK_tSTIM or WALK_tSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05563103.

PMID:38028272 | PMC:PMC10659019 | DOI:10.1089/neur.2023.0036

Front Hum Neurosci. 2022 Jun 9;16:868074. doi: 10.3389/fnhum.2022.868074. eCollection 2022.

ABSTRACT

Humans routinely modify their walking speed to adapt to functional goals and physical demands. However, damage to the central nervous system (CNS) often results in abnormal modulation of walking speed and increased risk of falls. There is considerable interest in treatment modalities that can provide safe and salient training opportunities, feedback about walking performance, and that may augment less reliable sensory feedback within the CNS after injury or disease. Fully immersive virtual reality technologies show benefits in boosting training-related gains in walking performance; however, they lack views of the real world that may limit functional carryover. Augmented reality and mixed reality head-mount displays (MR-HMD) provide partially immersive environments to extend the virtual reality benefits of interacting with virtual objects but within an unobstructed view of the real world. Despite this potential advantage, the feasibility of using MR-HMD visual feedback to promote goal-directed changes in overground walking speed remains unclear. Thus, we developed and evaluated a novel mixed reality application using the Microsoft HoloLens MR-HMD that provided real-time walking speed targets and augmented visual feedback during overground walking. We tested the application in a group of adults not living with disability and examined if they could use the targets and visual feedback to walk at 85%, 100%, and 115% of each individual's self-selected speed. We examined whether individuals were able to meet each target gait speed and explored differences in accuracy across repeated trials and at the different speeds. Additionally, given the importance of task-specificity to therapeutic interventions, we examined if walking speed adjustment strategies were consistent with those observed during usual overground walking, and if walking with the MR-HMD resulted in increased variability in gait parameters. Overall, participants matched their overground walking speed to the target speed of the MR-HMD visual feedback conditions (all p-values > 0.05). The percent inaccuracy was approximately 5% across all speed matching conditions and remained consistent across walking trials after the first overall walking trial. Walking with the MR-HMD did not result in more variability in walking speed, however, we observed more variability in stride length and time when walking with feedback from the MR-HMD compared to walking without feedback. The findings offer support for mixed reality-based visual feedback as a method to provoke goal-specific changes in overground walking behavior. Further studies are necessary to determine the clinical safety and efficacy of this MR-HMD technology to provide extrinsic sensory feedback in combination with traditional treatments in rehabilitation.

PMID:35754777 | PMC:PMC9218429 | DOI:10.3389/fnhum.2022.868074

J Neurotrauma. 2022 Dec;39(23-24):1756-1763. doi: 10.1089/neu.2022.0120. Epub 2022 Aug 30.

ABSTRACT

Incomplete spinal cord injury (iSCI) often results in lifelong walking impairments that limit functional independence. Thus, treatments that trigger enduring improvement in walking after iSCI are in high demand. Breathing brief episodes of low oxygen (i.e., acute intermittent hypoxia, AIH) enhances breathing and walking function in rodents and humans with chronic iSCI. Pre-clinical studies found that AIH also causes the accumulation of extracellular adenosine that undermines AIH-induced functional plasticity. Pharmacologically blocking adenosine A2a receptors (A2aR) prior to AIH resulted in a dramatic improvement in motor facilitation in rodents with iSCI; however, a similar beneficial effect in humans is unclear. Thus, we conducted a double-blind, placebo-controlled, crossover randomized study to test the hypothesis that a non-selective A2aR antagonist (i.e., caffeine) enhances AIH-induced effects on walking function in people with chronic (≥1yr) iSCI. We enrolled 12 participants to receive daily (5 days) caffeine or placebo (4 mg/kg) 30 min before breathing 15, 1.5-min low oxygen (AIH; F_IO₂ = 0.10) or SHAM (F_IO₂ = 0.21) episodes with 1-min intervals. We quantified walking function as the change in the 10-meter walk test (speed) and 6-min walk test (endurance) relative to baseline, on Day 5 post-intervention, and on follow-up Days 12 and 19. Participants walked faster (Day 19; p < 0.001) and farther (Day 19; p = 0.012) after caffeine+AIH and the boost in speed persisted more than after placebo+AIH or caffeine+SHAM (Day 19; p < 0.05). These results support our hypothesis that a caffeine pre-treatment to AIH training shows promise as a strategy to augment walking speed in persons with chronic iSCI.

PMID:35686460 | PMC:PMC9734018 | DOI:10.1089/neu.2022.0120

Exp Neurol. 2022 Jan;347:113891. doi: 10.1016/j.expneurol.2021.113891. Epub 2021 Oct 9.

ABSTRACT

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.

PMID:34637802 | PMC:PMC8820239 | DOI:10.1016/j.expneurol.2021.113891

Curr Phys Med Rehabil Rep. 2020 Sep;8(3):188-198. doi: 10.1007/s40141-020-00270-8. Epub 2020 Jun 24.

ABSTRACT

PURPOSE OF REVIEW: The reacquisition and preservation of walking ability are highly valued goals in spinal cord injury (SCI) rehabilitation. Recurrent episodes of breathing low oxygen (i.e., acute intermittent hypoxia, AIH) is a potential therapy to promote walking recovery after incomplete SCI via endogenous mechanisms of neuroplasticity. Here, we report on the progress of AIH, alone or paired with other treatments, on walking recovery in persons with incomplete SCI. We evaluate the evidence of AIH as a therapy ready for clinical and home use and the real and perceived challenges that may interfere with this possibility.

RECENT FINDINGS: Repetitive AIH is a safe and an efficacious treatment to enhance strength, walking speed and endurance, as well as, dynamic balance in persons with chronic, incomplete SCI.

SUMMARY: The potential for AIH as a treatment for SCI remains high, but further research is necessary to understand treatment targets and effectiveness in a large cohort of persons with SCI.

PMID:33738145 | PMC:PMC7963002 | DOI:10.1007/s40141-020-00270-8

Exp Neurol. 2021 Jun;340:113669. doi: 10.1016/j.expneurol.2021.113669. Epub 2021 Feb 27.

ABSTRACT

Persons living with incomplete spinal cord injuries (SCI) often struggle to regain independent walking due to deficits in walking mechanics. They often dedicate many weeks of gait training before benefits to emerge, with additional training needed for benefits to persist. Recent studies in humans with SCI found that daily bouts of breathing low oxygen (acute intermittent hypoxia, AIH) prior to locomotor training elicited persistent (weeks) improvement in overground walking speed and endurance. AIH-induced improvements in overground walking may result from changes in control strategies that also enhance intralimb coordination; however, this possibility remains untested. Here, we examined the extent to which daily AIH combined with walking practice (AIH + WALK) improved overground walking performance and intralimb motor coordination in persons with chronic, incomplete SCI.

METHODS: We recruited 11 persons with chronic (> 1 year), incomplete SCI to participate in a randomized, double-blind, balanced, crossover study. Participants first received either daily (5 consecutive days) AIH (15, 90-s episodes of 10.0% O₂ with 60s intervals at 20.9% O₂) or SHAM (15, 90s episodes at 20.9% O₂ with 60s intervals at 20.9% O₂) followed by 30-min of overground walking practice. They received the second treatment after a minimum 2-week washout period. We quantified overground walking performance, in terms of speed and endurance, using the 10-Meter Walk Test (10MWT) and 6-Minute Walk Test (6MWT), respectively. We quantified intralimb motor coordination using kinematic variability measures of foot trajectory (i.e., endpoint variability, EV) and of inter-joint coupling between the hip and knee, as well as between the knee and ankle joints (i.e., angular coefficient of correspondence, ACC). We compared the changes in walking performance relative to baseline (BL) between daily AIH + WALK and daily SHAM+WALK on treatment day 5 (T₅), 1-week follow-up (F₁), and 2-weeks follow-up (F₂). We also compared these changes between participants who used bilateral walking aids (N = 5) and those who did not. To assess the effects of daily AIH + WALK on intralimb coordination, we compared potential treatment-induced changes in EV and ACC relative to BL at F₁ and F₂.

RESULTS: Participants improved overground walking performance (speed and endurance) after daily AIH + WALK, but not SHAM+WALK. Following daily AIH + WALK, participants decreased their 10MWT time at T₅ by 28% (95% CI 0.2-10.1 s, p = 0.04), F₁ by 28% (95% CI 1.1-13.5 s, p = 0.01), and F₂ by 27% (95% CI 1.4-13.9 s, p = 0.01) relative to BL. The greatest decreases in the 10MWT occurred in participants who used bilateral walking aids (p < 0.05). We also found daily AIH + WALK resulted in an increase in 6MWT distance at T₅ by 22% (95% CI 13.3-72.6 m, p = 0.001), F₁ by 21% (95% CI 13.1-72.5 m, p = 0.001), and F₂ by 16% (95% CI 2.9-62.2 m, p = 0.02). However, measures of EV and ACC during self-selected walking conditions did not change following daily AIH + WALK (all p-values >0.50).

CONCLUSIONS: Consistent with prior studies, daily AIH + WALK triggered improvements in walking speed and endurance that persisted for weeks after treatment. Greatest improvements in speed occurred in participants who used bilateral walking aids. No change in EV and ACC may suggest that intralimb motor coordination was not a significant gait training priority during daily AIH + WALK.

PMID:33647273 | PMC:PMC8119335 | DOI:10.1016/j.expneurol.2021.113669

Exp Neurol. 2021 Jan;335:113483. doi: 10.1016/j.expneurol.2020.113483. Epub 2020 Sep 25.

ABSTRACT

Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plasticity in humans with chronic incomplete cervical SCI. During PCMS, we used 180 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ~1-2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve. During AIH, participants were exposed to brief alternating episodes of hypoxic inspired gas (1 min episodes of 9% O₂) and room air (1 min episodes of 20.9% O₂). We examined corticospinal function by measuring motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and voluntary motor output in the FDI muscle before and after 30 min of PCMS combined with AIH (PCMS+AIH) or sham AIH (PCMS+sham-AIH). The amplitude of MEPs evoked by magnetic and electrical stimulation increased after both protocols, but most after PCMS+AIH, consistent with the hypothesis that their combined effects arise from spinal plasticity. Both protocols increased electromyographic activity in the FDI muscle to a similar extent. Thus, PCMS effects on spinal synapses of hand motoneurons can be potentiated by AIH. The possibility of different thresholds for physiological vs behavioral gains needs to be considered during combinatorial treatments.

PMID:32987000 | PMC:PMC9208274 | DOI:10.1016/j.expneurol.2020.113483

BMC Neurol. 2020 Jul 8;20(1):273. doi: 10.1186/s12883-020-01851-9.

ABSTRACT

BACKGROUND: Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI (< 12 months) SCI. Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with subacute (< 12 months) SCI, presumably by harnessing endogenous mechanisms of plasticity that occur soon after injury.

METHODS: To test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O₂ with 60s intervals at 20.9% O₂) or daily SHAM (15, 90s episodes at 20.9% O₂ with 60s intervals at 20.9% O₂) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment.

DISCUSSION: The goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02632422 . Registered 16 December 2015.

PMID:32641012 | PMC:PMC7341658 | DOI:10.1186/s12883-020-01851-9

Am J Respir Crit Care Med. 2020 Sep 15;202(6):887-890. doi: 10.1164/rccm.202002-0245LE.

NO ABSTRACT

PMID:32369393 | PMC:PMC7491397 | DOI:10.1164/rccm.202002-0245LE

Gait Posture. 2020 Jan;75:121-128. doi: 10.1016/j.gaitpost.2019.10.023. Epub 2019 Oct 17.

ABSTRACT

BACKGROUND: Returning to community walking remains a major challenge for persons with incomplete spinal cord injury (iSCI) due, in part, to impaired interlimb coordination. Here, we examined spatial and temporal features of interlimb coordination during walking and their associations to gait deficits in persons with chronic iSCI.

RESEARCH QUESTION: Do deficits in spatial and temporal interlimb coordination correspond differentially to clinical indicators of walking performance in persons with iSCI?

METHODS: Sixteen persons with chronic iSCI and eleven able-bodied individuals participated in this study. Participants walked at self-selected gait speeds along an instrumented walkway that recorded left and right step lengths and times. We quantified interlimb coordination in terms of normalized differences between left and right step lengths (spatial asymmetry index) and step times (temporal asymmetry index), as well as, gap and phase coordination indices. We then assessed the extent to which these indices independently associated with clinical measures of walking performance.

RESULTS: Participants with iSCI demonstrated greater spatial and temporal asymmetry, as well as, reduced gap and phase interlimb coordination as compared to age-matched controls (p < 0.001). We found no linear relationships between spatial and temporal asymmetry indices (p > 0.05) or between gap and phase coordination indices (p > 0.05). Spatial and temporal asymmetry indices weakly correlated with SCI-FAI composite scores (r² = 0.26; p = 0.04). However, only spatial asymmetry indices strongly correlated with slower walking speed (r² = 0.51; p < 0.002). We also found participants who used a hand-held assistive device (walker) demonstrated great spatial asymmetry as compared to those who did not (p < 0.03).

SIGNIFICANCE: Differential impairments in spatial and temporal interlimb coordination correspond to overground walking deficits in persons with chronic iSCI. Spatial asymmetry associated with decreased walking speed and increased reliance on hand-held assistive devices. Gait training methods that target well-defined space and time domains of interlimb coordination may enhance overground gait training in persons with iSCI.

PMID:31675554 | PMC:PMC6883355 | DOI:10.1016/j.gaitpost.2019.10.023

Phys Ther. 2019 May 1;99(5):519-525. doi: 10.1093/ptj/pzz008.

ABSTRACT

Ongoing advances and discoveries in biotechnology will require physical therapists to stay informed and contribute to their development and implementation. The extent of our profession's involvement in how physical therapists engage biotechnology is determined by us. In this Perspective article, we advocate the need for our profession to educate clinicians alongside scientists, technologists, and engineers and empower them to collectively think more as codevelopers and less as "siloed" builders and consumers of biotechnology. In particular, we highlight the value of augmenting the physical therapy curricula to provide students with new levels of knowledge about the converging fields of engineering and physical therapy. We present successful examples of how such a concept can occur within physical therapist professional education programs and propose strategies to overcome perceived challenges that may stymie this possibility.

PMID:30690519 | PMC:PMC7325447 | DOI:10.1093/ptj/pzz008

J Neurotrauma. 2018 Sep 15;35(18):2143-2144. doi: 10.1089/neu.2018.5993.

NO ABSTRACT

PMID:30009669 | DOI:10.1089/neu.2018.5993

J Neurotrauma. 2018 Nov 1;35(21):2519-2529. doi: 10.1089/neu.2017.5538. Epub 2018 Jun 5.

ABSTRACT

Incomplete spinal cord injury (iSCI) often leads to partial disruption of spinal pathways that are important for motor control of walking. Persons with iSCI present with deficits in walking ability in part because of inconsistent leg kinematics during stepping. Although kinematic variability is important for normal walking, growing evidence indicates that excessive variability may limit walking ability and increase reliance on assistive devices (AD) after iSCI. The purpose of this study was to assess the effects of iSCI-induced impairments on kinematic variability during overground walking. We hypothesized that iSCI results in greater variability of foot and joint displacement during overground walking compared with controls. We further hypothesized that variability is larger in persons with limited walking speed and greater reliance on ADs. To test these hypotheses, iSCI and control subjects walked overground. Kinematic variability was quantified as step-to-step foot placement variability (end-point), and variability in hip-knee, hip-ankle, and knee-ankle joint space (angular coefficient of correspondence [ACC]). We characterized sensitivity of kinematic variability to cadence, auditory cue, and AD. Supporting our hypothesis, persons with iSCI exhibited greater kinematic variability than controls, which scaled with deficits in overground walking speed (p < 0.01). Significant correlation between ACC and end-point variability, and with walking speed, indicates that both are markers of walking performance. Moreover, hip-knee and hip-ankle ACC discriminated AD use, indicating that ACC may capture AD-specific control strategies. We conclude that increased variability of foot and joint displacement are indicative of motor impairment severity and may serve as therapeutic targets to restore walking after iSCI.

PMID:29648987 | PMC:PMC6205771 | DOI:10.1089/neu.2017.5538

Neurology. 2017 Oct 31;89(18):1904-1907. doi: 10.1212/WNL.0000000000004596. Epub 2017 Sep 29.

ABSTRACT

OBJECTIVE: To test the hypothesis that daily acute intermittent hypoxia (AIH) combined with hand opening practice improves hand dexterity, function, and maximum hand opening in persons with chronic, motor-incomplete, cervical spinal cord injury.

METHODS: Six participants completed the double-blind, crossover study. Participants received daily (5 consecutive days) AIH (15 episodes per day: 1.5 minutes of fraction of inspired oxygen [FIo₂] = 0.09, 1-minute normoxic intervals) followed by 20 repetitions of hand opening practice and normoxia (sham, FIo₂ = 0.21) + hand opening practice. Hand dexterity and function were quantified with Box and Block and Jebsen-Taylor hand function tests. We also recorded maximum hand opening using motion analyses and coactivity of extensor digitorum and flexor digitorum superficialis muscles using surface EMG.

RESULTS: Daily AIH + hand opening practice improved hand dexterity, function, and maximum hand opening in all participants. AIH + hand opening practice improved Box and Block Test scores vs baseline in 5 participants (p = 0.057) and vs sham + hand opening practice in all 6 participants (p = 0.016). All participants reduced Jebsen-Taylor Hand Function Test (JTHF) time after daily AIH + hand opening practice (-7.2 ± 1.4 seconds) vs baseline; 4 of 6 reduced JTHF time vs sham + hand opening practice (p = 0.078). AIH + hand opening practice improved maximum hand aperture in 5 of 6 participants (8.1 ± 2.7 mm) vs baseline (p = 0.018) and sham + hand opening practice (p = 0.030). In 5 participants, daily AIH-induced changes in hand opening were accompanied by improved EMG coactivity (p = 0.029).

CONCLUSIONS: This report suggests the need for further study of AIH as a plasticity "primer" for task-specific training in spinal cord injury rehabilitation. Important clinical questions remain concerning optimal AIH dosage, patient screening, safety, and effect persistence.

CLINICALTRIALSGOV IDENTIFIER: NCT01272336.

PMID:28972191 | PMC:PMC5664298 | DOI:10.1212/WNL.0000000000004596

J Neurotrauma. 2018 Feb 1;35(3):467-477. doi: 10.1089/neu.2017.5146. Epub 2017 Oct 27.

ABSTRACT

Persons with incomplete spinal cord injury (iSCI) face ongoing struggles with walking, including reduced speed and increased reliance on assistive devices (ADs). The forces underlying body weight support and gait, as measured by ground reaction forces (GRFs), are likely altered after iSCI because of weakness and AD dependence but have not been studied. The purpose of this study was to examine GRF production during overground walking after iSCI, because greater insight into GRF constraints is important for refining therapeutic interventions. Because of reduced and discoordinated motor output after iSCI, we hypothesized that persons with iSCI would exert smaller GRFs and altered GRF modifications to increased cadence compared with able-bodied (AB) persons, especially when using an AD. Fifteen persons with chronic iSCI, stratified into no AD (n = 7) and AD (n = 8) groups, walked across an instrumented walkway at self-selected and fast (115% self-selected) cadences. Fifteen age-matched AB controls walked at their own cadences and iSCI-matched conditions (cadence and AD). Results showed fore-aft GRFs are reduced in persons with iSCI compared with AB controls, with reductions greatest in persons dependent on an AD. When controlling for cadence and AD, propulsive forces were still lower in persons with iSCI. Compared with AB controls, persons with iSCI demonstrated altered GRF modifications to increased cadence. Persons with iSCI exhibit different stance-phase forces compared with AB controls, which are impacted further by AD use and slower walking speed. Minimizing AD use and/or providing propulsive biofeedback during walking could enhance GRF production after iSCI.

PMID:28762876 | PMC:PMC5793954 | DOI:10.1089/neu.2017.5146

Phys Ther. 2016 May;96(5):734-42. doi: 10.2522/ptj.20150063. Epub 2016 Feb 4.

ABSTRACT

The goal of regenerative medicine is to restore function through therapy at levels such as the gene, cell, tissue, or organ. For many disorders, however, regenerative medicine approaches in isolation may not be optimally effective. Rehabilitation is a promising adjunct therapy given the beneficial impact that physical activity and other training modalities can offer. Accordingly, "regenerative rehabilitation" is an emerging concentration of study, with the specific goal of improving positive functional outcomes by enhancing tissue restoration following injury. This article focuses on one emerging example of regenerative rehabilitation-namely, the integration of clinically based protocols with stem cell technologies following central nervous system injury. For the purposes of this review, the state of stem cell technologies for the central nervous system is summarized, and a rationale for a synergistic benefit of carefully orchestrated rehabilitation protocols in conjunction with cellular therapies is provided. An overview of practical steps to increase the involvement of physical therapy in regenerative rehabilitation research also is provided.

PMID:26847015 | PMC:PMC6281018 | DOI:10.2522/ptj.20150063

Neuron. 2015 Apr 8;86(1):38-54. doi: 10.1016/j.neuron.2015.02.042.

ABSTRACT

Neuromechanical principles define the properties and problems that shape neural solutions for movement. Although the theoretical and experimental evidence is debated, we present arguments for consistent structures in motor patterns, i.e., motor modules, that are neuromechanical solutions for movement particular to an individual and shaped by evolutionary, developmental, and learning processes. As a consequence, motor modules may be useful in assessing sensorimotor deficits specific to an individual and define targets for the rational development of novel rehabilitation therapies that enhance neural plasticity and sculpt motor recovery. We propose that motor module organization is disrupted and may be improved by therapy in spinal cord injury, stroke, and Parkinson's disease. Recent studies provide insights into the yet-unknown underlying neural mechanisms of motor modules, motor impairment, and motor learning and may lead to better understanding of the causal nature of modularity and its underlying neural substrates.

PMID:25856485 | PMC:PMC4392340 | DOI:10.1016/j.neuron.2015.02.042

Exp Brain Res. 2015 Mar;233(3):871-84. doi: 10.1007/s00221-014-4163-y. Epub 2014 Dec 16.

ABSTRACT

The intact neuromotor system prepares for object grasp by first opening the hand to an aperture that is scaled according to object size and then closing the hand around the object. After cervical spinal cord injury (SCI), hand function is significantly impaired, but the degree to which object-specific hand aperture scaling is affected remains unknown. Here, we hypothesized that persons with incomplete cervical SCI have a reduced maximum hand opening capacity but exhibit novel neuromuscular coordination strategies that permit object-specific hand aperture scaling during reaching. To test this hypothesis, we measured hand kinematics and surface electromyography from seven muscles of the hand and wrist during attempts at maximum hand opening as well as reaching for four balls of different diameters. Our results showed that persons with SCI exhibited significantly reduced maximum hand aperture compared to able-bodied (AB) controls. However, persons with SCI preserved the ability to scale peak hand aperture with ball size during reaching. Persons with SCI also used distinct muscle coordination patterns that included increased co-activity of flexors and extensors at the wrist and hand compared to AB controls. These results suggest that motor planning for aperture modulation is preserved even though execution is limited by constraints on hand opening capacity and altered muscle co-activity. Thus, persons with incomplete cervical SCI may benefit from rehabilitation aimed at increasing hand opening capacity and reducing flexor-extensor co-activity at the wrist and hand.

PMID:25511164 | PMC:PMC4320659 | DOI:10.1007/s00221-014-4163-y

Clin Neurophysiol. 2014 Oct;125(10):2024-35. doi: 10.1016/j.clinph.2014.02.001. Epub 2014 Feb 14.

ABSTRACT

OBJECTIVE: Incomplete spinal cord injury (iSCI) disrupts motor control and limits the ability to coordinate muscles for overground walking. Inappropriate muscle activity has been proposed as a source of clinically observed walking deficits after iSCI. We hypothesized that persons with iSCI exhibit lower locomotor complexity compared to able-body (AB) controls as reflected by fewer motor modules, as well as, altered module composition and activation.

METHODS: Eight persons with iSCI and eight age-matched AB controls walked overground at prescribed cadences. Electromyograms of fourteen single leg muscles were recorded. Non-negative matrix factorization was used to identify the composition and activation of motor modules, which represent groups of consistently co-activated muscles that accounted for 90% of variability in muscle activity.

RESULTS: Motor module number, composition, and activation were significantly altered in persons with iSCI as compared to AB controls during overground walking at self-selected cadences. However, there was no significant difference in module number between persons with iSCI and AB controls when cadence and assistive device were matched.

CONCLUSIONS: Muscle coordination during overground walking is impaired after chronic iSCI.

SIGNIFICANCE: Our results are indicative of neuromuscular constraints on muscle coordination after iSCI. Altered muscle coordination contributes to person-specific gait deficits during overground walking.

PMID:24618214 | PMC:PMC4133333 | DOI:10.1016/j.clinph.2014.02.001

Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27.

ABSTRACT

OBJECTIVES: To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI).

METHODS: Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349).

RESULTS: dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1-6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9-6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5-171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1-173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3-134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6-173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3-206.6 m, p < 0.001).

CONCLUSIONS: dAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI.

CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI.

PMID:24285617 | PMC:PMC3897437 | DOI:10.1212/01.WNL.0000437416.34298.43

Clin Neurophysiol. 2013 Jul;124(7):1373-80. doi: 10.1016/j.clinph.2013.01.013. Epub 2013 Feb 28.

ABSTRACT

OBJECTIVE: Modulation of the long-latency reflex (LLR) is important for sensorimotor control during interaction with different mechanical loads. Transcortical pathways usually contribute to LLR modulation, but the integrity of pathways projecting to the paretic and non-paretic arms of stroke survivors is compromised. We hypothesize that disruption of transcortical reflex pathways reduces the capacity for stroke survivors to appropriately regulate the LLR bilaterally.

METHODS: Elbow perturbations were applied to the paretic and non-paretic arms of persons with stroke, and the dominant arm of age-matched controls as subjects interacted with Stiff or Compliant environments rendered by a linear actuator. Reflexes were quantified using surface electromyograms, recorded from biceps.

RESULTS: LLR amplitude was significantly larger during interaction with the Compliant load compared to the Stiff load in controls. However, there was no significant change in LLR amplitude for the paretic or non-paretic arm of stroke survivors.

CONCLUSION: Modulation of the LLR is altered in the paretic and non-paretic arms after stroke.

SIGNIFICANCE: Our results are indicative of bilateral sensorimotor impairments following stroke. The inability to regulate the LLR may contribute to bilateral deficits in tasks that require precise control of limb mechanics and stability.

PMID:23453250 | PMC:PMC3674210 | DOI:10.1016/j.clinph.2013.01.013

J Neurophysiol. 2013 Feb;109(4):1045-54. doi: 10.1152/jn.00135.2012. Epub 2012 Dec 5.

ABSTRACT

Many common tasks compromise arm stability along specific directions. Such tasks can be completed only if the impedance of the arm is sufficient to compensate for the destabilizing effects of the task. During movement, it has been demonstrated that the direction of maximal arm stiffness, the static component of impedance, can be preferentially increased to compensate for directionally unstable environments. In contrast, numerous studies have shown that such control is not possible during postural tasks. It remains unknown if these findings represent a fundamental difference in the control of arm mechanics during posture and movement or an involuntary response to the destabilizing environments used in the movement studies but not yet tested during posture maintenance. Our goal was to quantify how arm impedance is adapted during postural tasks that compromise stability along specific directions. Our results demonstrate that impedance can be modulated to compensate for these instabilities during postural tasks but that the changes are modest relative to those previously reported during reaching. Our observed changes were primarily in the magnitude of end-point stiffness, but these were not sufficient to alter the direction of maximal stiffness. Furthermore, there were no substantial changes in the magnitude of end-point viscosity or inertia, suggesting that the primary change to arm impedance was a selective increase in stiffness to compensate for the destabilizing stiffness properties of the environment. We suggest that these modest changes provide an initial involuntary response to destabilizing environments prior to the larger changes that can be affected through voluntary interventions.

PMID:23221409 | PMC:PMC3569138 | DOI:10.1152/jn.00135.2012

Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5.

ABSTRACT

BACKGROUND: Neural plasticity may contribute to motor recovery following spinal cord injury (SCI). In rat models of SCI with respiratory impairment, acute intermittent hypoxia (AIH) strengthens synaptic inputs to phrenic motor neurons, thereby improving respiratory function by a mechanism known as respiratory long-term facilitation. Similar intermittent hypoxia-induced facilitation may be feasible in somatic motor pathways in humans.

OBJECTIVE: Using a randomized crossover design, the authors tested the hypothesis that AIH increases ankle strength in people with incomplete SCI.

METHODS: Ankle strength was measured in 13 individuals with chronic, incomplete SCI before and after AIH. Voluntary ankle strength was estimated using changes in maximum isometric ankle plantar flexion torque generation and plantar flexor electromyogram activity following 15 low oxygen exposures (Fio(2) = 0.09, 1-minute intervals). Results were compared with trials where subjects received sham exposure to room air.

RESULTS: AIH increased plantar flexion torque by 82 ± 33% (P < .003) immediately following AIH and was sustained above baseline for more than 90 minutes (P < .007). Increased ankle plantar flexor electromyogram activity (P = .01) correlated with increased torque (r(2) = .5; P < .001). No differences in plantar flexion strength or electromyogram activity were observed in sham experiments.

CONCLUSIONS: AIH elicits sustained increases in volitional somatic motor output in persons with chronic SCI. Thus, AIH has promise as a therapeutic tool to induce plasticity and enhance motor function in SCI patients.

PMID:21821826 | DOI:10.1177/1545968311412055

J Neurophysiol. 2010 Dec;104(6):3612-24. doi: 10.1152/jn.00804.2009. Epub 2010 Oct 20.

ABSTRACT

Patterns of stereotyped muscle coactivation, clinically referred to as synergies, emerge following stroke and impair arm function. Although researchers have focused on cortical contributions, there is growing evidence that altered stretch reflex pathways may also contribute to impairment. However, most previous reflex studies have focused on passive, single-joint movements without regard to their coordination during volitional actions. The purpose of this study was to examine the effects of stroke on coordinated activity of stretch reflexes elicited in multiple arm muscles following multijoint perturbations. We hypothesized that cortical injury results in increased stretch reflexes of muscles characteristic of the abnormal flexor synergy during active arm conditions. To test this hypothesis, we used a robot to apply position perturbations to impaired arms of 10 stroke survivors and dominant arms of 8 healthy age-matched controls. Corresponding reflexes were assessed during volitional contractions simulating different levels of gravitational support, as well as during voluntary flexion and extension of the elbow and shoulder. Reflexes were quantified by average rectified surface electromyogram, recorded from eight muscles spanning the elbow and shoulder. Reflex coordination was quantified using an independent components analysis. We found stretch reflexes elicited in the stroke group were significantly less sensitive to changes in background muscle activation compared with those in the control group (P < 0.05). We also observed significantly increased reflex coupling between elbow flexor and shoulder abductor-extensor muscles in stroke subjects relative to that in control subjects. This increased coupling was present only during volitional tasks that required elbow flexion (P < 0.001), shoulder extension (P < 0.01), and gravity opposition (P < 0.01), but not during the "no load" condition. During volitional contractions, reflex amplitudes scaled with the level of impairment, as assessed by Fugl-Meyer scores (r(2) = 0.63; P < 0.05). We conclude that altered reflex coordination is indicative of motor impairment level and may contribute to impaired arm function following stroke.

PMID:20962072 | PMC:PMC3007635 | DOI:10.1152/jn.00804.2009

Exp Brain Res. 2010 Nov;207(1-2):39-48. doi: 10.1007/s00221-010-2426-9. Epub 2010 Sep 28.

ABSTRACT

Simultaneous contraction of agonist and antagonist muscles acting about a joint influences joint stiffness and stability. Although several studies have shown that reflexes in the muscle lengthened by a joint perturbation are modulated during co-contraction, little attention has been given to reflex regulation in the antagonist (shortened) muscle. The goal of the present study was to determine whether co-contraction gives rise to altered reflex regulation across the joint by examining reflexes in the muscle shortened by a joint perturbation. Reflexes were recorded from electromyographic activity in elbow flexors and extensors while positional perturbations to the elbow joint were applied. Perturbations were delivered during isolated activation of the flexor or extensor muscles as well as during flexor and extensor co-contraction. Across the group, the shortening reflex in the elbow extensor switched from suppression during isolated extensor muscle activation to facilitation during co-contraction. The shortening reflex in the elbow flexor remained suppressive during co-contraction but was significantly smaller compared to the response obtained during isolated elbow flexor activation. This response in the shortened muscle was graded by the level of activation in the lengthened muscle. The lengthening reflex did not change during co-contraction. These results support the idea that reflexes are regulated across multiple muscles around a joint. We speculate that the facilitatory response in the shortened muscle arises through a fast-conducting oligosynaptic pathway involving Ib interneurons.

PMID:20878148 | PMC:PMC3045052 | DOI:10.1007/s00221-010-2426-9

Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:5938-41. doi: 10.1109/IEMBS.2009.5334751.

ABSTRACT

Using the upper limb to manipulate objects or tools requires maintenance of stable arm posture. The ability to maintain stable postures is dependent on the mechanical properties of the arm, which can be characterized by estimates of endpoint stiffness. In this study we quantified the endpoint stiffness of the human arm during postural interactions with mechanically imposed unstable loads. The purpose was to determine the extent to which arm stiffness is adapted according to the mechanical properties of the environment during postural tasks. We estimated the endpoint stiffness of the right arms of eight subjects as they interacted with four haptic environments: rigid, unstable along the direction of maximal endpoint stiffness and orthogonal to this direction, and a high-strength unstable environment also aligned to the orientation of maximal endpoint stiffness. The size and orientation of endpoint stiffness were quantified for each haptic condition. Stiffness size was increased along the directions of the destabilizing environments (p<0.003). However, the environments had no significant effect on stiffness orientation (p>0.26). These findings suggest that at a fixed posture interactions with unstable environments can induce moderate, task-appropriate changes in limb mechanics that are tuned to the environment. However, these changes are small relative to those that can be obtained by changing limb posture.

PMID:19965062 | PMC:PMC2892268 | DOI:10.1109/IEMBS.2009.5334751

J Neurophysiol. 2010 Jan;103(1):429-40. doi: 10.1152/jn.00679.2009. Epub 2009 Nov 11.

ABSTRACT

Stretch reflexes contribute to arm impedance and longer-latency stretch reflexes exhibit increased sensitivity during interactions with compliant or unstable environments. This increased sensitivity is consistent with a regulation of arm impedance to compensate for decreased stability of the environment, but the specificity of this modulation has yet to be investigated. Many tasks, such as tool use, compromise arm stability along specific directions, and stretch reflexes tuned to those directions could present an efficient mechanism for regulating arm impedance in a task-appropriate manner. To be effective, such tuning should adapt not only to the mechanical properties of the environment but to those properties in relation to the arm, which also has directionally specific mechanical properties. The purpose of this study was to investigate the specificity of stretch reflex modulation during interactions with mechanical environments that challenge arm stability. The tested environments were unstable, having the characteristics of a negative stiffness spring. These were either aligned or orthogonal to the direction of maximal endpoint stiffness for each subject. Our results demonstrate preferential increases in reflexes, elicited within 50-100 ms of perturbation onset, to perturbations applied specifically along the direction of the destabilizing environments. This increase occurred only when the magnitude of the environmental instability exceeded endpoint stiffness along the same direction. These results are consistent with task-specific reflex modulation tuned to the mechanical properties of the environment relative to those of the human arm. They demonstrate a highly adaptable, involuntary mechanism that may be used to modulate limb impedance along specific directions.

PMID:19906880 | PMC:PMC2807231 | DOI:10.1152/jn.00679.2009

PLoS One. 2009;4(5):e5411. doi: 10.1371/journal.pone.0005411. Epub 2009 May 1.

ABSTRACT

BACKGROUND: The human motor system is highly redundant, having more kinematic degrees of freedom than necessary to complete a given task. Understanding how kinematic redundancies are utilized in different tasks remains a fundamental question in motor control. One possibility is that they can be used to tune the mechanical properties of a limb to the specific requirements of a task. For example, many tasks such as tool usage compromise arm stability along specific directions. These tasks only can be completed if the nervous system adapts the mechanical properties of the arm such that the arm, coupled to the tool, remains stable. The purpose of this study was to determine if posture selection is a critical component of endpoint stiffness regulation during unconstrained tasks.

METHODOLOGY/PRINCIPAL FINDINGS: Three-dimensional (3D) estimates of endpoint stiffness were used to quantify limb mechanics. Most previous studies examining endpoint stiffness adaptation were completed in 2D using constrained postures to maintain a non-redundant mapping between joint angles and hand location. Our hypothesis was that during unconstrained conditions, subjects would select arm postures that matched endpoint stiffness to the functional requirements of the task. The hypothesis was tested during endpoint tracking tasks in which subjects interacted with unstable haptic environments, simulated using a 3D robotic manipulator. We found that arm posture had a significant effect on endpoint tracking accuracy and that subjects selected postures that improved tracking performance. For environments in which arm posture had a large effect on tracking accuracy, the self-selected postures oriented the direction of maximal endpoint stiffness towards the direction of the unstable haptic environment.

CONCLUSIONS/SIGNIFICANCE: These results demonstrate how changes in arm posture can have a dramatic effect on task performance and suggest that postural selection is a fundamental mechanism by which kinematic redundancies can be exploited to regulate arm stiffness in unconstrained tasks.

PMID:19412540 | PMC:PMC2671603 | DOI:10.1371/journal.pone.0005411

Annu Int Conf IEEE Eng Med Biol Soc. 2008;2008:5350-3. doi: 10.1109/IEMBS.2008.4650423.

ABSTRACT

To successfully complete a motor task, it is necessary to control not only the kinematics and dynamics of a limb, but also its mechanical properties. In a multijoint task such as the control of arm posture, limb mechanics are directional, resisting external disturbances more effectively in certain directions than others. It has been demonstrated that feedforward neuromotor pathways can regulate these directional characteristics of the arm to compensate for changes in the mechanical properties of the environment. However, it is unclear if spinal reflex pathways exhibit a similar specificity. The present results suggest that the sensitivity of the human stretch reflex also can be tuned to adapt the mechanical properties of the arm in a task appropriate manner. We hypothesized that the orientation of arm mechanics relative to the mechanical properties of the environment would influence reflex adaptation. Two destabilizing environments, oriented relative to the mechanical properties of the arm, were used to test this hypothesis. These environments were simulated using a 3 degrees of freedom (DOF) robot, which also was used to perturb arm posture. The resulting reflexes, assessed by electromyograms recorded from 8 muscles, were found to modulate in accordance with how the environmental instability was oriented relative to the mechanical properties of the arm. Our results suggest that stretch sensitive reflexes throughout the arm are modulated in a coordinated manner corresponding to the orientation of arm mechanics relative to the environment.

PMID:19163926 | PMC:PMC2729709 | DOI:10.1109/IEMBS.2008.4650423

Annu Int Conf IEEE Eng Med Biol Soc. 2008;2008:3558-61. doi: 10.1109/IEMBS.2008.4649974.

ABSTRACT

Following stroke, individuals often are unable to activate their elbow and shoulder muscles independently. There is growing evidence that altered reflex pathways may contribute to these abnormal patterns of activation or muscle synergies. Most studies investigating reflex function following stroke have examined only individual joints at rest. Thus, the purpose of this study was to quantify multijoint reflex contributions to the stereotyped muscle synergies commonly observed following stroke. We hypothesized that the patterns of reflex coordination mirror the abnormal muscle coactivity patterns previously reported for voluntary activation. 10 chronic stroke and 8 age-matched control subjects participated. Reflexes were elicited by perturbing the arm with a 3 degree of freedom robot while subjects exerted voluntary forces at the elbow and shoulder. The force conditions tested were selected to assess the influence of gravity and the influence of joint torque generation without gravity on reflex coordination. Reflex magnitude was quantified by the average rectified electromyogram, recorded from 8 muscles that span the elbow and shoulder. Patterns of reflex coordination were quantified using independent components analysis. Results show significant reflex coupling between elbow flexor and shoulder abductor-extensor muscles in stroke patients during isolated elbow and shoulder torque generation and during active arm support against gravity. Identified patterns of stretch reflex coordination were consistent with the stereotyped voluntary flexion synergy, suggesting reflex pathways contribute to abnormal muscle coordination following stroke.

PMID:19163477 | PMC:PMC2753470 | DOI:10.1109/IEMBS.2008.4649974

J Neurophysiol. 2008 May;99(5):2101-13. doi: 10.1152/jn.01094.2007. Epub 2008 Feb 20.

ABSTRACT

The human motor system regulates arm mechanics to produce stable postures during interactions with different physical environments. This occurs partly via involuntary mechanisms, including stretch reflexes. Previous single-joint studies demonstrated enhanced reflex sensitivity during interactions with compliant environments, suggesting reflex gain increases to enhance limb stability when that stability is not provided by the environment. This study examined whether similar changes in reflex gain are present throughout the limb following perturbations that simultaneously influence multiple joints. Furthermore, we investigated whether any observed modulation was accompanied by task-specific changes in reflex coordination across muscles, a question that cannot be addressed using single-joint perturbations. Reflexes were elicited during the maintenance of posture by perturbing the arm with a three degrees of freedom robot, configured to have isotropic stiffness of either 10 N/m (compliant) or 10 kN/m (stiff). Perturbation characteristics were matched in both environments. Reflex magnitude was quantified by the average rectified electromyogram, recorded from eight muscles crossing the elbow and shoulder. Reflex coordination was assessed using independent components analysis to compare reflex activation patterns during interactions with stiff and compliant environments. Stretch reflex sensitivity increased significantly in all muscles during interactions with the compliant environment and these changes were not due to changes in background muscle activity. However, there was no significant difference in the reflex coordination patterns observed during interactions with the stiff and compliant environments. These results suggest that reflex modulation occurred through altered use of fixed muscle coordination patterns rather than through a change in reflex coordination.

PMID:18287550 | PMC:PMC2810681 | DOI:10.1152/jn.01094.2007

J Clin Monit Comput. 2006 Jun;20(3):209-20. doi: 10.1007/s10877-006-9023-2. Epub 2006 Jun 15.

ABSTRACT

Functional electrical stimulation-induced leg cycle ergometry (FES-LCE) provides therapeutic exercise for persons with spinal cord injury (SCI). However, there exists no systematic approach to predict whether an individual has sufficient thigh muscle strength necessary for FES-LCE exercise.

OBJECTIVE: To develop and test a Probably Approximately Correct (PAC) learning model as a predictor of thigh muscle strengths sufficient for short-duration FES-LCE exercise and compare the model's performance with other well-known statistical methods.

METHODS: Six healthy male individuals with SCI, having age (32.0 +/- 12.5 years), height (1.8 +/- 0.04 m), and weight (79.12 +/- 10.76 kg), participated in static and dynamic experiments. During static experiments, absolute crank torque measurements were used to estimate thigh muscle strengths in response to maximum FES intensities of 70 mA, 105 mA, and 140 mA at fixed crank positions on an FES-LCE. During dynamic experiments, changes in power output measurements were used to classify rider performance as 'Fatigue' or 'No Fatigue' during short-duration FES-LCE at maximum stimulation intensities of 70 mA, 105 mA, and 140 mA and flywheel resistance levels of 0/8th, 1/8th, and 2/8th kilopounds. A Probably Approximately Correct (PAC) learning model was developed to classify static offline muscle strength observations with online rider performances. PAC's discriminatory power was compared with logistic regression (LR), Fisher's linear discriminant analysis (LDA), and an artificial neural network (ANN) model.

RESULTS: PAC and ANN learning models correctly identified 100% of the training examples. PAC's average performance on the validation set was 93.1%. The ANN and LR performed comparable with 92.8% and 93.1% accuracy, respectively. The LDA method faired well on the validation set at 89.9%.

CONCLUSIONS: PAC performed well in identifying muscle strengths associated with the online performance criterion. Although PAC did not perform best during cross-validation, this model has many advantages over the other methods. PAC can adapt to changes in classification schemes and is more amenable to theoretical analyses than the other methods. PAC learning has an intuitive design and may be a practical choice for classifying muscle strength profiles with well-defined performance criteria.

PMID:16775658 | DOI:10.1007/s10877-006-9023-2

IEEE Eng Med Biol Mag. 2004 Mar-Apr;23(2):62-71. doi: 10.1109/memb.2004.1310977.

NO ABSTRACT

PMID:15264472 | DOI:10.1109/memb.2004.1310977