Tapping into the human spinal locomotor centres with transspinal stimulation.

Human locomotion is controlled by spinal neuronal networks of similar properties, function, and organization to those described in animals. Transspinal stimulation affects the spinal locomotor networks and is used to improve standing and walking ability in paralyzed people. However, the function of locomotor centers during transspinal stimulation at different frequencies and intensities is not known. Here, we document the 3D joint kinematics and spatiotemporal gait characteristics during transspinal stimulation at 15, 30, and 50 Hz at sub-threshold and supra-threshold stimulation intensities. We document the temporal structure of gait patterns, dynamic stability of joint movements over stride-to-stride fluctuations, and limb coordination during walking at a self-selected speed in healthy subjects. We found that transspinal stimulation (1) affects the kinematics of the hip, knee, and ankle joints, (2) promotes a more stable coordination at the left ankle, (3) affects interlimb coordination of the thighs, and (4) intralimb coordination between thigh and foot, (5) promotes greater dynamic stability of the hips, (6) increases the persistence of fluctuations in step length variability, and lastly (7) affects mechanical walking stability. These results support that transspinal stimulation is an important neuromodulatory strategy that directly affects gait symmetry and dynamic stability. The conservation of main effects at different frequencies and intensities calls for systematic investigation of stimulation protocols for clinical applications.

Soleus H-reflex amplitude modulation during walking remains physiological during transspinal stimulation in humans.

The soleus H-reflex modulation pattern was investigated during stepping following transspinal stimulation over the thoracolumbar region at 15, 30, and 50 Hz with 10 kHz carry-over frequency above and below the paresthesia threshold. The soleus H-reflex was elicited by posterior tibial nerve stimulation with a single 1 ms pulse at an intensity that the M-wave amplitudes ranged from 0 to 15% of the maximal M-wave evoked 80 ms after the test stimulus, and the soleus H-reflex was half the size of the maximal H-reflex evoked on the ascending portion of the recruitment curve. During treadmill walking, the soleus H-reflex was elicited every 2 or 3 steps, and stimuli were randomly dispersed across the step cycle which was divided in 16 equal bins. For each subject and condition, the soleus M-wave and H-reflex were normalized to the maximal M-wave. The soleus background electromyographic (EMG) activity was estimated as the linear envelope for 50 ms duration starting at 100 ms before posterior tibial nerve stimulation for each bin. The gain was determined as the slope of the relationship between the soleus H-reflex and the soleus background EMG activity. The soleus H-reflex phase-dependent amplitude modulation remained unaltered during transspinal stimulation, regardless frequency, or intensity. Similarly, the H-reflex slope and intercept remained the same for all transspinal stimulation conditions tested. Locomotor EMG activity was increased in knee extensor muscles during transspinal stimulation at 30 and 50 Hz throughout the step cycle while no effects were observed in flexor muscles. These findings suggest that transspinal stimulation above and below the paresthesia threshold at 15, 30, and 50 Hz does not block or impair spinal integration of proprioceptive inputs and increases activity of thigh muscles that affect both hip and knee joint movement. Transspinal stimulation may serve as a neurorecovery strategy to augment standing or walking ability in upper motoneuron lesions.

Tapping Into the Human Spinal Locomotor Centres With Transspinal Stimulation.

Human locomotion is controlled by spinal neuronal networks of similar properties, function, and organization to those described in animals. Transspinal stimulation affects the spinal locomotor networks and is used to improve standing and walking ability in paralyzed people. However, the function of locomotor centers during transspinal stimulation at different frequencies and intensities is not known. Here, we document the 3D joint kinematics and spatiotemporal gait characteristics during transspinal stimulation at 15, 30, and 50 Hz at sub-threshold and supra-threshold stimulation intensities. We document the temporal structure of gait patterns, dynamic stability of joint movements over stride-to-stride fluctuations, and limb coordination during walking at a self-selected speed in healthy subjects. We found that transspinal stimulation 1) affects the kinematics of the hip, knee, and ankle joints, 2) promotes a more stable coordination at the left ankle, 3) improves interlimb coordination of the thighs, 4) improves intralimb coordination between thigh and foot, 5) promotes greater dynamic stability of the hips, and lastly 6) affects the mechanical stability of the joints. These results support that transspinal stimulation is an important neuromodulatory strategy that directly affects gait symmetry and dynamic stability. The conservation of main effects at different frequencies and intensities calls for systematic investigation of stimulation protocols for clinical applications.

Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial.

Background: The seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. However, even after multiple locomotor training sessions, abnormal muscle activity and coordination persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits and potentiate neuronal activity based on need. Transcutaneous spinal cord (transspinal) stimulation alters motoneuron excitability over multiple segments by bringing motoneurons closer to threshold, a prerequisite for effectively promoting spinal locomotor network neuromodulation and strengthening neural connectivity of the injured human spinal cord. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after spinal cord injury is unknown. Methods: Forty-five individuals with chronic spinal cord injury are receiving 40 sessions of robotic gait training primed with 30 Hz transspinal stimulation at the Thoracic 10 vertebral level. Participants are randomized to receive 30-minutes of active or sham transspinal stimulation during standing or active transspinal stimulation while supine followed by 30-minutes of robotic gait training. Over the course of locomotor training, the body weight support, treadmill speed, and leg guidance force are adjusted as needed for each participant based on absence of knee buckling during the stance phase and toe dragging during the swing phase. At baseline and after completion of all therapeutic sessions, neurophysiological recordings registering corticospinal and spinal neural excitability changes along with clinical assessment measures of standing and walking, and autonomic function via questionnaires regarding bowel, bladder and sexual function are taken. Discussion: The results of this mechanistic randomized clinical trial will demonstrate that tonic transspinal stimulation strengthens corticomotoneuronal connectivity and dynamic neuromodulation through posture-dependent corticospinal and spinal neuroplasticity. We anticipate that this mechanistic clinical trial will greatly impact clinical practice because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation. Additionally, by applying multiple interventions to accelerate motor recovery, we are employing a treatment regimen that reflects a true clinical approach. Trial registration: ClinicalTrials.gov: NCT04807764; Registered on March 19, 2021.

Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial.

BACKGROUND: The seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. However, even after multiple locomotor training sessions, abnormal muscle activity and coordination persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits and potentiate neuronal activity based on need. Transcutaneous spinal cord (transspinal) stimulation alters motoneuron excitability over multiple segments by bringing motoneurons closer to threshold, a prerequisite for effectively promoting spinal locomotor network neuromodulation and strengthening neural connectivity of the injured human spinal cord. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after spinal cord injury is unknown. METHODS: Forty-five individuals with chronic spinal cord injury are receiving 40 sessions of robotic gait training primed with 30 Hz transspinal stimulation at the Thoracic 10 vertebral level. Participants are randomized to receive 30 min of active or sham transspinal stimulation during standing or active transspinal stimulation while supine followed by 30 min of robotic gait training. Over the course of locomotor training, the body weight support, treadmill speed, and leg guidance force are adjusted as needed for each participant based on absence of knee buckling during the stance phase and toe dragging during the swing phase. At baseline and after completion of all therapeutic sessions, neurophysiological recordings registering corticospinal and spinal neural excitability changes along with clinical assessment measures of standing and walking, and autonomic function via questionnaires regarding bowel, bladder, and sexual function are taken. DISCUSSION: The results of this mechanistic randomized clinical trial will demonstrate that tonic transspinal stimulation strengthens corticomotoneuronal connectivity and dynamic neuromodulation through posture-dependent corticospinal and spinal neuroplasticity. We anticipate that this mechanistic clinical trial will greatly impact clinical practice because, in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation. Additionally, by applying multiple interventions to accelerate motor recovery, we are employing a treatment regimen that reflects a true clinical approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT04807764 . Registered on March 19, 2021.

Leveraging a virtual alley with continuously varying width modulates step width variability during self-paced treadmill walking.

Increased fall risk in older adults and clinical populations is linked with increased amount and altered temporal structure of step width variability. One approach to rehabilitation seeks to reduce fall risk in older adults by reducing the amount of step width variability and restoring the temporal structure characteristic of healthy young adults. The success of such a program depends on our ability to modulate step width variability effectively. To this end, we investigated how manipulation of the visual walking space in a virtual environment could modulate the amount and temporal structure of step width variability. Nine healthy adults performed self-paced treadmill walking in a virtual alley in a fixed-width Control condition (1.91 m) and two conditions in which the alley's width oscillated sinusoidally at 0.03 Hz: between 0.38 and 1.14 m and 0.38-2.67 m in Narrow and Wide conditions, respectively. The step width time series from each condition was evaluated using: (i) the standard deviation to identify changes in the amount of variability and (ii) the fractal scaling exponent estimated using detrended fluctuation analysis (DFA) to identify changes in the temporal structure of variability in terms of persistence in fluctuations. The Wide condition neither affected the standard deviation nor the fractal scaling exponent of step width time series. The Narrow condition did not affect the standard deviation of step width time series compared to the Control condition but significantly increased its fractal scaling exponent compared to the Control and Wide conditions, suggestive of more persistent fluctuations characteristic of a healthy gait. These results show that virtual reality based rehabilitative intervention can modulate step width variability to potentially reduce fall risk in older adults and clinical populations.

Physiological effects of cathodal electrode configuration for transspinal stimulation in humans.

Transspinal stimulation modulates neuronal excitability and promotes recovery in upper motoneuron lesions. The recruitment input-output curves of transspinal evoked potentials (TEPs) recorded from knee and ankle muscles, and their susceptibility to spinal inhibition, were recorded when the position, size, and number of the cathode electrode were arranged in four settings or protocols (Ps). The four Ps were the following: 1) one rectangular electrode placed at midline (KNIKOU-LAB4Recovery or K-LAB4Recovery; P-KLAB), 2) one square electrode placed at midline (P-2), 3) two square electrodes 1 cm apart placed at midline (P-3), and 4) one square electrode placed on each paravertebral side (P-4). P-KLAB and P-3 required less current to reach TEP threshold or maximal amplitudes. A rightward shift in TEP recruitment curves was evident for P-4, whereas the slope was increased for P-2 and P-4 compared with P-KLAB and P-3. TEP depression upon single and paired transspinal stimuli was pronounced in ankle TEPs but was less prominent in knee TEPs. TEP depression induced by single transspinal stimuli at 1.0 Hz was similar for most TEPs across protocols, but TEP depression induced by paired transspinal stimuli was different between protocols and was replaced by facilitation at 100-ms interstimulus interval for P-4. Our results suggest that P-KLAB and P-3 are preferred based on excitability threshold of motoneurons. P-KLAB produced more TEP depression, thereby maximizing the engagement of spinal neuronal pathways. We recommend P-KLAB to study neurophysiological mechanisms underlying transspinal stimulation or when used as a neuromodulation method for recovery in neurological disorders.NEW & NOTEWORTHY Transspinal stimulation with a rectangular cathode electrode (P-KLAB) requires less current to produce transspinal evoked potentials and maximizes spinal inhibition. We recommend P-KLAB for neurophysiological studies or when used as a neuromodulation method to enhance motor output and normalize muscle tone in neurological disorders.

Irregular Metronomes as Assistive Devices to Promote Healthy Gait Patterns.

Older adults and people suffering from neurodegenerative disease often experience difficulty controlling gait during locomotion, ultimately increasing their risk of falling. To combat these effects, researchers and clinicians have used metronomes as assistive devices to improve movement timing in hopes of reducing their risk of falling. Historically, researchers in this area have relied on metronomes with isochronous interbeat intervals, which may be problematic because normal healthy gait varies considerably from one step to the next. More recently, researchers have advocated the use of irregular metronomes embedded with statistical properties found in healthy populations. In this paper, we explore the effect of both regular and irregular metronomes on many statistical properties of interstride intervals. Furthermore, we investigate how these properties react to mechanical perturbation in the form of a halted treadmill belt while walking. Our results demonstrate that metronomes that are either isochronous or random break down the inherent structure of healthy gait. Metronomes with statistical properties similar to healthy gait seem to preserve those properties, despite a strong mechanical perturbation. We discuss the future development of this work in the context of networked augmented reality metronome devices.

Rhythmic auditory stimuli modulate movement recovery in response to perturbation during locomotion.

The capacity to recover after a perturbation is a well-known intrinsic property of physiological systems, including the locomotor system, and can be termed 'resilience'. Despite an abundance of metrics proposed to measure the complex dynamics of bipedal locomotion, analytical tools for quantifying resilience are lacking. Here, we introduce a novel method to directly quantify resilience to perturbations during locomotion. We examined the extent to which synchronizing stepping with two different temporal structured auditory stimuli (periodic and 1/f structure) during walking modulates resilience to a large unexpected perturbation. Recovery time after perturbation was calculated from the horizontal velocity of the body's center of mass. Our results indicate that synchronizing stepping with a 1/f stimulus elicited greater resilience to mechanical perturbations during walking compared with the periodic stimulus (3.3 s faster). Our proposed method may help to gain a comprehensive understanding of movement recovery behavior of humans and other animals in their ecological contexts.

Risk-of-falling related outcomes improved in community-dwelling older adults after a 6-week sideways walking intervention: a feasibility and pilot study.

BACKGROUND: Aging increases fall risk and alters gait mechanics and control. Our previous work has identified sideways walking as a potential training regimen to decrease fall risk by improving frontal plane control in older adults' gait. The purposes of this pilot study were to test the feasibility of sideways walking as an exercise intervention and to explore its preliminary effects on risk-of-falling related outcomes. METHODS: We conducted a 6-week single-arm intervention pilot study. Participants were community-dwelling older adults ≥ 65 years old with walking ability. Key exclusion criteria were neuromusculoskeletal and cardiovascular disorders that affect gait. Because initial recruitment rate through University of Nebraska at Omaha and Omaha community was slower than expected (3 participants∙week- 1), we expanded the recruitment pool through the Mind & Brain Health Labs registry of the University of Nebraska Medical Center. Individualized sideways walking intervention carried out under close supervision in a 200 m indoor walking track (3 days∙week- 1). Recruitment and retention capability, safety, and fidelity of intervention delivery were recorded. We also collected (open-label) walking speed, gait variability, self-reported and performance-based functional measures to assess participants' risk-of-falling at baseline and post-intervention: immediate, and 6 weeks after the completion of the intervention. RESULTS: Over a 7-month period, 42 individuals expressed interest, 21 assessed for eligibility (21/42), and 15 consented to participate (15/21). Most of the potential participants were reluctant to commit to a 6-week intervention. Desired recruitment rate was achieved after revising the recruitment strategy. One participant dropped out (1/15). Remaining participants demonstrated excellent adherence to the protocol. Participants improved on most outcomes and the effects remained at follow-up. No serious adverse events were recorded during the intervention. CONCLUSIONS: Our 6-week sideways walking training was feasible to deliver and demonstrated strong potential as an exercise intervention to improve risk-of-falling outcomes in community-dwelling older adults. In a future trial, alternative clinical tools should be considered to minimize the presence of ceiling/floor effects. A future large trial is needed to confirm sideways walking as a fall prevention intervention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04505527 . Retrospectively registered 10 August 2020.

Step width variability as a discriminator of age-related gait changes.

BACKGROUND: There is scientific evidence that older adults aged 65 and over walk with increased step width variability which has been associated with risk of falling. However, there are presently no threshold levels that define the optimal reference range of step width variability. Thus, the purpose of our study was to estimate the optimal reference range for identifying older adults with normative and excessive step width variability. METHODS: We searched systematically the BMC, Cochrane Library, EBSCO, Frontiers, IEEE, PubMed, Scopus, SpringerLink, Web of Science, Wiley, and PROQUEST databases until September 2018, and included the studies that measured step width variability in both younger and older adults during walking at self-selected speed. Data were pooled in meta-analysis, and standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. A single-decision threshold method based on the Youden index, and a two-decision threshold method based on the uncertain interval method were used to identify the optimal threshold levels (PROSPERO registration: CRD42018107079). RESULTS: Ten studies were retrieved (older adults = 304; younger adults = 219). Step width variability was higher in older than in younger adults (SMD = 1.15, 95% CI = 0.60; 1.70; t = 4.72, p = 0.001). The single-decision method set the threshold level for excessive step width variability at 2.14 cm. For the two-decision method, step width variability values above the upper threshold level of 2.50 cm were considered excessive, while step width variability values below the lower threshold level of 1.97 cm were considered within the optimal reference range. CONCLUSION: Step width variability is higher in older adults than in younger adults, with step width variability values above the upper threshold level of 2.50 cm to be considered as excessive. This information could potentially impact rehabilitation technology design for devices targeting lateral stability during walking.

Model-based reinforcement of Kinect depth data for human motion capture applications.

Motion capture systems have recently experienced a strong evolution. New cheap depth sensors and open source frameworks, such as OpenNI, allow for perceiving human motion on-line without using invasive systems. However, these proposals do not evaluate the validity of the obtained poses. This paper addresses this issue using a model-based pose generator to complement the OpenNI human tracker. The proposed system enforces kinematics constraints, eliminates odd poses and filters sensor noise, while learning the real dimensions of the performer's body. The system is composed by a PrimeSense sensor, an OpenNI tracker and a kinematics-based filter and has been extensively tested. Experiments show that the proposed system improves pure OpenNI results at a very low computational cost.