Cervical spinal cord angiography and vessel-selective perfusion imaging in the rat.

Arterial spin labeling (ASL) has been widely used to evaluate arterial blood and perfusion dynamics, particularly in the brain, but its application to the spinal cord has been limited. The purpose of this study was to optimize vessel-selective pseudocontinuous arterial spin labeling (pCASL) for angiographic and perfusion imaging of the rat cervical spinal cord. A pCASL preparation module was combined with a train of gradient echoes for dynamic angiography. The effects of the echo train flip angle, label duration, and a Cartesian or radial readout were compared to examine their effects on visualizing the segmental arteries and anterior spinal artery (ASA) that supply the spinal cord. Lastly, vessel-selective encoding with either vessel-encoded pCASL (VE-pCASL) or super-selective pCASL (SS-pCASL) were compared. Vascular territory maps were obtained with VE-pCASL perfusion imaging of the spinal cord, and the interanimal variability was evaluated. The results demonstrated that longer label durations (200 ms) resulted in greater signal-to-noise ratio in the vertebral arteries, improved the conspicuity of the ASA, and produced better quality maps of blood arrival times. Cartesian and radial readouts demonstrated similar image quality. Both VE-pCASL and SS-pCASL adequately labeled the right or left vertebral arteries, which revealed the interanimal variability in the segmental artery with variations in their location, number, and laterality. VE-pCASL also demonstrated unique interanimal variations in spinal cord perfusion with a right-sided dominance across the six animals. Vessel-selective pCASL successfully achieved visualization of the arterial inflow dynamics and corresponding perfusion territories of the spinal cord. These methodological developments provide unique insights into the interanimal variations in the arterial anatomy and dynamics of spinal cord perfusion.

Altered Cortical Activity during a Finger Tap in People with Stroke.

This study describes electroencephalography (EEG) measurements during a simple finger movement in people with stroke to understand how temporal patterns of cortical activation and network connectivity align with prolonged muscle contraction at the end of a task. We investigated changes in the EEG temporal patterns in the beta band (13-26 Hz) of people with chronic stroke (N = 10, 7 F/3 M) and controls (N = 10, 7 F/3 M), during and after a cued movement of the index finger. We quantified the change in beta band EEG power relative to baseline as activation at each electrode and the change in task-based phase-locking value (tbPLV) and beta band task-based coherence (tbCoh) relative to baseline coherence as connectivity between EEG electrodes. Finger movements were associated with a decrease in beta power (event related desynchronization (ERD)) followed by an increase in beta power (event related resynchronization (ERS)). The ERS in the post task period was lower in the stroke group (7%), compared to controls (44%) (p < 0.001) and the transition from ERD to ERS was delayed in the stroke group (1.43 s) compared to controls (0.90 s) in the C3 electrode (p = 0.007). In the same post movement period, the stroke group maintained a heightened tbPLV (p = 0.030 for time to baseline of the C3:Fz electrode pair) and did not show the decrease in connectivity in electrode pair C3:Fz that was observed in controls (tbPLV: p = 0.006; tbCoh: p = 0.023). Our results suggest that delays in cortical deactivation patterns following movement coupled with changes in the time course of connectivity between the sensorimotor and frontal cortices in the stroke group might explain clinical observations of prolonged muscle activation in people with stroke. This prolonged activation might be attributed to the combination of cortical reorganization and changes to sensory feedback post-stroke.

Comparison and optimization of pCASL and VSASL for rat thoracolumbar spinal cord MRI at 9.4 T.

PURPOSE: To evaluate pseudo-continuous arterial spin labeling (pCASL) and velocity-selective arterial spin labeling (VSASL) for quantification of spinal cord blood flow (SCBF) in the rat thoracolumbar spinal cord. METHODS: Labeling efficiency (LE) was compared between pCASL and three VSASL variants in simulations and both phantom and in vivo experiments at 9.4 T. For pCASL, the effects of label plane position and shimming were systematically evaluated. For VSASL, the effects of composite pulses and phase cycling were evaluated to reduce artifacts. Additionally, vessel suppression, respiratory, and cardiac gating were evaluated to reduce motion artifacts. pCASL and VSASL maps of spinal cord blood flow were acquired with the optimized protocols. RESULTS: LE of the descending aorta was larger in pCASL compared to VSASL variants. In pCASL, LE off-isocenter was improved by local shimming positioned at the label plane and the anatomical level of labeling for the thoracic cord was only viable at the level of the T10 vertebra. Cardiac gating was essential to reduce motion artifacts. Both pCASL and VSASL successfully demonstrated comparable SCBF values in the thoracolumbar cord. CONCLUSION: pCASL demonstrated high and consistent LE in the thoracic aorta, and VSASL was also feasible, but with reduced efficiency. A combination of cardiac gating and recording of actual post-label delays was important for accurate SCBF quantification. These results highlight the challenges and solutions to achieve sufficient ASL labeling and contrast at high field in organs prone to motion.

The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis.

BACKGROUND: Patients with kidney failure treated with hemodialysis (HD) may be at risk for cerebral hypoperfusion due to HD-induced BP decline in the setting of impaired cerebral autoregulation. Cerebrovascular reactivity (CVR), the cerebrovascular response to vasoactive stimuli, may be a useful indicator of cerebral autoregulation in the HD population and identify those at risk for cerebral hypoperfusion. We hypothesize that CVR combined with intradialytic BP changes will be associated with declines in cerebral oxygenation saturation (ScO2) during HD. METHODS: Participants completed the MRI scans on a non-HD day and cerebral oximetry during HD. We measured CVR with resting-state fMRI (rs-fMRI) without a gas challenge and ScO2 saturation with near-infrared spectroscopy. Regression analysis was used to examine the relationship between intradialytic cerebral oxygen desaturation, intradialytic BP, and CVR in different gray matter regions. RESULTS: Twenty-six patients on HD had complete data for analysis. Sixteen patients were men, 18 had diabetes, and 20 had hypertension. Mean±SD age was 65.3±7.2 years, and mean±SD duration on HD was 11.5±9.4 months. CVR in the anterior cingulate gyrus (ACG; P=0.03, r2 =0.19) and insular cortex (IC; P=0.03, r2 =0.19) regions negatively correlated with decline in intradialytic ScO2. Model prediction of intradialytic ScO2 improved when including intradialytic BP change and ultrafiltration rate to the ACG rsCVR (P<0.01, r2 =0.48) and IC rsCVR (P=0.02, r2 =0.35) models, respectively. CONCLUSIONS: We found significant relationships between regional rsCVR measured in the brain and decline in intradialytic ScO2. Our results warrant further exploration of using CVR in determining a patient's risk of cerebral ischemic injury during HD.

Quantitative assessments of finger individuation with an instrumented glove.

BACKGROUND: In clinical and research settings, hand dexterity is often assessed as finger individuation, or the ability to move one finger at a time. Despite its clinical importance, there is currently no standardized, sufficiently sensitive, or fully objective platform for these evaluations. METHODS: Here we developed two novel individuation scores and tested them against a previously developed score using a commercially available instrumented glove and data collected from 20 healthy adults. Participants performed individuation for each finger of each hand as well as whole hand open-close at two study visits separated by several weeks. Using the three individuation scores, intra-class correlation coefficients (ICC) and minimal detectable changes (MDC) were calculated. Individuation scores were further correlated with subjective assessments to assess validity. RESULTS: We found that each score emphasized different aspects of individuation performance while generating scores on the same scale (0 [poor] to 1 [ideal]). These scores were repeatable, but the quality of the metrics varied by both equation and finger of interest. For example, index finger intra-class correlation coefficients (ICC's) were 0.90 (< 0.0001), 0.77 (< 0.001), and 0.83 (p < 0.0001), while pinky finger ICC's were 0.96 (p < 0.0001), 0.88 (p < 0.0001), and 0.81 (p < 0.001) for each score. Similarly, MDCs also varied by both finger and equation. In particular, thumb MDCs were 0.068, 0.14, and 0.045, while index MDCs were 0.041, 0.066, and 0.078. Furthermore, objective measurements correlated with subjective assessments of finger individuation quality for all three equations (ρ = - 0.45, p < 0.0001; ρ = - 0.53, p < 0.0001; ρ = - 0.40, p < 0.0001). CONCLUSIONS: Here we provide a set of normative values for three separate finger individuation scores in healthy adults with a commercially available instrumented glove. Each score emphasizes a different aspect of finger individuation performance and may be more uniquely applicable to certain clinical scenarios. We hope for this platform to be used within and across centers wishing to share objective data in the physiological study of hand dexterity. In sum, this work represents the first healthy participant data set for this platform and may inform future translational applications into motor physiology and rehabilitation labs, orthopedic hand and neurosurgery clinics, and even operating rooms.

Quantifying Hand Strength and Isometric Pinch Individuation Using a Flexible Pressure Sensor Grid.

Modulating force between the thumb and another digit, or isometric pinch individuation, is critical for daily tasks and can be impaired due to central or peripheral nervous system injury. Because surgical and rehabilitative efforts often focus on regaining this dexterous ability, we need to be able to consistently quantify pinch individuation across time and facilities. Currently, a standardized metric for such an assessment does not exist. Therefore, we tested whether we could use a commercially available flexible pressure sensor grid (Tekscan F-Socket [Tekscan Inc., Norwood, MA, USA]) to repeatedly measure isometric pinch individuation and maximum voluntary contraction (MVC) in twenty right-handed healthy volunteers at two visits. We developed a novel equation informed by the prior literature to calculate isometric individuation scores that quantified percentage of force on the grid generated by the indicated digit. MVC intra-class correlation coefficients (ICCs) for the left and right hands were 0.86 (p < 0.0001) and 0.88 (p < 0.0001), respectively, suggesting MVC measurements were consistent over time. However, individuation score ICCs, were poorer (left index ICC 0.41, p = 0.28; right index ICC -0.02, p = 0.51), indicating that this protocol did not provide a sufficiently repeatable individuation assessment. These data support the need to develop novel platforms specifically for repeatable and objective isometric hand dexterity assessments.

Task effects on functional connectivity measures after stroke.

Understanding the effect of task compared to rest on detecting stroke-related network abnormalities will inform efforts to optimize detection of such abnormalities. The goal of this work was to determine whether connectivity measures obtained during an overt task are more effective than connectivity obtained during a "resting" state for detecting stroke-related changes in network function of the brain. This study examined working memory, discrete pedaling, continuous pedaling and language tasks. Functional magnetic resonance imaging was used to examine regional and inter-regional brain network function in 14 stroke and 16 control participants. Independent component analysis was used to identify 149 regions of interest (ROI). Using the inter-regional connectivity measurements, the weighted sum was calculated across only regions associated with a given task. Both inter-regional connectivity and regional connectivity were greater during each of the tasks as compared to the resting state. The working memory and discrete pedaling tasks allowed for detection of stroke-related decreases in inter-regional connectivity, while the continuous pedaling and language tasks allowed for detection of stroke-related enhancements in regional connectivity. These observations illustrate that task-based functional connectivity allows for detection of stroke-related changes not seen during resting states. In addition, this work provides evidence that tasks emphasizing different cognitive domains reveal different aspects of stroke-related reorganization. We also illustrate that within the motor domain, different tasks can reveal inter-regional or regional stroke-related changes, in this case suggesting that discrete pedaling required more central drive than continuous pedaling.

The Value of High Intensity Locomotor Training Applied to Patients With Acute-Onset Neurologic Injury.

Long-standing research in animal models and humans with stroke or incomplete spinal cord injury (iSCI) indicate that specific physical training variables, such as the specificity and amount of practice, may influence neurologic recovery and locomotor function. More recent data highlight the contributions of exercise intensity, as estimated indirectly by cardiovascular exertion, as potentially more important than previously considered. The effects of exercise intensity are well described in neurologically intact individuals, although confusion regarding the definitions of intensity and safety concerns have limited its implementation during physical rehabilitation of patients with neurologic injury. The purpose of this review is to delineate some of the evidence regarding the effects of exercise intensity during locomotor training in patients with stroke and iSCI. We provide specific definitions of exercise intensity used within the literature, describe methods used to ensure appropriate levels of exertion, and discuss potential adverse events and safety concerns during its application. Further details on the effects of locomotor training intensity on clinical outcomes, and on neuromuscular and cardiovascular function will be addressed as available. Existing literature across multiple studies and meta-analyses reveals that exercise training intensity is likely a major factor that can influence locomotor function after neurologic injury. To extend these findings, we describe previous attempts to implement moderate to high intensity interventions during physical rehabilitation of patients with neurologic injury, including the utility of specific strategies to facilitate implementation, and to navigate potential barriers that may arise during implementation efforts.

Visual oscillation effects on dynamic balance control in people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (PwMS) have balance deficits while ambulating through environments that contain moving objects or visual manipulations to perceived self-motion. However, their ability to parse object from self-movement has not been explored. The purpose of this research was to examine the effect of medial-lateral oscillations of the visual field and of objects within the scene on gait in PwMS and healthy age-matched controls using virtual reality (VR). METHODS: Fourteen PwMS (mean age 49 ± 11 years, functional gait assessment score of 27.8 ± 1.8, and Berg Balance scale score 54.7 ± 1.5) and eleven healthy controls (mean age: 53 ± 12 years) participated in this study. Dynamic balance control was assessed while participants walked on a treadmill at a self-selected speed while wearing a VR headset that projected an immersive forest scene. Visual conditions consisted of (1) no visual manipulations (speed-matched anterior/posterior optical flow), (2) 0.175 m mediolateral translational oscillations of the scene that consisted of low pairing (0.1 and 0.31 Hz) or (3) high pairing (0.15 and 0.465 Hz) frequencies, (4) 5 degree medial-lateral rotational oscillations of virtual trees at a low frequency pairing (0.1 and 0.31 Hz), and (5) a combination of the tree and scene movements in (3) and (4). RESULTS: We found that both PwMS and controls exhibited greater instability and visuomotor entrainment to simulated mediolateral translation of the visual field (scene) during treadmill walking. This was demonstrated by significant (p < 0.05) increases in mean step width and variability and center of mass sway. Visuomotor entrainment was demonstrated by high coherence between center of mass sway and visual motion (magnitude square coherence = ~ 0.5 to 0.8). Only PwMS exhibited significantly greater instability (higher step width variability and center of mass sway) when objects moved within the scene (i.e., swaying trees). CONCLUSION: Results suggest the presence of visual motion processing errors in PwMS that reduced dynamic stability. Specifically, object motion (via tree sway) was not effectively parsed from the observer's self-motion. Identifying this distinction between visual object motion and self-motion detection in MS provides insight regarding stability control in environments with excessive external movement, such as those encountered in daily life.

Role of the cortex in visuomotor control of arm stability.

Whereas numerous motor control theories describe the control of arm trajectory during reach, the control of stabilization in a constant arm position (i.e., visuomotor control of arm posture) is less clear. Three potential mechanisms have been proposed for visuomotor control of arm posture: 1) increased impedance of the arm through co-contraction of antagonistic muscles, 2) corrective muscle activity via spinal/supraspinal reflex circuits, and/or 3) intermittent voluntary corrections to errors in position. We examined the cortical mechanisms of visuomotor control of arm posture and tested the hypothesis that cortical error networks contribute to arm stabilization. We collected electroencephalography (EEG) data from 10 young healthy participants across four experimental planar movement tasks. We examined brain activity associated with intermittent voluntary corrections of position error and antagonist co-contraction during stabilization. EEG beta-band (13-26 Hz) power fluctuations were used as indicators of brain activity, and coherence between EEG electrodes was used as a measure of functional connectivity between brain regions. Cortical activity in the sensory, motor, and visual areas during arm stabilization was similar to activity during volitional arm movements and was larger than activity during co-contraction of the arm. However, cortical connectivity between the sensorimotor and visual regions was higher during arm stabilization compared with volitional arm movements and co-contraction of the arm. The difference in cortical activity and connectivity between tasks might be attributed to an underlying visuomotor error network used to update motor commands for visuomotor control of arm posture.NEW & NOTEWORTHY We examined cortical activity and connectivity during control of stabilization in a constant arm position (i.e., visuomotor control of arm posture). Our findings provide evidence for cortical involvement during control of stabilization in a constant arm position. A visuomotor error network appears to be active and may update motor commands for visuomotor control of arm posture.

Filter-probe diffusion imaging improves spinal cord injury outcome prediction.

OBJECTIVE: Diffusion-weighted imaging (DWI) is a powerful tool for investigating spinal cord injury (SCI), but has limited specificity for axonal damage, which is the most predictive feature of long-term functional outcome. In this study, a technique designed to detect acute axonal injury, filter-probe double diffusion encoding (FP-DDE), is compared with standard DWI for predicting long-term functional and cellular outcomes. METHODS: This study extends FP-DDE to predict long-term functional and histological outcomes in a rat SCI model of varying severities (n = 58). Using a 9.4T magnetic resonance imaging (MRI) system, a whole-cord FP-DDE spectroscopic voxel was acquired in 3 minutes at the lesion site and compared to DWI at 48 hours postinjury. Relationships with chronic (30-day) locomotor and histological outcomes were evaluated with linear regression. RESULTS: The FP-DDE measure of parallel diffusivity (ADC|| ) was significantly related to chronic hind limb locomotor functional outcome (R2 = 0.63, p < 0.0001), and combining this measurement with acute functional scores demonstrated prognostic benefit versus functional testing alone (p = 0.0007). Acute ADC|| measurements were also more closely related to the number of injured axons measured 30 days after the injury than standard DWI. Furthermore, acute FP-DDE images showed a clear and easily interpretable pattern of injury that closely corresponded with chronic MRI and histology observations. INTERPRETATION: Collectively, these results demonstrate FP-DDE benefits from greater specificity for acute axonal damage in predicting functional and histological outcomes with rapid acquisition and fully automated analysis, improving over standard DWI. FP-DDE is a promising technique compatible with clinical settings, with potential research and clinical applications for evaluation of spinal cord pathology. Ann Neurol 2018;83:37-50.

Biomechanical parameters of the elbow stretch reflex in chronic hemiparetic stroke.

We sought to determine the relative velocity sensitivity of stretch reflex threshold angle and reflex stiffness during stretches of the paretic elbow joint in individuals with chronic hemiparetic stroke, and to provide guidelines to streamline spasticity assessments. We applied ramp-and-hold elbow extension perturbations ranging from 15 to 150°/s over the full range of motion in 13 individuals with hemiparesis. After accounting for the effects of passive mechanical resistance, we modeled velocity-dependent reflex threshold angle and torque-angle slope to determine their correlation with overall resistance to movement. Reflex stiffness exhibited substantially greater velocity sensitivity than threshold angle, accounting for ~ 74% (vs. ~ 15%) of the overall velocity-dependent increases in movement resistance. Reflex stiffness is a sensitive descriptor of the overall velocity-dependence of movement resistance in spasticity. Clinical spasticity assessments can be streamlined using torque-angle slope, a measure of reflex stiffness, as their primary outcome measure, particularly at stretch velocities greater than 100°/s.

Use of imperceptible wrist vibration to modulate sensorimotor cortical activity.

Peripheral sensory stimulation has been used as a method to stimulate the sensorimotor cortex, with applications in neurorehabilitation. To improve delivery modality and usability, a new stimulation method has been developed in which imperceptible random-frequency vibration is applied to the wrist concurrently during hand activity. The objective of this study was to investigate effects of this new sensory stimulation on the sensorimotor cortex. Healthy adults were studied. In a transcranial magnetic stimulation (TMS) study, resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation for the abductor pollicis brevis muscle were compared between vibration on vs. off, while subjects were at rest. In an electroencephalogram (EEG) study, alpha and beta power during rest and event-related desynchronization (ERD) for hand grip were compared between vibration on vs. off. Results showed that vibration decreased EEG power and decreased TMS short-interval intracortical inhibition (i.e., disinhibition) compared with no vibration at rest. Grip-related ERD was also greater during vibration, compared to no vibration. In conclusion, subthreshold random-frequency wrist vibration affected the release of intracortical inhibition and both resting and grip-related sensorimotor cortical activity. Such effects may have implications in rehabilitation.

Effect of sensory attenuation on cortical movement-related oscillations.

This study examined the impact of induced sensory deficits on cortical, movement-related oscillations measured using electroencephalography (EEG). We hypothesized that EEG patterns in healthy subjects with induced sensory reduction would be comparable to EEG found after chronic loss of sensory feedback. EEG signals from 64 scalp locations were measured from 10 healthy subjects. Participants dorsiflexed their ankle after prolonged vibration of the tibialis anterior (TA). Beta band time frequency decompositions were calculated using wavelets and compared across conditions. Changes in patterns of movement-related brain activity were observed following attenuation of sensory feedback. A significant decrease in beta power of event-related synchronization was associated with simple ankle dorsiflexion after prolonged vibration of the TA. Attenuation of sensory feedback in young, healthy subjects led to a corresponding decrease in beta band synchronization. This temporary change in beta oscillations suggests that these modulations are a mechanism for sensorimotor integration. The loss of sensory feedback found in spinal cord injury patients contributes to changes in EEG signals underlying motor commands. Similar alterations in cortical signals in healthy subjects with reduced sensory feedback implies these changes reflect normal sensorimotor integration after reduced sensory input rather than brain plasticity. NEW & NOTEWORTHY Transient attenuation of sensory afferents in young, healthy adults led to similar changes in brain activity found previously in volunteers with incomplete spinal cord injury. Beta band power associated with ankle movement in these controls was attenuated after prolonged vibration of the tibialis anterior. Evoked potential measurements suggest that prolonged vibration reduces phasing across trials as the mechanism behind this attenuation of cortical activity.

Stepping responses to treadmill perturbations vary with severity of motor deficits in human SCI.

In this study, we investigated the responses to tread perturbations during human stepping on a treadmill. Our approach was to test the effects of perturbations to a single leg using a split-belt treadmill in healthy participants and in participants with varying severity of spinal cord injury (SCI). We recruited 11 people with incomplete SCI and 5 noninjured participants. As participants walked on an instrumented treadmill, the belt on one side was stopped or accelerated briefly during midstance to late stance. A majority of participants initiated an unnecessary swing when the treadmill was stopped in midstance, although the likelihood of initiating a step was decreased in participants with more severe SCI. Accelerating or decelerating one belt of the treadmill during stance altered the characteristics of swing. We observed delayed swing initiation when the belt was decelerated (i.e., the hip was in a more flexed position at time of swing) and advanced swing initiation with acceleration (i.e., hip extended at swing initiation). Furthermore, the timing and leg posture of heel strike appeared to remain constant, reflected by a sagittal plane hip angle at heel strike that remained the same regardless of the perturbation. In summary, our results supported the current understanding of the role of sensory feedback and central drive in the control of stepping in participants with incomplete SCI and noninjured participants. In particular, the observation of unnecessary swing during a stop perturbation highlights the interdependence of central and sensory drive in walking control. NEW & NOTEWORTHY Using a novel approach with a split-belt treadmill, we tested the effects of hip angle perturbations to a single leg in healthy participants and participants with varying severity of spinal cord injury (SCI). A majority of participants initiated an unnecessary swing when the treadmill was stopped in midstance, although the likelihood of initiating a step decreased with the severity of SCI. Our results demonstrated interdependence of central and sensory drive in walking control.

Stroke increases ischemia-related decreases in motor unit discharge rates.

Following stroke, hyperexcitable sensory pathways, such as the group III/IV afferents that are sensitive to ischemia, may inhibit paretic motor neurons during exercise. We quantified the effects of whole leg ischemia on paretic vastus lateralis motor unit firing rates during submaximal isometric contractions. Ten chronic stroke survivors (>1 yr poststroke) and 10 controls participated. During conditions of whole leg occlusion, the discharge timings of motor units were identified from decomposition of high-density surface electromyography signals during repeated submaximal knee extensor contractions. Quadriceps resting twitch responses and near-infrared spectroscopy measurements of oxygen saturation as an indirect measure of blood flow were made. There was a greater decrease in paretic motor unit discharge rates during the occlusion compared with the controls (average decrease for stroke and controls, 12.3 ± 10.0% and 0.1 ± 12.4%, respectively; P < 0.001). The motor unit recruitment thresholds did not change with the occlusion (stroke: without occlusion, 11.68 ± 5.83%MVC vs. with occlusion, 11.11 ± 5.26%MVC; control: 11.87 ± 5.63 vs. 11.28 ± 5.29%MVC). Resting twitch amplitudes declined similarly for both groups in response to whole leg occlusion (stroke: 29.16 ± 6.88 vs. 25.75 ± 6.78 Nm; control: 38.80 ± 13.23 vs 30.14 ± 9.64 Nm). Controls had a greater exponential decline (lower time constant) in oxygen saturation compared with the stroke group (stroke time constant, 22.90 ± 10.26 min vs. control time constant, 5.46 ± 4.09 min; P < 0.001). Ischemia of the muscle resulted in greater neural inhibition of paretic motor units compared with controls and may contribute to deficient muscle activation poststroke. NEW & NOTEWORTHY Hyperexcitable inhibitory sensory pathways sensitive to ischemia may play a role in deficient motor unit activation post stroke. Using high-density surface electromyography recordings to detect motor unit firing instances, we show that ischemia of the exercising muscle results in greater inhibition of paretic motor unit firing rates compared with controls. These findings are impactful to neurophysiologists and clinicians because they implicate a novel mechanism of force-generating impairment poststroke that likely exacerbates baseline weakness.

High-Intensity Variable Stepping Training in Patients With Motor Incomplete Spinal Cord Injury: A Case Series.

BACKGROUND AND PURPOSE: Previous data suggest that large amounts of high-intensity stepping training in variable contexts (tasks and environments) may improve locomotor function, aerobic capacity, and treadmill gait kinematics in individuals poststroke. Whether similar training strategies are tolerated and efficacious for patients with other acute-onset neurological diagnoses, such as motor incomplete spinal cord injury (iSCI), is unknown. Individuals with iSCI potentially have greater bilateral impairments. This case series evaluated the feasibility and preliminary short- and long-term efficacy of high-intensity variable stepping practice in ambulatory participants for more than 1 year post-iSCI. CASE SERIES DESCRIPTION: Four participants with iSCI (neurological levels C5-T3) completed up to 40 one-hour sessions over 3 to 4 months. Stepping training in variable contexts was performed at up to 85% maximum predicted heart rate, with feasibility measures of patient tolerance, total steps/session, and intensity of training. Clinical measures of locomotor function, balance, peak metabolic capacity, and gait kinematics during graded treadmill assessments were performed at baseline and posttraining, with more than 1-year follow-up. OUTCOMES: Participants completed 24 to 40 sessions over 8 to 15 weeks, averaging 2222 ± 653 steps per session, with primary adverse events of fatigue and muscle soreness. Modest improvements in locomotor capacity where observed at posttraining, with variable changes in lower extremity kinematics during treadmill walking. DISCUSSION: High-intensity, variable stepping training was feasible and tolerated by participants with iSCI although only modest gains in gait function or quality were observed. The utility of this intervention in patients with more profound impairments may be limited.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A200).

Rapid in vivo detection of rat spinal cord injury with double-diffusion-encoded magnetic resonance spectroscopy.

PURPOSE: Diffusion-weighted imaging is a common experimental tool for evaluating spinal cord injury (SCI), yet it suffers from complications that decrease its clinical effectiveness. The most commonly used technique, diffusion tensor imaging (DTI), is often confounded by effects of edema accompanying acute SCI, limiting its sensitivity to the important functional status marker of axonal integrity. The purpose of this study is to introduce a novel diffusion-acquisition method with the goal of overcoming these limitations. METHODS: A double diffusion encoding (DDE) pulse sequence was implemented with a diffusion-weighted filter orthogonal to the spinal cord for suppressing nonneural signals prior to diffusion weighting parallel to the cord. A point-resolved spectroscopy readout (DDE-PRESS) was used for improved sensitivity and compared with DTI in a rat model of SCI with varying injury severities. RESULTS: The DDE-PRESS parameter, restricted fraction, showed a strong relationship with injury severity (P < 0.001, R2 = 0.67). Although the whole-cord averaged DTI parameter values exhibited only minor injury relationships, a weighted region of interest (ROI) based DTI analysis improved sensitivity to injury (P < 0.001, R2 = 0.66). CONCLUSIONS: In a rat model of SCI, DDE-PRESS demonstrated high sensitivity to injury with substantial decreases in acquisition time and data processing. This method shows promise for application in rapid evaluation of SCI severity. Magn Reson Med 77:1639-1649, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Robotic Resistance Treadmill Training Improves Locomotor Function in Children With Cerebral Palsy: A Randomized Controlled Pilot Study.

OBJECTIVE: To determine whether applying controlled resistance forces to the legs during the swing phase of gait may improve the efficacy of treadmill training as compared with applying controlled assistance forces in children with cerebral palsy (CP). DESIGN: Randomized controlled study. SETTING: Research unit of a rehabilitation hospital. PARTICIPANTS: Children with spastic CP (N=23; mean age, 10.6y; range, 6-14y; Gross Motor Function Classification System levels, I-IV). INTERVENTIONS: Participants were randomly assigned to receive controlled assistance (n=11) or resistance (n=12) loads applied to the legs at the ankle. Participants underwent robotic treadmill training 3 times a week for 6 weeks (18 sessions). A controlled swing assistance/resistance load was applied to both legs starting from the toe-off to mid-swing phase of gait during training. MAIN OUTCOME MEASURES: Outcome measures consisted of overground walking speed, 6-minute walk distance, and Gross Motor Function Measure scores and were assessed pre and post 6 weeks of training and 8 weeks after the end of training. RESULTS: After 6 weeks of treadmill training in participants from the resistance training group, fast walking speed and 6-minute walk distance significantly improved (18% and 30% increases, respectively), and 6-minute walk distance was still significantly greater than that at baseline (35% increase) 8 weeks after the end of training. In contrast, overground gait speed and 6-minute walk distance had no significant changes after robotic assistance training. CONCLUSIONS: The results of the present study indicated that robotic resistance treadmill training is more effective than assistance training in improving locomotor function in children with CP.