Improved Disabilities of the Arm, Shoulder and Hand scores after myoelectric arm orthosis use at home in chronic stroke: A retrospective study.

BACKGROUND: Most stroke survivors have persistent upper limb impairments after completing standard clinical care. The resulting impairments can adversely affect their quality of life and ability to complete self-care tasks and remain employed, leading to increased healthcare and societal costs. A myoelectric arm orthosis can be used effectively to support the affected weak arm and increase an individual's use of that arm. OBJECTIVE: The study objective was to retrospectively evaluate the outcomes and clinical benefits provided by the MyoPro® orthosis in individuals 65 years and older with upper limb impairment secondary to a stroke. METHODS: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was administered to individuals who have chronic stroke both before and after receiving their myoelectric orthosis. A Generalized Estimating Equation model was analyzed. RESULTS: After using the MyoPro, 19 individuals with chronic stroke had a mean improvement (decrease) in DASH score of 18.07, 95% CI = (-25.41, -10.72), adjusted for 8 covariates. This large change in DASH score was statistically significant and clinically meaningful as participants self-reported an improvement with engagement in functional tasks. CONCLUSIONS: Use of the MyoPro increases independence in functional tasks as reported by the validated DASH outcome measure for older participants with chronic stroke.

Combining neuroimaging and brain stimulation to test alternative causal pathways for nicotine addiction in schizophrenia.

The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and schizophrenia patients (p = 0.006 to 0.07). In Study II with another 30 patient smokers, a proof-of-concept, patient- and rater-blind, randomized, sham-controlled rTMS design was used to test whether targeting the newly identified dmPFC location may causally enhance the rsFC and reduce nicotine addiction in schizophrenia. Although significant interactions were not observed, exploratory analyses showed that this dmPFC-extended amygdala rsFC was enhanced by 4-week active 10Hz rTMS (p = 0.05) compared to baseline; the severity of nicotine addiction showed trends of reduction after 3 and 4 weeks (p ≤ 0.05) of active rTMS compared to sham; Increased rsFC by active rTMS predicted reduction of cigarettes/day (R = -0.56, p = 0.025 uncorrected) and morning smoking severity (R = -0.59, p = 0.016 uncorrected). These results suggest that the dmPFC-extended amygdala circuit may be linked to nicotine addiction in schizophrenia and healthy individuals, and future efforts targeting its underlying pathophysiological mechanisms may yield more effective treatment for nicotine addiction.

Effects of noninvasive neuromodulation targeting the spinal cord on early learning of force control by the digits.

AIMS: Control of finger forces underlies our capacity for skilled hand movements acquired during development and reacquired after neurological injury. Learning force control by the digits, therefore, predicates our functional independence. Noninvasive neuromodulation targeting synapses that link corticospinal neurons onto the final common pathway via spike-timing-dependent mechanisms can alter distal limb motor output on a transient basis, yet these effects appear subject to individual differences. Here, we investigated how this form of noninvasive neuromodulation interacts with task repetition to influence early learning of force control during precision grip. METHODS: The unique effects of neuromodulation, task repetition, and neuromodulation coinciding with task repetition were tested in three separate conditions using a within-subject, cross-over design (n = 23). RESULTS: We found that synchronizing depolarization events within milliseconds of stabilizing precision grip accelerated learning but only after accounting for individual differences through inclusion of subjects who showed upregulated corticospinal excitability at 2 of 3 time points following conditioning stimulation (n = 19). CONCLUSIONS: Our findings provide insights into how the state of the corticospinal system can be leveraged to drive early motor skill learning, further emphasizing individual differences in the response to noninvasive neuromodulation. We interpret these findings in the context of biological mechanisms underlying the observed effects and implications for emerging therapeutic applications.

Goal conceptualization has distinct effects on spatial and temporal bimanual coordination after left- and right- hemisphere stroke.

Perception of task goal influences motor performance and coordination. In bimanual actions, it is unclear how one's perception of task goals influences bimanual coordination and performance in individuals with unilateral stroke. We characterized inter-limb coordination differences in individuals with chronic right- and left-hemisphere damaged (RCVA: n = 24, LCVA: n = 24) stroke and age-matched neurotypical controls (n = 24) as they completed bimanual reaching tasks under distinct goal conditions. In the dual-goal condition, participants reached to move two virtual bricks (cursors) assigned to each hand toward independent targets. In the common-goal condition, they moved a central common virtual brick representing both hands to a single, central target. Spatial and temporal coordination (cross-correlation coefficients of hand velocity and their time-lag), the redundant axis deviations (the hand deviations in the axis orthogonal to the axis along the cursor-target direction), and the contribution ratio of the paretic hand were measured. Compared to the dual-goal condition, reaching actions to the common-goal demonstrated better spatial bimanual coordination in all three participant groups. Temporal coordination was better during common-goal than dual-goal actions only for the LCVA group. Additionally, and novel to this field, sex, as a biological variable, differently influenced movement time and redundant axis deviation in participants with stroke under the common-goal condition. Specifically, female stroke survivors showed larger movements in the redundant axes and, consequently, longer movement times, which was more prominent in the LCVA group. Our results indicate that perception of task goals influences bimanual coordination, with common goal improving spatial coordination in neurotypical individuals and individuals with unilateral stroke and providing additional advantage for temporal coordination in those with LCVA. Sex influences bimanual performance in stroke survivors and needs to be considered in future investigations.

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

Force oscillations underlying precision grip in humans with lesioned corticospinal tracts.

Stability of precision grip depends on the ability to regulate forces applied by the digits. Increased frequency composition and temporal irregularity of oscillations in the force signal are associated with enhanced force stability, which is thought to result from increased voluntary drive along the corticospinal tract (CST). There is limited knowledge of how these oscillations in force output are regulated in the context of dexterous hand movements like precision grip, which are often impaired by CST damage due to stroke. The extent of residual CST volume descending from primary motor cortex may help explain the ability to modulate force oscillations at higher frequencies. Here, stroke survivors with longstanding hand impairment (n = 17) and neurologically-intact controls (n = 14) performed a precision grip task requiring dynamic and isometric muscle contractions to scale and stabilize forces exerted on a sensor by the index finger and thumb. Diffusion spectrum imaging was used to quantify total white matter volume within the residual and intact CSTs of stroke survivors (n = 12) and CSTs of controls (n = 14). White matter volumes within the infarct region and an analogous portion of overlap with the CST, mirrored onto the intact side, were also quantified in stroke survivors. We found reduced ability to stabilize force and more restricted frequency ranges in force oscillations of stroke survivors relative to controls; though, more broadband, irregular output was strongly related to force-stabilizing ability in both groups. The frequency composition and temporal irregularity of force oscillations observed in stroke survivors did not correlate with maximal precision grip force, suggesting that it is not directly related to impaired force-generating capacity. The ratio of residual to intact CST volumes contained within infarct and mirrored compartments was associated with more broadband, irregular force oscillations in stroke survivors. Our findings provide insight into granular aspects of dexterity altered by corticospinal damage and supply preliminary evidence to support that the ability to modulate force oscillations at higher frequencies is explained, at least in part, by residual CST volume in stroke survivors.

Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis.

Cerebral strokes can disrupt descending commands from motor cortical areas to the spinal cord, which can result in permanent motor deficits of the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted by neurotechnologies to restore movement. Here we report results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis ( NCT04512690 ). Participants were implanted for 29 d with two linear leads in the dorsolateral epidural space targeting spinal roots C3 to T1 to increase excitation of arm and hand motoneurons. We found that continuous stimulation through selected contacts improved strength (for example, grip force +40% SCS01; +108% SCS02), kinematics (for example, +30% to +40% speed) and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported. While we cannot conclusively evaluate safety and efficacy from two participants, our data provide promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke.

Detection of Stroke-Induced Visual Neglect and Target Response Prediction Using Augmented Reality and Electroencephalography.

We aim to build a system incorporating electroencephalography (EEG) and augmented reality (AR) that is capable of identifying the presence of visual spatial neglect (SN) and mapping the estimated neglected visual field. An EEG-based brain-computer interface (BCI) was used to identify those spatiospectral features that best detect participants with SN among stroke survivors using their EEG responses to ipsilesional and contralesional visual stimuli. Frontal-central delta and alpha, frontal-parietal theta, Fp1 beta, and left frontal gamma were found to be important features for neglect detection. Additionally, temporal analysis of the responses shows that the proposed model is accurate in detecting potentially neglected targets. These targets were predicted using common spatial patterns as the feature extraction algorithm and regularized discriminant analysis combined with kernel density estimation for classification. With our preliminary results, our system shows promise for reliably detecting the presence of SN and predicting visual target responses in stroke patients with SN.

Baseline Predictors of Response to Repetitive Task Practice in Chronic Stroke.

BACKGROUND: Repetitive task practice reduces mean upper extremity motor impairment in populations of patients with chronic stroke, but individual response is highly variable. A method to predict meaningful reduction in impairment in response to training based on biomarkers and other data collected prior to an intervention is needed to establish realistic rehabilitation goals and to effectively allocate resources. OBJECTIVES: To identify prognostic factors and better understand the biological substrate for reductions in arm impairment in response to repetitive task practice among patients with chronic (≥6 months) post-stroke hemiparesis. METHODS: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy and functional arm use in real-world tasks. Baseline measures include the Fugl-Meyer Assessment, Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, MRI, transcranial magnetic stimulation, kinematics, accelerometry, and genomic testing. RESULTS: Mean increase in FM-UE was 4.6 ± 1.0 SE, median 2.5. Approximately one-third of participants had a clinically meaningful response to the intervention, defined as an increase in FM ≥ 5. The selected logistic regression model had a receiver operating curve with AUC = .988 (Std Error = .011, 95% Wald confidence limits: .967-1) showed little evidence of overfitting. Six variables that predicted response represented impairment, functional, and genomic measures. CONCLUSION: A simple weighted sum of 6 baseline factors can accurately predict clinically meaningful impairment reduction after outpatient intensive practice intervention in chronic stroke. Reduction of impairment may be a critical first step to functional improvement. Further validation and generalization of this model will increase its utility in clinical decision-making.

Normal aging affects unconstrained three-dimensional reaching against gravity with reduced vertical precision and increased co-contraction: a pilot study.

Reaching for an object in space forms the basis for many activities of daily living and is important in rehabilitation after stroke and in other neurological and orthopedic conditions. It has been the object of motor control and neuroscience research for over a century, but studies often constrain movement to eliminate the effect of gravity or reduce the degrees of freedom. In some studies, aging has been shown to reduce target accuracy, with a mechanism suggested to be impaired corrective movements. We sought to explore how such changes in accuracy relate to changes in finger, shoulder and elbow movements during performance of reaching movements with the normal effects of gravity, unconstrained hand movement, and stable target locations. Three-dimensional kinematic data and electromyography were collected in 14 young (25 ± 6 years) and 10 older adults (68 ± 3 years) during second-long reaches to 3 targets aligned vertically in front of the participants. Older adults took longer to initiate a movement than the young adults and were more variable and inaccurate in their initial and final movements. Target height had greater effect on trajectory curvature variability in older than young adults, with angle variability relative to target position being greater in older adults around the time of peak speed. There were significant age-related differences in use of the multiple degrees of freedom of the upper extremity, with less variability in shoulder abduction in the older group. Muscle activation patterns were similar, except for a higher biceps-triceps co-contraction and tonic levels of some proximal muscle activation. These results show an age-related deficit in the motor planning and online correction of reaching movements against a predictable force (i.e., gravity) when it is not compensated by mechanical support.

Fine-tuning and Personalization of EEG-based Neglect Detection in Stroke Patients.

Spatial neglect (SN) is a neurological disorder that causes inattention to visual stimuli in the contralesional visual field, stemming from unilateral brain injury such as stroke. The current gold standard method of SN assessment, the conventional Behavioral Inattention Test (BIT-C), is highly variable and inconsistent in its results. In our previous work, we built an augmented reality (AR)-based BCI to overcome the limitations of the BIT-C and classified between neglected and non-neglected targets with high accuracy. Our previous approach included personalization of the neglect detection classifier but the process required rigorous retraining from scratch and time-consuming feature selection for each participant. Future steps of our work will require rapid personalization of the neglect classifier; therefore, in this paper, we investigate fine-tuning of a neural network model to hasten the personalization process.

Perturbation of cortical activity elicits regional and age-dependent effects on unconstrained reaching behavior: a pilot study.

Contributions from premotor and supplementary motor areas to reaching behavior in aging humans are not well understood. The objective of these experiments was to examine effects of perturbations to specific cortical areas on the control of unconstrained reaches against gravity by younger and older adults. Double-pulse transcranial magnetic stimulation (TMS) was applied to scalp locations targeting primary motor cortex (M1), dorsal premotor area (PMA), supplementary motor area (SMA), or dorsolateral prefrontal cortex (DLPFC). Stimulation was intended to perturb ongoing activity in the targeted cortical region before or after a visual cue to initiate moderately paced reaches to one of three vertical target locations. Regional effects were observed in movement amplitude both early and late in the reach. Perturbation of PMA increased reach distance before the time of peak velocity to a greater extent than all other regions. Reaches showed greater deviation from a straight-line path around the time of peak velocity and greater overall curvature with perturbation of PMA and M1 relative to SMA and DLPFC. The perturbation increased positional variability of the reach path at the time of peak velocity and the time elapsing after peak velocity. Although perturbations had stronger effects on reaches by younger subjects, this group exhibited less reach path variability at the time of peak velocity and required less time to adjust the movement trajectory thereafter. These findings support the role of PMA in visually guided reaching and suggest an age-related change in sensorimotor processing, possibly due to a loss of cortical inhibitory control.

Clinical Performance Measures for Stroke Rehabilitation: Performance Measures From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released the adult stroke rehabilitation and recovery guidelines in 2016. A working group of stroke rehabilitation experts reviewed these guidelines and identified a subset of recommendations that were deemed suitable for creating performance measures. These 13 performance measures are reported here and contain inclusion and exclusion criteria to allow calculation of rates of compliance in a variety of settings ranging from acute hospital care to postacute care and care in the home and outpatient setting.

Real-World Adherence to OnabotulinumtoxinA Treatment for Spasticity: Insights From the ASPIRE Study.

OBJECTIVE: To identify baseline characteristics and treatment-related variables that affect adherence to onabotulinumtoxinA treatment from the Adult Spasticity International Registry (ASPIRE) study. DESIGN: Prospective, observational registry (NCT01930786). SETTING: International clinical sites. PARTICIPANTS: Adults with spasticity (N=730). INTERVENTIONS: OnabotulinumtoxinA at clinician's discretion. MAIN OUTCOME MEASURES: Clinically meaningful thresholds used for treatment adherent (≥3 treatment sessions during 2-year study) and nonadherent (≤2 sessions). Data analyzed using logistic regression and presented as odds ratios (ORs) with 95% confidence intervals (CIs). Treatment-related variables assessed at sessions 1 and 2 only. RESULTS: Of the total population, 523 patients (71.6%) were treatment adherent with 5.3±1.6 sessions and 207 (28.4%) were nonadherent with 1.5±0.5 sessions. In the final model (n=626/730), 522 patients (83.4%) were treatment adherent and 104 (16.6%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=1.84; CI, 1.06-3.21; P=.030) and use of orthotics (OR=1.88; CI, 1.15-3.08; P=.012). Baseline characteristics associated with nonadherence: history of diplopia (OR=0.28; CI, 0.09-0.89; P=.031) and use of assistive devices (OR=0.51; CI, 0.29-0.90; P=.021). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.43; CI, 0.26-0.72; P=.001) and clinician dissatisfaction with onabotulinumtoxinA to manage pain (OR=0.18; CI, 0.05-0.69; P=.012). Of the population with stroke (n=411), 288 patients (70.1%) were treatment adherent with 5.3±1.6 sessions and 123 (29.9%) were nonadherent with 1.5±0.5 session. In the final stroke model (n=346/411), 288 patients (83.2%) were treatment adherent and 58 (16.8%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=2.99; CI, 1.39-6.44; P=.005) and use of orthotics (OR=3.18; CI, 1.57-6.45; P=.001). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.42; CI, 0.21-0.83; P=.013) and moderate/severe disability on upper limb Disability Assessment Scale pain subscale (OR=0.40; CI, 0.19-0.83; P=.015). CONCLUSIONS: These ASPIRE analyses demonstrate real-world patient and clinical variables that affect adherence to onabotulinumtoxinA and provide insights to help optimize management strategies to improve patient care.

Examining the influence of mental stress on balance perturbation responses in older adults.

BACKGROUND: Reach-to-grasp responses following balance perturbations are important to fall prevention but are often ineffective in older adults. The ability to shift attention from an ongoing cognitive task to balance related processes has been shown to influence reach-to-grasp effectiveness in older adults. However, the added influence of stress and anxiety - known to negatively affect attention shifting ability - has not yet been explored in relation to recovery from balance perturbations. Given that fear and anxiety over falling is a key fall risk factor, an understanding of how such a negative mental state may affect postural reactions is important. This study aimed to investigate the effect of varied induced emotional states on reach-to-grasp balance responses in older adults. METHODS: Healthy older adults (mean age 70.5 ± 5.38 years) stood laterally between 2 handrails with contact sensors. A safety harness with an integrated loadcell was worn to prevent falls and measure the amount of harness assistance (expressed as percent body weight). With instructions to grasp one rail to restore balance, participants' balance was laterally disturbed using surface translations under three randomized conditions: no cognitive task, neutral (verb generation) task, and mental stress task with negative prompts (paced auditory serial addition). The primary outcome was frequency of protective grasps. Secondary outcomes included frequency of harness assistance during trials with grasp errors as well as wrist movement time, trajectory distance, and peak velocity. RESULTS: Perceived level of distress was highest for the mental stress task compared to no task (p < 0.001) and neutral task conditions (p = 0.008). The mental stress task resulted in the lowest percentage of protective grasps (p < 0.001) in response to balance perturbations. Closer examination of trials that resulted in grasp errors (i.e., collisions or overshoots), revealed increased harness assistance and reduced peak velocity of wrist movement (p < 0.001) under the mental stress condition compared to grasp errors that occurred under the no task or neutral task condition. DISCUSSION AND CONCLUSION: Distressing mental thoughts immediately prior to a balance perturbation lead to reduced effectiveness in reach-to-grasp balance responses compared to no or neutral cognitive tasks and should be considered as a possible fall risk factor.

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans.

BACKGROUND: Transcutaneous stimulation of the external ear is thought to recruit afferents of the auricular vagus nerve, providing a means to activate noradrenergic pathways in the central nervous system. Findings from human studies examining the effects of auricular stimulation on noradrenergic biomarkers have been mixed, possibly relating to the limited and variable parameter space explored to date. OBJECTIVE: We tested the extent to which brief pulse trains applied to locations of auricular innervation (canal and concha) elicit acute pupillary responses (PRs) compared to a sham location (lobe). Pulse amplitude and frequency were varied systematically to examine effects on PR features. METHODS: Participants (n = 19) underwent testing in three separate experiments, each with stimulation applied to a different external ear location. Perceptual threshold (PT) was measured at the beginning of each experiment. Pulse trains (∼600 ms) consisting of different amplitude (0.0xPT, 0.8xPT, 1.0xPT, 1.5xPT, 2.0xPT) and frequency (25 Hz, 300 Hz) combinations were administered during eye tracking procedures. RESULTS: Stimulation to all locations elicited PRs which began approximately halfway through the pulse train and peaked shortly after the final pulse (≤1 s). PR size and incidence increased with pulse amplitude and tended to be greatest with canal stimulation. Higher pulse frequency shortened the latency of PR onset and peak dilation. Changes in pupil diameter elicited by pulse trains were weakly associated with baseline pupil diameter. CONCLUSION: (s): Auricular stimulation elicits acute PRs, providing a basis to synchronize neuromodulator release with task-related neural spiking which preclinical studies show is a critical determinant of therapeutic effects. Further work is needed to dissociate contributions from vagal and non-vagal afferents mediating activation of the biomarker.

Corticospinal recruitment of spinal motor neurons in human stroke survivors.

KEY POINTS: Muscle weakness after stroke results from damage to corticospinal fibres that structurally and functionally connect cerebral cortex to the spinal cord. Here, we show an asymmetry in corticospinal recruitment of spinal motor neurons that is linked to maximal voluntary output of hand muscles weakened by stroke. Spike timing-dependent plasticity of synapses between corticospinal and spinal motor neurons transiently reversed recruitment failures in some survivors. These modulatory effects were strongly associated with recruitment asymmetry and hand impairment. Our findings highlight the functional relevance of spinal motor neuron recruitment by corticospinal inputs and the viability of corticospinal motor neuronal synapses for restoring activation of lower motor neurons after stroke. ABSTRACT: Corticospinal input to spinal motor neurons is structurally and functionally altered by hemiparetic stroke. The pattern and extent to which corticospinal recruitment of spinal motor neurons is reorganized and whether such changes are linked to the severity of motor impairments is not well understood. Here, we performed experiments using the triple stimulation technique to quantify corticospinal recruitment of spinal motor neurons serving paretic and non-paretic intrinsic hand muscles of humans with longstanding motor impairment secondary to stroke (n = 13). We also examined whether recruitment failures could be transiently reversed by strengthening corticospinal-motoneuronal synaptic connectivity via targeted, temporally controlled non-invasive stimulation to elicit spike timing-dependent plasticity (STDP). Asymmetries were detected in corticospinal recruitment of spinal motor neurons, central conduction time and motor-evoked potential (MEP) latency. However, only recruitment asymmetry correlated with maximal voluntary motor output from the paretic hand. STDP-like effects were observed as an increase in spinal motor neuron recruitment. Control experiments to isolate the locus of plasticity demonstrated a modulation in MEPs elicited by electrical stimulation of primary motor cortex but not F-wave size or persistence, suggesting that plasticity was mediated through enhanced efficacy of residual corticospinal-motor neuronal synapses. The modulation in recruitment was strongly associated with baseline recruitment asymmetry and impairment severity. Our findings demonstrate that asymmetry in corticospinal recruitment of spinal motor neurons is directly related to impairments experienced by stroke survivors. These recruitment deficits may be partially and transiently reversed by spike timing-dependent plasticity of synapses between upper and lower motor neurons in the spinal cord, downstream of supraspinal circuits damaged by stroke.

Motor Recovery: How Rehabilitation Techniques and Technologies Can Enhance Recovery and Neuroplasticity.

There are now a large number of technological and methodological approaches to the rehabilitation of motor function after stroke. It is important to employ these approaches in a manner that is tailored to specific patient impairments and desired functional outcomes, while avoiding the hype of overly broad or unsubstantiated claims for efficacy. Here we review the evidence for poststroke plasticity, including therapy-related plasticity and functional imaging data. Early demonstrations of remapping in somatomotor and somatosensory representations have been succeeded by findings of white matter plasticity and a focus on activity-dependent changes in neuronal properties and connections. The methods employed in neurorehabilitation have their roots in early understanding of neuronal circuitry and plasticity, and therapies involving large numbers of repetitions, such as robotic therapy and constraint-induced movement therapy (CIMT), change measurable nervous systems properties. Other methods that involve stimulation of brain and peripheral excitable structures have the potential to harness neuroplastic mechanisms, but remain experimental. Gaps in our understanding of the neural substrates targeted by neurorehabilitation technology and techniques remain, preventing their prescriptive application in individual patients as well as their general refinement. However, with ongoing research-facilitated in part by technologies that can capture quantitative information about motor performance-this gap is narrowing. These research approaches can improve efforts to attain the shared goal of better functional recovery after stroke.

Neuromuscular Electrical Stimulation and High-Protein Supplementation After Subarachnoid Hemorrhage: A Single-Center Phase 2 Randomized Clinical Trial.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) survivors live with long-term residual physical and cognitive disability. We studied whether neuromuscular electrical stimulation (NMES) and high-protein supplementation (HPRO) in the first 2 weeks after SAH could preserve neuromotor and cognitive function as compared to standard of care (SOC) for nutrition and mobilization. METHODS: SAH subjects with a Hunt Hess (HH) grade > 1,modified Fisher score > 1 and BMI < 40 kg/m2 were randomly assigned to SOC or NMES + HPRO. NMES was delivered to bilateral quadricep muscles daily during two 30-min sessions along with HPRO (goal:1.8 g/kg/day) between post-bleed day (PBD) 0 and 14. Primary endpoint was atrophy in the quadricep muscle as measured by the percentage difference in the cross-sectional area from baseline to PBD14 on CT scan. All subjects underwent serial assessments of physical (short performance physical battery, SPPB) cognitive (Montreal Cognitive Assessment Scale, MoCA) and global functional recovery (modified Rankin Scale, mRS) at PBD 14, 42, and 90. RESULTS: Twenty-five patients (SOC = 13, NMES + HPRO = 12) enrolled between December 2017 and January 2019 with no between-group differences in baseline characteristics (58 years old, 68% women, 50% HH > 3). Median duration of interventions was 12 days (range 9-14) with completion of 98% of NMES sessions and 83% of goal HPRO, and no reported serious adverse events. There was no difference in caloric intake between groups, but HPRO + NMES group received more protein (1.5 ± 0.5 g/kg/d v 0.9 ± 0.4 g/kg/d, P < 0.01). Muscle atrophy was less in NMES + HPRO than the SOC group (6.5 ± 4.1% vs 12.5 ± 6.4%, P 0.01). Higher atrophy was correlated with lower daily protein intake (ρ = - 0.45, P = 0.03) and lower nitrogen balance (ρ = 0.47, P = 0.02); and worse 3 month SPPB (ρ = -  0.31, P = 0.1) and mRS (ρ = 0.4, P = 0.04). NMES + HPRO patients had a better median [25%,75] SPPB (12[10, 12] v. 9 [4, 12], P = 0.01) and mRS (1[0,2] v.2[1, 3], P = 0.04) than SOC at PBD 90. CONCLUSIONS: NMES + HPRO appears to be feasible and safe acutely after SAH and may reduce acute quadriceps muscle wasting with a lasting benefit on recovery after SAH.

Contraction Phase and Force Differentially Change Motor Evoked Potential Recruitment Slope and Interhemispheric Inhibition in Young Versus Old.

Interhemispheric interactions are important for arm coordination and hemispheric specialization. Unilateral voluntary static contraction is known to increase bilateral corticospinal motor evoked potential (MEP) amplitude. It is unknown how increasing and decreasing contraction affect the opposite limb. Since dynamic muscle contraction is more ecologically relevant to daily activities, we studied MEP recruitment using a novel method and short interval interhemispheric inhibition (IHI) from active to resting hemisphere at 4 phases of contralateral ECR contraction: Rest, Ramp Up [increasing at 25% of maximum voluntary contraction (MVC)], Execution (tonic at 50% MVC), and Ramp Down (relaxation at 25% MVC) in 42 healthy adults. We analyzed the linear portion of resting extensor carpi radialis (ECR) MEP recruitment by stimulating at multiple intensities and comparing slopes, expressed as mV per TMS stimulation level, via linear mixed modeling. In younger participants (age ≤ 30), resting ECR MEP recruitment slopes were significantly and equally larger both at Ramp Up (slope increase = 0.047, p < 0.001) and Ramp Down (slope increase = 0.031, p < 0.001) compared to rest, despite opposite directions of force change. In contrast, Active ECR MEP recruitment slopes were larger in Ramp Down than all other phases (Rest:0.184, p < 0.001; Ramp Up:0.128, p = 0.001; Execution: p = 0.003). Older (age ≥ 60) participants' resting MEP recruitment slope was higher than younger participants across all phases. IHI did not reduce MEP recruitment slope equally in old compared to young. In conclusion, our data indicate that MEP recruitment slope in the resting limb is affected by the homologous active limb contraction force, irrespective of the direction of force change. The active arm MEP recruitment slope, in contrast, remains relatively unaffected. Older participants had steeper MEP recruitment slopes and less interhemispheric inhibition compared to younger participants.