Shirley Ryan AbilityLab

Peripheral nerve injuries affect large numbers of individuals each year, often resulting in long-term disabilities due to impairments in motor and sensory function. With traditional treatment approaches, including surgical repair and rehabilitation, the most common outcome is incomplete recovery. This is compounded by the absence of FDA-approved medications to enhance nerve regeneration. Recent advances in therapeutic electrical stimulation techniques have shown promise to improve axonal regrowth and functional recovery. Typically administered perioperatively in a single 1-hour session, therapeutic electrical stimulation has demonstrated efficacy in both preclinical studies and small clinical trials by promoting faster and more complete axonal regeneration. To address the limitations of traditional therapeutic electrical stimulation, including infection risks or lead displacement, the recent development of bioresorbable nerve stimulator implants has introduced a groundbreaking solution. Furthermore, patient-specific factors, including age, sex, medical comorbidities, and genetic variability, notably interact with clinical outcomes and potential responsiveness to therapeutic electrical stimulation. Such genes include the prevalent Val66Met genetic polymorphism in the brain-derived neurotrophic factor gene (rs6265). Carriers of rs6265 have less nerve regeneration, impaired activity-dependent brain-derived neurotrophic factor secretion, and a diminished response to therapeutic electrical stimulation in preclinical studies. This highlights the growing importance of tailoring therapeutic electrical stimulation protocols to each patient for optimal outcomes. The future of therapeutic electrical stimulation in the treatment of peripheral nerve injury will involve the integration of more sophisticated nerve stimulators to deliver tailored therapeutic electrical stimulation protocols, with careful consideration given to patient-specific factors and personalized rehabilitation strategies to maximize functional recovery.

BACKGROUND Urinary incontinence after a stroke significantly affects patient outcomes and quality of life. It is commonly associated with uninhibited detrusor contractions, but the underlying neural mechanisms remain poorly understood. This study aimed to explore the brain activity patterns associated with volitional and involuntary bladder contractions in stroke survivors. METHODS This cohort study enrolled 15 stroke survivors with documented urinary incontinence and 9 healthy controls. Participants underwent simultaneous blood oxygen level–dependent functional magnetic resonance imaging of the brain and urodynamics, capturing 25 involuntary and 23 volitional bladder emptying events in patients with stroke and 35 volitional voiding events in healthy individuals. We used general linear modeling in functional magnetic resonance imaging analysis to discern neural activity patterns during these events and in the phases leading up to them, aiming to identify neural mechanisms underlying involuntary versus volitional urinary control. Statistical significance for neuroimaging analyses was set at P <0.005 with a minimum cluster size of 25 voxels. RESULTS During volitional emptying events, both healthy controls and stroke survivors exhibited increases in activation in regions implicated in sensorimotor control and executive decision-making, such as the brainstem, cingulate cortex, prefrontal cortex, and motor areas. In contrast, involuntary emptying events were associated with minimal changes in brain activity, suggesting minimal cortical involvement. Bladder filling preceding volitional contractions was associated with activity in the salience network (insula, anterior cingulate gyrus) in stroke survivors and healthy controls. Conversely, although there was an increase in overall blood oxygen level–dependent signal, activation of the salience network was conspicuously absent during bladder filling preceding involuntary contractions. CONCLUSIONS The findings suggest that the salience network plays an important role in maintaining urinary continence in stroke survivors. The inability to activate the salience network may underpin the pathophysiology of poststroke urinary incontinence. Interventions aimed at modulating this network could potentially ameliorate lower urinary tract symptoms in this patient population. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05301335.

Transcutaneous electrical nerve stimulation (TENS) is commonly used in research and clinical settings for pain management and augmenting somatosensory inputs for motor recovery. Besides its functional effect, TENS acutely alters kinesthesia and force steadiness. However, the short-term impact following a session of TENS on proprioception and motor unit behavior is unknown. We evaluated the effect of a session of TENS on the senses of force, joint position, touch, and discharge activity of motor units. Fifteen healthy participants underwent two experiments, each with two visits randomly administering TENS or sham-TENS. The sense of force (Exp. 1) and position (Exp. 2) were evaluated through matching trials by pinching a dial and rotating their wrist (ulnar deviation). Isometric pinch contractions were performed before and after the session of TENS or sham-TENS, in which electromyographic signals were recorded from the first dorsal interosseus (FDI) and abductor pollicis brevis (APB). Results showed that TENS acutely altered the senses of force, position, and touch, but only the sense of force remained altered following TENS. Motor unit discharge rates increased in both FDI and APB muscles for the same force output following TENS. A positive correlation was also observed between changes in motor unit discharge rates and changes in errors in force perception. These findings suggest that a session of TENS may have short-term effects on the input/output function of motoneurons (5 - 10 min in this study), which in turn may alter the sense of force. However, the precise timeline for these short-term aftereffects is unknown.

Education in quality improvement (QI) is linked to high-quality health care, and involving residents as key leadership in QI projects ensures a level of engagement to reinforce principles in practice. Obtaining timely laboratory data in inpatient settings is critical to decision making. This resident-led group identified that the established forms of communication regarding uncollected laboratory draws at this inpatient rehabilitation facility were not standardized. There was significant variance in communication between phlebotomists and clinicians. Based on a root cause analysis, the QI team concluded that a single unified email notifying clinicians about uncollected labs would be an effective and efficient communication method. A standardized email template was created and sent to the resident physicians and advanced practice providers during a two-week feasibility pilot. After a successful pilot intervention, the communication email was expanded to include attending physicians. The standardized weekday email was distributed 100% of the time during both two-week interventions. The residents leading the project gained a better understanding of the dynamics of interdisciplinary collaboration required within hospital operations to facilitate the success of a QI intervention.

Introduction Metabolic assessment of prosthetic gait is useful when comparing devices, interventions, or populations. However, the standard requirement to walk continuously for six minutes or more to reach steady state (SS) is difficult for many individuals with lower limb amputation. Our goal was to assess the concurrent validity of metabolic outcomes from shorter duration walking tests with those from the standard six-minute walk, in persons with transfemoral or transtibial amputation. Methods Thirty participants (amputation: 10 transfemoral, 10 transtibial, 10 none) performed three walking tests while data were collected with a wearable metabolic system: 1) two-minute treadmill walk plus 10-minute recovery, 2) six-minute treadmill walk, and 3) overground two-minute walk test (2MWT). Three different analyses were performed to correlate SS metabolic outcomes from minutes 5-6 of the six-minute treadmill walk with: 1) total oxygen uptake from the two-minute treadmill walk, incorporating excess post-exercise oxygen consumption (EPOC), 2) minute interval outcomes from minutes 1-4 of the six-minute treadmill walk, and 3) outcomes during minutes 1 and 2 of the 2MWT. Results Strong correlations were found between total oxygen uptake of the two-minute treadmill walk plus EPOC and SS oxygen uptake (Pearson r 0.86 to 0.94). Likewise, there were strong correlations between minute interval outcomes of minutes 2, 3, and 4 of the six-minute treadmill walk and SS outcomes (Pearson r 0.82 to > 0.99). Fewer significant correlations were observed when comparing 2MWT outcomes with SS outcomes (Pearson r 0.41 to 0.78). Conclusion Strong correlations between metabolic outcomes of shorter duration walking tests with SS outcomes suggest that treadmill walking tests as short as two minutes may be acceptable to compare energy expenditure between conditions in individuals with lower limb amputation for circumstances where longer duration tests would not be possible. Additionally, these shorter tests would be more similar to real-life activities and more accessible for those with lower limb amputation.

Motoneurons are the final common pathway for all motor commands and possess intrinsic electrical properties that must be tuned to control muscle across the full range of motor behaviours. Neuromodulatory input from the brainstem is probably essential for adapting motoneuron properties to match this diversity of motor tasks. A primary mechanism of this adaptation, control of dendritic persistent inward currents (PICs) in motoneurons by brainstem monoaminergic systems, generates both amplification and prolongation of synaptic inputs. While essential, there is an inherent tension between this amplification and prolongation. Although amplification by PICs allows for quick recruitment and acceleration of motoneuron discharge, PICs must be deactivated to derecruit motoneurons upon movement cessation. In contrast, during stabilizing or postural tasks, PIC‐induced prolongation of synaptic inputs is critical for sustained motoneuron discharge. Here, we designed two motor tasks that challenged the inhibitory control of PICs, generating unduly PIC prolongation that increases variability in human torque control. This included a paradigm combining a discrete motor task with a stabilizing task and another involving muscle length‐induced changes to the balance of excitatory and inhibitory inputs available for controlling PICs. We show that prolongation from PICs introduces difficulties in ankle torque control and that these difficulties are further degraded at shorter muscle lengths when PIC prolongation is greatest. These results highlight the necessity for inhibitory control of PICs and showcase issues introduced when inhibitory control is constrained. Our findings suggest that, like sensory systems, errors are inherent in motor systems. These errors are not due to problems in the perception of movement‐related sensory input but are embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) where pathological shifts in monoamines may further amplify these errors. image Key points All motor commands are processed via spinal motoneurons, whose intrinsic electrical properties are adapted by brainstem neuromodulatory input. The effects of these neuromodulatory inputs (i.e. persistent inward currents; PICs) must be tightly regulated by inhibitory inputs to allow for the large repertoire of human motor behaviours. We designed two motor tasks to restrict the ability of inhibitory synaptic inputs to control PICs and show that this generates substantial errors that reduce the precision of motor output in humans. Our findings suggest that errors are inherent in motor systems and embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) and may, speculatively, shed light on contributing factors to muscle cramps.

Muscular contractures are routinely observed in children with cerebral palsy (CP). The natural progression of gait leads to a reduction in passive range of motion. Here, we discuss the physiological properties of skeletal muscle tissue and the recent advances in our understanding of the biological basis of contractures. Skeletal muscles are highly organized structures composed of muscle cells, i.e., myofibers, arranged in parallel and series. Myofibers in turn are made up of the basic contractile proteins, actin and myosin, that form sarcomeres. Sarcomere length and force production are intricately associated such that at very long and short sarcomere lengths, there is a reduction in force-generating capacity. During normal postnatal development, stretch-induced longitudinal skeletal muscle growth by addition of sarcomeres is mediated by bone growth. In children with cerebral palsy, sarcomere lengths are overstretched and sarcomere number is lower, associated with a limitation in joint range of motion, suggesting reduced ability for muscle growth. Increase in muscle extracellular matrix content and increase in passive mechanical stiffness of fibers and fiber bundles are also observed. Satellite cells are resident stem cells required for myonuclei during postnatal development and repair of skeletal muscles throughout life. The satellite cell population is significantly altered in contractured muscles. Overall, these findings suggest that impaired muscle growth and contractures in children with CP may be related to alterations in muscle stem cell function during postnatal development.

Background Studies have shown that athletes with disabilities (AWDs) are often not provided with injury prevention and health promotion strategies via educational programs. Objective To assess the impact of a novel educational interventional workshop on the healthy lifestyle knowledge and implementation in a cohort of AWDs using a community‐based participatory research approach. We hypothesized that the Adaptive Health Education on Activity and Diet workshop would increase the participation of AWDs in healthy exercise and diet. Methods Participants enrolled in this educational interventional prospective cohort study consisted of AWDs participating in an urban adaptive sports program. The intervention included eight virtual educational sessions regarding nutrition, strength training, cardiovascular exercise, and health optimization taught by a multidisciplinary team. The outcome measures were participation in healthy lifestyle regarding diet and exercise, Patient‐Reported Outcomes Measurement Information System (PROMIS)‐29, and Godin Exercise scores. Results The mean age of the adaptive athletes ( n = 26) was 50.1 years (SD 15.4), with 50% male and 50% female. Primary disability diagnoses included spinal cord injury, brain injury, stroke, amputation, and cerebral palsy. The baseline physical function level PROMIS‐29 scores had a sustained increase (increase from pre to post to follow‐up) after the intervention ( p < .05). There was a nonsustained increase from pre to post intervention ( p < .05) in frequency of meal preparation and discussion of diet and exercise with a primary care physician. There was an overall increase in frequency of weight training three or more times a week ( p < .05). Discussion Our findings were consistent with our hypothesis that the workshop would increase participation in healthy diet and exercise. The significant improvements were in frequency of meal prep, weight training, and discussions of diet and exercise with primary care physicians. Conclusion Providing healthy lifestyle information through an educational workshop tailored to the community's needs, using a community‐based participatory research approach, can improve nutrition and exercise participation of AWDs.

Double-hit (DHL) and double expressor (DEL) DLBCL have poor prognosis with standard therapy but CART may overcome this poor prognostic impact. In this multicenter retrospective study, we sought to confirm this observation by evaluating survival outcomes among patients with relapsed/refractory DHL and DEL treated with CART and evaluate outcomes of relapse post-CART. A total of 408 adult patients with relapsed/refractory DLBCL from 13 academic centers were included based on the availability of DHL and DEL. All 408 patients were included in the DHL (n = 80) vs non-DHL (n = 328) analysis, while 333 patients were included in the analysis of DHL (n = 80) vs DEL (n = 74) vs non (n = 179). On MVA, there were no differences for PFS for DHL vs non-DHL (HR 0.8, 95%CI 0.5–1.3, p = 0.35) or DHL vs DEL vs other (three-way p value, p = 0.5). Response rates and toxicities were similar among groups. Patients with DEL had the highest relapse rates post-CART, while DHL had the worst overall survival after CART relapse. In sum, our data support the notion that CART cell therapy can overcome the poor prognostic impact of DHL and DEL DLBCL in the relapsed/refractory setting. Additionally, patients with DHL that relapse after CART have a very poor prognosis.

Objective Determine acute symptomatic, gait, and biological effects of lower extremity loading during lower body positive pressure (LBPP) treadmill walking in individuals with knee osteoarthritis (OA). Methods Participants with knee OA (n = 32) above the age of 50 performed two-45-minute walking sessions at least 1 week apart. Individuals walked at self-selected speed on the treadmill at 100% bodyweight (BW) or 50%BW. The primary outcome was change in serum cartilage oligomeric matrix protein (COMP), with other outcome measures including change in knee joint pain, exercise intensity, gait parameters, and the concentration of other serum biomarkers of joint disease. Results Across all timepoints, 50%BW walking, was associated with significant reductions in knee pain compared to 100%BW (p < 0.05 for all) with no significant difference in duration of moderate-intensity exercise. 50%BW was associated with significant decreases in cadence (p < 0.001) and increased stride length (p = 0.008). Biomarker analyses demonstrated 100%BW walking was associated with a significant increase in COMP at 45 minutes compared to baseline (p = 0.032), not observed with 50% BW. Conclusion 50%BW walking in knee OA using an LBPP treadmill acutely reduces joint pain, improves gait parameters, and does not increase markers of cartilage turnover. Future studies should investigate the longitudinal benefits of this rehabilitation approach.

Background The presence or absence of a motor evoked potential (MEP) in the post-stroke hemiparetic limb has been recommended by rehabilitation experts as a predictive biomarker which is ready for use in clinical trials. However, evidence remains limited for its prognostic value in the chronic stage. Objective Determine if MEP status (MEP+ or MEP−) obtained within 1 week of starting treatment (baseline) predicts the magnitude of response to intervention in individuals with chronic, moderate–severe hemiparesis. Methods This is a retrospective analysis using data from a single-blind randomized controlled trial. Seventy-six individuals ≥6 months post-stroke with a baseline Fugl-Meyer Assessment of the Upper Extremity (FMUE) score of 23 to 40 underwent 30 hours of upper limb (UL) training over 6 weeks. Participants were stratified by baseline MEP status. The primary endpoint was change in FMUE score from baseline to post-test. Results Seventy-three participants provided FMUE scores and MEP status at baseline. Individuals who were MEP+ (n = 49) demonstrated a mean FMUE change score of 5.09 (standard deviation [SD] = 3.8) while MEP− (n = 24) individuals demonstrated a mean change score of 5.04 (SD = 4.0). There were no significant differences between the groups (mean difference = 0.05, P = .96, 95% confidence interval [−1.99, 2.09]). Conclusions Our results demonstrate that MEP status at the start of an intervention in the chronic stage does not predict recovery for people with moderate–severe UL impairments. This finding directly challenges recent expert recommendations to stratify trial groups by MEP status, suggesting that such stratification may not effectively reduce variability or predict treatment response at the chronic stage. Clinical Trial Registration ClinicalTrials.gov, ID: NCT03517657.

Objective Seizure detection in epilepsy monitoring units (EMUs) is essential for the clinical assessment of drug‐resistant epilepsy. Automated video analysis using machine learning provides a promising aid for seizure detection, with resultant reduction in the resources required for diagnostic monitoring. We employ a three‐dimensional (3D) convolutional neural network with fully fine‐tuned backbone layers to identify seizures from EMU videos. Methods A two‐stream inflated 3D‐ConvNet architecture (I3D) classified video clips as a seizure or not a seizure. A pretrained action classifier was fine‐tuned on 11 h of video containing 49 tonic–clonic seizures from 25 patients monitored at a large academic hospital (site A) using leave‐one‐patient‐out cross‐validation. Performance was evaluated by comparing model predictions to ground‐truth annotations obtained from video‐electroencephalographic review by an epileptologist on videos from site A and a separate dataset from a second large academic hospital (site B). Results The model achieved a leave‐one‐patient‐out cross‐validation F1‐score of .960 ± .007 (mean ± SD) and area under the receiver operating curve score of .988 ± .004 at site A. Evaluation on full videos detected all seizures (95% binomial exact confidence interval = 94.1%–100%), with median detection latency of 0.0 s (interquartile range = 0.0–3.0) from seizure onset. The site A model had an average false alarm rate of 1.81 alarms per hour, although 36 of the 49 videos (73.5%) had no false alarms. Evaluation at site B demonstrated generalizability of the architecture and training strategy, although cross‐site evaluation (site A model tested on site B data and vice versa) resulted in diminished performance. Significance Our model demonstrates high performance in the detection of epileptic seizures from video data using a fine‐tuned I3D model and outperforms similar models identified in the literature. This study provides a foundation for future work in real‐time EMU seizure monitoring and possibly for reliable, cost‐effective at‐home detection of tonic–clonic seizures.

Combinatorial approaches targeting multiple aspects of spinal cord injury (SCI) pathophysiology are needed to maximize functional recovery. We hypothesized that strengthening corticospinal synapses via Hebbian stimulation and increasing neuronal transmission with 4-aminopyridine (4-AP, a potassium blocker) could accelerate locomotor recovery in individuals with chronic SCI. Participants were randomly assigned to receive 10 mg of 4-AP or placebo, where both groups followed with 60-min of Hebbian stimulation targeting corticospinal-motoneuronal synapses supplying leg muscles involved in locomotion and 60-min of standard exercise rehabilitation for 40 sessions over 8-14 weeks. During Hebbian stimulation, 720 paired pulses were delivered to elicit corticospinal action potentials via electrical stimulation of the thoracic spine, ensuring volleys reached the spinal cord 1-2 milliseconds before motoneurons were retrogradely activated through bilateral electrical stimulation of the femoral, common peroneal, and posterior tibial nerves (targeting the quadriceps femoris, tibialis anterior, and soleus muscles, respectively). Results showed that participants who received 4-AP exhibited significantly greater improvements in walking speed and endurance, corticospinal transmission, and light touch sensation compared to those who received the placebo. The minimal clinically important difference in walking speed and endurance was achieved after 20 sessions in the 4-AP group, but was not consistently reached in the placebo group. Although walking continued to improve in both groups over the course of 40 sessions, the 4-AP group demonstrated significantly greater progress. Improvement in the 4-AP group was still present twelve months later. These findings suggest that 4-AP represents a strategy to potentiate and accelerate Hebbian stimulation effects on motor recovery in individuals with chronic SCI.

Background Healthcare managers and administrators increasingly need to develop systems, structures and operations capable of improving the patient experience performance of their organisations or service delivery units. Aim To systematically review the effectiveness of organizational and service management interventions on standardized patient experience measure scores. Methods Six scientific databases, speciality journals and snowballing were used to identify English‐language, peer‐reviewed, contemporary studies (2015–2023) that examined the impact of service management or organizational interventions on the patient experience as a primary outcome. The studies needed to include inferential statistics on standardized, patient‐reported experience measures. Two independent reviewers performed the eligibility decisions and risk‐of‐bias appraisals. Results Nine papers were finally included. Three papers were on discrete, service‐level interventions, including two randomized controlled trials (RCTs) and one pre‐post study; one RCT achieved significant improvements by delaying the timing of bedside rounding versus maintaining the early morning schedule. One non‐randomized controlled study and two pre‐post studies addressed organisation‐wide approaches. Among those, one pre‐post study achieved significant improvements by having site managers meet regularly with an organizational oversight committee to compare the units' patient‐experience performance and setting improvement expectations. Finally, three observational, multi‐site comparative studies were included. These addressed self‐reported improvement approaches, implementation of a nursing excellence certification programme, and implementation of Patient Experience Offices. The latter was significantly associated with improved patient experience performance. Conclusion Selected discrete service‐level interventions and organizational approaches can lead to better patient experience outcomes, even though the evidence from the pre‐post and observational studies should be interpreted with caution.

Intense political behavior is associated with brain regions involved in emotional and cognitive processing. However, it remains unclear if this neuroanatomy is causal, compensatory, or otherwise correlated. We employed lesion network mapping in a cross-sectional study of 124 male military Veterans with penetrating head trauma. 40-45 years after the injury, participants reported current political behavior and recollection of political behavior pre-injury. Using a normative connectome database (n = 1000), we mapped the circuitry functionally connected to lesions associated with changes in intensity of political involvement, ideological polarity, and party affiliation. No significant neuroanatomical circuit was associated with political ideology or party affiliation, but a distinct circuit was associated with intensity of political involvement. Political involvement was more intense after lesions connected to the left dorsolateral prefrontal cortex and posterior precuneus, in the full sample and in conservative-leaning participants. Political involvement was less intense after lesions connected to the amygdala and anterior temporal lobe, in the full sample and in liberal-leaning participants. These effects survived cross-validation in the full sample (p=0.01) and in both conservative-leaning and liberal-leaning participants. These findings may inform cognitive mechanisms of political behavior as well as clinical assessment after brain lesions.

Active stability is essential to preventing dislocations and the focus of rehabilitation following dislocations. This is thought to arise from shoulder muscles compressing the humeral head into the glenoid (called concavity compression). However, shoulder muscles may also resist humeral head translation through increases in intrinsic muscle stiffness, an unexplored mechanism. Our objective was to quantify shoulder muscles’ contributions to changes in glenohumeral stiffness, or the resistance to humeral head translation. We hypothesized that primary shoulder movers (e.g., the pectoralis major or deltoid) would differ from rotator cuff muscles in how much they increase glenohumeral stiffness because they leverage their intrinsic stiffness in addition to concavity compression. We measured glenohumeral stiffness across a range of isometric muscle activation levels in shoulder abduction and used electromyography to estimate the contributions of rotator cuff muscles and primary shoulder movers. We then created a musculoskeletal model to evaluate individual muscle contributions to glenohumeral stiffness through both concavity compression and intrinsic muscle stiffness. We found that muscle activity in primary shoulder movers was a better predictor of active glenohumeral stiffness than in rotator cuff muscles (R2 = 0.81 vs 0.36, P < 0.001). Our musculoskeletal model demonstrated that concavity compression is the primary stabilizing mechanism for most shoulder muscles, yet the muscles that increase glenohumeral stiffness the most also do so considerably through their intrinsic muscle stiffness. Our results emphasize the importance of primary shoulder movers as active stabilizers of the glenohumeral joint and highlight their potential importance in preventing shoulder dislocations.