Rehabilitation Institute Of Chicago

DEVELOPMENT OF A NEURAL INTERFACE FOR POWERED LOWER LIMB PROCEDURES

ENGINEERING FOR NEUROLOGIC REHABILITATION

CENTER FOR SMART USE OF TECHNOLOGY TO ASSESS REAL-WORLD OUTCOMES (C-STAR)

ERROR-ENHANCED LEARNING & RECOVERY IN 2 & 3 DIMENSIONS

ADAPTIVE RECALIBRATION OF A PROSTHETIC LEG NEURAL CONTROL SYSTEM

APPLICATION OF TARGETED REINNERVATION FOR PEOPLE WITH TRANSRADIAL AMPUTATION

REHABILITATION ENGINEERING RESEARCH CENTERS

TECHNOLOGIES TO EVALUATE AND ADVANCE MANIPULATION AND MOBILITY (TEAMM)- RERC

COLLABORATIVE MACHINES ENHANCING THERAPIES (COMET)

SENSOR TECHNOLOGY APPLIED TO REHABILITATION IN STROKE - STARS

A MULTI-CENTER CLINICAL TRIAL TO EVALUATE THE EFFECTIVENESS OF INTERMITTENT HYPOXIA THERAPY IN INDIVIDUALS WITH SPINAL CORD INJURY

HOME AND COMMUNITY BASED SERVICES PERSON CENTERED OUTCOMES AND MEASUREMENTS

REHABILITATION RESEARCH TRAINING CENTER (RRTC) ON EMPLOYMENT FOR PEOPLE WITH PHYSICAL DISABILITIES

ENHANCING COMMUNITY LIVING AND INCREASING PARTICIPATION THROUGH SELF EFFICACY (ECLIPSE)

A NEUROMUSCULOSKELETAL INTERFACE FOR BIONIC ARMS: A RANDOMIZED CROSSOVER STUDY - LOSS OF AN ARM MAKES IT HARDER TO WORK, TO TAKE PART IN LEISURE ACTIVITIES, AND TO DO MANY OF THE TASKS NEEDED TO LEAD AN INDEPENDENT LIFE. USING AN ARTIFICIAL ARM (PROSTHESIS) CAN HELP WITH THESE ACTIVITIES, AND A LOT OF RESEARCH HAS GONE INTO DESIGNING ADVANCED PROSTHESES THAT CAN REPLACE THE MANY FUNCTIONS OF AN INTACT HAND AND ARM. HOWEVER, A PROSTHESIS IS TYPICALLY ATTACHED TO THE BODY USING A SOCKET, WHICH FITS OVER THE RESIDUAL LIMB. SOCKETS CAN CAUSE PROBLEMS WITH SKIN IRRITATION AND CAN BE UNCOMFORTABLE OR HOT TO WEAR FOR LONG PERIODS. ONE WAY AROUND THIS IS TO ATTACH THE PROSTHESIS DIRECTLY TO THE BONE OF THE RESIDUAL LIMB. THIS SOLVES THE PROBLEMS ASSOCIATED WITH WEARING A SOCKET, ALLOWS A WIDER RANGE OF MOVEMENT, AND THE MAKES THE PROSTHESIS FEEL MORE LIKE A PART OF THE USER’S BODY. THE PROSTHESIS IS ATTACHED TO A METAL ROD THAT IS INSERTED INTO THE ARM BONE DURING A TWO-STEP SURGERY. THE BONE THEN GROWS INTO THE METAL ROD, FORMING A STRONG PERMANENT ATTACHMENT. THIS PROCESS IS CALLED OSSEOINTEGRATION (OI). ANOTHER PROBLEM IS HOW TO CONTROL THE PROSTHESIS, I.E., HOW TO MAKE IT DO WHAT THE USER WANTS IT TO DO. SOME PROSTHESES ARE CONTROLLED USING SMALL ELECTRICAL SIGNALS (CALLED EMG SIGNALS) THAT ARE PRODUCED BY MUSCLES WHEN THEY CONTRACT. EMG SIGNALS ARE USUALLY RECORDED BY ELECTRODES PLACED ON THE SKIN OVER THE MUSCLE; THE SIGNALS ARE DECODED BY A COMPUTER ALGORITHM AND TURNED INTO CONTROL SIGNALS FOR THE PROSTHESIS. EMG SIGNALS RECORDED FROM THE SKIN SURFACE CAN BE UNRELIABLE, SO ANOTHER OPTION IS TO IMPLANT THE ELECTRODES ONTO THE MUSCLE. A SYSTEM CALLED OSSEOINTEGRATION OF PROSTHESES FOR THE REHABILITATION OF AMPUTEES (OPRA) USES OI TO ATTACH THE PROSTHESIS. A NEW VERSION OF THIS SYSTEM, E-OPRA, USES OI WITH IMPLANTED ELECTRODES. E-OPRA CAN ALSO BE USED TO STIMULATE PERIPHERAL NERVES SO THAT THE USER FEELS SOME SENSORY FEEDBACK FROM THE PROSTHESIS, WHICH ALSO MAY HELP WITH CONTROL OF THE DEVICE. OUR OBJECTIVE IS TO PERFORM TWO CLINICAL TRIALS TO FIRST TEST WHETHER E-OPRA PROVIDES BETTER FUNCTION AND COMFORT THAN OPRA, AND SECOND TO FIND OUT WHETHER E-OPRA IS BETTER WITH OR WITHOUT SENSORY FEEDBACK. OUR RATIONALE IS THAT DIRECTLY ATTACHING THE PROSTHESIS TO THE SKELETON HAS MANY ADVANTAGES OVER USE OF A SOCKET, THAT IMPLANTED ELECTRODES WILL PROVIDE CLEANER, MORE STABLE AND RELIABLE EMG SIGNALS THAN ELECTRODES AT THE SKIN SURFACE, AND THAT SENSORY FEEDBACK WILL HELP THE USER CONTROL THEIR DEVICE. WE THEREFORE EXPECT THAT THE E-OPRA SYSTEM WITH SENSORY FEEDBACK WILL PROVIDE IMPROVED PROSTHESIS CONTROL AND FUNCTION COMPARED TO CONVENTIONAL SOCKET-BASED SYSTEMS OR OI WITHOUT SENSORY FEEDBACK.

RRTC ON DEVELOPING OPTIMAL STRATEGIES IN EXERCISE AND SURVIVAL SKILLS TO INCREASE HEALTH AND FUNCTION

REHABILITATION RESEARCH AND TRAINING CENTERS

CRITICAL TIME WINDOW FOR REHABILITATION AFTER INCOMPLETE SPINAL CORD INJURY: EARLY VS LATE LOCOMOTOR TRAINING

REHABILITATION RESEARCH AND TRAINING CENTERS

REHABILITATION ENGINEERING RESEARCH CENTERS: TIMING INVESTIGATION DOSAGE IMPLEMENTATION (TIDI)

REHABILITATION ENGINEERING RESEARCH CENTERS: TECHNOLOGIES TO EVALUATE AND ADVANCE MOBILITY AND MANIPULATION (TEAMM) RERC

FROM NEURAL CONTROL OF MOVEMENT TO TREATMENTS FOR SPINAL CORD INJURY - PROJECT SUMMARY/ABSTRACT OVER THE LAST 15 YEARS, OUR NINDS-FUNDED RESEARCH HAS FOCUSED ON UNDERSTANDING TRANSMISSION IN DESCENDING MOTOR PATHWAYS AND SPINAL CORD NETWORKS DURING MOTOR BEHAVIORS IN HUMANS WITH AND WITHOUT SPINAL CORD INJURY (SCI), WITH THE LONG-TERM GOAL OF MAXIMIZING THE ACTIVITY OF SPARED PATHWAY CONNECTIONS TO ENHANCE RECOVERY POTENTIAL. OUR STUDIES REVEALED THAT IN PEOPLE WITH SCI, CORTICOSPINAL AND RETICULOSPINAL SYSTEMS CONTRIBUTE DIFFERENTIALLY TO MUSCLE WEAKNESS AND FUNCTIONALLY RELEVANT BEHAVIORS, SUCH AS FINE AND GROSS GRASPING MANIPULATIONS, COMPARED WITH CONTROL SUBJECTS. IMBALANCED CONTRIBUTIONS FROM THESE DESCENDING MOTOR SYSTEMS WERE FOUND WHEN SPASTICITY AND MUSCLE SPASMS WERE PRESENT, PROVIDING LIGHT FOR THE MECHANISMS OF HYPERREFLEXIA FOLLOWING SCI. MOTONEURON RESPONSIVENESS TO CORTICOSPINAL, RETICULOSPINAL, AND AFFERENT INPUT DECREASED IN A TASK- DEPENDENT MANNER. OUR RESEARCH GROUP PIONEERED THE USE OF SPIKE-TIMING DEPENDENT PLASTICITY IN THE CORTICOSPINAL PATHWAY, FROM BASIC PROOF-OF-PRINCIPLE STUDIES ON HEBBIAN PLASTICITY TO RANDOMIZED PLACEBO CONTROLLED CLINICAL TRIALS SHOWING THAT PLASTICITY AT CORTICOSPINAL-MOTONEURONAL SYNAPSES IMPROVES EXERCISE- MEDIATED RECOVERY AFTER CHRONIC INCOMPLETE SCI. IN THIS APPLICATION, WE REQUEST TO CONSOLIDATE TWO ONGOING NINDS-FUNDED PROPOSALS THAT FOCUS ON THE CONTROL OF VOLUNTARY MOVEMENT (R01NS090622) AND SPASTICITY AND MUSCLE SPASMS (R01NS100810). WE WILL LEVERAGE OUR EXISTING KNOWLEDGE TO PRODUCE NEW RESEARCH THAT CHALLENGES THE EXISTING PARADIGM BY INTEGRATING INFORMATION ACROSS RESIDUAL NETWORKS IN THE SUBACUTE AND CHRONIC PHASES OF SCI AND FOCUSES ON UNDERSTANDING: A) TRANSMISSION IN A WIDESPREAD SET OF SPARED DESCENDING MOTOR PATHWAYS AND SPINAL CIRCUITS, B) HYPERREFLEXIA IN THESE SPARED SYSTEMS, AND C) NEUROPLASTICITY-BASED THERAPIES. OUR RESEARCH PROTOCOL WILL BUILD ON OUR PAST SUCCESSES USING CUTTING-EDGE NEUROPHYSIOLOGICAL, NEUROIMAGING, AND BEHAVIORAL TOOLS. WE WILL EMPLOY MORE ADVANCED SPINAL CORD IMAGING METHODOLOGIES, HIGH-DENSITY SURFACE ELECTROMYOGRAPHY RECORDINGS, AND NEW PHYSIOLOGICAL EXAMINATIONS USING MULTIDIMENSIONAL BEHAVIORAL TOOLS TO ENHANCE OUR UNDERSTANDING OF RESIDUAL CONNECTIONS IN HUMANS WITH SUBACUTE AND CHRONIC SCI. SUCCESSFUL COMPLETION OF THIS RESEARCH WILL INCREASE OUR UNDERSTANDING OF THE NEURAL CONTROL OF MOVEMENT AND SYMPTOMS, INCLUDING SPASTICITY AND MUSCLE SPASMS, IN OTHER NEUROLOGICAL DISORDERS (I.E., STROKE, MULTIPLE SCLEROSIS, AND ALS). THIS RESEARCH ALSO MAY PROVIDE NEW AVENUES FOR TREATMENTS AND ASSESSMENT OF HUMANS WITH SCI AND OTHER NEUROLOGICAL DISORDERS.

CLINICAL TRIALS OF PATTERN RECOGNITION, ELECTRODE GRID, RIC ARM IN TMR

LOCOMOTOR FUNCTION FOLLOWING TRANSCUTANEOUS ELECTRICAL SPINAL CORD STIMULATION IN INDIVIDUALS WITH HEMIPLEGIC STROKE - PROJECT ABSTRACT APPROXIMATELY 70% OF THE MORE THAN 7.2 MILLION U.S. STROKE SURVIVORS EXPERIENCE PERSISTENT GAIT DEFICITS, INCLUDING REDUCED WALKING SPEED, ASYMMETRICAL WALKING PATTERNS, AND REDUCED LOWER LIMB COORDINATION, WHICH LIMIT THEIR CAPACITY FOR COMMUNITY AMBULATION. CURRENT REHABILITATION APPROACHES ARE BASED ON THE ASSUMPTION THAT STROKE IMPAIRS MOTOR CORTEX FUNCTION WHILE THE SPINAL CORD IS PRESERVED AND THUS FOCUS ON STIMULATING THE IPSILATERAL OR CONTRALATERAL MOTOR CORTEX DURING GAIT TRAINING TO ACTIVATE DORMANT OR NEW PATHWAYS. ALTHOUGH ANIMAL MODELS OF STROKE REVEAL SECONDARY DEGENERATION OF THE CERVICAL AND LUMBAR SPINAL CORD, SUGGESTING THAT DAMAGE TO THE SPINAL CORD MAY EFFECT FUNCTIONAL RECOVERY, LITTLE OR NO RESEARCH HAS BEEN DONE TO ELUCIDATE SPINAL CORD CHANGES IN HUMANS AFTER STROKE. OUR OBJECTIVE IS TO EVALUATE THE EFFECTS OF SPINAL STIMULATION COMBINED WITH GAIT TRAINING AFTER STROKE AND TO INVESTIGATE MECHANISMS UNDERLYING THESE EFFECTS. IN PRELIMINARY WORK, WE MEASURED SPINALLY EVOKED MOTOR POTENTIALS (SEMPS) GENERATED BY NON-INVASIVE, TRANSCUTANEOUS ELECTRICAL SPINAL STIMULATION IN 10 STROKE SURVIVORS, 10 AGE-MATCHED HEALTHY CONTROLS, AND 10 YOUNG HEALTHY SUBJECTS. STIMULATION THRESHOLDS WERE SIGNIFICANTLY HIGHER IN STROKE SURVIVORS THAN IN CONTROLS AND LATENCY WAS SIGNIFICANTLY DELAYED IN THE PARETIC SIDE COMPARED TO THE NON-PARETIC SIDE, INDICATING SECONDARY EFFECTS OF STROKE ON DOWNSTREAM SPINAL CIRCUITRY AND DESCENDING PATHWAYS. WE ALSO SHOWED THAT SPINAL STIMULATION + SYMMETRY-FOCUSED GAIT TRAINING (N=4) COMPARED TO GAIT TRAINING ALONE (N=4), SIGNIFICANTLY IMPROVED STEP-LENGTH SYMMETRY, WALKING SPEED (10-METER WALK TEST, 10MWT), AND WALKING ENDURANCE (6-MINUTE WALK TEST, 6MWT); THESE IMPROVEMENTS EXCEEDED THE MINIMAL CLINICALLY IMPORTANT DIFFERENCE FOR CHRONIC STROKE. THESE RESULTS SUPPORT OUR HYPOTHESIS THAT SPINAL STIMULATION MAY INCREASE GAIT TRAINING EFFICACY. IN AIM 1, WE WILL EVALUATE THE SHORT-TERM EFFECTS OF SPINAL STIMULATION AND SHAM STIMULATION, WITH OR WITHOUT SYMMETRY-FOCUSED GAIT TRAINING, ON GAIT FUNCTION (PRIMARY OUTCOME: STEP-LENGTH SYMMETRY) AND CORTICOSPINAL CIRCUITRY IN 25 STROKE SURVIVORS. IN AIM 2, WE WILL CONDUCT A RANDOMIZED CLINICAL TRIAL TO EVALUATE THE LONG-TERM EFFECTS OF SYMMETRY-FOCUSED GAIT TRAINING WITH STIM OR SHAM STIMULATION IN STROKE SURVIVORS (N=25 PER GROUP). THE PRIMARY OUTCOME WILL BE STEP-LENGTH SYMMETRY; SECONDARY OUTCOMES INCLUDE TEMPORAL GAIT SYMMETRY, SPEED (10MWT), MUSCLE ACTIVATION (ELECTROMYOGRAPHY), WALKING ENDURANCE (6MWT), ENERGY EXPENDITURE (COSMED K4B2), UPPER AND LOWER LIMB FUNCTION (FUGL-MEYER ASSESSMENT), HEALTH STATUS (STROKE IMPACT SCALE-16), AND COMMUNITY ACTIVITY (WEARABLE SENSORS, ACTIGRAPH LLC). WE WILL ALSO INVESTIGATE MECHANISMS UNDERLYING THE EFFECTS OF SPINAL STIMULATION BY EXAMINING SEMPS ELICITED IN LOWER LIMB MUSCLES BY CORTICAL/SUBCORTICAL STIMULATION OF CORTICOSPINAL AXONS AND INTRACORTICAL INHIBITION. THIS WORK WILL (I) IDENTIFY SHORT- AND LONG-TERM EFFECTS OF SPINAL STIMULATION, (II) VALIDATE SPINAL STIMULATION AS A NON-INVASIVE METHOD TO RESTORE GAIT IN CHRONIC STROKE, (III) IDENTIFY CLINICAL MEASURES THAT MAY DETERMINE RESPONSE TO SPINAL STIMULATION, AND (IV) IDENTIFY UNDERLYING NEUROMODULATORY MECHANISMS, WHICH MAY PROVIDE ADDITIONAL TREATMENT OPTIONS.

DEFINING TRAJECTORIES OF LINGUISTIC, COGNITIVE-COMMUNICATIVE AND QUALITY OF LIFE OUTCOMES IN APHASIA

CPS: LARGE: CYBERNETIC INTERFACES FOR THE RESTORATION OF HUMAN MOVEMENT THROUGH FUNCTIONAL ELECTRICAL STIMULATION

INTERNATIONAL EXPLORATION OF REHABILITATION LENGTH OF STAY FOLLOWING SPINAL CORD INJURY

MODULATING STIMULUS INTENSITY TO IMPROVE CLINICAL OUTCOMES IN APHASIA TREATMENT

REHABILITATION ENGINEERING RESEARCH CENTERS: MACHINES ASSISTING RECOVERY FROM STROKE AND SPINAL CORD INJURY FOR REINTEGRATION INTO SOCIETY (MARS3)

REAL-TIME CONTROL OF A POWERED PROSTHETIC LEG USING INTRAMUSCULAR EMG SIGNALS. NEW AWARD.

APHASIA REHABILITATION: MODULATING CUES, FEEDBACK & PRACTICE

EFFECT OF A NOVEL INTERVENTION USING DAILY INTERMITTENT HYPOXIA AND HIGH-INTENSITY TRAINING ON UPPER-LIMB FUNCTION IN INDIVIDUALS WITH SPINAL CORD IN

THE FUNCTIONAL IMPORTANCE OF POWERED WRIST FLEXION/EXTENSION AND SIMULTANEOUS CONTROL FOR UPPER LIMB PROSTHESES

NATIONAL INSTITUTE ON DISABILITY AND REHABILITATION RESEARCH - SPINAL CORD INJURY MODEL DEMONSTRATIONS

NATIONAL INSTITUTE ON DISABILITY AND REHABILITATION RESEARCH - REHABILITATION RESEARCH AND TRAINING CENTERS

UNDERSTANDING HOW POWERED COMPONENTRY IMPACTS K2-LEVEL TRANSFEMORAL AMPUTEE GAIT - PROJECT SUMMARY POWERED PROSTHETIC KNEE AND ANKLE JOINTS CAN ACTIVELY GENERATE TORQUE, POTENTIALLY ENABLING SAFE AND EFFICIENT PERFORMANCE OF MORE DEMANDING MOBILITY TASKS, SUCH AS ASCENDING RAMPS AND STAIRS OR PERFORMING SIT-TO-STAND TRANSITIONS, AND IMPROVING ENERGY EFFICIENCY. HOWEVER, AVAILABLE POWERED COMPONENTS HAVE BEEN ALMOST EXCLUSIVELY DEVELOPED FOR AND TESTED BY INDIVIDUALS AMBULATING AT MEDICARE FUNCTIONAL CLASSIFICATION LEVEL (MFCL) K3-OR K4. INDIVIDUALS DESIGNATED AS K2-LEVEL AMBULATORS (I.E., HAVE A MORE LIMITED AMBULATION CAPACITY) ARE TYPICALLY PRESCRIBED A PASSIVE PROSTHESIS, BUT THESE INDIVIDUALS HAVE BEEN SHOWN TO BENEFIT FROM MORE ADVANCED MICROPROCESSOR-CONTROLLED KNEES AND MAY GAIN ADDITIONAL BENEFIT FROM POWERED COMPONENTS. BECAUSE AVAILABLE POWERED COMPONENTS ARE HEAVY, WE DEVELOPED LIGHTWEIGHT, FULLY POWERED KNEE AND ANKLE COMPONENTS THAT CAN BE USED SEPARATELY OR TOGETHER AND ARE APPROPRIATE FOR K2-LEVEL AMBULATORS. THESE DEVICES WILL ALLOW US TO EVALUATE THE BENEFITS ASSOCIATED WITH PROVIDING POWER AT THE KNEE, ANKLE, OR KNEE AND ANKLE, AND THE TRADEOFFS ASSOCIATED WITH THE ADDITIONAL WEIGHT AND CONTROL COMPLEXITY OF ONE OR MORE POWERED COMPONENTS. OUR GOAL IS TO DETERMINE HOW POWERED PROSTHETIC COMPONENTS EFFECT FUNCTION—IN TERMS OF METABOLIC COST, GAIT BIOMECHANICS, AND FUNCTIONAL MOBILITY IN K2-LEVEL AMBULATORS WITH A UNILATERAL TRANSFEMORAL AMPUTATION, WHO USE A PRESCRIBED PASSIVE PROSTHESIS. WE WILL RECRUIT 20 INDIVIDUALS, WHO WILL PARTICIPATE IN THREE AIMS, WITH THE EXPECTATION THAT 15 WILL COMPLETE THE STUDY. FOR AIM 1, SUBJECTS WILL BE FIT FIRST WITH A FULLY PASSIVE DEVICE (OTTOBOCK C-LEG 4 MPK AND A TRITON 1C60 FOOT) AND THEN TO OUR FULLY POWERED DEVICE (KNEE-+ ANKLE PROSTHESIS). THEY WILL BE TRAINED TO USE EACH DEVICE BEFORE COMPLETING THE AMPUTEE MOBILITY PREDICTOR WITH PROSTHESIS (AMPPRO) (PRIMARY OUTCOME) AS WELL AS METABOLIC AND BIOMECHANICAL ASSESSMENTS, A SET OF STANDARD OUTCOME MEASURES, AND SELF-REPORT SURVEYS (SECONDARY OUTCOMES). FOR AIM 2, WE WILL EVALUATE COMBINATIONS OF POWERED KNEE + PASSIVE ANKLE AND PASSIVE KNEE + POWERED ANKLE, IN RANDOM ORDER. SUBJECTS WILL BE TRAINED TO USE EACH DEVICE, AND THE SAME PRIMARY AND SECONDARY OUTCOME MEASURES WILL BE PERFORMED TO ASSESS FUNCTIONAL BENEFITS AND THE EFFECTS OF ADDITIONAL WEIGHT AT THE KNEE OR ANKLE. IN AIM 3, WE WILL PROVIDE INTENSIVE TRAINING TO ENABLE SUBJECTS TO INDEPENDENTLY PERFORM TYPICAL ACTIVITIES OF DAILY LIVING AND ACHIEVE PERSONAL MOBILITY GOALS USING THE POWERED KNEE + ANKLE DEVICE, TO DETERMINE WHAT LEVEL OF IMPROVEMENT K2- LEVEL AMBULATORS CAN ATTAIN. SUBJECTS WILL AGAIN COMPLETE THE SAME PRIMARY AND SECONDARY OUTCOME MEASURES USING THE POWERED DEVICE AND WILL REPEAT THESE MEASURES USING THE PASSIVE DEVICE FROM AIM 1, TO ACCOMMODATE CARRYOVER OF TRAINING EFFECTS FROM PREVIOUS AIMS. THE ANTICIPATED OUTCOME IS AN UNDERSTANDING OF HOW POWER AND THE WEIGHT OF PROSTHETIC COMPONENTS AFFECT FUNCTION IN K2-LEVEL AMBULATORS, WHICH WILL ENABLE OPTIMAL SELECTION OF COMPONENTS TO IMPROVE FUNCTIONAL MOBILITY IN INDIVIDUALS WHO ARE DESIGNATED AS LIMITED COMMUNITY AMBULATORS AND CURRENTLY RESTRICTED TO PASSIVE DEVICES.

TARGETED REINNERVATION AND PATTERN-RECOGNITION CONTROL FOR TRANSRADIAL AMPUTEES

MIDWEST REGIONAL SPINAL CORD INJURY CARE SYSTEM

PERSONALIZED MOBILITY INTERVENTIONS USING SMART SENSOR RESOURCES FOR LOWER-LIMB PROSTHESES USERS

THE MIDWEST REGIONAL SPINAL CORD INJURY MODEL SYSTEM

IMPROVING AGED NEUROMUSCULAR HEALTH AND FUNCTION - PROJECT SUMMARY LOSS OF NEUROMUSCULAR FUNCTION AND REGENERATIVE CAPACITY IS A HALLMARK OF AGING; HOWEVER, THE CAUSE OF THIS AGE- RELATED DECLINE AND THE MOLECULAR PATHWAYS UNDERLYING THIS PROCESS REMAIN UNKNOWN AND NO CLINICAL INTERVENTION SUCCESSFULLY ARRESTS AGE-RELATED NEUROMUSCULAR DYSFUNCTION. THE LONG-TERM OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP AN EFFECTIVE STEM CELL-MEDIATED THERAPY TO AMELIORATE AGE-RELATED DETERIORATION OF NEUROMUSCULAR FUNCTION. OUR PREVIOUSLY PUBLISHED FINDINGS SHOW THAT TRANSPLANTATION OF OUR UNIQUE ADULT MULTIPOTENT MUSCLE-DERIVED STEM/PROGENITOR CELLS (MDSPCS) FROM YOUNG MICE PROMOTES FUNCTIONAL PERIPHERAL NERVE REGENERATION IN MICE WITH A SCIATIC NERVE DEFECT, DELAYS THE ONSET OF AGING-RELATED DISEASES, AND TRIPLES THE LIFESPAN IN MOUSE MODELS OF PROGERIA. IN ADDITION, INDUCED NEOVASCULARIZATION IN THE MUSCLES AND BRAIN—WHERE NO TRANSPLANTED CELLS WERE DETECTED—STRONGLY SUGGESTS A THERAPEUTIC PARACRINE/ENDOCRINE MECHANISM. MOST IMPORTANTLY, OUR RECENT PRELIMINARY RESULTS INDICATE THAT SYSTEMIC TRANSPLANTATION OF YOUNG MDSPCS INTO NATURALLY AGED MICE RESTORES PERIPHERAL NERVE HISTOLOGY AND MYELINATION, INCREASES SKELETAL MUSCLE WEIGHT AND FIBER CROSS-SECTIONAL AREA, DECREASES MUSCLE FIBROSIS, AND IMPROVES FUNCTIONAL MOBILITY AND GAIT. THESE NOVEL FINDINGS STRONGLY SUGGEST THAT YOUNG MDSPCS CAN MODULATE THE SYSTEMIC ENVIRONMENT OF AGED ANIMALS THROUGH SECRETED REJUVENATING FACTORS THAT ACTIVATE OR INHIBIT KEY MOLECULAR SIGNALING PATHWAYS CRITICAL FOR TISSUE REGENERATION. THUS, WE HYPOTHESIZE THAT YOUNG STEM CELLS—OR THE THERAPEUTIC FACTORS THEY SECRETE—CAN BE USED TO TREAT CHRONIC AGING-RELATED NEUROMUSCULAR IMPAIRMENTS. IN AIM 1, WE WILL DETERMINE TO WHAT EXTENT SYSTEMIC TREATMENT WITH YOUNG MDSPCS CAN REJUVENATE NEUROMUSCULAR TISSUE STRUCTURE AND MOTOR FUNCTION IN NATURALLY AGED MICE BY USING CLINICALLY RELEVANT TECHNIQUES SUCH AS REAL-TIME RESONANT REFLECTION SPECTROSCOPY (RRS), MUSCLE CONTRACTILE FORCE MEASUREMENT, NERVE CONDUCTION TESTING, AND LONGITUDINAL MOTOR FUNCTION TESTING OF MOBILITY, GAIT, AND MUSCLE FATIGUE. IN AIM 2, WE WILL IDENTIFY THE UNDERLYING MOLECULAR MECHANISM(S) OF NEUROMUSCULAR FUNCTIONAL IMPROVEMENTS RESULTING FROM TRANSPLANTATION OF YOUNG MDSPCS, USING MULTIPLEXING-TANDEM MASS SPECTROMETRY AND [PHOSPHOPROTEOMICS], AS WELL AS IDENTIFY PROTEINS CIRCULATING IN THE BLOOD SERUM INVOLVED IN THIS SYSTEMIC REJUVENATION. AIM 3 WILL UNCOVER KEY FACTORS SECRETED BY YOUNG MDSPCS THAT DRIVE NEUROMUSCULAR TISSUE REJUVENATION AND IMPROVE FUNCTION USING A QUANTITATIVE MULTIPLEX ANTIBODY ARRAY SYSTEM. TOGETHER, THESE AIMS WILL UNCOVER THE MECHANISMS OF YOUNG MDSPC-MEDIATED NEUROMUSCULAR TISSUE REJUVENATION AND FUNCTIONAL IMPROVEMENTS, IDENTIFY CIRCULATING BIOMARKERS THAT PREDICT NEUROMUSCULAR HEALTH IN AGED MAMMALS, AND FACILITATE THE DISCOVERY OF NOVEL STEM CELL–BASED THERAPEUTIC TARGETS FOR CLINICAL USE.

A MULTI-SCALE MODELING CONSTRUCT OF KNEE MECHANICS FOLLOWING ACL RECONSTRUCTION

IMPACT OF POWERED KNEE-ANKLE PROSTHESIS ON EVERYDAY COMMUNITY MOBILITY AND SOCIAL INTERACTION IN INDIVIDUALS WITH TRANSFEMORAL AMPUTATIONS

PREDICTIVE GAIT-BASED BIOMARKERS FOR FALL RISK IN LOWER-LIMB PROSTHESIS USERS - ABSTRACT FALLS ARE THE SECOND LEADING CAUSE OF UNINTENTIONAL DEATH WORLDWIDE AND LOWER LIMB PROSTHESIS USERS (LLPUS) CONSTITUTE AN EXCEPTIONALLY HIGH-RISK GROUP. OVER HALF OF LLPU FALL ANNUALLY WITH MANY FALLS RESULTING IN INJURIES.1 DESPITE THESE ALARMING STATISTICS, CLINICALLY ACCESSIBLE TOOLS FOR PREDICTING FALLS IN LLPU ARE CURRENTLY LACKING. A COMPREHENSIVE FALL PREVENTION RESEARCH PROGRAM SHOULD ADDRESS BARRIERS, SUCH AS POPULATION HETEROGENEITY AND SPECIFICITY OF MEASUREMENTS, AND IDENTIFY MODIFIABLE BIOMECHANICAL RISK FACTORS ACROSS LLPUS SUBGROUPS USING METHODS EASILY TRANSLATABLE INTO CLINICAL USE.4 GAIT ANALYSIS TO AS A SCREENING TOOL FOR FALLS HAS THE POTENTIAL TO SATISFY THESE REQUIREMENTS AND MARKERLESS MOTION CAPTURE MAKES IT POSSIBLE THAT ROUTINE GAIT ANALYSIS COULD BE FEASIBLY INTEGRATED INTO ROUTINE CLINICAL VISITS. THE OVERALL OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP A SENSITIVE AND SPECIFIC FALL SCREENING PROTOCOL FOR LOWER LIMB PROSTHETIC USERS THAT UTILIZES GAIT AND KINEMATIC ANALYSIS FROM MARKERLESS MOTION CAPTURE AND IS APPLIES TO A REPRESENTATIVE POPULATION OF LOWER LIMB PROSTHETIC USERS. WE WILL WORK TOWARDS THIS OBJECTIVE BY EVALUATING FALL RISK PREDICTORS FROM GAIT ANALYSIS AND COMPARING THEIR ACCURACY TO TRADITIONAL PERFORMANCE-BASED CLINICAL ASSESSMENTS. TO DO THIS, WE WILL COLLECT IN CLINIC MARKERLESS MOTION CAPTURE GAIT AND KINEMATIC DATA AS WELL AS COMMON CLINICAL ASSESSMENTS FROM 150 LOWER LIMB PROSTHETIC USERS. WE WILL THEN COLLECT PROSPECTIVE FALL HISTORY FROM THESE INDIVIDUALS FOR 1 YEAR TO DETERMINE THE SUBSET OF GAIT PARAMETERS OR CLINICAL ASSESSMENTS THAT BEST PREDICT AN INDIVIDUAL’S FUTURE FALL RISK. FINALLY, DURING THIS ONE-YEAR COLLECTION PERIOD, WE WILL USE WEARABLE SENSORS TO OBTAIN FURTHER KINEMATIC DATA ON FALL TYPE, DIRECTIONALITY, AND CIRCUMSTANCES TO DEVELOP A MODEL FOR INCIDENT RISK BASED ON FALL TYPE. THE RESULTS FROM THIS STUDY WILL PROVIDE IMPORTANT FINDINGS TO PREDICT FALL RISK FOR A REPRESENTATIVE, HETEROGENEOUS POPULATION OF LOWER LIMB PROSTHETIC USERS. IT WILL DETERMINE WHETHER FALL RISK CAN BE ACCURATELY PREDICTED FROM 3D GAIT ANALYSIS USING MARKERLESS MOTION CAPTURE. IF SUCCESSFUL, OUR PROPOSED WORK WILL PRODUCE A TRANSLATABLE APPROACH FOR SCREENING AT-RISK LOWER LIMB PROSTHETIC USERS AND WILL IDENTIFY BIOMECHANICAL RISK-FACTORS FOR SPECIFIC FALL TYPES. ALL MODELS AND TOOLS FOR THIS STUDY WILL BE MADE OPEN SOURCE IN OUR CONTINUED COMMITMENT TO OPEN ACCESS. FURTHER, WE ANTICIPATE THAT OUR TECHNIQUES MAY GENERALIZE TO OTHER POPULATIONS AT-RISK FOR FALLS, SUCH AS OLDER ADULTS OR STROKE SURVIVORS. ULTIMATELY, WE ENVISION THESE TOOLS BEING INTEGRATED INTO ROUTINE CLINICAL ENCOUNTERS AND A SUBSEQUENT RESEARCH STUDY TESTING WHETHER FALL-PREVENTION INTERVENTIONS INITIATED FROM CLINICAL GAIT ANALYSIS CAN REDUCE THE FREQUENCY OF PREVENTABLE FALLS.

THERAPEUTIC ELECTRICAL STIMULATION USING WIRELESS, RESORBABLE IMPLANTS TO ACCELERATE DIAPHRAGM MUSCLE REINNERVATION AFTER PHRENIC NEUROPATHY - PROJECT ABSTRACT: PHRENIC NEUROPATHY, A CONDITION THAT IMPAIRS DIAPHRAGM MUSCLE FUNCTION, OFTEN LEADS TO SERIOUS RESPIRATORY PROBLEMS AND REQUIRES MECHANICAL VENTILATION. OUR RESEARCH PROPOSAL AIMS TO ENHANCE RECOVERY FROM THIS CONDITION THROUGH A NOVEL THERAPEUTIC ELECTRICAL STIMULATION PROTOCOL, IN CONJUNCTION WITH A CUSTOM-MADE, WIRELESS, BIORESORBABLE IMPLANT. INFORMED BY A RISING INCIDENCE OF PHRENIC NEUROPATHY DUE TO COMPLICATIONS FROM SEVERE COVID-19 AND GREATER DIAGNOSTIC CAPABILITIES AND OTHER FACTORS, THIS PROPOSAL IS THE RESULT OF COLLABORATION AMONG A MULTIDISCIPLINARY TEAM WITH SUBSTANTIAL EXPERTISE IN ALL ASPECTS OF THIS PROPOSED WORK. IN GENERAL, THERE IS A COMMON MISCONCEPTION THAT RECOVERY FROM PERIPHERAL AXON INJURY IS USUALLY GOOD, DUE TO THE FACT THERE IS SOME SPONTANEOUS AXON REGENERATION, BUT THIS DOES NOT MATCH THE REALITY THAT RECOVERY IS ACTUALLY SLOW AND INCOMPLETE FOR APPROXIMATELY 90% OF PATIENTS. THIS IS ALSO TRUE FOR PATIENTS WITH PHRENIC NEUROPATHY. OUR DATA AND OTHERS SHOW THAT 68-96% OF THESE PATIENTS HAVE INCOMPLETE OR NO FUNCTIONAL RECOVERY OF THE DIAPHRAGM MUSCLE. DESPITE VARYING CAUSES OF PHRENIC NEUROPATHY, ITS IMPACT ON RESPIRATORY FUNCTION AND INDIVIDUAL QUALITY OF LIFE IS SIGNIFICANT. AT ITS WORST, PEOPLE WITH PHRENIC NEUROPATHY MAY REQUIRE MECHANICAL VENTILATION, BUT MORE TYPICALLY THEY ARE SEVERELY LIMITED IN THEIR ABILITY TO ENGAGE IN ROUTINE EXERTION REQUIRED FOR ACTIVITIES OF DAILY LIFE. CURRENTLY, CLINICAL AND SURGICAL APPROACHES DO NOT SUFFICIENTLY ADDRESS THE ISSUE OF SLOW AXON REGROWTH. OUR PROJECT AIMS TO RECTIFY THIS BY DEVELOPING A THERAPEUTIC ELECTRICAL STIMULATION PROTOCOL THAT CAN RESTORE DIAPHRAGM MUSCLE INNERVATION AND FUNCTION FASTER AND MORE COMPLETELY THAN EVER BEFORE. BRIEFLY, OUR APPROACH IS FOCUSED ON THREE SPECIFIC AIMS: 1) DETERMINING IF REPEATED THERAPEUTIC ELECTRICAL STIMULATION SESSIONS ARE MORE EFFECTIVE THAN A SINGLE SESSION, 2) ASSESSING IF REPEATED SESSIONS ENHANCE BRAIN-DERIVED NEUROTROPHIC FACTOR-TRKB SIGNALING MORE THAN A SINGLE SESSION OR CONTROL, AND 3) ESTABLISHING HOW ESSENTIAL BRAIN-DERIVED NEUROTROPHIC FACTOR-TRKB SIGNALING IS TO THE EFFECTS OF THERAPEUTIC ELECTRICAL STIMULATION TREATMENT. WE AIM TO DELIVER A NEW THERAPEUTIC ELECTRICAL STIMULATION PARADIGM TO ACCELERATE DIAPHRAGM MUSCLE INNERVATION AND IMPROVE FUNCTIONAL OUTCOMES AFTER PHRENIC NEUROPATHY, PROVIDING NEW INSIGHTS INTO THE UNDERLYING MECHANISM OF HOW BRAIN-DERIVED NEUROTROPHIC FACTOR-TRKB SIGNALING CAN ENHANCE MUSCLE REINNERVATION. THE PRIOR SUCCESS OF CLINICAL TRANSLATION FROM RAT MODEL TO HUMAN CLINICAL TRIALS FOR THERAPEUTIC ELECTRICAL STIMULATION TO TREAT OTHER NERVE INJURIES IMPLIES A GREAT OPPORTUNITY TO MOVE QUICKLY TOWARDS CLINICAL TRANSLATION UPON THE SUCCESSFUL COMPLETION OF THESE AIMS.

BUILDING ADVANCED CEREBRAL PALSY ASSISTIVE CARE SOLUTIONS (BACPACS) - CEREBRAL PALSY (CP) IS THE MOST COMMON CAUSE OF PEDIATRIC DISABILITY IN THE UNITED STATES, AFFECTING 2-3 OF EVERY 1000 CHILDREN. THE GOAL OF OUR FIVE-YEAR RERC IS TO ENHANCE CLINICAL CARE FOR CHILDREN WITH CP BY MAXIMIZING THEIR MOBILITY AND QUALITY OF LIFE THROUGH A COMPREHENSIVE APPROACH EVALUATING THE EFFECTIVENESS OF ASSISTIVE AND THERAPEUTIC TECHNOLOGIES THAT TARGET MUSCLES, NERVES, AND BIOMECHANICS. OUR RERC HAS THREE PRIMARY OBJECTIVES: 1) DEVELOP ASSISTIVE DEVICES THAT ARE SPECIFICALLY DESIGNED FOR CHILDREN, 2) EVALUATE THE EFFECTIVENESS OF NOVEL INTERVENTIONS THAT TO PROMOTE LONG-TERM BENEFITS FOR CHILDREN WITH CP, AND 3) DEVELOP CLINICAL MONITORING AND PREDICTION SYSTEMS TAILORED TO CHILDREN WITH CP THAT CAN INFORM PERSONALIZED THERAPY. THE OUTCOMES OF THIS RERC WILL INCLUDE: 1) PARENTS AND CAREGIVERS HAVING MORE POTENTIAL THERAPEUTIC OPTIONS WHEN SEEKING TREATMENT FOR THEIR CHILDREN, 2) CLINICIANS GAINING ACCESS TO MONITORING AND PREDICTIVE CLINICAL TOOLS THAT CAN GUIDE THEIR DEVELOPMENT OF TREATMENT PLANS ON A MORE INDIVIDUALIZED BASIS, AND 3) CHILDREN WITH CP HAVING ACCESS TO NEW POWERED ASSISTIVE DEVICES THAT CAN BE MODIFIED TO GROW WITH THEM. THE PRODUCTS OF OUR RERC FOR CHILDREN WITH CP WILL BE 1) NOVEL THERAPEUTIC PARADIGMS FOR IMPROVING MOBILITY AND QUALITY OF LIFE, INCLUDING AT-HOME THERAPY DEVICES, NERVOUS SYSTEM STIMULATION, AND PHARMACOLOGICAL TREATMENT–R1, R2; 2) A MACHINE-LEARNING MODEL TO PREDICT A CHILD’S RESPONSIVENESS TO THERAPEUTIC INTERVENTIONS–R3; 3) AN AUTOMATED MONITORING SYSTEM TO EVALUATE THE EFFECTIVENESS OF TREATMENT ON GAIT–D1; AND 4) A POWERED, LOW-COST EXOSKELETON THAT CAN BE EASILY MODIFIED AS A CHILD GROWS TO CONTINUALLY ASSIST THEIR INDEPENDENT MOBILITY–D2.

STRETCH REFLEX CONTRIBUTIONS TO MULTIJOINT COORDINATION

CONSULTATIVE PHYSICAL THERAPY: A PHYSICAL ACTIVITY AND EXERCISE IMPLEMENTATION STRATEGY IN PARKINSON'S - PROJECT SUMMARY/ABSTRACT: EXERCISE IS A SUBSET OF PHYSICAL ACTIVITY THAT IS STRUCTURED AND PLANNED, WITH A GOAL TO INCREASE FITNESS. REGULAR EXERCISE IS ASSOCIATED WITH SLOWER DECLINES IN PARKINSON’S-RELATED MOBILITY OUTCOMES AND QUALITY OF LIFE. HOWEVER, FEWER THAN HALF OF PEOPLE WITH PARKINSON’S DISEASE (PWP) ACHIEVE RECOMMENDED LEVELS OF EXERCISE. EXERCISE BARRIERS INCLUDE LOWKNOWLEDGE AND EXPECTATIONS OF THE BENEFITS, MOBILITY CONCERNS, AND LACK OF TIME OR CONVENIENT EXERCISE OPTIONS. RESEARCH IS NEEDED TO DETERMINE HOW TO FACILITATE EXERCISE INITIATION, PROGRESSION, AND MAINTENANCE IN PWP AND THOSE WITH OTHER DISABILITIES OR CHRONIC CONDITIONS. PHYSICAL THERAPY (PT) IS A HEALTHCARE SERVICE THAT CAN HELP PWP AND OTHER CONDITIONS TO ADDRESS PERSONAL AND ENVIRONMENTAL BARRIERS TO EXERCISE. WE HAVE SUCCESSFULLY PILOTED A CONSULTATIVE PT PROGRAM TO HELP PWP TO INCREASE AND MAINTAIN THEIR EXERCISE AND PHYSICAL FUNCTION. WE DISTINGUISH CONSULTATIVE PT FROM TRADITIONAL PT BY USING FEWER, LESS FREQUENT VISITS. ADDITIONALLY, CONSULTATIVE PT FOCUSES ON EXERCISE PROMOTION IN THE PRESENCE OF MINIMAL OR STABLE FUNCTIONAL DEFICITS, RATHER THAN BRIEF BUT INTENSE EPISODES OF PT FOR FUNCTIONAL GAINS. HOWEVER, REFERRAL TO CONSULTATIVE PT CHALLENGES TRADITIONAL PERCEPTIONS OF PT AS A TREATMENT FOR MOBILITY PROBLEMS. THE PROPOSED EFFECTIVENESS-IMPLEMENTATION HYBRID TYPE II STUDY WILL SYSTEMATICALLY EVALUATE CONSULTATIVE PT IN TWO DISSIMILAR CONTEXTS TO INFORM EFFECTIVE SUSTAINMENT, EQUITABLE SPREAD TO OTHER PARKINSON’S PROGRAMS, AND FUTURE SCALING TO OTHER POPULATIONS THAT CAN BENEFIT FROM EXERCISE MONITORING AND MAINTENANCE. FIRST, WE WILL USE MIXED EFFECTS REGRESSION MODELS TO EVALUATE DIFFERENCES IN 12-MONTH PHYSICAL ACTIVITY TRAJECTORIES BETWEEN INDIVIDUALS ENROLLED DURING PERIODS OF (1) STANDARD CARE, (2) WRITTEN EXERCISE GUIDANCE FROM NEUROLOGISTS, AND (3) CONSULTATIVEPT (AIM1). WE WILL ENROLL 96 PWP PER GROUP. WE HYPOTHESIZE THAT CONSULTATIVE PT WILL HELP PWP IMPROVE AND MAINTAIN EXERCISE PARTICIPATION, CONTROLLING FOR DISEASE-SPECIFIC FACTORS AND SOCIAL DETERMINANTS OF HEALTH. SECOND, WE WILL CONTRAST CONSULTATIVE PT IMPLEMENTATION DETERMINANTS, STRATEGIES, OUTCOMES, AND SUSTAINMENT BETWEEN ORGANIZATIONS IN TWO DISSIMILAR COMMUNITIES (AIM 2). WE WILL STUDY DETERMINANTS AT THE INDIVIDUAL, INTERPERSONAL, ORGANIZATIONAL, AND COMMUNITY LEVELS. WE HYPOTHESIZE THAT FACILITATED IMPLEMENTATION WILL LEAD TO SIMILAR FIDELITY, ADOPTION, ACCEPTABILITY, AND APPROPRIATENESS BETWEEN ORGANIZATIONS, BUT THAT THE LOWER-RESOURCED COMMUNITY WILL EXPERIENCE CHALLENGES TO REACH AND SUSTAINMENT. THIS PROPOSAL IS RESPONSIVE TO THE NATIONAL INSTITUTES OF HEALTH NOTICE OF SPECIAL INTEREST ON DEVELOPING AND TESTING MULTILEVEL PHYSICAL ACTIVITY INTERVENTIONS (NOT-OD-21-087). ADDITIONALLY, THE PROPOSED PROJECT ADDRESSES THE EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE ON CHILD HEALTH AND HUMAN DEVELOPMENT’S RESEARCH THEME TO ADVANCE SAFE AND EFFECTIVE THERAPEUTIC INTERVENTIONS FOR PEOPLE WITH DISABILITIES. TARGETING TWO DISSIMILAR COMMUNITIES WILL FACILITATE THE EQUITY OF THE CURRENT AND FUTURE WORK TO HELP US OPTIMIZE ABILITIES FOR ALL.

ALTERING ACTIVATION PATTERNS IN THE DISTAL UPPER EXTREMITY AFTER STROKE

SAFETY AND EFFICACY OF AMPAKINES FOR IMPROVEMENT OF BLADDER FUNCTION IN INDIVIDUALS WITH SCI.