Funding Awards

During its ten-year lifespan, NC NM4R awarded grant funding in three separate categories.

The Pilot Project Funding Program supported rehabilitation neuroscience research that utilizes neuromodulatory methods/technologies. The funded projects must represent a new direction for the PI and/or an innovative application of neuromodulatory methods/technologies. Our goal was to promote the growth of research in rehabilitation neuroscience that utilizes neuromodulatory techniques and methodologies by providing NM4R research resources and expertise towards the development of potential new projects that will be fundable and sustainable through extramural funding mechanisms. This mechanism funded four extrernal pilot grants per year for up to $37,500 for a 12-month period.

The Collaborative Opportunities Funding Program helped investigators overcome potential barriers in successful pilot data collection for clear, well-designed NM4R studies that have been developed through collaboration between the applicants and the NC NM4R. This program provided immediate funding for groups that had established through collaboration with NM4R investigators a scientifically meritorious, innovative research program needing a small budget for covering operational cost (e.g., subject remuneration, supplies). Operating on a rolling application with no set deadline, this mechanism provided up to $7,500 of short-term (a 6-month period) funding for up to 4 collaborative opportunities proposals per year.

The Joint NC NM4R and AR³T Neuromodulation and Regenerative Rehabilitation Funding Program supported development of novel lines of research that use combined neuromodulatory and regenerative medicine approaches to optimize functional outcomes. These two NIH/NCMRR-funded resource centers collaborated to offer this unique pilot funding opportunity to support researchers in the development of innovative, interdisciplinary research combining neuromodulation and technologies that promote regeneration. One $40,000 grant was awarded in 2021 to Koyal Garg, Ph.D, of Saint Louis University.

Pilot Project Funding Awards

2016-2017 Awards

Jane Joseph, Ph.D.

Medical University of South Carolina, Neurosciences

Learning Enhancement Through NeuroStimulation (LENS)

This project will use tDCS in combination with social skills learning in adolescents with Autism Spectrum Disorder to assess whether neurostimulation enhances social information processing. fMRI scanning will be used pre- and post-intervention to assess whether neurostimulation affects neurocircuitry related to social awareness and social anxiety.

Gerwin Schalk Ph.D.

Wadsworth Center/NYS Department of Health, National Center for Adaptive Neurotechnologies

First Step in Creating a Reflex Conditioning System for Clinical Use

Recent studies indicate that operant conditioning of the soleus H-reflex can improve walking in people with partial spinal cord injuries. Further clinical testing and wide dissemination of this promising new non-invasive therapeutic approach depend on development and validation of a robust clinically practical system that can be used by therapists in the clinic and ultimately by patients in their homes. The goal of this one-year project is to produce and validate a functioning prototype of this system.

Amit Sethi, Ph.D., OTR/L

University of Pittsburgh, Occupational Therapy

Combined Non-Invasive Transcranial Random Noise Current Stimulation and Functional Electrical Stimulation to Improve Hand Movement in Individuals with Moderate-to-Severe Impairments After Chronic Stroke

The current project aims to examine the neural mechanisms associated with change in hand movement in individuals with chronic stroke who receive combined non-invasive transcranial random noise current stimulation and functional electrical stimulation. Individuals will receive a total of 18 treatment sessions, three times a week for 6 weeks. We will examine measures of corticospinal excitability using transcranial magnetic stimulation before and after the treatment to understand the mechanisms influencing the treatment response and identify responders of the treatment.

James Sulzer, Ph.D.

The University of Texas at Austin, Mechanical Engineering

FMRI Operant Conditioning of Fine Motor Skills

After stroke, discoordination often prevents functional hand use, and recent research suggests that improved coordination is associated with specific cortical changes. The goal of this work is to induce these changes via neuromodulation. We will compare and contrast two different methods, rTMS and fMRI neurofeedback, in their ability to restore finger individuation in mildly impaired, chronic stroke patients.

2017-2018 Awards

Cognitive impairments are long-term issues for survivors of moderate-severe traumatic brain injury (TBI). The purpose of this randomized pilot trial is to evaluate the use of tDCS to enhance the effects of a cognitive computer training intervention provided three time per week for four weeks to persons with a history of TBI at least one year post injury. Outcome measures will include changes on neuropsychological measures, functional outcomes, and quality of life outcomes.

Carrie L. Peterson, Ph.D.

Virginia Commonwealth University, Biomedical Engineering

Intermittent Theta Burst Stimulation to Promote Motor Re-education After Upper Limb Reconstruction in Tetraplegia

Upper limb reconstruction is a rehabilitative option for individuals with tetraplegia, which surgically relocates a tendon or nerve of a non-paralyzed muscle to perform the function of or innervate a paralyzed muscle. The long-term goal of our research is to determine whether intermittent theta burst stimulation (iTBS) combined with physical rehabilitation can improve motor re-education after reconstruction. As a first step, the purpose of this project is to determine the effect of iTBS on corticomotor excitability of proximal muscles in non-impaired individuals and two groups of individuals with tetraplegia: individuals with and without upper limb reconstruction.

Gonzalo Revuelta, M.D.

Medical University of South Carolina, Neurology

Resetting Cortical Control in Freezing of Gait

There is growing evidence of increased cortical control of gait when patients with Parkinson's disease exhibit freezing of gait. We have reported that freezing can resolve following periods of immobilization. This project aims to release cortical governance of gait with inhibitory TMS followed by rehabilitation as a potential treatment for this condition.

2018-2019 Awards

Stacey DeJong, Ph.D., PT

University of Iowa, Department of Physical Therapy and Rehabilitation Science

Effects of Operant Up-Conditioning of Motor Evoked Potentials on Corticospinal and Spinal Reflex Excitability in People with Wrist Flexor Hypertonia after Stroke

Paresis after stroke is associated with diminished corticospinal excitability and often results in loss of upper limb function. This study expands the application of operant conditioning by examining whether people with stroke are able to increase wrist flexor motor evoked potentials elicited by transcranial magnetic stimulation. We will quantify the effects of this neuromodulation strategy on cortical representations, spinal reflex excitability, and wrist motor control. Please visit Dr. DeJong's profile page for more information.

Emily J. Fox, Ph.D., DPT, NCS & David. J. Clark, ScD

University of Florida, Department of Physical Therapy and Brooks Rehabilitation and University of Florida, Institute on Aging

Neuromodulation of Spinal Circuits to Enhance Practice-Related Performance on a Complex Walking Task

This study evaluates excitatory neuromodulation of the spinal cord during walking to enhance practice-related gains in performance and retention on an obstacle walking task. If transcutaneous spinal direct current stimulation (tsDCS) shows promise for improving practice effects, this study will provide the necessary data and justification for designing intervention trials that use spinal tsDCS as an adjuvant to walking rehabilitation. The proposed intervention techniques are low cost and translatable to real-world settings, which enhances the potential impact of this work on the well-being of older adults. Please visit Dr. Fox's profile page and Dr. Clark's profile page for more information.

Bernadette Gillick, Ph.D., MSPT, PT

McKnight Land Grant Professor, Department of Rehabilitation Medicine,University of Minnesota Medical School

Comparing Two Montages of Transcranial Direct Current Stimulation in Pediatric Stroke

Neuromodulatory interventions such as tDCS have recently been studied in children with unilateral cerebral palsy to enhance movement function, with many studies applying inhibitory tDCS to the contralesional hemisphere to balance interhemispheric inhibition between hemisphere. However, the optimal tDCS montage to produce changes in cortical excitability has not been thoroughly investigated. Using a single application of tDCS, we will test the effects of two tDCS montages, cathodal contralesional or anodal ipsilesional, on the cortical excitability after-effects. This research will guide future large clinical intervention trials incorporating tailored applications of non-invasive neuromodulation.

Dorothea Jenkins, M.D.

Medical University of South Carolina, Department of Pediatrics and Neonatology

Noninvasive Brain Stimulation to Improve Oromotor Function in Neonates

Preterm infants and term infants who suffer birth asphyxia are at high risk for motor problems, such as learning to take feeds by mouth, and may have to have a gastrostomy tube surgically placed into their stomach to be able to feed well enough to go home. Even after significant brain injury, we know that pairing rehabilitative training and brain stimulation increases neuroplasticity by remodeling motor cortex, leading to improved motor skills. As the first application of brain stimulation technology in human neonates, we will simultaneously deliver transcutaneous auricular vagus nerve stimulation with bottle feeding to boost motor cortical plasticity which may lead to better feeding. Please visit Dr. Jenkins's profile page for more information.

C. Nikki Arrington, Ph.D.

Georgia State University, Department of Psychology, GSU/GT Center for Advanced Brain Imaging

Examining the Effects of Intermittent Theta Burst Stimulation on the Neural Network Associated with Reading in Adult Struggling Readers

Developmental dyslexia (DD) is the most prevalent cause of brain-based reading deficits. This project’s goal is to advance our understanding of the neurobiological foundations of reading in adults with treatment-resistant DD. We will utilize intermittent theta burst stimulation, along with prestimulation neuroimaging, to systematically investigate targeted node engagement of specific regions of the reading network. Please visit the Georgia State/Georgia Tech Center for Advanced Brain Imaging website for more information.

Lisa McTeague, Ph.D.

Medical University of South Carolina, Department of Psychiatry

Neuromodulation and Plasticity in Cognitive Control Neurocircuitry in Chronic Stroke

As a first test of whether repetitive transcranial magnetic stimulation (rTMS) will induce plasticity in the cognitive control network among chronic stroke patients with neurocognitive impairments, we propose to apply excitatory rTMS to the contralesional dorsolateral prefrontal cortex. We also propose to implement a novel high-dose accelerated protocol (i.e., multiple sessions over three days). A typical course of rTMS entails one treatment/day for 4 to 6 weeks, which can be burdensome and reduce adherence. Accelerated protocols have been safe and effective in treating mood disorders. Establishing the safety and feasibility in chronic stroke is an essential short-term goal toward our longer-term goal of determining the optimal dose for enhancing neurocognition. Please visit Dr. McTeague's profile page for more information.

2019-2020 Awards

Evangelia G. Chrysikou, PhD

Drexel University, Psychology

Characterizing the Effects of tDCS Parameter Manipulation on Behavior and Physiology in the Language System

Aphasia is the most common cognitive deficit associated with stroke, affecting approximately 80,000 individuals in the United States annually, many of whom suffer from persistent, debilitating loss of communication abilities. While we and others have identified tDCS as a promising adjunct to traditional language therapies, the advancement of tDCS toward clinical use is hampered by the absence of clear understanding, even in healthy brains, of the relationships between key stimulation parameters and the effects of tDCS on brain activity and behavior. By clarifying these relationships, this study will enhance the fidelity of future tDCS studies for the treatment of aphasia as well as for many other acquired neurological deficits.  Please visit the Chrysikou Lab Page for more information.

Andrea Behrman, PhD

University of Louisville, Kentucky Spinal Cord Injury Research Center

Transcutaneous spinal stimulation: Augmenting training for attaining intrinsic trunk control in children with spinal cord injury
Our long term aim is to develop therapies to improve the ability of children with spinal cord injury to sit upright on their own. Children with paralyzed trunk muscles cannot sit upright and are at significant risk for developing scoliosis (a curved spine), pneumonia, pressure sores, and for undergoing surgery. Achieving the ability to sit upright may thus reduce the risk for scoliosis and surgery, improve a child’s health, reduce healthcare costs and enhance their quality of life.  Please visit The Kosair Charities Center for Pediatric NeuroRecovery for more information.

Nina Suresh, PhD

Shirley Ryan AbilityLab, Research Scientist

Can H-reflex down conditioning reduce spasticity in stroke survivors?
The neural mechanisms that contribute to hyperreflexia in individuals with spasticity following a hemispheric stroke remain largely unknown, and thereby difficult to target with current clinical interventions. Presently the pharmaceutical interventions available to stroke survivors for spasticity reduction also have considerable side effects such as drowsiness and a potential degradation of muscle structure and function. Our hypothesis is that targeted neuromodulation, if effective in reducing spasticity and effectively maintained due to changes at the MN level, would provide an alternative intervention for spasticity reduction in a cohort of stroke survivors with residual corticospinal connections to the targeted muscle, without detrimental side effects.  Please visit Dr. Suresh's page at the Shirley Ryan AbilityLab

Roy Hamilton, MD, M.S.

University of Pennsylvania, Neurology

Personalizing neuromodulation of cognitive control through precision intrinsic system mapping
This proposal takes initial steps toward developing personalized neuromodulation with respect to target selection. PrISM will account for individual variability in structural and functional anatomy, enabling clinicians and researchers to make reliable predictions about the cognitive or behavioral impact of delivering TMS. The system level dissociation between inhibitory and attentional control networks offers an ideal test-case for establishing the utility of our approach. Moreover, cognitive control dysfunction is shared across a number of psychiatric and neurological disorders including depression, schizophrenia, dementias, and stroke, and therefore represents a highly attractive therapeutic target for individualized stimulation.

Pranav J. Parikh, MBBS, PhD

University of Houston, Health and Human Performance

Neuromodulation to Improve Dynamic Balance in Stroke
Balance control is an important factor contributing to falls in stroke survivors. The aims of this proposal are to study the neural network underlying balance control in individuals with stroke using high resolution electroencephalography and determine whether this network can be modulated using theta burst transcranial magnetic stimulation. Our findings could lead to effective neuromodulation strategies and innovative closed-loop BMI-robotics to improve balance control in stroke patients.  Please visit the Parikh Lab page for more information.

Bashar Badran, PhD

Medical University of South Carolina, Psychiatry

taVNS-Paired TMS to Enhance Motor Cortex Excitability
This research proposal is a critical important step in further developing transcutaneous auricular vagus nerve stimulation (taVNS) as an assistive tool in the rehabilitation of motor function post-stroke. This work will help determine whether combining two forms of neuromodulation (rTMS and taVNS) will increase TMS-induced cortical excitability in the motor cortex when compared to single modality approaches. The information gathered from this study will set the stage for the next phase of clinical work with this exciting technology and contribute to a planned R21 submission by the PI further exploring the timing intricacies underlying the mechanism of taVNS-paired rehabilitation.

2020-2021 Awards

Andreana Benitez, Ph.D.

Medical University of South Carolina, Neurology

High-dose Accelerated rTMS to Cognitive Control Neurocircuitry in MCI: A Safety and Feasibility Study

Mild Cognitive Impairment (MCI) is the pre-dementia phase of neurodegenerative disease in which both cognitive decline and neuropsychiatric symptoms begin to impact patient functioning. As there are no established treatments for MCI, our goal in this open-label trial is to establish the safety, feasibility, and preliminary efficacy of high-dose accelerated repetitive transcranial magnetic stimulation for neurocognitive rehabilitation of MCI. These data will form the critical foundation for future randomized controlled trials to devise the optimum rTMS therapeutic delivery (with variations in dosing, targeting, and patient syndrome indications) with the ultimate goal of dementia prevention. Please visit the Benitez Lab page for more information.

Marian Dale, M.D., MCR

Oregon Health and Science University, Neurology

TMS for Modulation of Motor Control in PSP

The goal of this research is to develop effective therapies for debilitating balance impairment in progressive supranuclear palsy (PSP), a parkinsonian disorder with early and severe postural instability. The objective of this proposal is to investigate the effect of non-invasive, repetitive, cerebellar transcranial magnetic stimulation (TMS) on postural instability in PSP, by assessing balance before and after cerebellar TMS treatments and placebo treatments, using objective and sensitive outcomes. If successful, this proof-of-concept study for cerebellar neuromodulation in PSP will lead to better rehabilitation strategies in PSP, and may ultimately change the disease course of parkinsonism by increasing patients’ ability to maintain functional mobility. Please visit Dr. Dale's profile page for more information.

James Sulzer, Ph.D.

University of Texas at Austin, Mechanical Engineering

Simulating Operant Conditioning Performance

Operant H-reflex conditioning has great potential for treatment of reflex disorders without the adverse effects of drugs or surgery. However, we do not understand how operant H-reflex conditioning is processed by patients, risking enormous amounts of time and resources. Here we introduce a principled method of quantifying and eventually predicting the ability to perform operant H-reflex conditioning, resulting in a far more efficient way to improve training. Please visit Dr. Sulzer's profile page for more information.

Lee Fisher, Ph.D.

University of Pittsburgh, Department of Physical Medicine and Rehabilitation

Preventing Episodes of Phantom Limb Pain in Lower Limb Amputees

Phantom limb pain is a debilitating condition that significantly reduces the quality of life of amputees. This work aims to study the mechanisms of phantom limb pain and pinpoint a biomarker that can be used by a device to non-invasively and non-pharmacologically prevent pain. In a time where opioid addiction is ever present, alternative, safe, and effective pain treatments are warranted. Please visit Dr. Fisher's profile page for more information.

Ryan Zarzycki, PT, DPT, Ph.D.

Arcadia University, Physical Therapy

Non-invasive Brain Stimulation to Improve Quadriceps Muscle Function after Anterior Cruciate Ligament Reconstruction

Outcomes following Anterior Cruciate Ligament Reconstruction (ACLR) are not optimal with high reinjury rates (one in four patients) and chronic movement asymmetries associated with post-traumatic knee OA development (up to 74%). Neurostimulation has the potential to improve quadriceps dysfunction via neural mechanisms, mitigate quadriceps dysfunction, and improve outcomes after ACLR. Please visit Dr. Zarzycki's profile page for more information.

2021-2022 Awards

Dorothea Jenkins, M.D.

Medical University of South Carolina

Combining taVNS with early CIMT to improve rehabilitation of infants with Hemiplegia

Brain injury from preterm or complicated term birth increase the risk for one-sided motor weakness, called hemiplegic cerebral palsy (CP). Constraint-induced movement therapy (CIMT) is an intensive intervention designed to treat early motor deficits in these infants, but requires practicing for hours a day over many successive weeks, and is not widely available or feasible in many cases. Our aim in this study is to determine if adding neurostimulation via the transcutaneous auricular vagus nerve (taVNS) is feasible during a short course of CIMT and improves infant motor skills. We anticipate that this first application combining neuromodulation and the proven intervention of CIMT in infants with hemiplegia, will help prove the feasibility of the taVNS technique during CIMT and provide preliminary data for a future trial. Please visit Dr. Jenkins's MUSC Faculty Directory page for more information.

Jinsook Roh, Ph.D.

University of Houston, Biomedical Engineering

Examining the effects of operant conditioning of wrist extensor MEP on arm intermuscular coordination after stroke

Stroke often leads to abnormal intermuscular coordination and impaired motor function of the upper extremity (UE). Operant conditioning of a stimulus-triggered muscle response, which produces targeted plasticity in the targeted pathway and produces wider beneficial plasticity in multiple spinal/supraspinal pathways, could be one of the methods that improve corticospinal excitability and intermuscular coordination in the affected limb after stroke. This project aims to characterize the multiple UE muscles represented within a discrete primary motor cortex, by examining multiple muscle motor evoked potential (MEP) representation for UE muscle synergies post-stroke, and assess the effects of wrist extensor MEP up-conditioning on the impaired muscle synergy and motor function in post-stroke UE. Please visit Dr. Roh's Faculty Directory page for more information.

Ryan Solinsky, M.D.

Spaulding Rehabilitation Hospital, Harvard Medical School

Transcutaneous spinal neuromodulation to normalize autonomic phenotypes after spinal cord injury

Autonomic dysfunction is rampant following spinal cord injury, with significant clinical consequences and few options to improve its function. The goal of this research is to assess if transcutaneous spinal cord stimulation may normalize autonomic neuroregulation for these individuals. Please visit Dr. Solinsky's physician page for more information.

Mary Ellen Stoykov, Ph.D., MS, OTR/L

Shirley Ryan AbilityLab, Feinberg School of Medicine

Functional Connectivity in the Upper Limb for Individuals Post-Stroke

The neuroplastic mechanisms that enable some people with stroke to regain high quality control of their paretic arm post-stroke are unknown. There is broad consensus that the presence or absence of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex is the most useful biomarker to explain treatment response. However, some studies have shown that individuals who are MEP (-) can make clinically meaningful changes in impairment and function. This indicates the need to assess, in detail, the link between MEP (-) status and descending neural connectivity post-stroke. We intend to investigate a biomarker that is cost-effective and that may effectively predict treatment response (e.g., MEPs elicited by direct activation of corticospinal axons). Internationally, there is great interest in the prediction of treatment response post-stroke due to rising medical costs and frustration with minimal improvements in standard of care approaches. Please visit Dr. Stoykov's web page for more information.

Mike Urbin, Ph.D.

Veterans Health Foundation of Pittsburgh, VA Pittsburgh Healthcare System

Therapeutic potential of acute noradrenergic activation via auricular stimulation to support motor retraining after stroke

A monoaminergic surge that coincides with task-relevant events promotes neural plasticity to support learning. Our recent work demonstrates that short trains of electrical current applied to specific anatomical landmarks on the external ear acutely activates noradrenergic mechanisms. The broad objective of this project is to confirm biomarker engagement and test therapeutic potential in individuals with longstanding motor impairment secondary to stroke. Please visit Dr. Urbin's lab page for more information.

2022-2023 Awards

Victor Duenas, Ph.D.  

Syracuse University, College of Engineering and Computer Science, Mechanical and Aerospace Engineering

Operant Conditioning of Loading Response During Locomotion in People After Stroke

Stroke survivors experience low weight-bearing capacity and muscle weakness that impair their walking ability. The ankle joint and soleus muscle are critically important for locomotion, as they
store mechanical energy throughout the stance phase, leading to the burst of plantarflexor power at push-off for propulsion. However, plantarflexor activation and propulsive force are diminished in the paretic leg. By enhancing the excitability of Ib pathways, propulsive soleus activity and resulting force generation can be improved after stroke. The objective of this project is to develop a control strategy to modulate the soleus loading response in the stance phase using a wearable robotic device during treadmill walking. This project characterizes the plantarflexors’ loading response to be exploited as a novel target of neuromodulation through operant conditioning to enhance ankle power and propulsion, which can improve gait function after a stroke.  Please visit the Bionics, Systems and Control Lab page for more information.  

John Kindred, Ph.D.                               

Medical University of South Carolina, College of Health Professions

Effects of tDCS on post-stroke fatigue and inflammation

Fatigue is a common condition after an individual has a stroke. While the negative impacts of post-stroke fatigue are well known, our knowledge of the causes of post-stroke fatigue and effective treatments for post-stroke fatigue are lacking. This pilot study will investigate the possible benefits of transcranial direct current stimulation (tDCS), which uses small electrical currents supplied by a 9-volt battery, to reduce post-stroke fatigue. Previous reports have suggested small electrical currents, like those provided by tDCS, can impact glial cell activity and inflammatory markers. These factors have been suggested to play a role in the development and severity of post-stroke fatigue and fatigue in other neurological conditions.

Thorsten Rudroff, Ph.D.

University of Iowa, Department of Health and Human Physiology, Integrative Neurophysiology Laboratory

tDCS Treatment of Post-COVID-19 Fatigue

For survivors of severe COVID-19, overcoming the virus is just the beginning of an uncharted recovery path. Persistent fatigue following several weeks after COVID-19 infection is common and independent of severity of initial infection (hospitalized and non-hospitalized patients).  There is a critical need to develop inexpensive, effective, safe, and rapid treatments for the persistent fatigue experienced by recovered COVID-19 patients. Without such treatments, these patients will continue to experience fatiguing symptoms that significantly reduce their quality of life. One possible treatment modality is transcranial direct current stimulation (tDCS) which uses weak currents applied to the scalp to alter the excitability of cortical neurons by changing their spontaneous firing rate. The goal of this application is to investigate the short- and long-term effects of multiple sessions of 4 mA M1 tDCS on persistent fatigue in recovered COVID-19 patients. Our central hypothesis is that tDCS will improve fatigue short- and long-term, and thus will improve quality of life in recovered COVID-19 patients. This study will also offer important new information on persistent fatigue resulting from COVID-19 and will help clinicians raise awareness of its involvement as a neurologic manifestation during post-infection recovery. Please visit the Integrative Neurophysiology Laboratory page for more information.

Andrew Quesada Tan, Ph.D.

University of Colorado, Boulder, Integrative Physiology

Examining the relationship between changes in corticospinal excitability and motor learning after acute intermittent hypoxia in persons with incomplete spinal cord injury

Spinal cord injury (SCI) results in sensorimotor deficits, leading to chronic mobility impairments and loss of functional independence. Modest breathing modest bouts of low oxygen (acute intermittent hypoxia; AIH), is a promising intervention shown to enhance motor recovery in persons with spinal cord injury, yet we do not fully understand why AIH augments walking performance. Increases in corticospinal excitability are commonly interpreted as a marker of gains in motor output (e.g., speed) but may not necessarily reflect changes in motor learning and movement energetics after AIH induced plasticity. The objective of this study is to examine if AIH elicits improvements in lower limb control by measuring the capacity to learn a walking adaptation task as well as the ability to modulate metabolic expenditure during the motor learning process. Discerning the behavioral relevance of corticospinal excitability in relation to motor learning and metabolic expenditure may be a key feature in optimizing neurorehabilitation interventions in persons with SCI. Please visit the Sensorimotor Recovery and Neuroplasticity Laboratory page for more information.

Amanda Therrien, Ph.D.

Moss Rehabilitation Research Institute, Albert Einstein Healthcare Network

Motor learning after cerebellar damage: The role of the primary motor cortex

Cerebellar damage causes the disabling movement disorder ataxia, which is characterized by impaired movement coordination affecting all body movements. In the arms, ataxia causes reaching movements with irregular, oscillating, and prolonged trajectory paths. Physical and occupational therapy are the main options for managing ataxia, but current therapy interventions for this disorder are complicated by cerebellar damage impairing an important form of motor learning, called adaptation, which normally keeps movement well calibrated. We have recently shown that PWCA can learn to correct their reaching movements if they instead employ reinforcement learning (RL). Although many PWCA learned optimally in RL conditions, we found variability across individuals: some learned more than others. While adaptation critically relies on cerebellar integrity, RL depends more heavily on excitatory plasticity in the primary motor cortex (M1). Cerebellar damage has been shown to increases inhibitory activity in M1, which may hamper the plasticity needed for RL. The repetitive transcranial magnetic stimulation protocols of continuous and intermittent theta burst stimulation have been shown to modulate inhibition in M1. This study will systematically test whether increased inhibition in M1 predicts RL capacity and whether modulating inhibition in M1 can alter RL capacity in PWCA. The results of this study will determine whether we can predict which PWCA may benefit most from RL interventions and whether we can maximize that benefit with neuromodulation. Please visit the Sensorimotor Learning Laboratory page for more information.

2023-2024 Awards

Deborah Barany, Ph.D.

Assistant Professor, University of Georgia, Kinesiology

The effect of mild traumatic brain injury on corticospinal excitability during complex action preparation

After mild traumatic brain injury (mTBI), incomplete neurobiological recovery may underlie long-term functional deficits, even for people who are considered clinically recovered. Previous research has demonstrated residual motor deficits after mTBI, especially for tasks that require more complex and cognitively demanding action preparation. Yet, the relationship between differences in neural processing and deficits in complex action preparation is unknown. The objective of this study is to investigate the neurophysiology of complex action preparation and its alterations after mTBI. We will use transcranial magnetic stimulation to probe timing-specific changes in corticospinal excitability during an upper-limb reaction time task in healthy young participants and participants with a recent mTBI. We will test how modulation of corticospinal excitability may underlie reaction time differences for planning more complex movements, and whether mTBI affects corticospinal excitability during movement preparation. This work will help clarify the functional relevance of corticospinal excitability modulation for complex action preparation and inform novel rehabilitation approaches for improving functional motor outcomes after neurological injury.  Please visit Brain and Action Lab page for more information.

Parneet Grewal, M.D.

Assistant Professor, Medical University of South Carolina, Department of Neurology

Accelerated rTMS for Post-stroke Apathy: Targeting Amotivation Toward Improving Whole Health and Rehabilitation Engagement

Nearly 40% of chronic stroke patients experience difficulty with motivation, which impedes engagement in rehabilitation as well as daily life. Evidence suggests that the neurocircuitry responsible for loss of motivation after stroke is accessible to non-invasive repetitive transcranial magnetic stimulation. We propose to establish the safety, acceptability/tolerability and feasibility of a novel, personalized, high-dose “accelerated” form of repetitive transcranial magnetic stimulation (rTMS) targeted to the neurocircuit substrates of apathy and amotivation.  Please visit Dr. Grewals's faculty profile page for more information.

Alan Needle, Ph.D.

Associate Professor, Appalachian State University, Public Health and Exercise Science

Training ReActivation from the Cortex to the Knee (TRACK)

Maladaptive neuroplasticity is common following ligamentous injury, such as tears of the knee's anterior cruciate ligament (ACL), potentially contributing to long-term decrements in function and subsequent injury risk. Transcranial direct current stimulation (tDCS) has the potential to improve neural excitability and subsequently function in individuals with ACL injury; however, it's use has largely been aimed at neurologically impaired populations. This study will aim to integrate the fields of neuromodulation and musculoskeletal injury through a clinical trial utilizing tDCS in individuals who have undergone ACL reconstruction. Its success would ultimately provide an intervention capable of restoring typical function in patients with ligamentous injury, thereby addressing a barrier to rehabilitation that contributes to disability and decreases in health-related quality of life.  Please visit Dr. Needle's faculty profile page for more information.

Sharyl Samargia-Grivette, Ph.D., CCC-SLP

Associate Professor, University of Minnesota, Communications Sciences and Disorder    

Combining cerebellar tDCS with CILT in non-fluent aphasia: a novel approach to target discourse.

People who have aphasia after a stroke often have long term problems communicating that have negative impacts on their relationships, work and engagement in the community. The goal of this research is to find new ways of combining speech-language therapy with new technologies to improve communication skills in people who have aphasia.  Please visit the Neural Function and Recovery Lab page for more information.

Marlon Wong, PT, Ph.D.

Associate Professor of Clinical, University of Miami, Physical Therapy

Addressing Disparities in Neuromodulation for Rehabilitation: A Mixed Methods Approach to Optimize Access for Underserved Communities

Improving recruitment of participants from underserved communities in neurostimulation research is critical for us to better understand outcomes with these modalities. Additionally, it is important to recruit and retain participants from populations for whom findings will have the greatest impact. This project will provide the field with culturally sensitive videos to enhance the consent process, and our findings will inform strategies to recruit individuals from underserved communities who are at highest risk for persistent pain conditions yet are traditionally absent from neurostimulation research.  Please visit Dr. Wong's faculty profile page for more information.

2024-2025 Awards

Lorella Battelli, Ph.D.

Associate Professor, Beth Israel Deaconess Medical Center, Harvard Medical School, Cognitive Neurology

Home-Based Non-invasive Brain Stimulation to Boost Vision Recovery in Partial Cortical Blindness in a Virtual Reality Environment.

The proposed study will test, for the first time, the beneficial role of noninvasive transcranial electrical stimulation on vision re-learning in the damaged visual system in a virtual reality environment, that will be available for home use in the future. If successful, this will dramatically change current research and clinical practice in this patient population. This new procedure will be eventually available to a very large population of stroke patients who currently have no accessible and effective treatment for recovery. Please visit Dr. Batelli's faculty profile page to learn more.

Kevin Caulfield, Ph.D.

Assistant Professor, Medical University of South Carolina, Psychiatry

Personalized Bilateral Hippocampal Transcranial Focused Ultrasound for Mild Neurocognitive Disorder

Dementia is an ongoing and growing public health crisis worldwide, with mild neurocognitive disorder (mNCD)representing a critical early symptom juncture where interventions may be particularly impactful. Transcranial focused ultrasound (tFUS) is a form of noninvasive brain stimulation that can activate deep brain structures such as the hippocampus, but its therapeutic effects for memory improvement have not been fully elucidated. This NM4R pilot grant will determine the utility of personalized tFUS in healthy older adults and patients with mNCD, facilitating the development of a future clinical trial applying multisession tFUS with the goal of ultimately preventing dementia.

Siamak Salavatian, Ph.D.

Assistant Professor, University of Pittsburgh, Anesthesiology/Cardiology/Bioengineering

Cardiac Neuromodulation: Closed-loop Multimodal Artificial Intelligence-assisted Neuromodulation to Treat Autonomic Neural Disorder during Heart Failure

This pilot study addresses a pressing public health issue—heart failure, a condition affecting nearly a million people annually, leading to frequent hospitalizations and increased mortality. This limited investigation aims to explore the potential of a sophisticated neuromodulation therapy to treat the disorder in the heart’s nervous system that contributes to heart failure progression and fatal cardiac arrhythmias. While this initial study is only a preliminary step and will not provide a complete solution, it seeks to lay the groundwork for potentially life-saving innovations that could improve heart function and enhance the quality of life for heart failure patients in the future. Please visit Dr. Salavatian's faculty profile page to learn more.

Minoru “Shino” Shinohara, Ph.D.

Associate Professor, Georgia Institute of Technology, Integrative Physiology

Movement-Associated Transcutaneous Vagus Nerve Stimulation and Responsiveness Testing for Personalized Rehabilitation

This project will develop an integrated phone-based control system for movement-associated transcutaneous vagus nerve stimulation (tVNS) and also assess individual neuromodulation responsiveness to brief tVNS. It will seek to pave the way for a non-invasive and effective neuromodulation intervention that can enhance motor recovery in individuals affected by stroke and various neurological disorders, including spinal cord injury. The study will be conducted in the Human Neuromuscular Physiology Laboratory.

Michael Vesia, Ph.D.

Assistant Professor, University of Michigan, School of Kinesiology

Personalizing Multifocal Transcranial Direct Stimulation Dose to Target the Motor Network in Older Adults

The proposed study will establish a mechanistic basis for future research to determine the optimal positioning and current output of multifocal HD-tDCS electrodes, using biological variables to target a spatially distributed grasping network and improve motor function. Please visit University of Michigan's Brain Behavior Lab page to learn more.b2lab.org.

Collaborative Opportunities Funding Awards

2018 Award

James Sulzer, Ph.D.

The University of Texas at Austin, Mechanical Engineering

Can RF H-reflex be operantly conditioned?

The long-term goal of this research is to alleviate hyperreflexia of the rectus femoris (RF) in people with Stiff-Knee gait (SKG) following stroke. Operant H-reflex conditioning is a promising remedy for hyperreflexia since it is believed to modulate the supposed cause of hyperreflexia, presynaptic inhibition of Ia afferents. However, there are currently no published studies showing whether operant RF H-reflex conditioning is possible. We hypothesize that healthy individuals can down-regulate RF H-reflex activation compared to baseline performance in a standing posture. We plan to publish the results of this full experiment in a journal publication and use it as pilot data for an upcoming R21 resubmission on application of RF H-reflex down-conditioning to stroke patients with SKG. 

2019 Award

Ellyn Riley, Ph.D. CCC-SLP

Syracuse University, Communication Sciences & Disorders

Improving Aphasia Outcomes through tDCS-mediated Attention Management The objective of this project is to determine if tDCS to DLPFC will result in better language recovery. A pilot study using this approach with 11 unimpaired controls showed greater than chance accuracy on a grammaticality judgment task for active tDCS but not sham. See Artificial grammar learning with transcranial direct current stimulation (tDCS): A pilot study for further information. This project aims to test this approach in persons with aphasia.

2022 Award

Jing Nong Liang, PT, Ph.D.

University of Nevada, Physical Therapy

Operant Conditioning of Reciprocal Inhibition on Ankle Plantarflexors in People After Stroke

The central hypothesis of our current research is that restoring RI via operant conditioning can improve walking post-stroke. Specifically, we hypothesize that up-conditioning RI on plantarflexors can improve ankle motion during walking, thus improving stroke-impaired gait. Towards examining that, this pilot project aims to obtain the preliminary data demonstrating the feasibility of RI-conditioning and time course of RI changes over the course of up-conditioning. We will also obtain preliminary data assessing functional impacts of RI-conditioning on stroke-impaired gait.

Operant conditioning of RI has been shown to be feasible in rodents, but has not been examined in people with impaired RI due to stroke. By providing the initial results of RI conditioning in people post-stroke, this pilot study will help us develop the RI conditioning protocol for improving stroke-impaired gait. Results of this study are expected to greatly strengthen our planned NIH R03 and/or R21 application on improving post-stroke gait through up-conditioning of reciprocal inhibition.

2023 Award

Jinsook Roh, Ph.D.

University of Houston, Biomedical Engineering

Effects of MEP up-conditioning on the impaired muscle synergy in upper extremity of people after stroke

Dr. Roh’s group designed and developed the wrist force measurement device system to assess how muscle synergies function during 2- and 3-D wrist rotation force generation. The device system had been finalized and tested at Dr. Roh’s lab at University of Houston. Now it is ready to be used for characterizing impaired upper extremity (UE) muscle synergies and how they may change after a successful neuromodulation intervention improves UE motor function in stroke survivors.

The goal is to develop a collaborative R01, R21, or a similar scale grant application to examine UE muscle synergies as potential mechanisms of impaired motor performance and coordination, and how induction of targeted neuroplasticity in the key corticospinal pathway may change impaired muscle synergy characteristics. To work towards this goal, we have planned the following collaborative activities; (1) MEP conditioning will be administered in several stroke survivors at the MUSC EPOC lab; (2) muscle synergy assessments will be administered at the MUSC EPOC lab by trained personnel from Dr. Roh’s lab; (3) muscle synergy analysis will be performed at Dr. Roh’s lab; (4) and study findings will be disseminated by the two groups.

Joint NC NM4R and AR³T Neuromodulation and Regenerative Rehabilitation Funding Awards

2021 Award

Koyal Garg, Ph.D.

Assistant Professor of Biomedical Engineering at Saint Louis University

Combined Application of Regenerative and Rehabilitative Therapies to Enhance Muscle Mass and Function Following Volumetric Muscle Loss

Traumatic injuries such as volumetric muscle loss (VML) can dysregulate regenerative responses, causing impaired function and permanent disability. This proposal will integrate previously optimized regenerative and rehabilitative technologies to accelerate functional recovery of muscle tissue following trauma. Readily translatable technologies being investigated in this proposal could significantly improve the quality of life in VML injured patients.