Past Projects
- Independent Replication of Motor Cortex and Cervical Spinal Cord Electrical Stimulation to Promote Forelimb Motor Function After Spinal Cord Injury in Rats
This study addressed the clinical challenge of cervical spinal cord injury (SCI), a condition where most patients retain residual corticospinal tract connections that can be targeted for functional recovery. The primary objective was to independently validate a paired cortex and spinal cord stimulation protocol, originally developed in the Martin Laboratory, to establish a foundation for translating the therapy to human use. The methodology employed a combined paradigm of intermittent theta burst stimulation (iTBS) to the cortex, serving as a translational mimic of repetitive transcranial magnetic stimulation and non-invasive transcutaneous direct current stimulation to the spinal cord.
The results demonstrated that spinal cord-injured animals receiving this paired stimulation performed significantly better on behavioral tasks challenging forelimb function compared to those receiving sham treatments. Furthermore, histological evidence showed increased axonal sprouting below the lesion site in the stimulation group, confirming enhanced structural plasticity. By replicating these findings with a large effect size in an independent laboratory, this project validated the robustness of the approach and earned strong endorsement from the SCI clinical and research community. This study provided the necessary evidence to move the protocol into trials with larger animal models before eventual human application.
Support: NYS Department of Health Spinal Cord Injury Board C31291GG - (JHM)
Relevant Publication
- Paired Motor Cortex and Cervical Spinal Cord Stimulation to Corticospinal Tract Connections and Functional Recovery After Spinal Cord Injury
This research addressed the physiological basis of paralysis following spinal cord injury (SCI), which often results from damage to the corticospinal tract (CST). This is the primary pathway connecting the motor cortex to the spinal cord. Because a portion of the CST is frequently spared even in cases of severe paralysis, these remaining fibers provided a critical anatomical substrate for therapeutic intervention. While independent electrical stimulation of either the brain or the spinal cord had previously shown efficacy in improving motor function, this project investigated the hypothesis that paired stimulation could amplify these effects by simultaneously strengthening cortical signals and increasing spinal cord sensitivity.
To test this, the researchers developed a novel, inert, and pliable electrode array designed for safe and effective neural stimulation. In experimental rat models of CST damage, the electrodes were tested to define optimal locations and parameters for neural pairing. Results demonstrated that pairing epidural motor cortex stimulation with epidural cervical spinal cord stimulation resulted in superior potentiation of the forelimb muscle responses compared to either stimulation site used alone or other control conditions. Notably, the study found that repeating this paired protocol led to persistent potentiation of CST responses that remained after the stimulation ended.
The project concluded that this induced plasticity occurred at the level of the spinal cord, confirming the potential of paired stimulation as a robust mechanism for neural reorganization. By defining these effective parameters, the study advanced the therapeutic potential of neuromodulation and laid the groundwork for the Spinal Cord Associated Plasticity (SCAP) Protocol for enabling functional recovery in individuals living with paralysis due to CST damage.
Relevant Publication
- Combining 4-AP with Motor Training to Promote Forelimb Motor Recovery in Rats with Pyramidal Tract Injury
This research addressed the recovery of forelimb movement, which remains a primary unmet need for patients with cervical spinal cord injury (SCI). Having previously demonstrated that the drug 4-Aminopyridine (4-AP) could significantly raise neural excitability within circuits spared after injury, this project sought to investigate how to optimally combine 4-AP with motor training to produce lasting functional improvements.
The study utilized a three-pronged methodology to assess changes in supination function using our in-house developed knob supination task. This approach integrated behavior testing, anatomical tract tracing, and physiological confirmation to identify exactly which neural pathways assumed control of motor function following treatment. By evaluating the synergies between pharmacological intervention and physical rehabilitation, the project aimed to establish a new rationale for using 4-Aminopyridine to potentiate the effects of motor training.
Support: NYS - DOH01 PART 2 2017 C33269GG NY State’s Innovative, Developmental or Exploratory Activities in Spinal Cord Injury
Relevant Publication
- Dissecting and Strengthening Corticospinal Connections After Spinal Cord Injury Using Advanced Neuroscience Methods
This project investigated the neural mechanisms of spontaneous recovery after spinal cord injury (SCI) by identifying and modulating specific neural circuits essential for restoring movement. Using anterograde viral tracers injected into the forelimb motor cortex, the study mapped the survival and branching of axons across the C4 lesion site and into the C6 spinal cord, providing a high-resolution anatomical map of the circuits responsible for restoring function.
To test the functional necessity of these pathways, a chemogenetic inactivation system was employed; by delivering a Cre-dependent DREADD (hM4Di) to the motor cortex and AAV9-Cre to the cervical spinal cord, we selectively silenced the ipsilateral corticospinal tract. The results demonstrated that inactivating this specific circuit significantly degraded both spontaneous recovery and gains from electrical stimulation, confirming these pathways as critical substrates for targeted, high-precision therapeutic interventions.
Funding - Associated grant: Individual Post-Doctoral Award Contract Number: DOH01-C30859GG-3450000
New York State Department of Health (NYSDOH) Spinal Cord Injury Research Board (SCIRB)
Relevant Publication - Combined Therapy for Forelimb Area Motor Cortex and Spinal Cord Epidural Stimulation to Improve Hand Function after Spinal Cord Injury and Identifying the Responsible Pathway
This project investigated whether paired electrical stimulation could strengthen residual neural connections to restore hand function after spinal cord injury (SCI). While individual stimulation of the motor cortex or spinal cord offered limited benefits, this study utilized a novel approach—convergent paired motor cortex and cervical epidural stimulation-to augment weak connections in rats following a bilateral C4 contusion. By comparing treated animals against sham controls using the supination knob and IBB food manipulation tasks, the study quantified the therapeutic potential of this dual-stimulation protocol for fine motor recovery.
To identify the specific neural substrates that mediated these gains, the study employed targeted inactivation of the cortico-reticular connection. It was hypothesized that this pathway was essential for the stimulation-induced recovery; the results confirmed this by demonstrating that functional improvements were significantly abrogated post-inactivation compared to pre-inactivation levels and control groups. This research provided critical insights into how spared motor connections can be recruited, offering a blueprint for high-precision neuromodulation therapies in human cervical SCI.
- Motor Cortex Electrical Stimulation to Augment Spontaneous Recovery After Chronic Subcortical Stroke
This project developed a reproducible animal model for subcortical motor system strokes, which disrupt the axonal connections between the motor cortex and spinal cord while leaving the structures themselves intact. By performing electrophysiological motor mapping and viral tracing of fibers originating in the forelimb and hindlimb motor cortex, the study successfully localized the specific pathways within the internal capsule. To create a precise lesion, an optrode was utilized to identify forelimb responses and trigger a photothrombotic ablation of the targeted fibers.
The results revealed largely separate anatomical representations for the forelimb and hindlimb within the internal capsule, allowing for a highly selective injury. This targeted lesion caused lasting impairments in forelimb function while successfully preserving hindlimb fibers, demonstrating the model's high specificity. This research provided a reliable platform for studying the pathophysiology of white matter damage and established a standardized method for screening future therapeutic strategies for subcortical stroke.
Associated grants: NIHR01
Relevant Publication - Repairing Sensorimotor Connections After Neonatal Lesion in Rats
This project investigated the neural mechanisms underlying the enhanced plasticity of the young brain following nervous system injury. Because neonatal rats often exhibit significant functional recovery compared to adults, this study sought to understand how early-life connections between the brain and spinal cord adapt and strengthen after injury. Using neural tracers to map circuit reorganization and behavioral tasks to quantify motor deficits after neonatal pyramidotomy, the research explored whether spared brain-spinal cord connections could be further bolstered through electrical stimulation.
The results revealed that the uninjured hemisphere in neonatal rats could adapt to encode separate, independent control for both the unimpaired and the impaired forelimbs. This finding provided a critical anatomical and functional explanation for why early-life injuries result in superior recovery outcomes compared to injuries sustained later in development. By identifying how the young nervous system naturally optimizes its remaining circuitry, this research established a framework for developing targeted therapies for human patients with early-onset brain or spinal injuries.
Associated grants: This study was supported by funding from National Institutes of Health (NIH)-National Institute of Neurological Disorders and Stroke (NINDS) K08 NS073796 and The Thomas and Agnes Carvel Foundation.
Relevant Publication - Optimizing Paired Brain and Spinal Cord Stimulation: A Key Step to Restore Arm and Hand Function in People with Central Nervous System Injury
The Movement Recovery Lab at the Weinberg Family CP Center conducted this project to translate laboratory breakthroughs into a clinical framework for individuals with cervical spinal cord injury (SCI). Building on foundational research, the lab had previously identified the specific brain-to-spinal cord motor and sensory connections that enabled paired electrical stimulation to strengthen muscle responses. After successfully demonstrating that this dual-stimulation approach improved forelimb function in rats and augmented muscle responses in patients undergoing spine surgery, this project focused on optimizing the "dose" and pattern of stimulation required for human application.
To achieve this, the lab utilized an automated, closed-loop system that employed machine learning algorithms to identify the most effective stimulation parameters. By analyzing muscle response size and the duration of neural augmentation in rats, specialized software identified the ideal electrode configurations, pulse frequencies, and waveforms to maximize functional gains. This data-driven optimization was then paired with sophisticated neural modeling-using finite element analysis (FEA) and mathematical neuron models to map the resulting electric fields and identify the exact biological structures being activated.
This two-pronged approach leveraged the experimental flexibility of rat models to explore a vast parameter space while using neural modeling to ensure those findings were biologically translatable to humans. By creating a comprehensive database of stimulation patterns and their functional efficacy, the project established a precise logic for neuromodulation. Ultimately, this work provided the roadmap for strengthening weak neural connections in people living with cerebral palsy, spinal cord injury, and other debilitating motor conditions.
Funding - Travis Roy Foundation - Long-Lasting, Softening Spinal Cord Stimulators
This project addressed a critical gap in neuroprosthetics: the lack of chronically stable electrode technology for the cervical spinal cord. While lumbar stimulation has successfully restored leg movement, cervical applications have been hampered by the mechanical mismatch between stiff electrodes and the delicate, mobile spinal cord. To resolve this, the lab collaborated with the Walter Voit group at UT Dallas to develop and test novel softening spinal cord stimulation (SCS) arrays. These arrays, composed of TiN electrodes on a specialized polymer substrate, were designed to be rigid for surgical insertion but soften at body temperature to conform perfectly to the spinal cord's surface.
The study demonstrated the superior safety, stability, and efficacy of these arrays in awake, behaving rats over a simulated 29-week period. Unlike traditional Parylene-C arrays, the softening electrodes minimized tissue inflammation and prevented migration without damaging the spinal cord tissue. In vivo testing confirmed that the arrays could evoke robust EMG responses with minimal current (under 1 mA) and successfully facilitated the strengthening of motor circuits through paired brain and spinal stimulation.
By merging expertise in materials science with motor control, this research established a safe, effective interface for the rat cervical spinal cord. The project proved that subjects with softening arrays maintained normal forepaw dexterity and achieved stronger, more lasting excitation of spinal circuits compared to those with conventional rigid electrodes. These findings provided a foundational tool for understanding how epidural stimulation modulates excitability in the behaving nervous system and paved the way for more durable human neural interfaces.
Relevant Publication - Paired Brain and Spinal Cord Stimulation to Augment Motor Responses in Humans
This project addressed the critical challenge of translating successful animal-model neuromodulation to human clinical applications. While research in rats demonstrated that coordinated electrical stimulation of the brain and spinal cord could augment spared connections and restore function, the organization of the human cervical spinal cord remained poorly understood due to its limited accessibility. To bridge this gap, the study utilized a unique clinical opportunity to perform electrical stimulation in patients already undergoing indicated cervical spine surgery (multilevel laminectomy).
The study pursued two primary objectives: mapping the human spinal cord's specific responses to electrical stimulation and utilizing those maps to optimize the timing and location of paired brain-spinal cord stimulation. By recording muscle responses in a surgical setting, the research successfully characterized the excitability of human spinal circuits in real-time.
The findings from this project provided the first direct physiological evidence of how the human cervical spinal cord responds to targeted neuromodulation. This knowledge established the essential logic for designing future therapeutic protocols aimed at strengthening weak neural connections and improving movement in individuals living with spinal cord injury, cerebral palsy, and other debilitating motor disorders.