Exploring the Feasibility of Bidirectional Spinal Cord Machine Interface Through Sensing and Stimulation of Axonal Bundles

IEEE Transactions on Neural Systems and Rehabilitation Engineering · 2025-01-01

Spinal cord injury (SCI) patients experience long-term deficits in motor and sensory functions. While brain-machine interface (BMI) has shown great promise for restoring neurological functions after SCI, spinal cord-machine interface (SCMI) offers unique advantages, such as more defined somatotopy and the compact organization of neural elements in the spinal cord. In the current study, we aim to demonstrate the feasibility of sensing and evoking compound action potentials (CAPs) via electrode implantation in spinal cord axonal bundles, an essential prerequisite for advancing SCMI development. To do so, we designed microelectrode arrays (MEA) optimized for recording and stimulation in the spinal cord. For sensory mapping, the MEAs were inserted into the lumbar dorsal column (i.e., the fasciculus gracilis) to determine somatotopic representations corresponding to tactile stimulation across lower body regions and assess proprioceptive signals with varying hip positions. For stimulations, at the L3 level, we delivered electrical pulses both rostrally, along ascending afferent tracts (dorsal column), and caudally, down descending corticospinal tract. We successfully captured axonal CAPs from the dorsal columns with high spatial precision that corresponded to known dermatomal somatotopy. Proprioceptive changes produced by abduction at the hip resulted in modulation of discharge frequency in the dorsal column axons. We demonstrated that stimulation pulses emitted by a caudally placed electrode could be propagated up the ascending fibers and be intercepted by a rostrally placed electrode array along the same axonal tracts. We also confirmed that electrical pulses can be directed down descending corticospinal tracts resulting in specific activations of lower limb muscles. These findings set a critical groundwork for developing closed-loop, bidirectional SCMI systems capable of sensing and modulating spinal cord activity.

1009 In-House Microelectrode Arrays Detect Urodynamic Changes in Spinal Cord Compound Action Potentials

Neurosurgery · 2025-03-14

INTRODUCTION: Neurogenic bladder dysfunction secondary to spinal cord injuries (SCI) significantly decreases quality of life and predisposes patients to severe sequelae, such as urinary tract infections and septicemia. Spinal cord-machine interface (SCMI) is a promising approach to restore bladder functions. In this study, we fabricated integrated planar microelectrode arrays (MEA) for the detection of axonal compound action potentials (CAPs). This enabled the recording of axonal signals corresponding to bladder filling and bladder volume, an essential component for the development of a bidirectional, closed loop bladder-control neuroprostheses. METHODS: We fabricated 16- and 32-channel MEA on a shank probe that was inserted into the dorsolateral white matter containing the ascending Lissauer's tract, of six female Sprague-Dawley rats via a T12-L1 laminectomy. Bladders were surgically catheterized and 0.9% normal saline was infused at a constant rate, held, emptied, and repeated for multiple trials. Firing rates were correlated with different bladder states. RESULTS: Distinct firing rate changes within the Lissauer tract were observed during bladder filling, holding and emptying states. We mostly observed axonal CAPs that were maximally active during filling or holding states, with reduction in firing rates during emptying. These CAP patterns could be repeatedly detected only via their specific channels, confirming the spatial specificity of our electrode interface. CONCLUSIONS: Bladder states are differentially encoded by specific regions in the Lissauer tract and coding varies between filling, holding and emptying phases. In decoding such axonal signals, MEA could serve as a viable means to detect the bladder states in patients with SCI. Additionally, this electrode interface can be more broadly applied for other applications of SCMI beyond restoration of bladder function.

Human spinal cord activation during filling and emptying of the bladder

Nature Communications · 2025-07-15 · 1 citations

The spinal cord is essential for processing sensory information and regulating autonomic functions, such as bladder control, which is critical for urinary continence and voiding. Understanding how the spinal cord represents bladder pressure can provide valuable insights into the neural mechanisms underlying bladder control and contribute to developing better therapies for bladder dysfunction. However, measuring neural activity in the human spinal cord is notoriously challenging due to its small size and the surrounding bony and fascial enclosures, limiting the effectiveness of traditional neuroimaging techniques. Functional ultrasound imaging (fUSI) is a minimally invasive, emerging modality that overcomes these barriers, offering high sensitivity, spatial coverage, and spatiotemporal resolution for studying neural dynamics. Here, we combine fUSI with urodynamically controlled bladder filling and emptying to examine hemodynamic responses in the human spinal cord during one cycle of micturition. Using intravesical bladder pressure recordings, we identify spinal cord regions with hemodynamic signals that strongly correlate with bladder pressure. Furthermore, a linear support vector machine regression model (SVM-r) trained on the fUSI power Doppler signal reveals relevant spinal cord regions and accurately reconstructs bladder pressure changes. Our findings provide evidence of bladder pressure-responsive regions in the spinal cord, where hemodynamic signals strongly correlate with bladder pressure.

Functional ultrasound imaging of the human spinal cord

Neuron · 2024-03-07 · 16 citations

Restoration of Over-Ground Walking via Non-Invasive Neuromodulation Therapy: A Single-Case Study

Journal of Clinical Medicine · 2023-11-28 · 3 citations

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking, and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown as measured by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-m walking test with the aid of a walking frame and ankle-foot orthoses. The successful sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

Physiological characterization of instrumental learning in the spinal cord using the Paw Withdrawal Learning paradigm

Physiology · 2023-05-01

Following spinal cord injury (SCI), sensory and motor functions are severely disrupted yet the spinal circuitry below the injury site continues to maintain active and functional neuronal properties (Edgerton, 2004). The spinal cord is endogenously capable of several forms of adaptive plasticity, including functional re-training with exercise, instrumental, and Pavlovian learning. The paw withdrawal learning (PaWL) paradigm represents a simple spinal instrumental learning model (Jindrich 2019). Briefly, in mice whose spinal cords are completely transected (ST) at mid-thoracic (T7-T9) level, the tibialis anterior (TA) muscle is given a sub maximal threshold shock to a hind leg when the leg is extended below a 1mm imposed threshold from a baseline starting position. The contingent group mice learn to maintain the shocked leg, in a flexed position while the experimentally coupled noncontingent group of mice do not acquire the flexed position. To demonstrate the acquisition of the flexed paw hold is mediated through muscle-specific proprioceptive inputs and a time dependent modification of the spinal interneuronal network associated with the TA motor pool, we measured the TA muscle activity using acute EMG during PaWL in both Contingent stim and non-contingent stim groups. To demonstrate that TA specific sensory afferents are critical in PaWL, we blocked the proprioceptive muscle and the cutaneous afferents using Lidocaine. During PaWL, the TA muscle showed significant EMG activity when compared to medial gastrocnemius and vastus lateralis muscles. We detected greater TA muscle activity in the Contingent stim compared to the non-contingent groups. The significant increase in the EMG amplitude in the TA muscle and time-frequency and power relationships in the contingent group, but not the non-contingent group, suggests that the successful learning requires a temporal engagement of the spinal sensorimotor network. CSULA Mini-Grant 2020 and Joseph/Gomez-Pinilla R01NS056413 (Diversity Supplement) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Combining spinal neuromodulation and activity based neurorehabilitation therapy improves sensorimotor function in cerebral palsy

Frontiers in Rehabilitation Sciences · 2023-07-26 · 11 citations

Motor dysfunction in individuals with cerebral palsy (CP) such as the inability to initiate voluntary movements, walking with compensatory movement patterns, and debilitating spasticity is due to the aberrant neural connectivity between the brain and spinal cord. We tested the efficacy of noninvasive spinal cord neuromodulation (SCiP™, SpineX Inc.) with activity-based neurorehabilitation therapy (ABNT) in improving the sensorimotor function in six children with CP. Children received 8 weeks of either SCiP™ or sham therapy with ABNT ( n = 3 per group). At the end of 8 weeks, all participants received 8 weeks of SCiP™ therapy with ABNT. Follow up assessments were done at week 26 (10 weeks after the last therapy session). Sensorimotor function was measured by the Gross Motor Function Measure 88 (GMFM88) test. We observed minimal change in sham group (mean 6% improvement), however, eight weeks of SCiP™ therapy with ABNT resulted in statistically and clinically relevant improvement in GMFM88 scores (mean 23% increase from baseline). We also observed reduced scores on the modified Ashworth scale only with SCiP™ therapy (−11% vs. +5.53% with sham). Similar improvements were observed in sham group but only after the cross over to SCiP™ therapy group at the end of the first eight weeks. Finally, sixteen weeks of SCiP™ therapy with ABNT resulted in further improvement of GMFM88 score. The improvement in GMFM88 scores were maintained at week 26 (10 weeks after the end of therapy), suggesting a sustained effect of SCiP™ therapy.

Dynamic electrical stimulation enhances the recruitment of spinal interneurons by corticospinal input

Experimental Neurology · 2023-10-29 · 5 citations

Spinal facilitation of descending motor input

bioRxiv (Cold Spring Harbor Laboratory) · 2023-07-03 · 1 citations

Highly varying patterns of electrostimulation (Dynamic Stimulation, DS) delivered to the dorsal cord through an epidural array with 18 independent electrodes transiently facilitate corticospinal motor responses, even after spinal injury. To partly unravel how corticospinal input are affected by DS, we introduced a corticospinal platform that allows selective cortical stimulation during the multisite acquisition of cord dorsum potentials (CDPs) and the simultaneous supply of DS. Firstly, the epidural interface was validated by the acquisition of the classical multisite distribution of CDPs on the dorsal cord and their input-output profile elicited by pulses delivered to peripheral nerves. Apart from increased EMGs, DS selectively increased excitability of the spinal interneurons that first process corticospinal input, without changing the magnitude of commands descending from the motor cortex, suggesting a novel correlation between muscle recruitment and components of cortically-evoked CDPs. Finally, DS increases excitability of post-synaptic spinal interneurons at the stimulation site and their responsiveness to any residual supraspinal control, thus supporting the use of electrical neuromodulation whenever the motor output is jeopardized by a weak volitional input, due to a partial disconnection from supraspinal structures and/or neuronal brain dysfunctions.

Restoration of Over-Ground Walking via Non-invasive Neuromodulation Therapy

Preprints.org · 2023-09-28 · 3 citations

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long-considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-meter walking test with the aid of a walking frame and ankle foot orthoses. The success in the sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.