Biology subjects

Gopinath, C.

Publications and source records attributed to Gopinath, C..

4 recordsLinked to original sources

bioRxiv2026

Functional Somatotopy of Lumbar Dorsal Rootlets and its Role in Selective Recruitment via Lateral Spinal Cord Stimulation

ObjectiveLateral spinal cord stimulation (LSCS) is a promising approach for restoring somatosensory feedback in lower-limb amputees, but its spatial selectivity remains limited. Percepts often spread to unintended regions of the residual limb, and reducing electrode contact size may not improve focality. This study investigated whether the anatomical organization of lumbar dorsal rootlets (DR) imposes fundamental constraints on LSCS selectivity. ApproachAcute neurophysiology experiments were performed in six adult cats. Both LSCS and individual DR stimulation were conducted in the same animals. For DR stimulation, bipolar hook electrodes were used to stimulate individual DR, while antidromic compound action potentials (CAPs) were recorded from femoral and sciatic nerve branches instrumented with nerve cuffs. For LSCS, custom 32-contact epidural paddle electrodes were placed over the lateral surface of the spinal cord at corresponding vertebral levels. Recruitment thresholds, dynamic ranges, and response patterns were analyzed across spinal levels, and DR recruitment patterns were directly compared to those evoked by LSCS within the same animals. Main resultsA clear rostrocaudal organization was observed across spinal levels during stimulation of individual DR, with femoral branches predominantly recruited at L4-L5 and sciatic branches at L6-L7. However, no somatotopic organization was found across DR within each spinal level; individual DR frequently co-activated multiple branches within the same group, and selective recruitment could only be maintained over a narrow dynamic range (median [~]10 {micro}A). LSCS exhibited even a narrower dynamic range ([~]5 {micro}A) but closely mirrored DR recruitment patterns, indicating that LSCS activates sensory afferents in a manner determined by the organizational structure of the DR. SignificanceThese findings demonstrate that the limited spatial selectivity of LSCS can largely be attributed to the coarse organization of DR within each root level rather than due to limitations of epidural electrode design. Moving electrodes intradurally or reducing contact size further is unlikely to substantially improve focality. Instead, improving paddle stability to ensure consistent placement over the appropriate spinal levels may be a more effective strategy for enhancing percept localization.

neuroscience↗

bioRxiv2025

SpIC3D imaging: Spinal In-situ Contrast 3D imaging

High-definition visualization techniques are critical for understanding the neuroanatomy of the spinal cord, an essential structure for sensorimotor and autonomic functions, in both healthy and pathological conditions. Magnetic resonance imaging (MRI) is a common method for visualizing neural structures in 3D. However, techniques for spinal cord MRI have historically achieved limited visualization of rootlets and nerves, especially at lower spinal levels, due to their highly complex and compact organization. Here we developed a spinal in-situ contrast 3D imaging (SpIC3D) method that allows visualization of spinal compartments in fixed animal and human specimens with ultra-high resolution at various spinal levels. Using SpIC3D, we achieved quantification of neuronal cell density in dorsal root ganglia, multi-segment identification of individual rootlets and roots, and volumetric reconstruction of multiple spinal structures for computational modeling. SpIC3D provides a basis for accelerated spinal pathology characterization and personalized spinal cord stimulation treatments.

neuroscience↗

bioRxiv2024

High-frequency amplitude-modulated sinusoidal stimulation induces desynchronized yet controllable neural firing

Regaining sensory feedback is critical for people living with limb amputation. Electrical stimulation of sensory fibers in peripheral nerves has been shown to restore focal percepts in the missing limb. However, conventional rectangular current pulses induce sensations often described as unnatural, likely due to the synchronous and periodic nature of activity they evoke. Here we introduce a fast-oscillating amplitude-modulated sinusoidal (FAMS) stimulation waveform that desynchronizes neural activity. Using computational modeling, we show that sinusoidal waveforms evoke asynchronous and irregular firing patterns, with frequency-dependent effects. Leveraging both low- and high-frequency mechanisms, FAMS exploits membrane nonlinearities to enhance neuron-specific differences. In a feline model of peripheral nerve stimulation, FAMS evoked activity that was more asynchronous than conventional rectangular pulses, while remaining easily controllable with simple stimulation parameters. Importantly, in human experiments using noninvasive stimulation of the median nerve, participants reported that FAMS evoked more natural sensations compared to rectangular biphasic pulses in a two-alternative forced-choice task. The preference for FAMS increased at higher intensities above sensory threshold, despite intensity-matched stimulation across waveform types. These findings provide evidence that reduced synchrony in afferent recruitment translates into more naturalistic and comfortable sensory percepts. Together, our results establish FAMS as a promising biomimetic stimulation strategy with potential for clinical applications in sensory feedback restoration. One Sentence SummaryA new electrical stimulation waveform allows for evoking and controlling more naturalistic neural activity than can be achieved with traditional stimulation waveforms.

bioengineering↗

bioRxiv2021

High-density spinal cord stimulation selectively activates lower urinary tract afferents

Epidural spinal cord stimulation (SCS) has recently been reported as a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. We asked whether sacral SCS could be used to target the lower urinary tract. Here we show that high-density epidural SCS over the sacral spinal cord and cauda equina of anesthetized cats evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral epidural SCS always recruited the pelvic and pudendal nerves and selectively recruited these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways. This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.

bioengineering↗