Biology subjects

Carmel, J. B.

Publications and source records attributed to Carmel, J. B..

3 recordsLinked to original sources

bioRxiv2023

Non-invasive vagus nerve stimulation improves sensory performance in humans

Accurate senses depend on high-fidelity encoding by sensory receptors and error-free processing in the brain. Progress has been made towards restoring damaged sensory receptors. However, methods for on-demand treatment of impaired central sensory processing are scarce. Prior invasive studies demonstrated that continuous vagus nerve stimulation (VNS) in rodents can activate the locus coeruleus-norepinephrine system to rapidly improve central sensory processing. Here, we investigated whether transcutaneous VNS improves sensory performance in humans. We conducted three sham-controlled experiments, each with 12 neurotypical adults, that measured the effects of transcutaneous VNS on metrics of auditory and visual performance, and heart rate variability (HRV). Continuous stimulation was delivered to cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve while participants performed psychophysics tasks or passively viewed a display. Relative to sham stimulation, tcVNS improved auditory performance by 37% (p=0.00052) and visual performance by 23% (p=0.038). Participants with lower performance during sham conditions experienced larger tcVNS-evoked improvements (p=0.0040). Lastly, tcVNS increased HRV during passive viewing, corroborating vagal engagement. No evidence for an effect of taVNS was observed. These findings validate the effectiveness of tcVNS in humans and position it as a method for on-demand interventions of impairments associated with central sensory processing dysfunction.

neuroscience↗

bioRxiv2022

An actionable map of arm and hand muscle responses to electrical stimulation of the dorsal cervical spinal cord in humans

While epidural stimulation of the lumbar spinal cord has emerged as a powerful modality for recovery of movement, how it should be targeted to the cervical spinal cord to activate arm and hand muscles is not well-understood, particularly in humans. We sought to map muscle responses to posterior epidural cervical spinal cord stimulation in humans. We hypothesized that lateral stimulation over the dorsal root entry zone would be most effective, and responses would be strongest in the muscles innervated by the stimulated segment. Twenty-five people undergoing clinically indicated cervical spine surgery were consented to map motor responses. During surgery, stimulation was performed in midline and lateral positions at multiple exposed segments; six arm and three leg muscles were recorded on each side of the body. Across all segments and muscles tested, lateral stimulation produced stronger muscle responses than midline despite similar latency and shape of responses. Muscles innervated at a cervical segment had the largest responses from stimulation at that segment, but responses were also observed in muscles innervated at other cervical segments and in leg muscles. The cervical responses were clustered in rostral (C4-C6) and caudal (C7-T1) cervical segments. Strong responses to lateral stimulation are likely due to the proximity of stimulation to afferent axons. Small changes in response sizes to stimulation of adjacent cervical segments argues for local circuit integration, and distant muscle responses suggest activation of long propriospinal connections. This map can help guide cervical stimulation to improve arm and hand function. New and noteworthyA map of muscle responses to cervical epidural stimulation during clinically indicated surgery revealed strongest activation when stimulating laterally compared to midline, and differences to be weaker than expected across different segments. In contrast, waveform shapes and latencies were most similar when stimulating midline and laterally indicating activation of overlapping circuitry. Thus, a map of the cervical spinal cord reveals organization and may help guide stimulation to activate arm and hand muscles strongly and selectively. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/478182v2_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@136b6c8org.highwire.dtl.DTLVardef@11a0c45org.highwire.dtl.DTLVardef@11baf9corg.highwire.dtl.DTLVardef@a62d62_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Paired motor cortex and spinal cord epidural stimulation strengthens sensorimotor connections and improves forelimb function after cervical spinal cord injury in rats.

Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects. In addition, the targeted circuits are inferred, rather than tested directly. In contrast, we sought to target the strong convergence between motor and sensory systems in the spinal cord. We developed spinal cord associative plasticity (SCAP), precisely timed pairing of motor cortex and dorsal spinal cord stimulations, to target this interaction. We tested the hypothesis that properly timed paired stimulation would strengthen the sensorimotor connections in the spinal cord and improve recovery after spinal cord injury (SCI). We tested physiological effects of paired stimulation, the pathways that mediate it, and its function in a preclinical trial. Subthreshold spinal cord stimulation strongly augmented motor cortex evoked muscle potentials at the time they were paired, but only when they arrived synchronously in the spinal cord. This paired stimulation effect depended on both cortical descending motor and spinal cord proprioceptive afferents; selective inactivation of either of these pathways fully abrogated the paired stimulation effect. SCAP, repetitive pairing of these pathways for 5 or 30 minutes in awake rats, increased spinal excitability for hours after pairing ended. To apply SCAP as therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical SCI as in uninjured rats, demonstrating that spared connections after moderate SCI were sufficient to support plasticity. In a blinded trial, rats received a moderate C4 contusive SCI. Ten days after injury, they were randomized to 30 minutes of SCAP each day for 10 days or sham stimulation. Rats with SCAP had significantly improved function on the primary outcome measure, a test of dexterity during manipulation of food, at 50 days after SCI. In addition, rats with SCAP had persistently stronger responses to cortical and spinal stimulation than sham stimulation rats, indicating a spinal locus of plasticity. SCAP rats had lasting improvements in H-reflex modulation. The groups had no difference in the rat grimace scale, a measure of pain. We conclude that SCAP strengthens sensorimotor connections within the spinal cord, resulting in improved reflex modulation and forelimb function after moderate SCI. Since both motor cortex and spinal cord stimulation are performed routinely in humans, this approach can be trialed in people with SCI or other disorders that damage sensorimotor connections and impair dexterity.

neuroscience↗