Biology subjects

Carmel, J. B.

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

6 recordsLinked to original sources

bioRxiv2025

Electrode position, size, and orientation determine efficacy of cervical epidural stimulation to recruit forelimb muscles in rats

Target engagement determines therapeutic efficacy. In spinal cord stimulation (SCS), efficacy depends on the attributes of the electrodes used to deliver stimulation, particularly their position, interelectrode distance, size, and current orientation. We tested the effects of these electrode parameters using cervical stimulation to elicit forelimb muscle responses in the rat. We implanted devices over the C6 dorsal root entry zone (DREZ) in eight rats and measured responses in six forelimb muscles. We used custom designed electrode arrays to systematically vary position, distance, and size with linear arrays, and current orientation with circular arrays. Stimulation consisted of biphasic and pseudomonophasic pulse shapes with bipolar or distant return, and a high-definition montage with four returns surrounding a central contact to increase local current density. Efficacy was calculated from the motor thresholds of recruitment curves, and parameters were compared using linear mixed models. For position, stimulation over the DREZ was most effective, reducing thresholds by 25.9% (p = 0.0002) relative to the midline; efficacy decreased as the electrode was positioned medial or lateral to the DREZ. For distance, placing the electrodes farther apart significantly improved efficacy (p = 0.0022). For size, large electrodes increased SCS efficacy, reducing thresholds by 21.5% (p = 0.0026) relative to small electrodes. After accounting for position and distance, current orientation did not affect SCS efficacy. Lastly, the high-definition montage decreased efficacy, increasing thresholds by 16.7% (p = 0.003) relative to monopolar stimulation with a distant return. In conclusion, electrode position, distance, and size had the greatest effect on SCS efficacy, with the optimal parameters combining large electrodes at the DREZ position with a distant return. These results have the potential to lower the current needed to engage cervical spinal circuitry and to inform the design of SCS systems to improve dexterity in people with neurological injury or disease.

neuroscience↗

bioRxiv2024

Cervical transcutaneous vagus nerve stimulation enhances speech recognition in noise: A crossover, placebo-controlled study

Speech comprehension in noisy environments remains a significant challenge, even among individuals with clinically normal hearing and users of hearing aids and cochlear implants. While conventional assistive hearing devices address limitations in the auditory periphery, they do not directly enhance the brains capacity to segregate speech from background noise. Because tonic vagus nerve stimulation (VNS) has demonstrated potential for rapidly improving central sensory processing, this study investigated whether tonic transcutaneous cervical VNS (tcVNS) can augment speech-in-noise intelligibility. Two cohorts of older human adults (60-84 years) participated in a placebo-controlled, crossover study. Participants completed speech-in-noise assessments using either QuickSIN or AzBio sentences, while receiving tonic tcVNS to the neck, or placebo stimulation to the neck-shoulder junction. Speech-in-noise performance was assessed by measuring participants accuracy in repeating sentences presented at varying signal-to-noise ratios (SNR) within background babble. Tonic tcVNS improved speech-in-noise intelligibility compared to placebo. At the group-level, the SNR threshold for 50% speech intelligibility (SNR-50) improved by 0.76 dB in QuickSIN (p=0.016) and by 0.38 dB in AzBio (p=0.045). For individual participants, 50% demonstrated improvements that met a minimum clinically important difference (MCID) of 1 dB. Tonic tcVNS evoked progressively greater improvements as SNR increased in QuickSIN (p=0.021) and AzBio (p=0.00023), with the largest gains above 0 dB SNR. In 55% of participants, tcVNS improved intelligibility beyond an MCID benchmark of 4.9% at 5 dB SNR. While the magnitude of tcVNS-evoked improvements was inversely related to baseline speech-in-noise impairment (p=0.028), with the most impaired individuals demonstrating the largest gains, it did not correlate with hearing loss severity (p=0.97) or age (p=0.88). Our findings indicate that tonic tcVNS can evoke immediate and clinically meaningful enhancements in speech-in-noise comprehension. This suggests tcVNS may complement conventional assistive hearing technologies and inform novel therapies for sensory processing disorders.

neuroscience↗

bioRxiv2024

Selective injury of thalamocortical tract in neonatal rats impairs forelimb use: modelvalidation and behavioral effects

Unilateral brain injury in neonates results in largely contralateral hand function in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. To validate that the sensory tract injury impairs dexterity, we modeled the most common site of sensory tract injury in neonates by targeting the thalamocortical tract. In the postnatal day 7 rats, we used three types of lesions to the thalamocortical tract: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the thalamocortical tract, while sparing the adjacent corticospinal tract in the internal capsule. To measure the impact on dexterity, the cylinder exploration and pasta handling tests were used to test the changes of forelimb use at 8 weeks after injury when the rats reached maturity. Lesions to the thalamocortical tract were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury. Overall, specific sensory system lesions of the thalamocortical tract impair forelimb use, suggesting a key role for skilled movement.

neuroscience↗

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↗