Generating artificial sensations with spinal cord stimulation in primates and rodents.
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ABSTRACT:
SUBMITTER: Yadav AP
PROVIDER: S-EPMC8316418 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and objectivesThe restoration of touch to fingers and fingertips is critical to achieving dexterous neuroprosthetic control for individuals with sensorimotor dysfunction. However, localized fingertip sensations have not been evoked via intracortical microstimulation (ICMS).MethodsUsing a novel intraoperative mapping approach, we implanted electrode arrays in the finger areas of left and right somatosensory cortex and delivered ICMS over a 2-year period in a human participant with spinal cord injury.ResultsStimulation evoked tactile sensations in 8 fingers, including fingertips, spanning both hands. Evoked percepts followed expected somatotopic arrangements. The subject was able to reliably identify up to 7 finger-specific sites spanning both hands in a finger discrimination task. The size of the evoked percepts was on average 33% larger than a finger pad, as assessed via manual markings of a hand image. The size of the evoked percepts increased modestly with increased stimulation intensity, growing 21% as pulse amplitude increased from 20 to 80 µA. Detection thresholds were estimated on a subset of electrodes, with estimates of 9.2 to 35 µA observed, roughly consistent with prior studies.DiscussionThese results suggest that ICMS can enable the delivery of consistent and localized fingertip sensations during object manipulation by neuroprostheses for individuals with somatosensory deficits.Clinicaltrialsgov identifierNCT03161067.
| S-EPMC8865889 | biostudies-literature
Project description:Spinal cord stimulation has become an important modality in pain treatment especially for neuropathic pain conditions refractory to pharmacotherapy. However, the molecular control of inhibitory and excitatory mechanisms observed after spinal cord stimulation are poorly understood. Here, we used RNA-seq to identify differences in the expression of genes and gene networks in spinal cord tissue from nerve-injured rats with and without repetitive conventional spinal cord stimulation treatment. Five weeks after chronic constrictive injury to the left sciatic nerve, male and female rats were randomized to receive repetitive spinal cord stimulation or no treatment. Rats receiving spinal cord stimulation underwent epidural placement of a miniature stimulating electrode and received seven sessions of spinal cord stimulation (50 Hz, 80% motor threshold, 0.2 ms, constant current bipolar stimulation, 120 min/session) over four consecutive days. Within 2 h after the last spinal cord stimulation treatment, the L4-L6 spinal segments ipsilateral to the side of nerve injury were harvested and used to generate libraries for RNA-seq. Our RNA-seq data suggest further increases of many existing upregulated immune responses in chronic constrictive injury rats after repetitive spinal cord stimulation, including transcription of cell surface receptors and activation of non-neuronal cells. We also demonstrate that repetitive spinal cord stimulation represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density. Our transcriptional studies suggest a potential relationship between specific genes and the therapeutic effects observed in patients undergoing conventional spinal cord stimulation after nerve injury. Furthermore, our results may help identify new therapeutic targets for improving the efficacy of conventional spinal cord stimulation and other chronic pain treatments.
| S-EPMC6293371 | biostudies-literature
Project description:ObjectiveTo evaluate the impact of using transcutaneous electrical spinal cord stimulation (TSCS) on upper and lower extremity function in individuals with chronic spinal cord injury (SCI).DesignProspective case series.SettingSCI specific rehabilitation hospital.ParticipantsA convenience sample (N = 7) of individuals with tetraplegia who had previously been discharged from outpatient therapy due to a plateau in progress.InterventionsIndividuals participated in 60 min of upper extremity (UE) functional task-specific practice (FTP) in combination with TSCS and 60 min of locomotor training in combination with TSCS 5x/week.Main outcome measuresThe primary outcome for this analysis was the Capabilities of Upper Extremity Test (CUE-T). Secondary outcomes include UE motor score (UEMS), LE motor score (LEMS), sensation (light touch and pin prick), Nine-Hole Peg Test, 10 meter walk test, 6 min walk test, and 5 min stand test.ResultsSeven individuals (four motor complete; three motor incomplete) completed 20-80 sessions UE and LE training augmented with TSCS and without any serious adverse events. Improvements were reported on the CUE-T in all seven individuals. Two individuals improved their ASIA impairment scale (AIS) classification (B to C; C to D) and two individuals improved their neurologic level of injury by one level (C4-C5; C5-C6). Sensation improved in five individuals and all four who started out with motor complete SCIs were able to voluntarily activate their LEs on command in the presence of stimulation.ConclusionIndividuals with chronic SCI who had previously demonstrated a plateau in function after an intensive outpatient therapy program were able to improve in a variety of UE and LE outcomes in response to TSCS without any adverse events. This was a small pilot study and future fully powered studies with comparative interventions need to be completed to assess efficacy.
| S-EPMC9396932 | biostudies-literature
Project description:Paired associative stimulation at the spinal cord (spinal PAS) has been shown to increase muscle force and dexterity by strengthening the corticomuscular connection, through spike timing dependent plasticity. Typically, transcranial magnetic stimulation (TMS) and transcutaneous peripheral nerve electrical stimulation (PNS) are often used in spinal PAS. PNS targets superficial nerve branches, by which the number of applicable muscles is limited. Alternatively, a muscle can be activated by positioning the stimulation electrode on the "motor point" (MPS), which is the most sensitive location of a muscle to electrical stimulation. Although this can increase the number of applicable muscles for spinal PAS, nobody has tested whether MPS can be used for the spinal PAS to date. Here we investigated the feasibility of using MPS instead of PNS for spinal PAS. Ten healthy male individuals (26.0 ± 3.5 yrs) received spinal PAS on two separate days with different stimulation timings expected to induce (1) facilitation of corticospinal excitability (REAL) or (2) no effect (CONTROL) on the soleus. The motor evoked potentials (MEP) response curve in the soleus was measured prior to the spinal PAS, immediately after (0 min) and at 10, 20, 30 min post-intervention as a measure of corticospinal excitability. The post-intervention MEP response curve areas were larger in the REAL condition than the CONTROL conditions. Further, the post-intervention MEP response curve areas were significantly larger than pre-intervention in the REAL condition but not in the CONTROL condition. We conclude that MPS can facilitate corticospinal excitability through spinal PAS.
| S-EPMC7729006 | biostudies-literature
Project description:Background: Chronic spinal cord injury (SCI) portends a low probability of recovery, especially in the most severe subset of motor-complete injuries. Active spinal cord stimulation with or without intensive locomotor training has been reported to restore movement after traumatic SCI. Only three cases have been reported where participants developed restored volitional movement with active stimulation turned off after a period of chronic stimulation and only after intensive rehabilitation with locomotor training. It is unknown whether restoration of movement without stimulation is possible after stimulation alone. Objective: We describe the development of spontaneous volitional movement (SVM) without active stimulation in a subset of participants in the Epidural Stimulation After Neurologic Damage (ESTAND) trial, in which locomotor training is not prescribed as part of the study protocol, and subject's rehabilitation therapies are not modified. Methods: Volitional movement was evaluated with the Brain Motor Control Assessment using sEMG recordings and visual examination at baseline and at follow-up visits with and without stimulation. Additional functional assessment with a motor-assisted bicycle exercise at follow-up with and without stimulation identified generated work with and without effort. Results: The first seven participants had ASIA Impairment Scale (AIS) A or B thoracic SCI, a mean age of 42 years, and 7.7 years post-injury on average. Four patients developed evidence of sustained volitional movement, even in the absence of active stimulation after undergoing chronic epidural spinal cord stimulation (eSCS). Significant increases in volitional power were found between those observed to spontaneously move without stimulation and those unable (p < 0.0005). The likelihood of recovery of spontaneous volitional control was correlated with spasticity scores prior to the start of eSCS therapy (p = 0.048). Volitional power progressively improved over time (p = 0.016). Additionally, cycling was possible without stimulation (p < 0.005). Conclusion: While some SVM after eSCS has been reported in the literature, this study demonstrates sustained restoration without active stimulation after long-term eSCS stimulation in chronic and complete SCI in a subset of participants. This finding supports previous studies suggesting that "complete" SCI is likely not as common as previously believed, if it exists at all in the absence of transection and that preserved pathways are substrates for eSCS-mediated recovery in clinically motor-complete SCI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03026816.
| S-EPMC7340010 | biostudies-literature
Project description: Not available
| S-EPMC8374589 | biostudies-literature
Project description:Sexual dysfunction is a common consequence for women with spinal cord injury (SCI); however, current treatments are ineffective, especially in the under-prioritized population of women with SCI. This case-series, a secondary analysis of the Epidural Stimulation After Neurologic Damage (E-STAND) clinical trial aimed to investigate the effect of epidural spinal cord stimulation (ESCS) on sexual function and distress in women with SCI. Three females, with chronic, thoracic, sensorimotor complete SCI received daily (24 h/day) tonic ESCS for 13 months. Questionnaires, including the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) were collected monthly. There was a 3.2-point (13.2%) mean increase in total FSFI from baseline (24.5 ± 4.1) to post-intervention (27.8 ± 6.6), with a 4.8-50% improvement in the sub-domains of desire, arousal, orgasm and satisfaction. Sexual distress was reduced by 55%, with a mean decrease of 12 points (55.4%) from baseline (21.7 ± 17.2) to post-intervention (9.7 ± 10.8). There was a clinically meaningful change of 14 points in the International Standards for Neurological Classification of Spinal Cord Injury total sensory score from baseline (102 ± 10.5) to post-intervention (116 ± 17.4), without aggravating dyspareunia. ESCS is a promising treatment for sexual dysfunction and distress in women with severe SCI. Developing therapeutic interventions for sexual function is one of the most meaningful recovery targets for people with SCI. Additional large-scale investigations are needed to understand the long-term safety and feasibility of ESCS as a viable therapy for sexual dysfunction. Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03026816, NCT03026816.
| S-EPMC10167769 | biostudies-literature
Project description: Not available
| S-EPMC9990744 | biostudies-literature
Project description:The histological assessment of spinal cord tissue in three dimensions has previously been very time consuming and prone to errors of interpretation. Advances in tissue clearing have significantly improved visualization of fluorescently labelled axons. While recent proof-of-concept studies have been performed with transgenic mice in which axons were prelabeled with GFP, investigating axonal regeneration requires stringent axonal tracing methods as well as the use of animal models in which transgenic axonal labeling is not available. Using rodent models of spinal cord injury, we labeled axon tracts of interest using both adeno-associated virus and chemical tracers and performed tetrahydrofuran-based tissue clearing to image multiple axon types in spinal cords using light sheet and confocal microscopy. Using this approach, we investigated the relationships between axons and scar-forming cells at the injury site as well as connections between sensory axons and motor pools in the spinal cord. In addition, we used these methods to trace axons in nonhuman primates. This reproducible and adaptable virus-based approach can be combined with transgenic mice or with chemical-based tract-tracing methods, providing scientists with flexibility in obtaining axonal trajectory information from transparent tissue.
| S-EPMC4444235 | biostudies-literature
Project description:ObjectivesThe burden of pain after spinal cord injury (SCI), which may occur above, at, or below injury level, is high worldwide. Spinal cord stimulation (SCS) is an important neuromodulation pain therapy, but its efficacy in SCI pain remains unclear. In SCI rats, we tested whether conventional SCS (50 Hz, 80% motor threshold [MoT]) and 1200 Hz, low-intensity SCS (40% MoT) inhibit hind paw mechanical hypersensitivity, and whether conventional SCS attenuates evoked responses of wide-dynamic range (WDR) neurons in lumbar spinal cord.Materials and methodsMale rats underwent a moderate contusive injury at the T9 vertebral level. Six to eight weeks later, SCS or sham stimulation (120 min, n = 10) was delivered through epidural miniature electrodes placed at upper-lumbar spinal cord, with using a crossover design. Mechanical hypersensitivity was examined in awake rats by measuring paw withdrawal threshold (PWT) to stimulation with von Frey filaments. WDR neurons were recorded with in vivo electrophysiologic methods in a separate study of anesthetized rats.ResultsBoth conventional SCS and 1200 Hz SCS increased PWTs from prestimulation level in SCI rats, but the effects were modest and short-lived. Sham SCS was not effective. Conventional SCS (10 min) at an intensity that evokes the peak Aα/β waveform of sciatic compound action potential did not inhibit WDR neuronal responses (n = 19) to graded or repeated electrical stimulation that induces windup.ConclusionsConventional SCS and 1200 Hz, low-intensity SCS modestly attenuated below-level mechanical hypersensitivity after SCI. Inhibition of WDR neurons was not associated with pain inhibition from conventional SCS.
| S-EPMC7855640 | biostudies-literature