Autonomic dysreflexia in urological practice: pathophysiology, prevention and treatment considerations.

PURPOSE: Spinal cord injury (SCI) leads to sensorimotor impairments; however, it can also be complicated by significant autonomic dysfunction, including cardiovascular and lower urinary tract (LUT) dysfunctions. Autonomic dysreflexia (AD) is a dangerous cardiovascular complication of SCI often overlooked by healthcare professionals. AD is characterized by a sudden increase in blood pressure (BP) that can result in severe cardiovascular and cerebrovascular complications. In this review, we provide an overview on the clinical manifestations, risk factors, underlying mechanisms, and current approaches in prevention and management of AD. METHODS: After conducting a literature research, we summarized relevant information regarding the clinical and pathophysiological aspects in the context of urological clinical practice CONCLUSIONS: The most common triggers of AD are those arising from LUT, such as bladder distention and urinary tract infections. Furthermore, AD is commonly observed in individuals with SCI during urological procedures, including catheterization, cystoscopy and urodynamics. Although significant progress in the clinical assessment of AD has been made in recent decades, effective approaches for its prevention and treatment are currently lacking.

Web-Based Information on Spinal Cord Stimulation: Qualitative Assessment of Publicly Accessible Online Resources.

BACKGROUND: Despite the growing accessibility of web-based information related to spinal cord stimulation (SCS), the content and quality of commonly encountered websites remain unknown. OBJECTIVE: This study aimed to assess the content and quality of web-based information on SCS. METHODS: This qualitative study was prospectively registered in Open Science Framework. Google Trends was used to identify the top trending, SCS-related search queries from 2012 to 2022. Top queried terms were then entered into separate search engines. Information found on websites within the first 2 pages of results was extracted and assessed for quality using the DISCERN instrument, the Journal of the American Medical Association benchmark criteria, and the Health on the Net Foundation code of conduct certification. Website readability and SCS-related information were also assessed. RESULTS: After exclusions, 42 unique sites were identified (scientific resources: n=6, nonprofit: n=12, for-profit: n=20, news or media: n=2, and personal or blog: n=2). Overall, information quality was moderate (DISCERN). Few sites met all the Journal of the American Medical Association benchmark criteria (n=3, 7%) or had Health on the Net Foundation certification (n=7, 16%). On average, information was difficult to read, requiring a 9th- to 10th-grade level of reading comprehension. Sites described SCS subcategories (n=14, 33%), indications (n=38, 90%), contraindications (n=14, 33%), side effects or risks (n=28, 66%), device considerations (n=25, 59%), follow-up (n=22, 52%), expected outcomes (n=31, 73%), provided authorship details (n=20, 47%), and publication dates (n=19, 45%). The proportion of for-profit sites reporting authorship information was comparatively less than other site types (n=3, 15%). Almost all sites focused on surgically implanted SCS (n=37, 88%). On average, nonprofit sites contained the greatest number of peer-reviewed reference citations (n=6, 50%). For-profit sites showed the highest proportion of physician or clinical referrals among site types (n=17, 85%) indicating implicit bias (ie, auto-referral). CONCLUSIONS: Overall, our findings suggest the public may be exposed to incomplete or dated information from unidentifiable sources that could put consumers and patient groups at risk.

REPORT-SCS: minimum reporting standards for spinal cord stimulation studies in spinal cord injury.

Objective.Electrical spinal cord stimulation (SCS) has emerged as a promising therapy for recovery of motor and autonomic dysfunctions following spinal cord injury (SCI). Despite the rise in studies using SCS for SCI complications, there are no standard guidelines for reporting SCS parameters in research publications, making it challenging to compare, interpret or reproduce reported effects across experimental studies.Approach.To develop guidelines for minimum reporting standards for SCS parameters in pre-clinical and clinical SCI research, we gathered an international panel of expert clinicians and scientists. Using a Delphi approach, we developed guideline items and surveyed the panel on their level of agreement for each item.Main results.There was strong agreement on 26 of the 29 items identified for establishing minimum reporting standards for SCS studies. The guidelines encompass three major SCS categories: hardware, configuration and current parameters, and the intervention.Significance.Standardized reporting of stimulation parameters will ensure that SCS studies can be easily analyzed, replicated, and interpreted by the scientific community, thereby expanding the SCS knowledge base and fostering transparency in reporting.

Heart Rate Variability-Based Prediction of Autonomic Dysreflexia After Spinal Cord Injury.

Autonomic dysreflexia (AD) is a common autonomic complication of spinal cord injury (SCI) characterized by a sudden increase is blood pressure triggered by peripheral stimulation, such as bladder distention. Iatrogenic AD events often occur during various medical procedures including urodynamic assessments (UDSs) used to evaluate lower urinary tract (LUT) function in individuals with SCI. To date, there are no established clinical practices that would allow early detection of the development of episodes of AD. Heart rate variability (HRV) is a reliable and non-invasive metric for evaluating autonomic regulation of the cardiovascular system, with demonstrated utility in people with SCI during UDSs. We aim to provide a comprehensive evaluation of cardiovascular function during UDS-induced AD using ultra-short-term HRV analysis and identify changes in cardiovascular dynamics to predict the onset of AD. We assessed cardiovascular data in a total of 24 participants with sensorimotor complete SCI above T6 (17 males, 7 females, median age = 43 [36-50] years) who experienced AD during UDS. We used continuous electrocardiographic recordings to evaluate HRV in 60 sec overlapping windows during filling cystometry. The mean of "normal-to-normal" heartbeats (meanNN), its standard deviation (SDNN), and the root mean square of successive differences (RMSSD) were calculated and used in all subsequent analyses. We found that SDNN and RMSSD diminished during the early phase of bladder filling and sharply increased during AD. Using the lowest point of statistical variability in heart rate (i.e., SDNN), we were able to predict AD events within 240 sec (percentile 25-percentile 75: 172-339 sec) before the first systolic blood pressure peak after AD onset (sensitivity = 0.667; specificity = 0.875). Our results indicated a temporary increase in sympathetic activity during the early phase of bladder filling, which is followed by an increase in parasympathetic outflow to the heart when AD occurs. These findings have significant clinical implications that extend beyond the context of UDS and demonstrate the importance of identifying early changes in HRV in order to accurately predict AD episodes in people living with SCI.

The Microbiological Burden of Short-Term Catheter Reuse in Individuals with Spinal Cord Injury: A Prospective Study.

Despite the risk of developing catheter-associated urinary tract infections (CAUTI), catheter reuse is common among people with spinal cord injury (SCI). This study examined the microbiological burden and catheter surface changes associated with short-term reuse. Ten individuals with chronic SCI reused their catheters over 3 days. Urine and catheter swab cultures were collected daily for analysis. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analyses were used to assess catheter surface changes. Catheter swab cultures showed no growth after 48 h (47.8%), skin flora (28.9%), mixed flora (17.8%), or bacterial growth (5.5%). Asymptomatic bacteriuria was found for most participants at baseline (n = 9) and all at follow-up (n = 10). Urine samples contained Escherichia coli (58%), Klebsiella pneumoniae (30%), Enterococcus faecalis (26%), Acinetobacter calcoaceticus-baumannii (10%), Pseudomonas aeruginosa (6%) or Proteus vulgaris (2%). Most urine cultures showed resistance to one or more antibiotics (62%). SEM images demonstrated structural damage, biofilm and/or bacteria on all reused catheter surfaces. XPS analyses also confirmed the deposition of bacterial biofilm on reused catheters. Catheter surface changes and the presence of antibiotic-resistant bacteria were evident following short-term reuse, which may increase susceptibility to CAUTI in individuals with SCI despite asymptomatic bacteriuria.

Motor and autonomic concomitant health improvements with neuromodulation and exercise (MACHINE) training: a randomised controlled trial in individuals with spinal cord injury.

INTRODUCTION: Motor and autonomic dysfunctions are widespread among people with spinal cord injury (SCI), leading to poor health and reduced quality of life. Exercise interventions, such as locomotor training (LT), can promote sensorimotor and autonomic recovery post SCI. Recently, breakthroughs in SCI research have reported beneficial effects of electrical spinal cord stimulation (SCS) on motor and autonomic functions. Despite literature supporting the independent benefits of transcutaneous SCS (TSCS) and LT, the effect of pairing TSCS with LT is unknown. These therapies are non-invasive, customisable and have the potential to simultaneously benefit both sensorimotor and autonomic functions. The aim of this study is to assess the effects of LT paired with TSCS in people with chronic SCI on outcomes of sensorimotor and autonomic function. METHODS AND ANALYSIS: Twelve eligible participants with chronic (>1 year) motor-complete SCI, at or above the sixth thoracic segment, will be enrolled in this single-blinded, randomised sham-controlled trial. Participants will undergo mapping for optimisation of stimulation parameters and baseline assessments of motor and autonomic functions. Participants will then be randomly assigned to either LT+TSCS or LT+Sham stimulation for 12 weeks, after which postintervention assessments will be performed to determine the effect of TSCS on motor and autonomic functions. The primary outcome of interest is attempted voluntary muscle activation using surface electromyography. The secondary outcomes relate to sensorimotor function, cardiovascular function, pelvic organ function and health-related quality of life. Statistical analysis will be performed using two-way repeated measures Analysis of variance (ANOVAs) or Kruskal-Wallis and Cohen's effect sizes. ETHICS AND DISSEMINATION: This study has been approved after full ethical review by the University of British Columbia's Research Ethics Board. The stimulator used in this trial has received Investigation Testing Authorisation from Health Canada. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars. TRIAL REGISTRATION NUMBER: NCT04726059.

Effect of epidural spinal cord stimulation on female sexual function after spinal cord injury.

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.

Spinal Cord Stimulation Prevents Autonomic Dysreflexia in Individuals with Spinal Cord Injury: A Case Series.

Spinal cord injury (SCI) results in severe cardiovascular dysfunction due to the disruption of supraspinal control. Autonomic dysreflexia (AD), an uncontrolled rise in blood pressure in response to peripheral stimuli including common bowel routine, digital anorectal stimulation (DARS), reduces the quality of life, and increases morbidity and mortality. Recently, spinal cord stimulation (SCS) has emerged as a potential intervention to mitigate unstable blood pressure following SCI. The objective of this case series was to test the real-time effect of epidural SCS (eSCS) at the lumbosacral spinal cord, the most common implant location, on mitigating AD in individuals with SCI. We recruited three individuals with cervical and upper thoracic motor-complete SCI who have an implanted epidural stimulator. We demonstrated that eSCS can reduce the elevation in blood pressure and prevent DARS-induced AD. The blood pressure variability analysis indicated that eSCS potentially reduced vascular sympathetic nervous system activity during DARS, compared to without eSCS. This case series provides evidence to support the use of eSCS to prevent AD episodes during routine bowel procedures, improving the quality of life for individuals with SCI and potentially reducing cardiovascular risks.

Mapping the Iceberg of Autonomic Recovery: Mechanistic Underpinnings of Neuromodulation following Spinal Cord Injury.

Spinal cord injury leads to disruption in autonomic control resulting in cardiovascular, bowel, and lower urinary tract dysfunctions, all of which significantly reduce health-related quality of life. Although spinal cord stimulation shows promise for promoting autonomic recovery, the underlying mechanisms are unclear. Based on current preclinical and clinical evidence, this narrative review provides the most plausible mechanisms underlying the effects of spinal cord stimulation for autonomic recovery, including activation of the somatoautonomic reflex and induction of neuroplastic changes in the spinal cord. Areas where evidence is limited are highlighted in an effort to guide the scientific community to further explore these mechanisms and advance the clinical translation of spinal cord stimulation for autonomic recovery.

Effects of non-invasive spinal cord stimulation on lower urinary tract, bowel, and sexual functions in individuals with chronic motor-complete spinal cord injury: Protocol for a pilot clinical trial.

INTRODUCTION: Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled "Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury" is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. METHODS AND ANALYSIS: Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. ETHICS AND DISSEMINATION: Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders.

May I Have This Dance: A Case-Series on the Acute Cardiometabolic Demand of Wheelchair Dancing in Recreational Dancers with Spinal Cord Injury.

OBJECTIVES: This case-series investigated energy expenditure, cardiovascular responses, and psychosocial outcomes during two wheelchair dancing routines with different tempos. METHODS: Three individuals with chronic, non-traumatic spinal cord injuries [males, mean age 42 (13) years, C3-T12, AIS D, schwannoma=1, poliomyelitis=1, ependymoma=1] performed slow (rumba, 80 bpm) and fast (salsa, 170 bpm) wheelchair dance routines. Physiological [heart rate, blood pressure, relative oxygen consumption (VO2), metabolic task equivalent] and psychosocial parameters [ratings of perceived exertion, enjoyment and Brunel Mood Score] were measured pre, during, and post-dancing. RESULTS: All participants showed an elevation in heart rate and relative VO2 from rest to dancing with a subsequent decrease in these parameters post-dance for both routines. Relative to the slow dance routine, two out of three participants demonstrated greater heart rate, relative VO2, ratings of perceived exertion, and enjoyment during the fast dance routine. For all three participants, metabolic task equivalents ranged from 1.7-2.4 (slow) and 2.1-3.8 (fast), suggesting the intervention was of light to moderate intensity for slow and fast dance routines, respectively. Enjoyment ratings ranged from "quite a bit" to "extremely." No differences in Brunel mood subscales were observed. CONCLUSION: This case-series offers a preliminary understanding of the acute cardiometabolic and psychosocial responses to wheelchair dance routines of differing intensities per¬formed by individuals with spinal cord injury. Responsiveness observed among these participants suggests the potential use of wheelchair dance for promoting physical activity and improving psychological well-being.

When the whole is greater than the sum of its parts: a scoping review of activity-based therapy paired with spinal cord stimulation following spinal cord injury.

Spinal cord injury (SCI) results in both motor and autonomic impairments, which can negatively affect independence and quality of life and increase morbidity and mortality. Despite emerging evidence supporting the benefits of activity-based training and spinal cord stimulation as two distinct interventions for sensorimotor and autonomic recovery, the combined effects of these modalities are currently uncertain. This scoping review evaluated the effectiveness of paired interventions (exercise + spinal neuromodulation) for improving sensorimotor and autonomic functions in individuals with SCI. Four electronic databases were searched for peer-reviewed manuscripts (Medline, Embase, CINAHL, and EI-compedex Engineering Village) and data were independently extracted by two reviewers using pre-established extraction tables. A total of 15 studies representing 79 participants were included in the review, of which 73% were conducted within the past 5 years. Only two of the studies were randomized controlled studies, while the other 13 studies were case or case-series designs. Compared with activity-based training alone, spinal cord stimulation combined with activity-based training improved walking and voluntary muscle activation, and augmented improvements in lower urinary tract, bowel, resting metabolic rate, peak oxygen consumption, and thermoregulatory function. Spinal neuromodulation in combination with use-dependent therapies may provide greater neurorecovery and induce long-term benefits for both motor and autonomic function beyond the capacity of traditional activity-based therapies. However, evidence for combinational approaches is limited and there is no consensus for outcome measures or optimal protocol parameters, including stimulation settings. Future large-scale randomized trials into paired interventions are warranted to further investigate these preliminary findings.

Activity-dependent plasticity and spinal cord stimulation for motor recovery following spinal cord injury.

Spinal cord injuries lead to permanent physical impairment despite most often being anatomically incomplete disruptions of the spinal cord. Remaining connections between the brain and spinal cord create the potential for inducing neural plasticity to improve sensorimotor function, even many years after injury. This narrative review provides an overview of the current evidence for spontaneous motor recovery, activity-dependent plasticity, and interventions for restoring motor control to residual brain and spinal cord networks via spinal cord stimulation. In addition to open-loop spinal cord stimulation to promote long-term neuroplasticity, we also review a more targeted approach: closed-loop stimulation. Lastly, we review mechanisms of spinal cord neuromodulation to promote sensorimotor recovery, with the goal of advancing the field of rehabilitation for physical impairments following spinal cord injury.

Multisite Transcutaneous Spinal Stimulation for Walking and Autonomic Recovery in Motor-Incomplete Tetraplegia: A Single-Subject Design.

OBJECTIVE: This study investigated the effect of cervical and lumbar transcutaneous spinal cord stimulation (tSCS) combined with intensive training to improve walking and autonomic function after chronic spinal cord injury (SCI). METHODS: Two 64-year-old men with chronic motor incomplete cervical SCI participated in this single-subject design study. They each underwent 2 months of intensive locomotor training and 2 months of multisite cervical and lumbosacral tSCS paired with intensive locomotor training. RESULTS: The improvement in 6-Minute Walk Test distance after 2 months of tSCS with intensive training was threefold greater than after locomotor training alone. Both participants improved balance ability measured by the Berg Balance Scale and increased their ability to engage in daily home exercises. Gait analysis demonstrated increased step length for each individual. Both participants experienced improved sensation and bowel function, and 1 participant eliminated the need for intermittent catheterization after the stimulation phase of the study. CONCLUSION: These results suggest that noninvasive spinal cord stimulation might promote recovery of locomotor and autonomic functions beyond traditional gait training in people with chronic incomplete cervical SCI. IMPACT: Multisite transcutaneous spinal stimulation may induce neuroplasticity of the spinal networks and confer functional benefits following chronic cervical SCI.

Automated lever task with minimum antigravity movement for rats with cervical spinal cord injury.

BACKGROUND: Although there is currently no cure for paralysis due to spinal cord injury (SCI), the highest treatment priority is restoring arm and hand function for people with cervical SCI. Preclinical animal models provide an opportunity to test innovative treatments, but severe cervical injury models require significant time and effort to assess responses to novel interventions. Moreover, there is no behavioral task that can assess forelimb movement in rats with severe cervical SCI unable to perform antigravity movements. NEW METHOD: We developed a novel lever pressing task for rats with severe cervical SCI. We employed an automated adaptive algorithm to train animals using open-source software and commercially available hardware. We found that using the adaptive training required only 13.3 ± 2.5 training days to achieve behavioral proficiency. The lever press task could quantify immediate and long-term improvements in severely impaired forelimb function effectively. This behavior platform has potential to facilitate rehabilitative training and assess effects of therapeutic modalities following SCI. COMPARISON WITH EXISTING METHODS: There is no existing assessment aiming to quantify forelimb extension movement in rodents without function against gravity. We found that the new lever press task in the antigravity position could assess the severity of cervical SCI as well as the compensatory movement in the proximal forelimb less affected by the injury. CONCLUSIONS: This study demonstrates that the new behavioral task is capable of tracking the functional changes with various therapies in rats with severe forelimb impairments in a cost- and time-efficient manner.

Glassy Carbon Neural Interface for Chronic Epidural Stimulation in Rats with Cervical Spinal Cord Injury.

There is growing evidence on the efficacy of electrical stimulation delivered via spinal neural interfaces to improve functional recovery following spinal cord injury. For such interfaces, carbon-based neural arrays are fast becoming recognized as a compelling material and platform due to biocompatibility and long-term electrochemical stability. Here, we introduce the design, fabrication, and in vivo characterization of a novel cervical epidural implant with carbon-based surface electrodes. Through finite element analysis and mechanical load tests, we demonstrated that the array could safely withstand loads applied to it during implantation and natural movement of the subject with minimal stress levels. Furthermore, the long-term in vivo performance of this neural array consisting of glassy carbon surface electrodes was investigated through acute and chronic spinal motor evoked potential recordings and electrode impedance tests in rats. We demonstrated stable stimulation performance for at least four weeks in a rat model of spinal cord injury. Lastly, we found that impedance measurements on all carbon-based spinal arrays were generally stable over time up to four weeks after implantation, with a slight increase in impedance in subsequent weeks when tested in spinally injured rats. Taken together, this study demonstrated the potential for carbon-based electrodes as a spinal neural interface to accelerate both mechanistic research and functional restoration in animal models of spinal cord injury.

Japanese translation and linguistic validation of the Prosthetic Limb Users Survey of Mobility (PLUS-M).

BACKGROUND: Self-report survey instruments can be used to improve clinical care for lower-limb prosthesis users on a global scale by pooling comparable health outcomes data from multiple countries. The language translation process is critical to the quality and comparability of a translated survey instrument. OBJECTIVES: The goals of this research were to translate the Prosthetic Limb Users Survey of Mobility (PLUS-M) item bank from English to Japanese using established guidelines, and linguistically validate the translated instrument by assessing its clarity, comprehension, and cultural applicability with Japanese prosthesis users. STUDY DESIGN: Instrument translation and qualitative interviews. METHODS: The translation process included two forward translations, reconciliation, backward translation, and review by clinical experts in Japan. Adult lower-limb prosthesis users participated in a linguistic validation study by responding to translated survey items and providing item-by-item feedback through cognitive interviews. RESULTS: Following expert reviews, translated items were classified as grammatically and contextually unchanged (n = 21), minor revision required (n = 19), major revision required (n = 3), or removed (n = 1). Cognitive interviews with 10 participants indicated that additional revisions were required (n = 4). Items were revised and retested until it was determined that they were clear, well understood, and culturally applicable. CONCLUSIONS: Use of a multistep translation and linguistic validation processes resulted in a linguistically comparable Japanese translation of the PLUS-M item bank. Japanese translations of the PLUS-M 7- and 12-item short forms were created for use in clinical practice and research. Availability of these linguistically comparable instruments is expected to facilitate opportunities for international comparison of prosthetic mobility data.

Graphene on glassy carbon microelectrodes demonstrate long-term structural and functional stability in neurophysiological recording and stimulation.

Objective.There is a growing interest in the use of carbon and its allotropes for microelectrodes in neural probes because of their inertness, long-term electrical and electrochemical stability, and versatility. Building on this interest, we introduce a new electrode material system consisting of an ultra-thin monoatomic layer of graphene (Gr) mechanically supported by a relatively thicker layer of glassy carbon (GC).Approach.Due to its high electrical conductivity and high double-layer capacitance, Gr has impressive electrical and electrochemical properties, two key properties that are useful for neural recording and stimulation applications. However, because of its two-dimensional nature, Gr exhibits a lack of stiffness in the transverse direction and hence almost non-existent flexural and out-of-plane rigidity that will severely limit its wider use. On the other hand, GC is one of carbon's important allotropes and consists of three-dimensional microstructures of Gr fragments with a natural molecular similarity to Gr. Further, GC has exceptional chemical inertness, good electrical properties, high electrochemical stability, purely capacitive charge injection, and fast surface electrokinetics coupled with lithography patternability. This makes GC an ideal candidate for addressing Gr's lack of out-of-plane rigidity through providing a matching sturdier and robust mechanical backing. Combining the strengths of these two allotropes of carbon, we introduce a new neural probe that consists of ∼1 nm thick layer of patterned Gr microelectrodes supported by another layer of 3-5µm thick patterned GC.Main results. We present the fabrication technology for the newGr on GC(graphene on glassy carbon) microelectrodes and the accompanying pattern transfer technology on flexible substrate and report on the bond between these two allotropes of carbon through FTIR, surface morphology through SEM, topography through atomic force microscopy, and microstructure imaging through scanning transmission electron microscopy. A long-term (18 weeks)in vivostudy of the use of theseGr on GCmicroelectrodes assessed the quality of the electrocorticography-based neural signal recording and stimulation through electrophysiological measurements. The probes were demonstrated to be functionally and structurally stable over the 18 week period with minimal glial response-the longest reported so far for Gr-based microelectrodes.Significance.TheGr on GCmicroelectrodes presented here offers a compelling case for expanding the potentials of Gr-based technology in the broad areas of neural probes.

Brain-Computer-Spinal Interface Restores Upper Limb Function After Spinal Cord Injury.

Brain-computer interfaces (BCIs) are an emerging strategy for spinal cord injury (SCI) intervention that may be used to reanimate paralyzed limbs. This approach requires decoding movement intention from the brain to control movement-evoking stimulation. Common decoding methods use spike-sorting and require frequent calibration and high computational complexity. Furthermore, most applications of closed-loop stimulation act on peripheral nerves or muscles, resulting in rapid muscle fatigue. Here we show that a local field potential-based BCI can control spinal stimulation and improve forelimb function in rats with cervical SCI. We decoded forelimb movement via multi-channel local field potentials in the sensorimotor cortex using a canonical correlation analysis algorithm. We then used this decoded signal to trigger epidural spinal stimulation and restore forelimb movement. Finally, we implemented this closed-loop algorithm in a miniaturized onboard computing platform. This Brain-Computer-Spinal Interface (BCSI) utilized recording and stimulation approaches already used in separate human applications. Our goal was to demonstrate a potential neuroprosthetic intervention to improve function after upper extremity paralysis.

Transcutaneous Spinal Cord Stimulation Restores Hand and Arm Function After Spinal Cord Injury.

Paralysis of the upper extremity severely restricts independence and quality of life after spinal cord injury. Regaining control of hand and arm movements is the highest treatment priority for people with paralysis, 6-fold higher than restoring walking ability. Nevertheless, current approaches to improve upper extremity function typically do not restore independence. Spinal cord stimulation is an emerging neuromodulation strategy to restore motor function. Recent studies using surgically implanted electrodes demonstrate impressive improvements in voluntary control of standing and stepping. Here we show that transcutaneous electrical stimulation of the spinal cord leads to rapid and sustained recovery of hand and arm function, even after complete paralysis. Notably, the magnitude of these improvements matched or exceeded previously reported results from surgically implanted stimulation. Additionally, muscle spasticity was reduced and autonomic functions including heart rate, thermoregulation, and bladder function improved. Perhaps most striking is that all six participants maintained their gains for at least three to six months beyond stimulation, indicating functional recovery mediated by long-term neuroplasticity. Several participants resumed their hobbies that require fine motor control, such as playing the guitar and oil painting, for the first time in up to 12 years since their injuries. Our findings demonstrate that non-invasive transcutaneous electrical stimulation of the spinal networks restores movement and function of the hands and arm for people with both complete paralysis and long-term spinal cord injury.