Upper extremity function is the highest priority of tetraplegics for improving quality of life. We aim to determine the therapeutic potential of transcutaneous electrical spinal cord stimulation for restoration of upper extremity function. We tested the hypothesis that cervical stimulation can facilitate neuroplasticity that results in long-lasting improvement in motor control. A 62-year-old male with C3, incomplete, chronic spinal cord injury (SCI) participated in the study. The intervention comprised three alternating periods: 1) transcutaneous spinal stimulation combined with physical therapy (PT); 2) identical PT only; and 3) a brief combination of stimulation and PT once again. Following four weeks of combined stimulation and physical therapy training, all of the following outcome measurements improved: the Graded Redefined Assessment of Strength, Sensation, and Prehension test score increased 52 points and upper extremity motor score improved 10 points. Pinch strength increased 2- to 7-fold in left and right hands, respectively. Sensation recovered on trunk dermatomes, and overall neurologic level of injury improved from C3 to C4. Most notably, functional gains persisted for over 3 month follow-up without further treatment. These data suggest that noninvasive electrical stimulation of spinal networks can promote neuroplasticity and long-term recovery following SCI.

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We present a new class of carbon-based neural probes that consist of homogeneous glassy carbon (GC) microelectrodes, interconnects and bump pads. These electrodes have purely capacitive behavior with exceptionally high charge storage capacity (CSC) and are capable of sustaining more than 3.5 billion cycles of bi-phasic pulses at charge density of 0.25 mC/cm2. These probes enable both high SNR (>16) electrical signal recording and remarkably high-resolution real-time neurotransmitter detection, on the same platform. Leveraging a new 2-step, double-sided pattern transfer method for GC structures, these probes allow extended long-term electrical stimulation with no electrode material corrosion. Cross-section characterization through FIB and SEM imaging demonstrate strong attachment enabled by hydroxyl and carbonyl covalent bonds between GC microstructures and top insulating and bottom substrate layers. Extensive in-vivo and in-vitro tests confirmed: (i) high SNR (>16) recordings, (ii) highest reported CSC for non-coated neural probe (61.4 ± 6.9 mC/cm2), (iii) high-resolution dopamine detection (10 nM level - one of the lowest reported so far), (iv) recording of both electrical and electrochemical signals, and (v) no failure after 3.5 billion cycles of pulses. Therefore, these probes offer a compelling multi-modal platform for long-term applications of neural probe technology in both experimental and clinical neuroscience.

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.

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Spinal cord injuries (SCI) result 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 last five years. Only two of the studies were randomized controlled studies, while the other 13 studies were case or case-series designs. Compared to 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.

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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 3–5 μm thick patterned GC. Main results. We present the fabrication technology for the new Gr 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 vivo study of the use of these Gr on GC microelectrodes 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. The Gr on GC microelectrodes presented here offers a compelling case for expanding the potentials of Gr-based technology in the broad areas of neural probes.