Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury.

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, 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. 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. Spinal cord associative plasticity, repetitive pairing of these pathways for 5 or 30 min in awake rats, increased spinal excitability for hours after pairing ended. To apply spinal cord associative plasticity as therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical spinal cord injury as in uninjured rats, demonstrating that spared connections after moderate spinal cord injury were sufficient to support plasticity. In a blinded trial, rats received a moderate C4 contusive spinal cord injury. Ten days after injury, they were randomized to 30 min of spinal cord associative plasticity each day for 10 days or sham stimulation. Rats with spinal cord associative plasticity had significantly improved function on the primary outcome measure, a test of dexterity during manipulation of food, at 50 days after spinal cord injury. In addition, rats with spinal cord associative plasticity had persistently stronger responses to cortical and spinal stimulation than sham stimulation rats, indicating a spinal locus of plasticity. After spinal cord associative plasticity, rats had near normalization of H-reflex modulation. The groups had no difference in the rat grimace scale, a measure of pain. We conclude that spinal cord associative plasticity strengthens sensorimotor connections within the spinal cord, resulting in partial recovery of reflex modulation and forelimb function after moderate spinal cord injury. Since both motor cortex and spinal cord stimulation are performed routinely in humans, this approach can be trialled in people with spinal cord injury or other disorders that damage sensorimotor connections and impair dexterity.

Resistance Temperature Detectors Fabricated via Dual Fused Deposition Modeling of Polylactic Acid and Polylactic Acid/Carbon Black Composites.

Planar-type resistance temperature detectors (P-RTDs) were fabricated via fused deposition modeling by dual nozzle extrusion. The temperature-sensing element of the fabricated sensor was printed with electrically conductive polylactic acid/carbon black (PLA/CB) composite, while the structural support was printed with a PLA insulator. The temperature-dependent resistivity change of PLA/CB was evaluated for different stacking sequences of PLA/CB layers printed with [0°/0°], [-45°/45°], and [0°/90°] plies. Compared to a PLA/CB filament used as 3D printing source material, the laminated structures exhibited a response over 3 times higher, showing a resistivity change from -10 to 40 Ω∙cm between -15 and 50 °C. Then, using the [0°/90°] plies stacking sequence, a P-RTD thermometer was fabricated in conjunction with a Wheatstone bridge circuit for temperature readouts. The P-RTD yielded a temperature coefficient of resistance of 6.62 %/°C with high stability over repeated cycles. Fabrication scalability was demonstrated by realizing a 3 × 3 array of P-RTDs, allowing the temperature profile detection of the surface in contact with heat sources.

Targeted Infarction of the Internal Capsule in the Rat Using Microstimulation Guidance.

Background and Purpose- Lacunar strokes are subcortical infarcts with small size and high disability rates, largely due to injury of the corticospinal tract in the internal capsule (IC). Current rodent models of lacunar infarcts are created based on stereotactic coordinates. We tested the hypothesis that better understanding of the somatotopy of the IC and guiding the lesion with electrical stimulation would allow a more accurate lesion to the forelimb axons of the IC. Methods- We performed electrophysiological motor mapping and viral tracing to define the somatotopy of the IC of Sprague Dawley rats. For the lesion, we used an optrode, which contains an electrode to localize forelimb responses and an optical fiber to deliver light. The infarct was induced when light activated the photothrombotic agent Rose Bengal, which was administered systemically. Results- We found largely a separate distribution of the forelimb and hindlimb axons in the IC, both by microstimulation mapping and tract tracing. Microstimulation-guided IC lesions ablated the forelimb axons of the IC in rats and caused lasting forelimb impairments while largely preserving the hindlimb axons of the IC and surrounding gray matter. Conclusions- Stimulation guidance enabled selective and reproducible infarcts of the forelimb axons of the IC in rats. Visual Overview- An online visual overview is available for this article.