In this study, we evaluated the role of residual supraspinal and afferent signaling and their convergence on the sublesional spinal network in subject diagnosed with complete paralysis (AIS-A).Methods: A combination of electrophysiologic techniques with positional changes and subject-driven reinforcement maneuvers was implemented in this study. Electrical stimulation was applied transcutaneously at the T9-L2 vertebra levels and the spinal cord motor evoked potentials (SEMP) were recorded from leg muscles. To test the influence of positional changes, the subject was placed in (i) supine, (ii) upright with partial body weight bearing and (iii) vertically suspended without body weight bearing positions.Results: Increase in amplitude of SEMP was observed during transition from supine to upright position, supporting the role of sensory input in lumbosacral network excitability. Additionally, amplitudes of SEMP were facilitated during reinforcement maneuvers, indicating a supralesional influence on sub-lesional network. After initial assessment, subject underwent rehabilitation therapy with following electrophysiological testing that reviled facilitation of SEMP. Conclusion:These results demonstrate that combination of electrophysiological techniques with positional and reinforcement maneuvers can add to the diagnostics of discomplete SCI. These findings also support an idea that integration of supraspinal and afferent information on sub-lesional circuitry plays a critical role in facilitation of spinal sensorimotor network in discomplete SCI.

Glycine receptors (GlyRs) are indispensable to maintain excitatory/inhibitory balance in neuronal circuits controlling reflex and rhythmic motor behaviors. Here we have developed Glyght, the first GlyR ligand controlled with light. It is selective over other cys-loop receptors, active in vivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understand inhibitory circuits in intact animals, and to develop drug-based phototherapies.

Electrical stimulation of the cerebral cortex (ESCC) has been used to treat intractable neuropathic pain for nearly two decades, however, no standardized approach for this technique has been developed. In order to optimize targeting and validate the effect of ESCC before placing the permanent grid, we introduced initial assessment with trial stimulation, using a temporary grid of subdural electrodes. In this retrospective study we evaluate the role of electrode location on cerebral cortex in control of neuropathic pain and the role of trial stimulation in target-optimization for ESCC. Location of the temporary grid electrodes and location of permanent electrodes were evaluated in correlation with the long-term efficacy of ESCC. The results of this study demonstrate that the long-term effect of subdural pre-motor cortex stimulation is at least the same or higher compare to effect of subdural motor or combined pre-motor and motor cortex stimulation. These results also demonstrate that the initial trial stimulation helps to optimize permanent electrode positions in relation to the optimal functional target that is critical in cases when brain shift is expected. Proposed methodology and novel results open a new direction for development of neuromodulation techniques to control chronic neuropathic pain.