Modulation of H-reflex responses and frequency-dependent depression by repetitive spinal electromagnetic stimulation: From rats to humans and back to chronic spinal cord injured rats.

The lack of propagation of signals through survived fibers is among the major reasons for functional loss after incomplete spinal cord injury (SCI). Our recent results of animal studies demonstrate that spinal electromagnetic stimulation (SEMS) can enhance transmission in damaged spinal cord, and this type of modulation depends on the function of NMDA receptors at the neuronal networks below the injury level. Here, our pilot human study revealed that administration of repetitive SEMS induced long-lasting modulation of H-responses in both healthy and participants with chronic SCI. In order to understand the mechanisms underlying these effects, we have used an animal model and examined effects of SEMS on H-responses. Effects of SEMS on H-responses, frequency-dependent depression (FDD) of H-reflex, and possible underlying mechanisms have been examined in both naïve and rats with SCI. Our results demonstrate that consistent with the effects of SEMS on H-reflex seen in humans, repetitive SEMS induced similar modulation in excitability of peripheral nerve responses in both non-injured and rats with SCI. Importantly, our results confirmed the reduced FDD of H-reflex in SCI animals and revealed that SEMS was able to recover FDD in rats with chronic SCI. Using intraspinal injections of the NMDA receptor blocker MK-801, we have identified NMDA receptors as an important contributor to these SEMS-induced effects in rats with SCI. These results identify SEMS as a novel non-invasive technique for modulation of neuro-muscular circuits and, importantly, modulation of spinal networks after chronic SCI.

Assessment of Workspace Attributes Under Simulated Index Finger Proximal Interphalangeal Arthrodesis.

This article presented an assessment of quantitative measures of workspace (WS) attributes under simulated proximal interphalangeal (PIP) joint arthrodesis of the index finger. Seven healthy subjects were tested with the PIP joint unconstrained (UC) and constrained to selected angles using a motion analysis system. A model of the constrained finger was developed in order to address the impact of the inclusion of prescribed joint arthrodesis angles on WS attributes. Model parameters were obtained from system identification experiments involving flexion-extension (FE) movements of the UC and constrained finger. The data of experimental FE movements of the constrained finger were used to generate the two-dimensional (2D) WS boundaries and to validate the model. A weighted criterion was formulated to define an optimal constraint angle among several system parameters. Results indicated that a PIP joint immobilization angle of 40-50 deg of flexion maximized the 2D WS. The analysis of the aspect ratio of the 2D WS indicated that the WS was more evenly distributed as the imposed PIP joint constraint angle increased. With the imposed PIP joint constraint angles of 30 deg, 40 deg, 50 deg, and 60 deg of flexion, the normalized maximum distance of fingertip reach was reduced by approximately 3%, 4%, 7%, and 9%, respectively.

Spinal electro-magnetic stimulation combined with transgene delivery of neurotrophin NT-3 and exercise: novel combination therapy for spinal contusion injury.

Our recent terminal experiments revealed that administration of a single train of repetitive spinal electromagnetic stimulation (sEMS; 35 min) enhanced synaptic plasticity in spinal circuitry following lateral hemisection spinal cord injury. In the current study, we have examined effects of repetitive sEMS applied as a single train and chronically (5 wk, every other day) following thoracic T10 contusion. Chronic studies involved examination of systematic sEMS administration alone and combined with exercise training and transgene delivery of neurotrophin [adeno-associated virus 10-neurotrophin 3 (AAV10-NT3)]. Electrophysiological intracellular/extracellular recordings, immunohistochemistry, behavioral testing, and anatomical tracing were performed to assess effects of treatments. We found that administration of a single sEMS train induced transient facilitation of transmission through preserved lateral white matter to motoneurons and hindlimb muscles in chronically contused rats with effects lasting for at least 2 h. These physiological changes associated with increased immunoreactivity of GluR1 and GluR2/3 glutamate receptors in lumbar neurons. Systematic administration of sEMS alone for 5 wk, however, was unable to induce cumulative improvements of transmission in spinomuscular circuitry or improve impaired motor function following thoracic contusion. Encouragingly, chronic administration of sEMS, followed by exercise training (running in an exercise ball and swimming), induced the following: 1) sustained strengthening of transmission to lumbar motoneurons and hindlimb muscles, 2) better retrograde transport of anatomical tracer, and 3) improved locomotor function. Greatest improvements were seen in the group that received exercise combined with sEMS and AAV-NT3.

Transcranial magnetic stimulation (TMS) responses elicited in hindlimb muscles as an assessment of synaptic plasticity in spino-muscular circuitry after chronic spinal cord injury.

Electromagnetic stimulation applied at the cranial level, i.e. transcranial magnetic stimulation (TMS), is a technique for stimulation and neuromodulation used for diagnostic and therapeutic applications in clinical and research settings. Although recordings of TMS elicited motor-evoked potentials (MEP) are an essential diagnostic tool for spinal cord injured (SCI) patients, they are reliably recorded from arm, and not leg muscles. Mid-thoracic contusion is a common SCI that results in locomotor impairments predominantly in legs. In this study, we used a chronic T10 contusion SCI rat model and examined whether (i) TMS-responses in hindlimb muscles can be used for evaluation of conduction deficits in cortico-spinal circuitry and (ii) if plastic changes at spinal levels will affect these responses. In this study, plastic changes of transmission in damaged spinal cord were achieved by repetitive electro-magnetic stimulation applied over the spinal level (rSEMS). Spinal electro-magnetic stimulation was previously shown to activate spinal nerves and is gaining large acceptance as a non-invasive alternative to direct current and/or epidural electric stimulation. Results demonstrate that TMS fails to induce measurable MEPs in hindlimbs of chronically SCI animals. After facilitation of synaptic transmission in damaged spinal cord was achieved with rSEMS, however, MEPs were recorded from hindlimb muscles in response to single pulse TMS stimulation. These results provide additional evidence demonstrating beneficial effects of TMS as a diagnostic technique for descending motor pathways in uninjured CNS and after SCI. This study confirms the ability of TMS to assess plastic changes of transmission occurring at the spinal level.