The destruction and hollowing of entire tissue segments represent an insurmountable barrier to axonal regeneration and therapeutics in chronic spinal cord injury. To circumvent this problem, we engineered neural prosthetics, by assembling electrospun nanofibers and self-assembling peptides into composite guidance channels and transplanted them into the cysts of a postcontusive, chronic spinal cord injury rat model, also providing delivery of proregenerative cytokines. Six months later conspicuous cord reconstruction was observed. The cyst was replaced by newly formed tissue comprising neural and stromal cells. Nerve fibers were interspersed between and inside the guidance channels, spanning the lesion, amidst a well-developed vascular network, basal lamina, and myelin. This was accompanied by a significant improvement in the activity of ascending and descending motor pathways and the global locomotion score. Thus by engineering nanostructured matrices into neuroprosthetics, it is possible to recreate an anatomical, structural, and histological framework, which leads to the replacement of large, hollow tissue gaps in the chronically injured spinal cord, fostering axonal regeneration and neurological recovery.
Excitability of the H-reflex in the relaxed flexor digitorum superficialis (FDS) muscle was tested in five subjects observing a reaching and grasping action. The amplitude of the FDS H-reflex was modulated with a peak occurring during the hand-opening phase of the observed movement. When the H-reflex was facilitated by subliminal transcranial magnetic stimulation (TMS), the modulation was larger than for an unconditioned reflex of similar size. This suggests that the primary motor cortex excitability is modulated by action viewing and reasonably causes the motoneuronal excitability changes. Moreover, motor evoked potentials (MEPs) were elicited by supraliminal TMS in FDS, flexor carpi radialis (FCR) and first dorsal interosseus (FDI) when observing the same movement. MEP amplitude was modulated in FDS with the same time-course as the H-reflex, the peak excitability occurring during hand opening. In FDI, however, the maximal excitability occurred during finger closing while in FCR no correlation was found with the movement phases. Finally the EMG activity of FCR, FDS and FDI was recorded while the subjects were actually performing a grasping movement similar to the one observed. In all subjects and for each muscle there was a clear-cut correspondence between the time-course of the excitability modulation of MEPs and the temporal pattern of EMG recruitment. In conclusion, the present study suggests that 'motor resonance' subliminally activates the same motor pathways that would be overtly recruited in each observer when actually performing the observed movement, reproducing the personal strategy adopted in the same task.
In monkeys, motor outputs from premotor cortex (PM) involve cortico-cortical connections with primary motor cortex (M1). However, in humans, the functional organization of PM and its relationship with the corticospinal tract (CST) is still uncertain. This study was carried out in 21 patients undergoing intraoperative brain mapping prior to tumor resection. The left ventrolateral premotor cortex (vlPM-BA6) was identified preoperatively by functional magnetic resonance imaging, and then investigated intraoperatively using high frequency direct electrical stimulation (HF-DES) of the convexity of M1 and vlPM-BA6, with simultaneous recording of motor-evoked potentials (MEPs) from oro-facial, hand and arm muscles. The somatotopy, organization of evoked responses, latency of MEPs, and cortical excitability of vlPM-BA6 were compared with reference data from M1. vlPM-BA6 was found to be less excitable, with significantly longer MEP latencies than M1. In addition to the pure oro-facial and hand-arm muscle representation, a "transition oro-hand zone" was identified in vlPM-BA6. The longer latency of vlPM-BA6 MEPs suggests that human vlPM could act on spinal motoneurons either directly through more slowly conducting CST fibers or via less direct pathways through M1, brainstem, or spinal mechanisms. The results help in disclosing the very different roles of vlPM and M1 in motor control.
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