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The human soleus H-reflex is commonly tested as an indicator of the reflex excitability of the calf muscles with infrequent stimuli to a subject seated and at rest. However, the reflex varies widely with the level of voluntary contraction and with the time history of stimulation. We studied two aspects of this variation. Antagonist (tibialis anterior) activation decreases the response, while increasing agonist (soleus) activation increases the H-reflex to a peak after which it declines. In subjects with large H-reflexes at rest, the reflex peaked at low levels of contraction. In contrast, in subjects with small H-reflexes at rest, the reflex peaked at higher levels of contraction for reasons that were elucidated using a realistic computer model. A parabolic curve fitted the maximum amplitude of the H-reflex in the model and over the entire range of contractile levels studied. The second aspect studied was post-activation depression or homosynaptic depression (HD), which has been described previously as a reduction of a second H-reflex elicited shortly after an initial reflex. We confirmed the presence of HD in resting, seated subjects for intervals up to 4 s. However, by voluntarily activating the soleus muscle, HD was drastically reduced when seated and abolished when standing. This suggests that HD may be absent in normal, functional movements and perhaps in clinical conditions that alter H-reflexes. Meaningful, quantitative measurements of reflex excitability can only be made under voluntary activity that mimics the condition of interest.

Successful clinical translation of prospective cytoprotectants will likely occur only with treatments that improve functional recovery in preclinical (rodent) studies. Despite this assumption, many rely solely on histopathologic end points or the use of one or two simple behavioral tests. Presently, we used a battery of tests to gauge recovery after a unilateral intracerebral hemorrhagic stroke (ICH) targeting the striatum. In total, 60 rats (N = 15 per group) were stereotaxically infused with 0 (SHAM), 0.06 (MILD lesion), 0.12 (MODERATE lesion), or 0.18 U (SEVERE lesion) of bacterial collagenase. This created a range of injury akin to moderate (from SEVERE to MODERATE or MODERATE to MILD lesion size ∼30% reduction) and substantial cytoprotection (SEVERE to MILD lesion size—51% reduction). Post-ICH functional testing occurred over 30 days. Tests included the horizontal ladder and elevated beam tests, swimming, limb-use asymmetry (cylinder) test, a Neurologic Deficit Scale, an adhesive tape removal test of sensory neglect, and the staircase and single pellet tests of skilled reaching. Most tests detected significant impairments (versus SHAM), but only a few (e.g., staircase) frequently distinguished among ICH groups and none consistently differentiated among all ICH groups. However, by using a battery of tests we could behaviorally distinguish groups. Thus, preclinical testing would benefit from using a battery of behavioral tests as anything less may miss treatment effects. Such testing must be based on factors including the type of lesion, the postoperative delay and the time required to complete testing.

Paired associative stimulation (PAS) involves paired-stimulation pulses at both the head (via transcranial magnetic stimulation) and the periphery (via peripheral nerve stimulation). The purpose of PAS, when applied to the spinal cord, is to induce neuroplasticity and upregulate the corticospinal tract leading to effector muscles. While limited research has suggested that it is possible to produce neuroplasticity through spinal PAS, all such studies have provided stimulation at a fixed frequency of 0.1 or 0.2 Hz.The present study therefore sought to compare the effectiveness of a typical 0.1 Hz paradigm with a 1 Hz paradigm, and a paradigm which provided stimulation in 5 Hz "bursts". Two inter-stimulus intervals were tested: one which was expected to produce synchronous pre- and post-synaptic activation at the spinal synapse, and one which was not. The peripheral stimulation was applied at the wrist, to induce thumb adduction.None of the paradigms were able to successfully induce neuroplasticity in a consistent manner.The high between-subject variability in this study suggests that responses to the spinal PAS treatment may have been highly individual. This serves to highlight a potential limitation of the spinal PAS treatment, which is that its effectiveness may not be universal, but rather dependent on each specific recipient. This may be a challenge faced by spinal PAS should it continue to be tested as a potential novel therapy.

Objectives Functional electrical stimulation (FES) has been shown to facilitate the recovery of grasping function in individuals with incomplete spinal cord injury. Neurophysiological theory suggests that this benefit may be further enhanced by a more consistent pairing of the voluntary commands sent from the user's brain down their spinal cord with the electrical stimuli applied to the user's periphery. The objective of the study was to compare brain-machine interfaces (BMIs)-controlled and electromyogram (EMG)-controlled FES therapy to three more well-researched therapies, namely, push button-controlled FES therapy, voluntary grasping (VOL), and BMI-guided voluntary grasping. Materials and Methods Ten able-bodied participants underwent one hour of each of five grasping training modalities, including BMI-controlled FES (BMI-FES), EMG-controlled FES (EMG-FES), conventional push button-controlled FES, VOL, and BMI-guided voluntary grasping. Assessments, including motor-evoked potential, grip force, and maximum voluntary contraction, were conducted immediately before and after each training period. Results Motor-evoked potential-based outcome measures were more upregulated following BMI-FES and especially EMG-FES than they were following VOL or FES. No significant changes were found in the more functional outcome measures. Conclusions These results provide preliminary evidence suggesting the potential of BMI-FES and EMG-FES to induce greater neuroplastic changes than conventional therapies, although the precise mechanism behind these changes remains speculative. Further investigation will be required to elucidate the underlying mechanisms and to conclusively determine whether these effects can translate into better long-term functional outcomes and quality of life for individuals with spinal cord injury.

17 β-estradiol reduces cell death after global and focal ischemia and subarachnoid hemorrhage in rodents. Presently, we tested whether estrogen improves outcome after intracerebral hemorrhage (ICH) in male rats. Rats were implanted subcutaneously with 0.05, 0.25, or 0.50 mg pellets of estrogen (21-day release) or subjected to a sham procedure. Two weeks after implantation, they were given a striatal ICH via an infusion of collagenase. The three estrogen groups had significantly smaller lesions at a 7-day survival. Some rats had core temperature measured with an implanted telemetry probe, which also measured whole-body movements. Estrogen did not affect temperature nor activity levels after ICH. A second study with 0.25 mg pellets, administered once or twice, showed persistent histologic protection (30 days) and some functional benefit (e.g., elevated beam). A spectrophotometric hemoglobin assay showed that the 0.25 mg dose significantly reduced hemorrhagic blood volume at 12 hours after ICH. Regardless, estrogen did not lessen cerebral edema at 2 days after ICH and functional benefits were not consistently found on all tests (e.g., cylinder task). In summary, estrogen pretreatment reduces injury after ICH, in part by reducing bleeding. Estrogen may thus lessen injury and improve outcome after ICH in humans.

Cerebral ischemia and hemorrhage (stroke) are leading causes of death and disability. The goal of experimental cytoprotectants (neuroprotection) for stroke is to reduce cell death and thereby improve functional outcome. Rodents (rat, gerbil, mouse) are most commonly used to model ischemic and hemorrhagic insults. Despite the fact that behavioral recovery is the clinical endpoint of greater concern, many cytoprotection studies rely solely upon histopathological endpoints (e.g., infarct volume) to gauge treatment efficacy (DeBow et al., 2003; Can. J. Neurol. Sci). Furthermore, those studies that assess recovery often use only a neurological deficit score (NDS; e.g., paw placement, spontaneous rotation) and do not use more demanding / informative tests (e.g., skilled reaching). Successful translation of putative cytoprotectants from rodent models to human will depend upon how well treatments are initially assessed. Many functional tests are available in the rat and have been used in focal ischemia studies. Presently, we used a battery of functional tests, which are sensitive to sensory and motor system dysfunction, to gauge outcome after an intracerebral hemorrhagic stroke (ICH) largely targeting the striatum. Sixty adult male Sprague Dawley rats (N = 15 per group) were stereotaxically infused with 1 L of sterile saline containing 0 (SHAM), 0.06 (MILD lesion), 0.12 (MODERATE lesion), or 0.18 U (SEVERE lesion) of bacterial collagenase. Testing began one day following ICH and was repeated over 30 days. Tests included the horizontal ladder and beam walking tests, swimming, limb-use asymmetry (cylinder) test, a NDS, an adhesive tape removal test of sensory neglect, and the staircase and single pellet tests of skilled reaching. At present, the NDS, staircase, neglect and single-pellet tests have been analyzed. Overall, these tests revealed significant impairments (vs. SHAM) that improved over time (e.g., deficits on the NDS were greatest on days 1 and 2). However, despite significant differences in lesion size, we were often unable to statistically distinguish between MILD and MODERATE or MODERATE and SEVERE groups (e.g., neglect test). As for skilled reaching, the staircase test revealed significant contralateral forelimb impairments in the three ICH groups and was often able to distinguish among ICH groups. The SEVERE group also had significant ipsilateral impairments. Skilled reaching impairments were also found with the single-pellet test in the ICH groups. However, it was not possible to compare success among ICH groups because many rats in the MODERATE and SEVERE groups completely switched limb preference. Indeed, a detailed analysis of the entire reaching sequence with the contralateral limb was only possible in the SHAM and MILD groups. In conclusion, multiple behavioral tests are needed to comprehensively evaluate functional recovery after ICH. However, some tests (e.g., neglect test) are either not recommended for this model owing to the time required to test animals, variability, and the insensitivity to lesion size, or are of limited use (e.g., for small lesions). Finally, our results show that modest neuroprotection (e.g., reducing lesion size from SEVERE to MODERATE) may not consistently improve functional recovery, thereby necessitating the use of several tests.