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•Functional ultrasound quantifies hemodynamics with high resolution in the spinal cord.•Hemodynamics is related to the frequency of epidural stimulation (20–40 Hz).•Changes in hemodynamics are related to sub- or supra-threshold motor output.•Responses in dorsal and ventral spinal regions may reflect a neural-vascular coupling.•Observed neural-vascular coupling may reflect spinal cord functional organization. In this study functional ultrasound (fUS) imaging has been implemented to explore the local hemodynamics response induced by electrical epidural stimulation and to study real-time in vivo functional changes of the spinal cord, taking advantage of the superior spatiotemporal resolution provided by fUS. By quantifying the hemodynamics and electromyographic response features, we tested the hypothesis that the temporal hemodynamics response of the spinal cord to electrical epidural stimulation could reflect modulation of the spinal circuitry and accordingly respond to the changes in parameters of electrical stimulation. The results of this study for the first time demonstrate that the hemodynamics response to electrical stimulation could reflect a neural-vascular coupling of the spinal cord. Response in the dorsal areas to epidural stimulation was significantly higher and faster compared to the response in ventral spinal cord. Positive relation between the hemodynamics and the EMG responses was observed at the lower frequencies of epidural stimulation (20 and 40 Hz), which according to our previous findings can facilitate spinal circuitry after spinal cord injury, compared to higher frequencies (200 and 500 Hz). These findings suggest that different mechanisms could be involved in spinal cord hemodynamics changes during different parameters of electrical stimulation and for the first time provide the evidence that neural-vascular coupling of the spinal cord circuitry could be related to specific organization of spinal cord vasculature and hemodynamics.

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). 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. 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. 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.

The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman’s reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD’s immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz ( p < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control ( p < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.

In this study, the neuroanatomy of the swine lumbar spinal cord, particularly the spatial orientation of dorsal roots was correlated to the anatomical landmarks of the lumbar spine and to the magnitude of motor evoked potentials during epidural electrical stimulation (EES). We found that the proximity of the stimulating electrode to the dorsal roots entry zone across spinal segments was a critical factor to evoke higher peak-to-peak motor responses. Positioning the electrode close to the dorsal roots produced a significantly higher impact on motor evoked responses than rostro-caudal shift of electrode from segment to segment. Based on anatomical measurements of the lumbar spine and spinal cord, significant differences were found between L1-L4 to L5-L6 segments in terms of spinal cord gross anatomy, dorsal roots and spine landmarks. Linear regression analysis between intersegmental landmarks was performed and L2 intervertebral spinous process length was selected as the anatomical reference in order to correlate vertebral landmarks and the spinal cord structures. These findings present for the first time, the influence of spinal cord anatomy on the effects of epidural stimulation and the role of specific orientation of electrodes on the dorsal surface of the dura mater in relation to the dorsal roots. These results are critical to consider as spinal cord neuromodulation strategies continue to evolve and novel spinal interfaces translate into clinical practice.

The case of a 37-year-old woman who suffered from spinal cord infarction (SI), resulting in a complete spinal cord injury (AIS A, neurological level T10), and autonomic dysfunction is presented. This study aimed to assess the effect of transcutaneous Spinal Cord Electrical Stimulation (tSCS) on improving motor, sensory, and autonomic function after SI. During the first 8 months, tSCS was applied alone, then, physical therapy (PT) was included in the sessions (tSCS+PT), until completion of 20 months. Compared to baseline, at 20 months, an increase in ISNCSCI motor (50 vs. 57) and sensory scores (light touch, 72 vs. 82; pinprick, 71 vs. 92) were observed. Neurogenic Bladder Symptoms Score (NBSS) changed from 27 at baseline to 17 at 20 months. ISAFSCI scores in sacral autonomic function improved from 0 pts (absent function) to 1 pt. (altered function) indicating better sphincter control. EMG recordings during volitional movements, including overground stepping with 80% of body weight support showed activity in gluteus medialis, tensor fascia latae, sartorius, rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius medialis, indicating a partial reversion of paralysis. RMS analysis indicated higher activity during “tSCS on” compared to “tSCS off” during overground stepping in bilateral rectus femoris ( p < 0.001) and gastrocnemius medialis ( p < 0.01); and unilateral biceps femoris, and tibialis anterior ( p < 0.001). As this is the first report on the use of tSCS in the case of SI, future studies in a case series are warranted.

Here, we report the effect of newly regenerated axons via scaffolds on reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation (EES). Motor recovery was evaluated for 7 weeks after spinal transection and following implantation with scaffolds seeded with neurotrophin producing Schwann cell and with rapamycin microspheres. Combined treatment with scaffolds and EES-enabled stepping led to functional improvement compared to groups with scaffold or EES, although, the number of axons across scaffolds was not different between groups. Re-transection through the scaffold at week 6 reduced EES-enabled stepping, still demonstrating better performance compared to the other groups. Greater synaptic reorganization in the presence of regenerated axons was found in group with combined therapy. These findings suggest that newly regenerated axons through cell-containing scaffolds with EES-enabled motor training reorganize the sub-lesional circuitry improving motor recovery, demonstrating that neuroregenerative and neuromodulatory therapies cumulatively enhancing motor function after complete SCI.

Dual florigen response in potatoes The seasonality of plant developmental processes such as flowering and tuber formation is dependent largely on changes in day length. This response is mediated in Arabidopsis , tomato and rice plants by a mobile protein known as FLOWERING LOCUS T (FT), the main component of the long-range florigen signal. A study of the potato ( Solanum tuberosum ) now shows that floral and tuberization transitions are controlled by two different FT -like genes ( StSP3D and StSP6A ) that respond to independent environmental cues. Seasonal fluctuations in day length regulate important aspects of plant development such as the flowering transition or, in potato ( Solanum tuberosum ), the formation of tubers. Day length is sensed by the leaves, which produce a mobile signal transported to the shoot apex or underground stems to induce a flowering transition or, respectively, a tuberization transition. Work in Arabidopsis, tomato and rice ( Oryza sativa ) identified the mobile FLOWERING LOCUS T (FT) protein as a main component of the long-range ‘florigen’, or flowering hormone, signal 1 , 2 , 3 . Here we show that expression of the Hd3a gene, the FT orthologue in rice, induces strict short-day potato types 4 to tuberize in long days. Tuber induction is graft transmissible and the Hd3a–GFP protein is detected in the stolons of grafted plants, transport of the fusion protein thus correlating with tuber formation. We provide evidence showing that the potato floral and tuberization transitions are controlled by two different FT -like paralogues (St SP3D and St SP6A ) that respond to independent environmental cues, and show that an autorelay mechanism involving CONSTANS modulates expression of the tuberization-control St SP6A gene.

In a previous report, we found neurons with ON-OFF and OFF-ON firing activity in the obex reticular formation during scratching. The aim of the present study was to examine whether the spinal neurons also exhibit this type of activity in relation to the \"postural stage\" of fictive scratching in the cat. We found that the extensor and intermediate scratching neurons exhibit an ON-OFF firing rate; conversely, the flexor neurons show an OFF-ON activity, relative to every scratching episode. These patterns of spiking activity are similar to those found in neurons from the obex reticular formation during scratching. Our findings provide support to the following hypotheses. First, there is a possible functional link between supraspinal and spinal, ON-OFF and OFF-ON neuronal groups. Second, the fictive goal-directed motor action to maintain the fictive \"postural stage\" of the hindlimb during fictive scratching is associated with the neuronal tonic activity of the OFF-ON spinal neurons, whereas the ON-OFF spinal neurons are associated with an extensor tone that occurred prior the postural stage.

Motoneurons, the final common path of the central nervous system, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we show that extrasynaptic α5 subunit-containing GABAA receptors (α5GABAAR) co-localize with choline acetyltransferase (ChAT) suggesting that these receptors are expressed in motoneurons. In these cells, α5GABAA receptors may be activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

Peripheral and autonomic neuropathy are common in type 2 diabetes; they are associated with oxidative stress and inflammation. Cocoa, rich in polyphenols, may offer neuroprotective benefits. This study evaluated the effect of cocoa supplementation on the biochemical, clinical, and somatosensory profile of neuropathy in individuals with type 2 diabetes. A 12-week, double-blind controlled trial involved 39 subjects randomized to receive cocoa capsules (50 mg polyphenols) or placebo (methylcellulose). Evaluations included glycemic and lipid profiles, neutrophil/lymphocyte ratio, blood pressure, standardized questionnaires, anthropometric measurements, and the rate-dependent depression of the H-reflex. In the cocoa group, the Toronto score decreased by 2.63 points and the BEST score decreased by 1.45 points. In the placebo group, these reductions were 1.84 and 2.21 points, respectively. Neither difference was statistically significant between groups (p > 0.05). Quality-of-Life questionnaire score decreased by 9.2 points in the cocoa group, but without significant difference to the placebo group (p = 0.501). Fasting glucose and HbA1c levels decreased in the placebo group by 38 mg/dL (0.28%) but were not significantly different from the cocoa group (p > 0.05). No other intra- or inter-group differences were significant (p > 0.05). Cocoa supplementation did not show significant improvements over the placebo in the measured outcomes. Both groups showed persistent abnormalities in spinal somatosensory processing, with an RDD of the H-reflex ≥ 0.5.