Sensory Afferent Signals Research Articles

The effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in primary premature ejaculation: a pilot study.

Penile hypersensitivity is not the whole penis, but rather only a part of the penis. Though local anesthetic can prolong intravaginal ejaculation latency time by reducing penile hypersensitivity, the effect on the hypersensitive and nonsensitive areas of penis is still unclear. The study aimed to explore whether the effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation. Penile neurophysiological tests were performed on 290 patients with primary premature ejaculation. The sensory threshold, latency, and amplitude were recorded before and after the topical application of a local anesthetic (lidocaine cream) on the penis. Local anesthetics increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference but only prolonged the latency of the hypersensitive areas. According to the neurophysiological results, 149 of 290 patients with primary premature ejaculation had normal penile sensitivity and 141 had penile hypersensitivity. While penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive, and may be that only a part of the penis is hypersensitive, and we examined the following hypersensitivities: glans hypersensitivity only (14 cases), shaft hypersensitivity only (77 cases), and whole penis hypersensitivity (50 cases). Local anesthetics (lidocaine cream) increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference (P < .001) but only prolonged the latency of the hypersensitive areas (P < .001), and the latency of the nonsensitive areas was not different (P > .05). The present discovery implies that it is possible to improve ejaculation by applying local anesthetics externally to the hypersensitive areas of the penis to reduce the afferent local sensory signals, and improve intravaginal ejaculation latency time through accurately decreasing penile sensibility. This is the first large-sample study to explore the difference of local anesthetics' effects on the hypersensitive and nonsensitive areas of the penis by means of neurophysiological methods in premature ejaculation. Our study exclusively examines alterations in penile evoked potential following electrical stimulation, which may not entirely encompass shifts in penile receptivity during sexual activity. The effects of local anesthetics on the same penis varied with penile sensitivity, and can only prolong the latency of hypersensitive area of the penis. The effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation.

Epididymal Fat-Derived Sympathoexcitatory Signals Exacerbate Neurogenic Hypertension in Obese Male Mice Exposed to Early Life Stress.

[Figure: see text].

2: Sensorimotor Myoelectric Control Using Surface Based Regenerative Peripheral Nerve Interface (RPNI)

Purpose:Although advanced prosthetic devices have the potential to allow fine-motor movements and extract somatosensory signals via sensitive pressure sensors, an ideal interface to integrate the human nervous system with the prosthetic doesn’t exist. Furthermore, the requirement for the implantation of indwelling electrodes and prohibitive costs limits the application of current technologies. The Regenerative Peripheral Nerve Interface (RPNI) was developed as a stable biologic interface on the notion of providing physiologic end-organ targets for regenerating axons by implantation of a residual nerve into an autogenous free muscle graft. Despite providing intuitive motor control, RPNI sensory feedback is limited and also relies on implantable electrodes for myoelectric signal transmission. To address these challenges, we investigated the placement of RPNIs underneath the defatted skin in rats to capture myoelectric signals using surface electrodes. This strategy simultaneously provides sensory feedback through the sensory reinnervation of the overlying skin.Methods:Utilizing six male F344 rats, the right tibial nerve was transected distally in the thigh before entering the leg’s posterior compartment. Subsequently, the left side extensor digitorum longus (EDL) muscle was harvested and co-apted with the proximal segment of the tibial nerve for RPNI fabrication. The RPNI was placed and secured in between the biceps femoris muscle near the skin while the side opposite to the nerve coaptation was facing the dermis. The overlying skin was defatted and fixed on top of the superficial RPNI (S-RPNI). At two months post-surgery, functional motor reinnervation was evaluated by electrical stimulation of the tibial nerve and compound muscle action potentials (CMAPs) were recorded using surface electrodes. Sensory feedback was assessed by electrical and mechanical stimulation of the skin to respectively record sensory nerve action potentials (SNAPs) and sensory afferent signals. The S-RPNI construct and its overlying skin were subsequently harvested and processed for immunohistochemistry and whole-mount immunostaining.Results:Recording muscle CMAPs from the skin was readily feasible in all animals, showing robust signals with minimal noise distortion (366 µV ± 86.3). Electrical stimulation of the skin on the lateral thigh, which is not innervated by the tibial nerve normally, resulted in classic tri-phasic SNAP generation in this nerve. Brushing the overlying skin using a cotton swab generated synchronized monomorphic afferent signals. Sensory reinnervation of the skin was shown using IHC. Whole-mount staining of the muscle component showed regenerated muscle with new neuromuscular junctions (NMJs) and spatial segregation of sensory fibers toward their end-target organ.Conclusion:Superficially placed RPNI is a viable and an alternate methodology that is simple to implicate and has the potential to transmit simultaneous, real-time, and independent sensory and motor signals between the residual nerve and the prostheses.

Integration of predictions and afferent signals in body ownership

We aimed at investigating the contribution of sensory predictions triggered by the sight of an object moving towards the body for the sense of body ownership. We used a recently developed psychophysical discrimination task to assess body ownership in the rubber hand illusion. In this task, the participants had to choose which of the two right rubber hands in view felt most like their own, and the ownership discriminations were fitted to psychometric curves. In the current study, we occluded the visual impressions of the object moving towards one of the rubber hands (during the first two-thirds of the path) and only revealed the final third of the object's movement trajectory when it touched the rubber hand (approach-occluded condition). Alternatively, we occluded only the final part so that the main part of the movement towards the model hand was visible (touch-occluded). We compared these two conditions to an illusion baseline condition where the object was visible during the entire trajectory and contact (no-occlusion). The touch-occluded condition produced equally strong hand ownership as the baseline condition with no occlusion, while ownership perception was significantly reduced when vision of the object approaching the rubber hand was occluded (approach-occluded). Our results show that tactile predictions generated from seeing an object moving towards the body are temporally exact, and they contribute to the rubber hand illusion by integrating with temporally congruent afferent sensory signals. This finding highlights the importance of multisensory predictions in peripersonal space, object permanence, and the interplay between bottom-up sensory signals and top-down predictions in body ownership.

Altered hand proprioception following regional anesthesia as a cause of traumatic jersey finger: Report of two cases

The sense of body ownership is being increasingly studied by manipulating incoming signals from the periphery with local anesthetics. We sought to understand how altered proprioception induced by anesthesia triggered a traumatic jersey finger, immediately postoperatively, in two patients who underwent surgical carpal tunnel release. Multiple mechanisms contributed to these postoperative injuries associated with a fall. Hand anesthesia deprives the brain of important afferent sensory information and modifies hand size perception in the brain. Moreover, it blocks efferent motor signals that contribute to the perception of hand position with sensory afferent signals. When the patients fell, their movement control was inadequate, generating a strong contraction of the hand extrinsic flexor muscles, against forceful distal phalanx extension. Lastly, both patients had removed their numb operated hand from their arm sling. Disrupted sensory and motor paths modify self-attribution of the hand, and thus halt adequate efferent commands. Protecting the operated hand until full sensory and motor control is regained could have prevented such rare accidents from happening. Level of evidence: V

Continuous supplementary tactile feedback can be applied (and then removed) to enhance precision manipulation

BackgroundHuman sensorimotor control of dexterous manipulation relies on afferent sensory signals. Explicit tactile feedback is generally not available to prosthetic hand users, who have to rely on incidental information sources to partly close the control loop, resulting in suboptimal performance and manipulation difficulty. Recent studies on non-invasive supplementary sensory feedback indicated that time-discrete vibrational feedback delivered upon relevant mechanical events outperforms continuous tactile feedback. However, we hypothesize that continuous tactile feedback can be more effective in non-routine manipulation tasks (i.e., tasks where the grip force is modified reactively in response to the sensory feedback due to the unpredictable behavior of the manipulated object, such as picking and holding a virtual fragile object) if delivered to highly sensitive areas. We further hypothesize that this continuous tactile feedback is not necessary during all the duration of the manipulation task, since adaptation occurs.MethodsWe investigated the effectiveness of continuous tactile feedback in precision manipulation, together with a new sensory feedback policy, where the continuous tactile feedback is gradually removed when the grasp reaches a steady state (namely, transient tactile feedback). We carried out an experiment in a virtual-reality setting with custom tactile feedback devices, which can apply continuous pressure and vibrations, attached to the thumb and index finger. We enrolled 24 healthy participants and instructed them to pick and hold a fragile virtual cube without breaking it. We compared their manipulation performance when using four different sensory feedback methods, i.e., no tactile feedback, discrete vibrations, continuous tactile feedback, and transient tactile feedback. The latter consisted of gradually removing the continuous feedback in the static phase of the grasp.ResultsContinuous tactile feedback leads to a significantly larger number of successful trials than discrete vibrational cues and no feedback conditions, yet the gradual removal of the continuous feedback yields to comparable outcomes. Moreover, the participants preferred the continuous stimuli over the vibrational cues and the removal in the static phase did not significantly impact their appreciation of the continuous tactile feedback.ConclusionsThese results advocate for the use of continuous supplementary tactile feedback for fine manipulation control and indicate that it can seamlessly be removed in the static phase of the grasp, possibly due to the mechanism of sensory adaptation. This encourages the development of energy-efficient supplementary feedback devices for prosthetic and telemanipulation applications, where encumbrance and power consumption are burdensome constraints.

Solving Baroreceptor Mystery: Role of PIEZO Ion Channels.

Baroreceptors are pressure sensors on specialized neurons that specifically detect stretch within arterial walls, which occurs when BP increases. When baroreceptors are stretched, they transmit afferent (sensory) signals to the nucleus tractus solitarii in the medulla. These signals inhibit

Abstract 36: Viability and Signal Transduction with the Composite Regenerative Peripheral Nerve Interface (C-RPNI)

PURPOSE: There have been many advancements in the field of neuroprosthetics for functional restoration following limb loss. However, devices that provide prosthetic users with intuitive, simultaneous motor control and somatosensory feedback have not yet been realized. Critical to the evolution of this ideal bioprosthetic device is the development of a reliable, biologic human-machine interface that facilitates transmission of both efferent motor signals for device control, and afferent somatosensory information. The Composite Regenerative Peripheral Nerve Interface (C-RPNI) is a novel biologic interface that demonstrates promise in this role. The C-RPNI is a surgical construct composed of a transected, mixed peripheral nerve implanted between a composite free graft consisting of de-epithelialized glaborous skin and skeletal muscle. The purpose of the present study was to investigate the viability and bidirectional signal transduction capabilities of the C-RPNI. METHODS: C-RPNIs were surgically implanted on the end of transected common peroneal nerves of thirty F344 rats using de-epithelialized dermal grafts harvested from glaborous skin of isogenic donor rat hindpaws and free skeletal muscle grafts from the animal’s contralateral limb. Thirty animals underwent endpoint testing at three months (n=15) and at six months (n=15). Electrophysiologic testing was performed to determine both the in vivo efferent and afferent signal transduction capabilities of C-RPNIs following electrical stimulation. C-RPNI constructs were also harvested for histologic evaluation at both three- and six-month study endpoints. RESULTS: C-RPNI constructs remained viable over the study period with regeneration and revascularization evident on histologic analysis. At both three and six months, electrical stimulation of proximal peroneal nerve evoked efferent signals (CMAPs) and muscle contractions that were measured from the free muscle graft component of the C-RPNI. The average CMAP amplitude recorded from the muscle was 6.3 ± 1.4 mV at three months and 6.1 ± 1.6 mV at six months. The average conduction velocity was 11.0 ± 2.7 m/sec at three months and 12.0 ± 2.0m/sec at six months. Electrical stimulation of the dermal side of the C-RPNI evoked afferent signals (CSNAPs) in the proximal peroneal nerve at both three and sixth months. The average peak-to-peak CSNAP amplitude was 391.6 ± 145.0 µV at three months and 267.1 ± 143.8 µV at six months. The average conduction velocity with an average conduction velocity was 11.6 ± 3.0 m/sec at three months and 9.6 ± 2.4 m/sec at six months. CONCLUSIONS: C-RPNI constructs remained viable with preserved innervation for six months following implantation. Recorded efferent motor signals and evoked afferent signals remained robust over time. The C-RPNI facilitates bidirectional signal transduction of both efferent motor signals and afferent sensory signals. This confirmation of bidirectional signal transduction in the C-RPNI validates the potential role of the C-RPNI in human-machine interfacing.

Innervation of the Nose and Nasal Region of the Rat: Implications for Initiating the Mammalian Diving Response.

Most terrestrial animals demonstrate an autonomic reflex that facilitates survival during prolonged submersion under water. This diving response is characterized by bradycardia, apnea and selective increases in peripheral vascular resistance. Stimulation of the nose and nasal passages is thought to be primarily responsible for providing the sensory afferent signals initiating this protective reflex. Consequently, the primary objective of this research was to determine the central terminal projections of nerves innervating the external nose, nasal vestibule and nasal passages of rats. We injected wheat germ agglutinin (WGA) into specific external nasal locations, into the internal nasal passages of rats both with and without intact anterior ethmoidal nerves (AENs), and directly into trigeminal nerves innervating the nose and nasal region. The central terminations of these projections within the medulla were then precisely mapped. Results indicate that the internal nasal branch of the AEN and the nasopalatine nerve, but not the infraorbital nerve (ION), provide primary innervation of the internal nasal passages. The results also suggest afferent fibers from the internal nasal passages, but not external nasal region, project to the medullary dorsal horn (MDH) in an appropriate anatomical way to cause the activation of secondary neurons within the ventral MDH that express Fos protein during diving. We conclude that innervation of the anterior nasal passages by the AEN and nasopalatine nerve is likely to provide the afferent information responsible for the activation of secondary neurons within MDH during voluntary diving in rats.

Restoration of the nasopharyngeal response after bilateral sectioning of the anterior ethmoidal nerve in the rat.

In response to stimulation of the nasal passages with volatile ammonia vapors, the nasopharyngeal reflex produces parasympathetically mediated bradycardia, sympathetically mediated increased peripheral vascular tone, and apnea. The anterior ethmoidal nerve (AEN), which innervates the anterior nasal mucosa, is thought to be primarily responsible for providing the sensory afferent signals that initiate these protective reflexes, as bilateral sectioning causes an attenuation of this response. However, recent evidence has shown cardiovascular responses to nasal stimulation with ammonia vapors are fully intact 9 days after bilateral AEN sectioning, and are similar to control animals without bilaterally sectioned AENs. To investigate this restoration of the nasopharyngeal response, we recorded the cardiorespiratory responses to nasal stimulation with ammonia vapors immediately after, and 3 and 9 days after, bilateral AEN sectioning. We also processed brainstem tissue for Fos to determine how the restoration of the nasopharyngeal response would affect the activity of neurons in the medullary dorsal horn (MDH), the part of the ventral spinal trigeminal nucleus caudalis region that receives primary afferent signals from the nose and nasal passages. We found 3 days after bilateral AEN sectioning the cardiorespiratory responses to nasal stimulation are partially restored. The bradycardic response to nasal stimulation is significantly more intense 3 days after AEN sectioning compared to Acute AEN sectioning. Surprisingly, 3 days after AEN sectioning the number of Fos‐positive neurons within MDH decreased, even though the cardiorespiratory responses to nasal stimulation intensified. Collectively these findings indicate that, besides the AEN, there are alternate sensory pathways that can activate neurons within the trigeminal nucleus in response to nasal stimulation. The findings further suggest trigeminal neuronal plasticity involving these alternate sensory pathways occurs in as few as 3 days after bilateral AEN sectioning. Finally, activation of even a significantly reduced number of MDH neurons is sufficient to initiate the nasopharyngeal response.

Improve of dysphagia with electrostimulation after a stroke

Patients who have suffered a stroke may have dysphagia in more than 30% of cases. When the alteration is located in the bulbar area, since the neural control of swallowing is located at the bulbar level, where the centers responsible for processing the afferent sensory signals and programming the motor deglutory sequence are located this percentage increases. The goal of treatment is to obtain secure and sufficient oral intake for adequate hydration and nutrition. Treatment techniques are designed to change the physiology of swallowing. Neuromuscular electrical stimulation can also be performed as studies have shown that this treatment appears to help people with moderate dysphagia. Clinical observation: we present the case of a 44-year-old woman who suffered laterobulbar ischemic Ictus. The physical exam, showed dysarthria, facial paresis and limb dysmetry without motor deficit and severe alteration of swallowing. Fibroendoscopic studies were performed and oral diet was contraindicated thus enteral nutrition was required from the time of admission. Speech therapy plus the application of electrostimulation was initiated. After 4 months of treatment, enteral nutrition was removed and the patient was able to change to a complete oral diet. Patients who are diagnosed of a bulbar stroke have a high percentage of swallowing dysfunction. Swallowing therapy with electrical stimulation may help clinical improvement of dysphagia.

Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds.

Interactions between cervical and lumbar spinal circuits are mediated by long propriospinal neurons (LPNs). Ablation of descending LPNs in mice disturbs left-right coordination at high speeds without affecting fore-hind alternation. We developed a computational model of spinal circuits consisting of four rhythm generators coupled by commissural interneurons (CINs), providing left-right interactions, and LPNs, mediating homolateral and diagonal interactions. The proposed CIN and diagonal LPN connections contribute to speed-dependent gait transition from walk, to trot, and then to gallop and bound; the homolateral LPN connections ensure fore-hind alternation in all gaits. The model reproduces speed-dependent gait expression in intact and genetically transformed mice and the disruption of hindlimb coordination following ablation of descending LPNs. Inputs to CINs and LPNs can affect interlimb coordination and change gait independent of speed. We suggest that these interneurons represent the main targets for supraspinal and sensory afferent signals adjusting gait.

Enhanced Muscle Afferent Signals during Motor Learning in Humans

Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a functionof adaptation state. Specifically, spindle control was independent of concurrent muscle activity butwas specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning.

Delayed Visual Feedback of One's Own Action Promotes Sense of Control for Auditory Events.

Sense of control refers to one’s feelings to control environmental events through one’s own action. A prevailing view is that the sense of control is strong (or is not diminished) when predicted sensory signals, which are generated in motor control mechanisms, are consistent with afferent sensory signals. Such intact sense of control often leads to the misjudgment of temporal relation between timings of one’s action and its effect (so-called, intentional binding). The present study showed that the intentional binding could be enhanced by the delayed visual feedback of an agent’s action. We asked participants to press a button to produce a tone as action outcome. In some conditions, they were given the delayed visual feedback of their button press. Participants judged whether the onset of the auditory outcome was delayed from the timing of their button press. Consequently, delay detection thresholds were significantly higher when the feedback was given 0.2 and 0.4 s delays than when no feedback was displayed to the participants. The results indicate that action agents misjudge the timing of their action (button press) in the presence of the delayed visual feedback of their action. Interestingly, delay detection thresholds were strongly correlated with the subjective magnitude of the sense of control. Thus, the sense of control is possibly determined by cross-modal processing for action-related and outcome-related sensory signals.

A network model comprising 4 segmental, interconnected ganglia, and its application to simulate multi-legged locomotion in crustaceans.

Inter-segmental coordination is crucial for the locomotion of animals. Arthropods show high variability of leg numbers, from 6 in insects up to 750 legs in millipedes. Despite this fact, the anatomical and functional organization of their nervous systems show basic similarities. The main similarities are the segmental organization, and the way the function of the segmental units is coordinated. We set out to construct a model that could describe locomotion (walking) in animals with more than 6 legs, as well as in 6-legged animals (insects). To this end, we extended a network model by Daun-Gruhn and Tóth (Journal of Computational Neuroscience, doi: 10.1007/s10827-010-0300-1 , 2011). This model describes inter-segmental coordination of the ipsilateral legs in the stick insect during walking. Including an additional segment (local network) into the original model, we could simulate coordination patterns that occur in animals walking on eight legs (e.g., crayfish). We could improve the model by modifying its original cyclic connection topology. In all model variants, the phase relations between the afferent segmental excitatory sensory signals and the oscillatory activity of the segmental networks played a crucial role. Our results stress the importance of this sensory input on the generation of different stable coordination patterns. The simulations confirmed that using the modified connection topology, the flexibility of the model behaviour increased, meaning that changing a single phase parameter, i.e., gating properties of just one afferent sensory signal was sufficient to reproduce all coordination patterns seen in the experiments.

Single 5HTR2A-1438 A/G nucleotide polymorphism affects performance in a metacontrast masking task: Implications for vulnerability testing and neuromodulation of pyramidal cells

It is known that 5HTR2A (rs6311) receptors have high concentration in the cortical layer-5 pyramidal neurons and that these receptors play an important role in the modulation of neurocognitive functions. For example, layer-5 pyramidal neurons mediate cellular level integrative interaction of primary sensory afferent signals and top-down signals exerting contextual modulatory influence. It is also known that genetic variability of 5HTR2A is implicated in individual differences in mental processes. Interestingly, serotonin selectively enhances the asynchronous type of glutamate release when modulating the activity of cortical layer-5 pyramidal neurons, with a post-stimulation delay of this effect at about 50ms. There are not many behavioral tasks capable of tapping that small temporal intervals in terms of change of the values of independent variables leading to an observable change in the subjects’ behavior. However, in the metacontrast masking vision task stimulus onset asynchronies between target and mask critical for the change in the expression of the masking effect correspond to this small temporal value. Thus we hypothesized that genetic variability in 5HTR2A (rs6311) is likely to be associated with different behavioral effects of metacontrast masking and more specifically, that because A allele carriers typically demonstrate greater promoter activity, target-to-mask asynchrony variations should have stronger impact on the masking effect especially with this group of subjects. We obtained support for this hypothesis, but only when target and mask shapes were mutually incongruent.

Cortical regulation of dopaminergic neurons: role of the midbrain superior colliculus

Dopaminergic (DA) neurons respond to stimuli in a wide range of modalities, although the origin of the afferent sensory signals has only recently begun to emerge. In the case of vision, an important source of short-latency sensory information seems to be the midbrain superior colliculus (SC). However, longer-latency responses have been identified that are less compatible with the primitive perceptual capacities of the colliculus. Rather, they seem more in keeping with the processing capabilities of the cortex. Given that there are robust projections from the cortex to the SC, we examined whether cortical information could reach DA neurons via a relay in the colliculus. The somatosensory barrel cortex was stimulated electrically in the anesthetized rat with either single pulses or pulse trains. Although single pulses produced small phasic activations in the colliculus, they did not elicit responses in the majority of DA neurons. However, after disinhibitory intracollicular injections of the GABAA antagonist bicuculline, collicular responses were substantially enhanced and previously unresponsive DA neurons now exhibited phasic excitations or inhibitions. Pulse trains applied to the cortex led to phasic changes (excitations to inhibitions) in the activity of DA neurons at baseline. These were blocked or attenuated by intracollicular administration of the GABAA agonist muscimol. Taken together, the results indicate that the cortex can communicate with DA neurons via a relay in the SC. As a consequence, DA neuronal activity reflecting the unexpected occurrence of salient events and that signaling more complex stimulus properties may have a common origin.

Peri-Procedural Care of Renal Nerve Ablation Candidates

Percutaneous catheter-based transluminal renal nerve ablation (RNA) by delivery of radiofrequency energy constitutes a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RNA. In this review we summarize current recommendations for appropriate patient selection for RNA and multimodal strategies in order to optimize pharmacological treatment for resistant hypertension. The safety and efficacy of the RNA based on published trials are also presented. Furthermore, a detailed description of the periprocedural management, the methodology of the RNA procedure and appropriate follow-up are provided. In conclusion, in order to improve the overall clinical outcome and achieve optimal management of resistant hypertensive patients before and after the RNA, experienced and certified centers are of major importance.

Plasticity of the Injured Human Spinal Cord: Insights Revealed by Spinal Cord Functional MRI

IntroductionWhile numerous studies have documented evidence for plasticity of the human brain there is little evidence that the human spinal cord can change after injury. Here, we employ a novel spinal fMRI design where we stimulate normal and abnormal sensory dermatomes in persons with traumatic spinal cord injury and perform a connectivity analysis to understand how spinal networks process information.MethodsSpinal fMRI data was collected at 3 Tesla at two institutions from 38 individuals using the standard SEEP functional MR imaging techniques. Thermal stimulation was applied to four dermatomes in an interleaved timing pattern during each fMRI acquisition. SCI patients were stimulated in dermatomes both above (normal sensation) and below the level of their injury. Sub-group analysis was performed on healthy controls (n = 20), complete SCI (n = 3), incomplete SCI (n = 9) and SCI patients who recovered full function (n = 6).ResultsPatients with chronic incomplete SCI, when stimulated in a dermatome of normal sensation, showed an increased number of active voxels relative to controls (p = 0.025). There was an inverse relationship between the degree of sensory impairment and the number of active voxels in the region of the spinal cord corresponding to that dermatome of abnormal sensation (R2 = 0.93, p<0.001). Lastly, a connectivity analysis demonstrated a significantly increased number of intraspinal connections in incomplete SCI patients relative to controls suggesting altered processing of afferent sensory signals.ConclusionsIn this work we demonstrate the use of spinal fMRI to investigate changes in spinal processing of somatosensory information in the human spinal cord. We provide evidence for plasticity of the human spinal cord after traumatic injury based on an increase in the average number of active voxels in dermatomes of normal sensation in chronic SCI patients and an increased number of intraspinal connections in incomplete SCI patients relative to healthy controls.

ESH Position Paper

Experts from the European Society of Hypertension prepared this position paper in order to summarize current evidence, unmet needs and practical recommendations on the application of percutaneous transluminal ablation of renal nerves [renal denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RND. Clinical studies have documented that catheter-based RDN decreases both efferent sympathetic and afferent sensory nerve traffic leading to clinically meaningful systolic and diastolic blood pressure (BP) reductions in patients with resistant hypertension. This position statement intends to facilitate a better understanding of the effectiveness, safety, limitations and issues still to be addressed with RDN.