Long-interval afferent inhibition measurement using two different methods: Normative values, repeatability and reliability.

BACKGROUND: The mechanism of Short-Latency Afferent Inhibition (SAI) is relatively well understood. In contrast, Long-Latency Afferent Inhibition (LAI) has not been as extensively studied as SAI, and its underlying mechanism remains unclear. OBJECTIVE/HYPOTHESIS: This study had two primary objectives: first, to determine the optimal ISIs for LAI measured by amplitude changes (A-LAI) using high-resolution ISI ranges; and second, to compare measurements of LAI by threshold-tracking (T-LAI). METHODS: Twenty-eight healthy volunteers (12 males aged 24- 45 years) participated in the study. Paired peripheral electrical and transcranial magnetic stimulation (TMS) stimuli (TS1mv) were applied at varying (ISIs)- 100, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000 ms. RESULTS: Both A-LAI and T-LAI showed that LAI decreased progressively from a peak at 200 or 250 ms to 1000 ms. Using the A-LAI method, pronounced inhibition was observed at three specific ISIs: 100 ms, 250 ms and 450 ms. When A-LAI values were converted to equivalent threshold changes, they did not differ significantly from T-LAI. Reliability at distinguishing individuals, as indicated by intraclass correlation coefficient (ICC) was greater for A-LAI, with a peak value of 0.82 at 250 ms. CONCLUSION(S): The study demonstrates that ISIs of 100 ms and 250 ms can be reliably used in amplitude measurement LAI. The study demonstrates that both LAI measurements record a similar decline of inhibition with increasing ISI.

Short-latency afferent inhibition is reduced in people with multiple sclerosis during fatiguing muscle contractions.

Understanding how inhibitory pathways influence motor cortical activity during fatiguing contractions may provide valuable insight into mechanisms associated with multiple sclerosis (MS) muscle activation. Short-latency afferent inhibition (SAI) reflects inhibitory interactions between the somatosensory cortex and the motor cortex, and although SAI is typically reduced with MS, it is unknown how SAI is regulated during exercise-induced fatigue. The current study examined how SAI modulates motor evoked potentials (MEPs) during fatiguing contractions. Fourteen people with relapsing-remitting MS (39 ± 6 years, nine female) and 10 healthy individuals (36 ± 6 years, six female) participated. SAI was induced by stimulation of the median nerve that was paired with TMS over the motor representation of the abductor pollicis brevis. A contraction protocol was employed that depressed force generating capacity using a sustained 3-min 15% MVC, immediately followed by a low-intensity (15% MVC) intermittent contraction protocol so that MEP and SAI could be measured during the rest phases of each duty cycle. Similar force, electromyography and MEP responses were observed between groups. However, the MS group had significantly reduced SAI during the contraction protocol compared to the healthy control group (p < .001). Despite the MS group reporting greater scores on the Fatigue Severity Scale and Modified Fatigue Impact Scale, these scales did not correlate with inhibitory measures. As there were no between-group differences in SSEPs, MS-related SAI differences during the fatiguing contractions were most likely associated with disease-related changes in central integration.

Comparative localization of colorectal sensory afferent central projections in the mouse spinal cord dorsal horn and caudal medulla dorsal vagal complex.

The distal colon and rectum (colorectum) are innervated by spinal and vagal afferent pathways. The central circuits into which vagal and spinal afferents relay colorectal nociceptive information remain to be comparatively assessed. To address this, regional colorectal retrograde tracing and colorectal distension (CRD)-evoked neuronal activation were used to compare the circuits within the dorsal vagal complex (DVC) and dorsal horn (thoracolumbar [TL] and lumbosacral [LS] spinal levels) into which vagal and spinal colorectal afferents project. Vagal afferent projections were observed in the nucleus tractus solitarius (NTS), area postrema (AP), and dorsal motor nucleus of the vagus (DMV), labeled from the rostral colorectum. In the NTS, projections were opposed to catecholamine and pontine parabrachial nuclei (PbN)-projecting neurons. Spinal afferent projections were labeled from rostral through to caudal aspects of the colorectum. In the dorsal horn, the number of neurons activated by CRD was linked to pressure intensity, unlike in the DVC. In the NTS, 13% ± 0.6% of CRD-activated neurons projected to the PbN. In the dorsal horn, at the TL spinal level, afferent input was associated with PbN-projecting neurons in lamina I (LI), with 63% ± 3.15% of CRD-activated neurons in LI projecting to the PbN. On the other hand, at the LS spinal level, only 18% ± 0.6% of CRD-activated neurons in LI projected to the PbN. The collective data identify differences in the central neuroanatomy that support the disparate roles of vagal and spinal afferent signaling in the facilitation and modulation of colorectal nociceptive responses.

Calcium-Sensitive Subthreshold Oscillations and Electrical Coupling in Principal Cells of Mouse Dorsal Cochlear Nucleus.

In higher sensory brain regions, slow oscillations (0.5-5 Hz) associated with quiet wakefulness and attention modulate multisensory integration, predictive coding, and perception. Although often assumed to originate via thalamocortical mechanisms, the extent to which subcortical sensory pathways are independently capable of slow oscillatory activity is unclear. We find that in the first station for auditory processing, the cochlear nucleus, fusiform cells from juvenile mice (of either sex) generate robust 1-2 Hz oscillations in membrane potential and exhibit electrical resonance. Such oscillations were absent prior to the onset of hearing, intrinsically generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) and persistent Na+ conductances (NaP) interacting with passive membrane properties, and reflected the intrinsic resonance properties of fusiform cells. Cx36-containing gap junctions facilitated oscillation strength and promoted pairwise synchrony of oscillations between neighboring neurons. The strength of oscillations were strikingly sensitive to external Ca2+, disappearing at concentrations >1.7 mM, due in part to the shunting effect of small-conductance calcium-activated potassium (SK) channels. This effect explains their apparent absence in previous in vitro studies of cochlear nucleus which routinely employed high-Ca2+ extracellular solution. In contrast, oscillations were amplified in reduced Ca2+ solutions, due to relief of suppression by Ca2+ of Na+ channel gating. Our results thus reveal mechanisms for synchronous oscillatory activity in auditory brainstem, suggesting that slow oscillations, and by extension their perceptual effects, may originate at the earliest stages of sensory processing.

Sensorimotor integration in cranial muscles tested by short- and long-latency afferent inhibition.

OBJECTIVE: To compressively investigate sensorimotor integration in the cranial-cervical muscles in healthy adults. METHODS: Short- (SAI) and long-latency afferent (LAI) inhibition were probed in the anterior digastric (AD), the depressor anguli oris (DAO) and upper trapezius (UT) muscles. A transcranial magnetic stimulation pulse over primary motor cortex was preceded by peripheral stimulation delivered to the trigeminal, facial and accessory nerves using interstimulus intervals of 15-25 ms and 100-200 ms for SAI and LAI respectively. RESULTS: In the AD, both SAI and LAI were detected following trigeminal nerve stimulation, but not following facial nerve stimulation. In the DAO, SAI was observed only following trigeminal nerve stimulation, while LAI depended only on facial nerve stimulation, only at an intensity suprathreshold for the compound motor action potential (cMAP). In the UT we could only detect LAI following accessory nerve stimulation at an intensity suprathreshold for a cMAP. CONCLUSIONS: The results suggest that integration of sensory inputs with motor output is profoundly influenced by the type of sensory afferent involved and by the functional role played by the target muscle. SIGNIFICANCE: Data indicate the importance of taking into account the sensory receptors involved as well as the function of the target muscle when studying sensorimotor integration, both in physiological and neurological conditions.

Vagal sensory pathway for the gut-brain communication.

The communication between the gut and brain is crucial for regulating various essential physiological functions, such as energy balance, fluid homeostasis, immune response, and emotion. The vagal sensory pathway plays an indispensable role in connecting the gut to the brain. Recently, our knowledge of the vagal gut-brain axis has significantly advanced through molecular genetic studies, revealing a diverse range of vagal sensory cell types with distinct peripheral innervations, response profiles, and physiological functions. Here, we review the current understanding of how vagal sensory neurons contribute to gut-brain communication. First, we highlight recent transcriptomic and genetic approaches that have characterized different vagal sensory cell types. Then, we focus on discussing how different subtypes encode numerous gut-derived signals and how their activities are translated into physiological and behavioral regulations. The emerging insights into the diverse cell types and functional properties of vagal sensory neurons have paved the way for exciting future directions, which may provide valuable insights into potential therapeutic targets for disorders involving gut-brain communication.

Quantifying spatial acuity of frequency resolved midair ultrasound vibrotactile stimuli.

Spatial acuity is a fundamental property of any sensory system. In the case of the somatosensory system, the two-point discrimination (2PD) test has long been used to investigate tactile spatial resolution. However, the somatosensory system comprises three main mechanoreceptive channels: the slowly adapting channel (SA) responds to steady pressure, the rapidly adapting channel (RA) responds to low-frequency vibration, and the Pacinian channel (PC) responds to high-frequency vibration. The use of mechanical stimuli in the classical 2PD test means that previous studies on tactile acuity have primarily focussed on the pressure-sensitive channel alone, while neglecting other submodalities. Here, we used a novel ultrasound stimulation to systematically investigate the spatial resolution of the two main vibrotactile channels. Contrary to the textbook view of poor spatial resolution for PC-like stimuli, across four experiments we found that high-frequency vibration produced surprisingly good spatial acuity. This effect remained after controlling for interchannel differences in stimulus detectability and perceived intensity. Laser doppler vibrometry experiments confirmed that the acuity of the PC channel was not simply an artifact of the skin's resonance to high-frequency mechanical stimulation. Thus, PC receptors may transmit substantial spatial information, despite their sparse distribution, deep location, and large receptive fields.

Multiple sensor theory in airway mechanosensory units.

Two conventional doctrines govern airway mechanosensory interpretation: One-Sensor Theory (OST) and Line-Labeled Theory (LLT). In OST, one afferent fiber connects to a single sensor. In LLT, a different type of sensor sends signals via its specific line to a particular brain region to evoke its reflex. Thus, airway slowly adapting receptors (SARs) inhibit breathing and rapidly adapting receptors (RARs) stimulate breathing. However, recent studies show many different mechanosensors connect to a single afferent fiber (Multiple-Sensor Theory, MST). That is, SARs and RARs may send different types of information through the same afferent pathway, indicating different information has been integrated at the sensory unit level. Thus, a sensory unit is not merely a transducer (textbook concept), but also a processor. MST is a conceptual shift. Data generated over last eight decades under OST require re-interpretation.

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning.

Skilled motor ability depends on efficiently integrating sensory afference into the appropriate motor commands. Afferent inhibition provides a valuable tool to probe the procedural and declarative influence over sensorimotor integration during skilled motor actions. This manuscript describes the methodology and contributions of short-latency afferent inhibition (SAI) for understanding sensorimotor integration. SAI quantifies the effect of a convergent afferent volley on the corticospinal motor output evoked by transcranial magnetic stimulation (TMS). The afferent volley is triggered by the electrical stimulation of a peripheral nerve. The TMS stimulus is delivered to a location over the primary motor cortex that elicits a reliable motor-evoked response in a muscle served by that afferent nerve. The extent of inhibition in the motor-evoked response reflects the magnitude of the afferent volley converging on the motor cortex and involves central GABAergic and cholinergic contributions. The cholinergic involvement in SAI makes SAI a possible marker of declarative-procedural interactions in sensorimotor performance and learning. More recently, studies have begun manipulating the TMS current direction in SAI to tease apart the functional significance of distinct sensorimotor circuits in the primary motor cortex for skilled motor actions. The ability to control additional pulse parameters (e.g., the pulse width) with state-of-the-art controllable pulse parameter TMS (cTMS) has enhanced the selectivity of the sensorimotor circuits probed by the TMS stimulus and provided an opportunity to create more refined models of sensorimotor control and learning. Therefore, the current manuscript focuses on SAI assessment using cTMS. However, the principles outlined here also apply to SAI assessed using conventional fixed pulse width TMS stimulators and other forms of afferent inhibition, such as long-latency afferent inhibition (LAI).

Afferent volley from the digital nerve induces short-latency facilitation of perceptual sensitivity and primary sensory cortex excitability.

The present study examined whether the perceptual sensitivity and excitability of the primary sensory cortex are modulated by the afferent volley from the digital nerve of a conditioned finger within a short period of time. The perceptual threshold of an electrical stimulus to the index finger (test stimulus) was decreased by a conditioning stimulus to the index finger 4 or 6 ms before the test stimulus, or by a stimulus to the middle or ring finger 2 ms before that. This is explained by the view that the afferent volleys from the digital nerves of the fingers converge in the somatosensory areas, causing spatial summation of the afferent inputs through a small number of synaptic relays, leading to the facilitation of perceptual sensitivity. The N20 component of the somatosensory-evoked potential was facilitated by a conditioning stimulus to the middle finger 4 ms before a test stimulus or to the thumb 2 ms before the test stimulus. This is explained by the view that the afferent volley from the digital nerve of the finger adjacent to the tested finger induces lateral facilitation of the representation of the tested finger in the primary sensory cortex through a small number of synaptic relays.

Contralateral Afferent Input to Lumbar Lamina I Neurons as a Neural Substrate for Mirror-Image Pain.

Mirror-image pain arises from pathologic alterations in the nociceptive processing network that controls functional lateralization of the primary afferent input. Although a number of clinical syndromes related to dysfunction of the lumbar afferent system are associated with the mirror-image pain, its morphophysiological substrate and mechanism of induction remain poorly understood. Therefore, we used ex vivo spinal cord preparation of young rats of both sexes to study organization and processing of the contralateral afferent input to the neurons in the major spinal nociceptive projection area Lamina I. We show that decussating primary afferent branches reach contralateral Lamina I, where 27% of neurons, including projection neurons, receive monosynaptic and/or polysynaptic excitatory drive from the contralateral Aδ-fibers and C-fibers. All these neurons also received ipsilateral input, implying their involvement in the bilateral information processing. Our data further show that the contralateral Aδ-fiber and C-fiber input is under diverse forms of inhibitory control. Attenuation of the afferent-driven presynaptic inhibition and/or disinhibition of the dorsal horn network increased the contralateral excitatory drive to Lamina I neurons and its ability to evoke action potentials. Furthermore, the contralateral Aßδ-fibers presynaptically control ipsilateral C-fiber input to Lamina I neurons. Thus, these results show that some lumbar Lamina I neurons are wired to the contralateral afferent system whose input, under normal conditions, is subject to inhibitory control. A pathologic disinhibition of the decussating pathways can open a gate controlling contralateral information flow to the nociceptive projection neurons and, thus, contribute to induction of hypersensitivity and mirror-image pain.SIGNIFICANCE STATEMENT We show that contralateral Aδ-afferents and C-afferents supply lumbar Lamina I neurons. The contralateral input is under diverse forms of inhibitory control and itself controls the ipsilateral input. Disinhibition of decussating pathways increases nociceptive drive to Lamina I neurons and may cause induction of contralateral hypersensitivity and mirror-image pain.

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway.

BACKGROUND: Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined. OBJECTIVE: To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats. METHODS: Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively. RESULTS: Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects. CONCLUSION: Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.

Experimental environment improves the reliability of short-latency afferent inhibition.

Evidence indicates attention can alter afferent inhibition, a Transcranial Magnetic Stimulation (TMS) evoked measure of cortical inhibition following somatosensory input. When peripheral nerve stimulation is delivered prior to TMS, a phenomenon known as afferent inhibition occurs. The latency between the peripheral nerve stimulation dictates the subtype of afferent inhibition evoked, either short latency afferent inhibition (SAI) or long latency afferent inhibition (LAI). While afferent inhibition is emerging as a valuable tool for clinical assessment of sensorimotor function, the reliability of the measure remains relatively low. Therefore, to improve the translation of afferent inhibition within and beyond the research lab, the reliability of the measure must be improved. Previous literature suggests that the focus of attention can modify the magnitude of afferent inhibition. As such, controlling the focus of attention may be one method to improve the reliability of afferent inhibition. In the present study, the magnitude and reliability of SAI and LAI was assessed under four conditions with varying attentional demands focused on the somatosensory input that evokes SAI and LAI circuits. Thirty individuals participated in four conditions; three conditions were identical in their physical parameters and varied only in the focus of directed attention (visual attend, tactile attend, non- directed attend) and one condition consisted of no external physical parameters (no stimulation). Reliability was measured by repeating conditions at three time points to assess intrasession and intersession reliability. Results indicate that the magnitude of SAI and LAI were not modulated by attention. However, the reliability of SAI demonstrated increased intrasession and intersession reliability compared to the no stimulation condition. The reliability of LAI was unaffected by the attention conditions. This research demonstrates the impact of attention/arousal on the reliability of afferent inhibition and has identified new parameters to inform the design of TMS research to improve reliability.

Modulation of spinal circuits following phase-dependent electrical stimulation of afferent pathways.

Objective.Peripheral electrical stimulation (PES) of afferent pathways is a tool commonly used to induce neural adaptations in some neural disorders such as pathological tremor or stroke. However, the neuromodulatory effects of stimulation interventions synchronized with physiological activity (closed-loop strategies) have been scarcely researched in the upper-limb. Here, the short-term spinal effects of a 20-minute stimulation protocol where afferent pathways were stimulated with a closed-loop strategy named selective and adaptive timely stimulation (SATS) were explored in 11 healthy subjects.Approach. SATS was applied to the radial nerve in-phase (INP) or out-of-phase (OOP) with respect to the muscle activity of the extensor carpi radialis (ECR). The neural adaptations at the spinal cord level were assessed for the flexor carpi radialis (FCR) by measuring disynaptic Group I inhibition, Ia presynaptic inhibition, Ib facilitation from the H-reflex and estimation of the neural drive before, immediately after, and 30 minutes after the intervention.Main results.SATS strategy delivered electrical stimulation synchronized with the real-time muscle activity measured, with an average delay of 17 ± 8 ms. SATS-INP induced increased disynaptic Group I inhibition (77 ± 23% of baseline conditioned FCR H-reflex), while SATS-OOP elicited the opposite effect (125 ± 46% of baseline conditioned FCR H-reflex). Some of the subjects maintained the changes after 30 minutes. No other significant changes were found for the rest of measurements.Significance.These results suggest that the short-term modulatory effects of phase-dependent PES occur at specific targeted spinal pathways for the wrist muscles in healthy individuals. Importantly, timely recruitment of afferent pathways synchronized with specific muscle activity is a fundamental principle that shall be considered when tailoring PES protocols to modulate specific neural circuits. (NCT number 04501133).

Tactile sensorimotor training does not alter short- and long-latency afferent inhibition.

Sensorimotor integration refers to the process of combining incoming sensory information with outgoing motor commands to control movement. Short-latency afferent inhibition (SAI), and long-latency afferent inhibition (LAI) are neurophysiological measures of sensorimotor integration collected using transcranial magnetic stimulation. No studies to date have investigated the influence of tactile discrimination training on these measures. This study aimed to determine whether SAI and LAI are modulated following training on a custom-designed tactile discrimination maze task. Participants performed a 'high difficulty' and 'low difficulty' maze training condition on separate visits. On an additional visit, no maze training was performed to serve as a control condition. Despite evidence of performance improvements during training, there were no significant changes in SAI or LAI following training in either condition. The total number of errors during maze training was significantly greater in the high-difficulty condition compared with the low-difficulty condition. These findings suggest that sensorimotor maze training for 30 min is insufficient to modify the magnitude of SAI and LAI.

The T-type calcium channel Ca V 3.2 regulates bladder afferent responses to mechanical stimuli.

ABSTRACT: The bladder wall is innervated by a complex network of afferent nerves that detect bladder stretch during filling. Sensory signals, generated in response to distension, are relayed to the spinal cord and brain to evoke physiological and painful sensations and regulate urine storage and voiding. Hyperexcitability of these sensory pathways is a key component in the development of chronic bladder hypersensitivity disorders including interstitial cystitis/bladder pain syndrome and overactive bladder syndrome. Despite this, the full array of ion channels that regulate bladder afferent responses to mechanical stimuli have yet to be determined. Here, we investigated the role of low-voltage-activated T-type calcium (Ca V 3) channels in regulating bladder afferent responses to distension. Using single-cell reverse-transcription polymerase chain reaction and immunofluorescence, we revealed ubiquitous expression of Ca V 3.2, but not Ca V 3.1 or Ca V 3.3, in individual bladder-innervating dorsal root ganglia neurons. Pharmacological inhibition of Ca V 3.2 with TTA-A2 and ABT-639, selective blockers of T-type calcium channels, dose-dependently attenuated ex-vivo bladder afferent responses to distension in the absence of changes to muscle compliance. Further evaluation revealed that Ca V 3.2 blockers significantly inhibited both low- and high-threshold afferents, decreasing peak responses to distension, and delayed activation thresholds, thereby attenuating bladder afferent responses to both physiological and noxious distension. Nocifensive visceromotor responses to noxious bladder distension in vivo were also significantly reduced by inhibition of Ca V 3 with TTA-A2. Together, these data provide evidence of a major role for Ca V 3.2 in regulating bladder afferent responses to bladder distension and nociceptive signalling to the spinal cord.

Short-and long-latency afferent inhibition of the human leg motor cortex by H-reflex subthreshold electrical stimulation at the popliteal fossa.

In humans, peripheral sensory stimulation inhibits subsequent motor evoked potentials (MEPs) induced by transcranial magnetic stimulation; this process is referred to as short- or long-latency afferent inhibition (SAI or LAI, respectively), depending on the inter-stimulus interval (ISI) length. Although upper limb SAI and LAI have been well studied, lower limb SAI and LAI remain under-investigated. Here, we examined the time course of the soleus (SOL) muscle MEP following electrical tibial nerve (TN) stimulation at the popliteal fossa at ISIs of 20-220 ms. When the conditioning stimulus intensity was three-fold the perceptual threshold, MEP amplitudes were inhibited at an ISI of 220 ms, but not at shorter ISIs. TN stimulation just below the Hoffman (H)-reflex threshold intensity inhibited MEP amplitudes at ISIs of 30, 35, 100, 180 and 200 ms. However, the relationship between MEP inhibition and the P30 latency of somatosensory evoked potentials (SEPs) did not show corresponding ISIs at the SEP P30 latency that maximizes MEP inhibition. To clarify whether the site of afferent-induced MEP inhibition occurs at the cortical or spinal level, we examined the time course of SOL H-reflex following TN stimulation. H-reflex amplitudes were not significantly inhibited at ISIs where MEP inhibition occurred but at an ISI of 120 ms. Our findings indicate that stronger peripheral sensory stimulation is required for lower limb than for upper limb SAI and LAI and that lower limb SAI and LAI are of cortical origin. Moreover, the direct pathway from the periphery to the primary motor cortex may contribute to lower limb SAI.

Natriuretic Peptides-New Targets for Neurocontrol of Blood Pressure via Baroreflex Afferent Pathway.

Natriuretic peptides (NPs) induce vasodilation, natriuresis, and diuresis, counteract the renin-angiotensin-aldosterone system and autonomic nervous system, and are key regulators of cardiovascular volume and pressure homeostasis. Baroreflex afferent pathway is an important reflex loop in the neuroregulation of blood pressure (BP), including nodose ganglion (NG) and nucleus tractus solitarius (NTS). Dysfunction of baroreflex would lead to various hypertensions. Here, we carried out functional experiments to explore the effects of NPs on baroreflex afferent function. Under physiological and hypertensive condition (high-fructose drinking-induced hypertension, HFD), BP was reduced by NPs through NG microinjection and baroreflex sensitivity (BRS) was enhanced via acute intravenous NPs injection. These anti-hypertensive effects were more obvious in female rats with the higher expression of NPs and its receptor A/B (NPRA/NPRB) and lower expression of its receptor C (NPRC). However, these effects were not as obvious as those in HFD rats compared with the same gender control group, which is likely to be explained by the abnormal expression of NPs and NPRs in the hypertensive condition. Our data provide additional evidence showing that NPs play a crucial role in neurocontrol of BP regulation via baroreflex afferent function and may be potential targets for clinical management of metabolic-related hypertension.

Transcutaneous vagus nerve stimulation - A brief introduction and overview.

Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation. The procedure requires surgery, has side-effects, is expensive and not readily available. Consequently, transcutaneous VNS (tVNS) has been developed 20 years ago as non-invasive, less expensive, and easily applicable alternative. Since the vagus nerve reaches the skin at the outer acoustic canal and ear, and reflex-responses such as the ear-cough-reflex or the auriculo-cardiac reflex have been observed upon auricular stimulation, the ear seems well suited for tVNS. However, several sensory nerves with variable fiber-density and significant overlap innervate the outer ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve, greater auricular nerve, and to some extent the lesser occipital nerve. VNS requires activation of Aß-fibers which are far less present in the ABVN than the cervical vagus nerve. Thus, optimal stimulation sites and parameters, and tVNS-algorithms need to be further explored. Unravelling central pathways and structures that mediate tVNS-effects is another challenge. tVNS impulses reach the nucleus of the solitary tract and activate the locus-coeruleus-norepinephrine system. However, many more brain areas are activated or deactivated upon VNS, including structures of the central autonomic network and the limbic system. Still, the realm of therapeutic tVNS applications grows rapidly and includes medication-refractory epilepsies, depressive mood disorders, headaches including migraine, pain, heart failure, gastrointestinal inflammatory diseases and many more. tVNS might become a standard tool to enhance autonomic balance and function in various autonomic, neurological, psychiatric, rheumatologic, as well as other diseases.

High-frequency oscillations-based precise temporal resolution of short latency afferent inhibition in the human brain.

OBJECTIVE: Sensorimotor integration is a crucial process for adaptive behaviour and can be explored non-invasively with a conditioned transcranial magnetic stimulation (TMS) paradigm - i.e. short-latency afferent inhibition (SAI). To gain insight into the sensorimotor integration phenomenon, we used two different approaches to combine peripheral and cortical stimulation in the SAI paradigm, measuring not only the latency of low frequency somatosensory evoked potentials (SEPs) but also the peaks of high frequency oscillations (HFOs) underlying SEPs. METHODS: The interstimulus intervals (ISIs) between the electrical stimulation of the median nerve and the motor cortex magnetic stimulation were determined relative to the latency of the earliest SEPs cortical potential (N20) or the HFOs peaks. In particular, the first and last negative and positive peaks of HFOs were extracted through a custom-made MATLAB script. RESULTS: Thirty-three healthy subjects participated in this study. We found out that muscle responses after TMS were suppressed when ISIs were comprised between -1 to +3 ms relative to the N20 peak and at all ISIs relative to HFOs peaks, except for the first negative peak. CONCLUSIONS: Coupling peripheral and cortical stimulation at early interstimulus intervals - before the SEPs N20 peak - may modulate muscle response. SIGNIFICANCE: Our findings confirm that afferent inhibition is produced both through a direct (thalamus-motor cortex) and indirect (thalamus-somatosensory-motor cortex) pathway.