RESUMO
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.
Assuntos
Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Estimulação do Nervo Vago/métodos , Estimulação Elétrica Nervosa Transcutânea/métodos , Nervo Vago/fisiologia , Encéfalo/fisiologia , Vias Aferentes/fisiologiaRESUMO
BACKGROUND: Maintaining energy homeostasis is vital and supported by vagal signaling between digestive organs and the brain. Previous research has established a gastric network in the brain that is phase synchronized with the rhythm of the stomach, but tools to perturb its function were lacking. OBJECTIVE: To evaluate whether stomach-brain coupling can be acutely increased by non-invasively stimulating vagal afferent projections to the brain. METHODS: Using a single-blind randomized crossover design, we investigated the effect of acute right-sided transcutaneous auricular vagus nerve stimulation (taVNS) versus sham stimulation on stomach-brain coupling. RESULTS: In line with preclinical research, taVNS increased stomach-brain coupling in the nucleus of the solitary tract (NTS) and the midbrain while boosting coupling across the brain. Crucially, in the cortex, taVNS-induced changes in coupling occurred primarily in transmodal regions and were associated with changes in hunger ratings as indicators of the subjective metabolic state. CONCLUSIONS: taVNS increases stomach-brain coupling via an NTS-midbrain pathway that signals gut-induced reward, indicating that communication between the brain and the body is effectively modulated by vago-vagal signaling. Such insights may help us better understand the role of vagal afferents in orchestrating the recruitment of the gastric network which could pave the way for novel neuromodulatory treatments.
Assuntos
Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Vias Aferentes/fisiologia , Estudos Cross-Over , Humanos , Método Simples-Cego , Núcleo Solitário/fisiologia , Estômago , Nervo Vago/fisiologiaRESUMO
Our increasing knowledge about gut-brain interaction is revolutionising the understanding of the links between digestion, mood, health, and even decision making in our everyday lives. In support of this interaction, the vagus nerve is a crucial pathway transmitting diverse gut-derived signals to the brain to monitor of metabolic status, digestive processes, or immune control to adapt behavioural and autonomic responses. Hence, neuromodulation methods targeting the vagus nerve are currently explored as a treatment option in a number of clinical disorders, including diabetes, chronic pain, and depression. The non-invasive variant of vagus nerve stimulation (VNS), transcutaneous auricular VNS (taVNS), has been implicated in both acute and long-lasting effects by modulating afferent vagus nerve target areas in the brain. The physiology of neither of those effects is, however, well understood, and evidence for neuronal response upon taVNS in vagal afferent projection regions in the brainstem and its downstream targets remain to be established. Therefore, to examine time-dependent effects of taVNS on brainstem neuronal responses in healthy human subjects, we applied taVNS during task-free fMRI in a single-blinded crossover design. During fMRI data acquisition, we either stimulated the left earlobe (sham), or the target zone of the auricular branch of the vagus nerve in the outer ear (cymba conchae, verum) for several minutes, both followed by a short 'stimulation OFF' period. Time-dependent effects were assessed by averaging the BOLD response for consecutive 1-minute periods in an ROI-based analysis of the brainstem. We found a significant response to acute taVNS stimulation, relative to the control condition, in downstream targets of vagal afferents, including the nucleus of the solitary tract, the substantia nigra, and the subthalamic nucleus. Most of these brainstem regions remarkably showed increased activity in response to taVNS, and these effect sustained during the post-stimulation period. These data demonstrate that taVNS activates key brainstem regions, and highlight the potential of this approach to modulate vagal afferent signalling. Furthermore, we show that carry-over effects need to be considered when interpreting fMRI data in the context of general vagal neurophysiology and its modulation by taVNS.
Assuntos
Tronco Encefálico/fisiologia , Imageamento por Ressonância Magnética/métodos , Estimulação do Nervo Vago/métodos , Nervo Vago/fisiologia , Adaptação Fisiológica , Adulto , Afeto , Vias Aferentes/fisiologia , Sistema Nervoso Autônomo/fisiologia , Estudos Cross-Over , Feminino , Humanos , Masculino , Sistema Nervoso Periférico/fisiologia , Estimulação Elétrica Nervosa TranscutâneaRESUMO
2'-Fucosyllactose (2'-FL) is one of the predominant oligosaccharides found in human milk and has several well-established beneficial effects in the host. It has previously been shown that 2'-FL can improve the metabolic phenotype in high-fat (HF)-fed mice. Here we investigated whether dietary supplementation with 2'-FL was associated with improved intestinal barrier integrity, signaling in the vagal afferent pathway and cognitive function. Mice were fed either a low-fat (LF, 10% fat per kcal) or HF (45% fat per kcal) diet with or without supplementation of 2'-FL (10% w/w) in the diet for 8 weeks. Body weight, energy intake, fat and lean mass, intestinal permeability (ex vivo in Ussing chambers), lipid profiles, gut microbiome and microbial metabolites, and cognitive functions were measured. Vagal afferent activity was measured via immunohistochemical detection of c-Fos protein in the brainstem in response to peripheral administration of cholecystokinin (CCK). 2'-FL significantly attenuated the HF-induced increase in fat mass and energy intake. 2'-FL significantly reduced intestinal permeability and significantly increased expression of interleukin (IL)-22, a cytokine known for its protective role in the intestine. Additionally, 2'-FL led to changes in the gut microbiota composition and in the associated microbial metabolites. Signaling in the vagal afferent pathway was improved but there was no effect on cognitive function. In conclusion, 2'-FL supplementation improved the metabolic profiles, gut barrier integrity, lipid metabolism and signaling in the vagal afferent pathway. These findings support the utility of 2'-FL in the control of gut barrier function and metabolic homeostasis under a metabolic challenge.
Assuntos
Vias Aferentes/fisiologia , Eixo Encéfalo-Intestino/fisiologia , Suplementos Nutricionais , Mucosa Intestinal/fisiologia , Leite Humano/química , Trissacarídeos/administração & dosagem , Nervo Vago/fisiologia , Animais , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Encéfalo/metabolismo , Ceco/metabolismo , Ceco/microbiologia , Dieta com Restrição de Gorduras , Dieta Hiperlipídica , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Masculino , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Trissacarídeos/sangueRESUMO
OBJECTIVE: To determine how long it takes for neural impulses to travel along peripheral nerve fibers in living humans. METHODS: A collision test was performed to measure the conduction velocity distribution of the ulnar nerve. Two stimuli at the distal and proximal sites were used to produce the collision. Compound muscle or nerve action potentials were recorded to perform the measurements on the motor or mixed nerve, respectively. Interstimulus interval was set at 1-5 ms. A quadri-pulse technique was used to measure the refractory period and calibrate the conduction time. RESULTS: Compound muscle action potential produced by the proximal stimulation started to emerge at the interstimulus interval of about 1.5 ms and increased with the increment in interstimulus interval. Two groups of motor nerve fibers with different conduction velocities were identified. The mixed nerve showed a wider conduction velocity distribution with identification of more subgroups of nerve fibers than the motor nerve. CONCLUSIONS: The conduction velocity distributions in high resolution on a peripheral motor and mixed nerve are different and this can be measured with the collision test. SIGNIFICANCE: We provided ground truth data to verify the neuroimaging pipelines for the measurements of latency connectome in the peripheral nervous system.
Assuntos
Eletromiografia/métodos , Condução Nervosa , Nervos Periféricos/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Potenciais de Ação , Adulto , Vias Aferentes/fisiologia , Vias Eferentes/fisiologia , Potencial Evocado Motor , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Tempo de ReaçãoRESUMO
Various types of acute/chronic nociceptive stimuli cause neuroendocrine responses such as activation of the hypothalamo-neurohypophysial [oxytocin (OXT) and arginine vasopressin (AVP)] system and hypothalamo-pituitary adrenal (HPA) axis. Chronic multiple-arthritis activates the OXT/AVP system, but the effects of acute mono-arthritis on the OXT/AVP system in the same animals has not been simultaneously evaluated. Further, AVP, not corticotropin-releasing hormone (CRH), predominantly activates the HPA axis in chronic multiple-arthritis, but the participation of AVP in HPA axis activation in acute mono-arthritis remains unknown. Therefore, we aimed to simultaneously evaluate the effects of acute mono-arthritis on the activity of the OXT/AVP system and the HPA axis. In the present study, we used an acute mono-arthritic model induced by intra-articular injection of carrageenan in a single knee joint of adult male Wistar rats. Acute mono-arthritis was confirmed by a significant increase in knee diameter in the carrageenan-injected knee and a significant decrease in the mechanical nociceptive threshold in the ipsilateral hind paw. Immunohistochemical analysis revealed that the number of Fos-immunoreactive (ir) cells in the ipsilateral lamina I-II of the dorsal horn was significantly increased, and the percentage of OXT-ir and AVP-ir neurons expressing Fos-ir in both sides of the supraoptic (SON) and paraventricular nuclei (PVN) was increased in acute mono-arthritic rats. in situ hybridization histochemistry revealed that levels of OXT mRNA and AVP hnRNA in the SON and PVN, CRH mRNA in the PVN, and proopiomelanocortin mRNA in the anterior pituitary were also significantly increased in acute mono-arthritic rats. Further, plasma OXT, AVP, and corticosterone levels were significantly increased in acute mono-arthritic rats. These results suggest that acute mono-arthritis activates ipsilateral nociceptive afferent pathways at the spinal level and causes simultaneous and integrative activation of the OXT/AVP system. In addition, the HPA axis is activated by both AVP and CRH in acute mono-arthritis with a distinct pattern compared to that in chronic multiple-arthritis.
Assuntos
Artrite/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Doença Aguda , Vias Aferentes/fisiologia , Animais , Arginina Vasopressina/sangue , Arginina Vasopressina/genética , Artrite/genética , Artrite/metabolismo , Artrite/patologia , Hormônio Liberador da Corticotropina/sangue , Hormônio Liberador da Corticotropina/genética , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Masculino , Neurônios/fisiologia , Dor Nociceptiva/etiologia , Dor Nociceptiva/genética , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/fisiopatologia , Ocitocina/sangue , Ocitocina/genética , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/patologia , Pró-Opiomelanocortina/sangue , Pró-Opiomelanocortina/genética , Ratos , Ratos WistarRESUMO
Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450-500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway.NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.
Assuntos
Terapia por Estimulação Elétrica/métodos , Esvaziamento Gástrico , Plexo Lombossacral/fisiologia , Neurônios Nitrérgicos/fisiologia , Reflexo , Nervos Espinhais/fisiologia , Estômago/inervação , Nervo Vago/fisiologia , Vias Aferentes/fisiologia , Animais , Vias Eferentes/fisiologia , Gastroparesia/fisiopatologia , Gastroparesia/terapia , Masculino , Ratos Sprague-DawleyRESUMO
Metabolic feedback between the gut and the brain relayed via the vagus nerve contributes to energy homeostasis. We investigated in healthy adults whether non-invasive stimulation of vagal afferents impacts energy homeostasis via efferent effects on metabolism or digestion. In a randomized crossover design, we applied transcutaneous auricular vagus nerve stimulation (taVNS) while recording efferent metabolic effects using simultaneous electrogastrography (EGG) and indirect calorimetry. We found that taVNS reduced gastric myoelectric frequency (p = .008), but did not alter resting energy expenditure. We conclude that stimulating vagal afferents induces gastric slowing via vagal efferents without acutely affecting net energy expenditure at rest. Collectively, this highlights the potential of taVNS to modulate digestion by activating the dorsal vagal complex. Thus, taVNS-induced changes in gastric frequency are an important peripheral marker of brain stimulation effects.
Assuntos
Motilidade Gastrointestinal , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação do Nervo Vago/métodos , Adulto , Vias Aferentes/fisiologia , Animais , Encéfalo/fisiologia , Metabolismo Energético , Humanos , Masculino , Nervo Vago/fisiologiaRESUMO
OBJECTIVE: To assess the lasting effects on sensory nerve membrane excitability of transcutaneous peripheral nerve stimulation with cathodal direct currents (pDCS). METHODS: We performed pDCS in 10 healthy subjects with the active electrode placed over the distal right forearm and the reference electrode on the back of the right hand. We used 5×5cm rubber electrodes and the current applied was 2.5mA during 15min. Three pDCS sessions were performed on the same day: first, a baseline stimulation was performed, followed by a sham stimulation and lastly a cathodal stimulation. Median sensory nerve excitability measurements were performed at baseline and immediately after each pDCS session using the TRONDNF nerve excitability protocol of the QTRAC program (measurement on the second finger). RESULTS: The protocol was completed and well tolerated in all subjects. RRP (relative refractory period) and refractoriness at 2.5ms were significantly different across the three study conditions, with a significant increase of RRP immediately following cathodal stimulation compared with baseline assessment (mean 4.2 versus 5.3, P=0.002). Other measurements were not modulated by the intervention. Sham-stimulation did not change axonal excitability. CONCLUSIONS: Cathodal pDCS stimulation increased RRP of sensory fibers, but no other consistent long-lasting effect was observed. This finding might suggest a reduction of sensory fiber excitability induced by cathodal pDCS.
Assuntos
Vias Aferentes/fisiologia , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana , Humanos , Fibras Nervosas/fisiologia , Estimulação Magnética Transcraniana/métodos , Estimulação Elétrica Nervosa Transcutânea/métodosRESUMO
In the mouse whisker system, the contribution of L6 corticothalamic cells (L6 CT) to cortical and thalamic processing of the whisker deflection direction was investigated. A genetically defined population of L6 CT cells project to infragranular GABAergic interneurons that hyperpolarize neurons in somatosensory barrel cortex (BC). Optogenetic activation of these neurons switched BC to an adapted mode in which excitatory cells lost their angular tuning. In contrast, however, this was not the case with a general activation of inhibitory interneurons via optogenetic activation of Gad2-expressing cells. The decrease in angular tuning, when L6 CT cells were activated, was due to changes in cortical inhibition, and not inherited from changes in the thalamic output. Furthermore, L6 CT driven cortical inhibition, but not the general activation of GABAergic interneurons, abolished adaptation to whisker responses. In the present study, evidence is presented that a subpopulation of L6 CT activates a specific circuit of GABAergic interneurons that will predispose neocortex toward processing of tactile information requiring multiple whisker touches, such as in a texture discrimination task.
Assuntos
Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Tálamo/fisiologia , Vibrissas/fisiologia , Vias Aferentes/fisiologia , Animais , Feminino , Neurônios GABAérgicos/fisiologia , Masculino , Camundongos , Inibição Neural/fisiologia , Percepção do Tato/fisiologiaRESUMO
The gustatory system contributes to the flavor of foods and beverages and communicates information about nutrients and poisons. This system has evolved to detect and ultimately respond to hydrophilic molecules dissolved in saliva. Taste receptor cells, located in taste buds and distributed throughout the oral cavity, activate nerve afferents that project to the brainstem. From here, information propagates to thalamic, subcortical, and cortical areas, where it is integrated with information from other sensory systems and with homeostatic, visceral, and affective processes. There is considerable divergence, as well as convergence, of information between multiple regions of the central nervous system that interact with the taste pathways, with reciprocal connections occurring between the involved regions. These widespread interactions among multiple systems are crucial for the perception of food. For example, memory, hunger, satiety, and visceral changes can directly affect and can be affected by the experience of tasting. In this chapter, we review the literature on the central processing of taste with a specific focus on the anatomic and physiologic responses of single neurons. Emphasis is placed on how information is distributed along multiple systems with the goal of better understanding how the rich and complex sensations associated with flavor emerge from large-scale, systems-wide, interactions.
Assuntos
Vias Aferentes/fisiologia , Encéfalo/fisiologia , Neurônios/fisiologia , Paladar/fisiologia , Vias Aferentes/anatomia & histologia , Animais , Encéfalo/anatomia & histologia , Humanos , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Tálamo/anatomia & histologia , Tálamo/fisiologiaRESUMO
An important goal in Brain-Computer Interfacing (BCI) is to find and enhance procedural strategies for users for whom BCI control is not sufficiently accurate. To address this challenge, we conducted offline analyses and online experiments to test whether the classification of different types of motor imagery could be improved when the training of the classifier was performed on the data obtained with the assistive muscular stimulation below the motor threshold. 10 healthy participants underwent three different types of experimental conditions: a) Motor imagery (MI) of hands and feet b) sensory threshold neuromuscular electrical stimulation (STM) of hands and feet while resting and c) sensory threshold neuromuscular electrical stimulation during performance of motor imagery (BOTH). Also, another group of 10 participants underwent conditions a) and c). Then, online experiments with 15 users were performed. These subjects received neurofeedback during MI using classifiers calibrated either on MI or BOTH data recorded in the same experiment. Offline analyses showed that decoding MI alone using a classifier based on BOTH resulted in a better BCI accuracy compared to using a classifier based on MI alone. Online experiments confirmed accuracy improvement of MI alone being decoded with the classifier trained on BOTH data. In addition, we observed that the performance in MI condition could be predicted on the basis of a more pronounced connectivity within sensorimotor areas in the frequency bands providing the best performance in BOTH. These finding might offer a new avenue for training SMR-based BCI systems particularly for users having difficulties to achieve efficient BCI control. It might also be an alternative strategy for users who cannot perform real movements but still have remaining afferent pathways (e.g., ALS and stroke patients).
Assuntos
Ondas Encefálicas/fisiologia , Interfaces Cérebro-Computador , Imaginação/fisiologia , Atividade Motora/fisiologia , Limiar Sensorial/fisiologia , Adulto , Vias Aferentes/fisiologia , Calibragem , Estimulação Elétrica , Eletroencefalografia , Humanos , Neurorretroalimentação/fisiologiaRESUMO
Neocortical circuits are sensitive to experience, showing both anatomical and electrophysiological changes in response to altered sensory input. We examined input- and cell-type-specific changes in thalamo- and intracortical pathways during learning using an automated, home-cage sensory association training (SAT) paradigm coupling multi-whisker stimulation to a water reward. We found that the posterior medial nucleus (POm) but not the ventral posterior medial (VPM) nucleus of the thalamus drives increased cortical activity after 24 h of SAT, when behavioral evidence of learning first emerges. Synaptic strengthening within the POm thalamocortical pathway was first observed at thalamic inputs to L5 and was not generated by sensory stimulation alone. Synaptic changes in L2 were delayed relative to L5, requiring 48 h of SAT to drive synaptic plasticity at thalamic and intracortical inputs onto L2 Pyr neurons. These data identify the POm thalamocortical circuit as a site of rapid synaptic plasticity during learning and suggest a temporal sequence to learning-evoked synaptic changes in the sensory cortex.
Assuntos
Vias Aferentes/fisiologia , Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Células Receptoras Sensoriais/fisiologia , Córtex Somatossensorial/fisiologia , Tálamo/fisiologia , Animais , Macaca mulatta , Masculino , Modelos Neurológicos , Dinâmica não Linear , Amplitude de Movimento Articular/fisiologia , Vibrissas/inervaçãoRESUMO
BACKGROUND: Electrical stimulation on select areas of the external auricular dermatome influences the autonomic nervous system. It has been postulated that activation of the Auricular Branch of the Vagus Nerve (ABVN) mediates such autonomic changes. However, the underlying neural pathways mediating these effects are unknown and, further, our understanding of the anatomical distribution of the ABVN in the auricle has now been questioned. OBJECTIVE: To investigate the effects of electrical stimulation of the tragus on autonomic outputs in the rat and probe the underlying neural pathways. METHODS: Central neuronal projections from nerves innervating the external auricle were investigated by injections of the transganglionic tracer cholera toxin B chain (CTB) into the right tragus of Wistar rats. Physiological recordings of heart rate, perfusion pressure, respiratory rate and sympathetic nerve activity were made in an anaesthetic free Working Heart Brainstem Preparation (WHBP) of the rat and changes in response to electrical stimulation of the tragus analysed. RESULTS: Neuronal tracing from the tragus revealed that the densest CTB labelling was within laminae III-IV of the dorsal horn of the upper cervical spinal cord, ipsilateral to the injection sites. In the medulla oblongata, CTB labelled afferents were observed in the paratrigeminal nucleus, spinal trigeminal tract and cuneate nucleus. Surprisingly, only sparse labelling was observed in the vagal afferent termination site, the nucleus tractus solitarius. Recordings made from rats at night time revealed more robust sympathetic activity in comparison to day time rats, thus subsequent experiments were conducted in rats at night time. Electrical stimulation was delivered across the tragus for 5â¯min. Direct recording from the sympathetic chain revealed a central sympathoinhibition by up to 36% following tragus stimulation. Sympathoinhibition remained following sectioning of the cervical vagus nerve ipsilateral to the stimulation site, but was attenuated by sectioning of the upper cervical afferent nerve roots. CONCLUSIONS: Inhibition of the sympathetic nervous system activity upon electrical stimulation of the tragus in the rat is mediated at least in part through sensory afferent projections to the upper cervical spinal cord. This challenges the notion that tragal stimulation is mediated by the auricular branch of the vagus nerve and suggests that alternative mechanisms may be involved.
Assuntos
Vértebras Cervicais , Frequência Cardíaca/fisiologia , Células Receptoras Sensoriais/fisiologia , Medula Espinal/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Nervo Vago/fisiologia , Vias Aferentes/fisiologia , Animais , Tronco Encefálico/fisiologia , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Núcleo Solitário/fisiologia , Estimulação do Nervo Vago/métodosRESUMO
BACKGROUND: Tibialis Anterior (TA) cutaneous reflex (CR) activity evoked following cutaneous stimulation of the plantar (Pl) surface (Pl-TA CR) has demonstrated hyperreflexia and damage of inhibitory mechanisms in subjects with spinal cord injury (SCI) and spasticity. OBJECTIVES: To modulate Pl-TA CR and Soleus H-reflex activity with transcutaneous electrical nerve stimulation (TENS) and vibratory stimulation of the plantar pad during rest and controlled isometric plantarflexion. METHODS: Non-injured subjects (n = 11) and individuals with incomplete SCI with (n = 14) and without spasticity (n = 14) were recruited. The effect of TENS and vibratory stimuli on Pl-TA CR and soleus H-reflex activity were assessed during rest and controlled ramp-and-hold plantarflexion. RESULTS: Vibration failed to inhibit H-reflex activity during rest or plantarflexoin following SCI compared to healthy subjects. In contrast, vibration-induced inhibition of Pl-TA CR was specifically detected in SCI spastic subjects during both rest and the hold phase of plantarflexion. TENS inhibited Pl-TA CR activity in the SCI spasticity group only during hold plantarflexion. CONCLUSIONS: Plantar vibratory stimuli inhibited the pl-TA CR, but not the H reflex, during rest and controlled movement in SCI spastic subjects. Assessment of Pl-TA CR modulation should contribute to the development of modality-specific sensory stimuli programmes for the neurorehabilitation of SCI spasticity.
Assuntos
Espasticidade Muscular/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Adulto , Vias Aferentes/fisiologia , Feminino , Reflexo H/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Espasticidade Muscular/reabilitação , Músculo Esquelético/inervação , Reabilitação Neurológica/métodos , Reflexo Anormal , Traumatismos da Medula Espinal/reabilitaçãoRESUMO
KEY POINTS: This investigation assessed the influence of group III/IV muscle afferents on small muscle mass exercise performance from a skeletal muscle bioenergetics perspective. Group III/IV muscle afferent feedback was attenuated with lumbar intrathecal fentanyl during intermittent isometric single-leg knee-extensor all-out exercise, while 31 P-MRS was used to assess skeletal muscle bioenergetics. Attenuation of group III/IV muscle afferent feedback improved exercise performance during the first minute of exercise, due to an increase in total ATP production with no change in the ATP cost of contraction. However, exercise performance was not altered during the remainder of the protocol, despite a sustained increase in total ATP production, due to an exacerbated ATP cost of contraction. These findings reveal that group III/IV muscle afferents directly limit exercise performance during small muscle mass exercise, but, due to their critical role in maintaining skeletal muscle contractile efficiency, with time, the benefit of attenuating the muscle afferents is negated. ABSTRACT: The direct influence of group III/IV muscle afferents on exercise performance remains equivocal. Therefore, all-out intermittent isometric single-leg knee-extensor exercise and phosphorous magnetic resonance spectroscopy (31 P-MRS) were utilized to provide a high time resolution assessment of exercise performance and skeletal muscle bioenergetics in control conditions (CTRL) and with the attenuation of group III/IV muscle afferent feedback via lumbar intrathecal fentanyl (FENT). In both conditions, seven recreationally active men performed 60 maximal voluntary quadriceps contractions (MVC; 3 s contraction, 2 s relaxation), while knee-extensor force and 31 P-MRS were assessed during each MVC. The cumulative integrated force was significantly greater (8 ± 6%) in FENT than CTRL for the first minute of the all-out protocol, but was not significantly different for the second to fifth minutes. Total ATP production was significantly greater (16 ± 21%) in FENT than CTRL throughout the all-out exercise protocol, due to a significantly greater anaerobic ATP production (11 ± 13%) in FENT than CTRL with no significant difference in oxidative ATP production. The ATP cost of contraction was not significantly different between FENT and CTRL for the first minute of the all-out protocol, but was significantly greater (29 ± 34%) in FENT than in CTRL for the second to fifth minutes. These findings reveal that group III/IV muscle afferents directly limit exercise performance during small muscle mass exercise, but, due to their critical role in maintaining skeletal muscle contractile efficiency, with time, the benefit from muscle afferent attenuation is negated.
Assuntos
Vias Aferentes/fisiologia , Metabolismo Energético , Exercício Físico , Contração Muscular , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Trifosfato de Adenosina/metabolismo , Adulto , Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacosRESUMO
There is ample evidence from basic research in neuroscience of the importance of local corticocortical networks. Millimetric resolution is achievable with current functional magnetic resonance imaging (fMRI) scanners and sequences, and consequently a number of "local" activity similarity measures have been defined to describe patterns of segregation and integration at this spatial scale. We have introduced the use of IsoDistant Average Correlation (IDAC), easily defined as the average fMRI temporal correlation of a given voxel with other voxels placed at increasingly separated isodistant intervals, to characterize the curve of local fMRI signal similarities. IDAC curves can be statistically compared using parametric multivariate statistics. Furthermore, by using red-green-blue color coding to display jointly IDAC values belonging to three different distance lags, IDAC curves can also be displayed as multidistance IDAC maps. We applied IDAC analysis to a sample of 41 subjects scanned under two different conditions, a resting state and an auditory-visual continuous stimulation. Multidistance IDAC mapping was able to discriminate between gross anatomofunctional cortical areas and, moreover, was sensitive to modulation between the two brain conditions in areas known to activate and deactivate during audiovisual tasks. Unlike previous fMRI local similarity measures already in use, our approach draws special attention to the continuous smooth pattern of local functional connectivity.
Assuntos
Vias Aferentes/fisiologia , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Correlação de Dados , Rede Nervosa/fisiologia , Estimulação Acústica , Adulto , Vias Aferentes/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Simulação por Computador , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Modelos Neurológicos , Rede Nervosa/diagnóstico por imagem , Oxigênio/sangue , Estimulação Luminosa , Adulto JovemRESUMO
Neuronal networks in the spinal cord generate and execute all locomotor-related movements by transforming descending signals from supraspinal areas into appropriate rhythmic activity patterns. In these spinal networks, neurons that arise from the same progenitor domain share similar distribution patterns, neurotransmitter phenotypes, morphological and electrophysiological features. However, subgroups of them participate in different functionally distinct microcircuits to produce locomotion at different speeds and of different modalities. To better understand the nature of this network complexity, here we characterized the distribution of parvalbumin (PV), calbindin D-28 k (CB) and calretinin (CR) which are regulators of intracellular calcium levels and can serve as anatomical markers for morphologically and potential functionally distinct neuronal subpopulations. We observed wide expression of CBPs in the adult zebrafish, in several spinal and reticulospinal neuronal populations with a diverse neurotransmitter phenotype. We also found that several spinal motoneurons express CR and PV. However, only the motoneuron pools that are responsible for generation of fast locomotion were CR-positive. CR can thus be used as a marker for fast motoneurons and might potentially label the fast locomotor module. Moreover, CB was mainly observed in the neuronal progenitor cells that are distributed around the central canal. Thus, our results suggest that during development the spinal neurons utilize CB and as the neurons mature and establish a neurotransmitter phenotype they use CR or/and PV. The detailed characterization of CBPs expression, in the spinal cord and brainstem neurons, is a crucial step toward a better understanding of the development and functionality of neuronal locomotor networks.
Assuntos
Vias Aferentes/fisiologia , Encéfalo/citologia , Proteínas de Ligação ao Cálcio/metabolismo , Locomoção/fisiologia , Neurônios Motores/metabolismo , Medula Espinal/citologia , Vias Aferentes/diagnóstico por imagem , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Dextranos/metabolismo , Feminino , Masculino , Microscopia Confocal , Proteínas do Tecido Nervoso/metabolismo , Neurotransmissores/metabolismo , Parvalbuminas , Rodaminas/metabolismo , Medula Espinal/diagnóstico por imagem , Medula Espinal/metabolismo , Peixe-ZebraRESUMO
BACKGROUND: As a potential new treatment for overactive bladder (OAB), we investigated the feasibility of non-invasively activating multiple nerve targets in the lower leg. METHODS: In healthy participants, surface electrical stimulation (frequency = 20 Hz, pulse width = 200 µs) was used to target the tibial nerve, saphenous nerve, medial plantar nerve, and lateral plantar nerve. At each location, the stimulation amplitude was increased to define the thresholds for evoking (1) cutaneous sensation, (2) target nerve recruitment and (3) maximum tolerance. RESULTS: All participants were able to tolerate stimulation amplitudes that were 2.1 ± 0.2 (range = 2.0 to 2.4) times the threshold for activating the target nerve. CONCLUSIONS: Non-invasive electrical stimulation can activate neural targets at levels that are consistent with evoking bladder-inhibitory reflex mechanisms. Further work is needed to test the clinical effects of stimulating one or more neural targets in OAB patients.
Assuntos
Recrutamento Neurofisiológico/fisiologia , Nervo Tibial/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Bexiga Urinária Hiperativa/fisiopatologia , Bexiga Urinária Hiperativa/terapia , Adulto , Vias Aferentes/fisiologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Roller massage (RM) interventions have shown acute increases in range of motion (ROM) and pain pressure threshold (PPT). It is unclear whether the RM-induced increases can be attributed to changes in neural or muscle responses. The purpose of this study was to evaluate the effect of altered afferent input via application of RM on spinal excitability, as measured with the Hoffmann (H-) reflex. A randomized within-subjects design was used. Three 30-s bouts of RM were implemented on a rested, nonexercised, injury-free muscle with 30 s of rest between bouts. The researcher applied RM to the plantar flexors at three intensities of pain: high, moderate, and sham. Measures included normalized M-wave and H-reflex peak-to-peak amplitudes before, during, and up to 3 min postintervention. M-wave and H-reflex measures were highly reliable. RM resulted in significant decreases in soleus H-reflex amplitudes. High-intensity, moderate-intensity, and sham conditions decreased soleus H-reflex amplitudes by 58%, 43%, and 19%, respectively. H-reflexes induced with high-intensity rolling discomfort or pain were significantly lower than moderate and sham conditions. The effects were transient in nature, with an immediate return to baseline following RM. This is the first evidence of RM-induced modulation of spinal excitability. The intensity-dependent response observed indicates that rolling pressure or pain perception may play a role in modulation of the inhibition. Roller massage-induced neural modulation of spinal excitability may explain previously reported increases in ROM and PPT. NEW & NOTEWORTHY Recent evidence indicates that the benefits of foam rolling and roller massage are primarily accrued through neural mechanisms. The present study attempts to determine the neuromuscular response to roller massage interventions. We provide strong evidence of roller massage-induced neural modulation of spinal excitability to the soleus. It is plausible that reflex inhibition may explain subsequent increases in pain pressure threshold.