Showing papers on "Reflex published in 2014"

Neural Control of the Lower Urinary Tract

Abstract: This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

Pathophysiology of spasticity: implications for neurorehabilitation.

Abstract: Spasticity is the velocity-dependent increase in muscle tone due to the exaggeration of stretch reflex. It is only one of the several components of the upper motor neuron syndrome (UMNS). The central lesion causing the UMNS disrupts the balance of supraspinal inhibitory and excitatory inputs directed to the spinal cord, leading to a state of disinhibition of the stretch reflex. However, the delay between the acute neurological insult (trauma or stroke) and the appearance of spasticity argues against it simply being a release phenomenon and suggests some sort of plastic changes, occurring in the spinal cord and also in the brain. An important plastic change in the spinal cord could be the progressive reduction of postactivation depression due to limb immobilization. As well as hyperexcitable stretch reflexes, secondary soft tissue changes in the paretic limbs enhance muscle resistance to passive displacements. Therefore, in patients with UMNS, hypertonia can be divided into two components: hypertonia mediated by the stretch reflex, which corresponds to spasticity, and hypertonia due to soft tissue changes, which is often referred as nonreflex hypertonia or intrinsic hypertonia. Compelling evidences state that limb mobilisation in patients with UMNS is essential to prevent and treat both spasticity and intrinsic hypertonia.

Reflex control of inflammation by sympathetic nerves, not the vagus

Abstract: We investigated a neural reflex that controls the strength of inflammatory responses to immune challenge - the inflammatory reflex. In anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 60 μg kg(-1)), we found strong increases in plasma levels of the key inflammatory mediator tumour necrosis factor α (TNFα) 90 min later. Those levels were unaffected by previous bilateral cervical vagotomy, but were enhanced approximately 5-fold if the greater splanchnic sympathetic nerves had been cut. Sham surgery had no effect, and plasma corticosterone levels were unaffected by nerve sections, so could not explain this result. Electrophysiological recordings demonstrated that efferent neural activity in the splanchnic nerve and its splenic branch was strongly increased by LPS treatment. Splenic nerve activity was dependent on inputs from the splanchnic nerves: vagotomy had no effect on the activity in either nerve. Together, these data demonstrate that immune challenge with this dose of LPS activates a neural reflex that is powerful enough to cause an 80% suppression of the acute systemic inflammatory response. The efferent arm of this reflex is in the splanchnic sympathetic nerves, not the vagi as previously proposed. As with other physiological responses to immune challenge, the afferent pathway is presumptively humoral: the present data show that vagal afferents play no measurable part. Because inflammation sits at the gateway to immune responses, this reflex could play an important role in immune function as well as inflammatory diseases.

The contribution of a central pattern generator in a reflex-based neuromuscular model

Abstract: Although the concept of central pattern generators (CPGs) controlling locomotion in vertebrates is widely accepted, the presence of specialized CPGs in human locomotion is still a matter of debate. An interesting numerical model developed in the 90s' demonstrated the important role CPGs could play in human locomotion, both in terms of stability against perturbations, and in terms of speed control. Recently, a reflex-based neuro-musculo-skeletal model has been proposed, showing a level of stability to perturbations similar to the previous model, without any CPG components. Although exhibiting striking similarities with human gaits, the lack of CPG makes the control of speed/step length in the model difficult. In this paper, we hypothesize that a CPG component will offer a meaningful way of controlling the locomotion speed. After introducing the CPG component in the reflex model, and taking advantage of the resulting properties, a simple model for gait modulation is presented.The results highlight the advantages that a feedforward component can have in terms of gait modulation.

Systems and methods for the measurement of vestibulo-ocular reflex to improve human performance in an occupational environment

Abstract: A portable eye reflex measuring device for use in an ambulatory occupational environment is disclosed. The eye reflex measuring device compares data from an eye movement detector with data from a head movement detector at a frequency or frequencies in the range of 0.01 Hertz to 15 Hertz to determine eye response to head movement. The gain and phase of the eye response is calculated using a Fourier transform. The device includes a central processing unit for receiving the eye movement data, for receiving the head movement data, and for calculating the Fourier transform. Typical human physiological conditions that can be measured can include vestibulo-ocular reflex, dynamic visual acuity, dynamic visual stability, or retinal image stability.

Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats

Abstract: Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception.

State-dependent and reflex drives to the upper airway: basic physiology with clinical implications.

Abstract: The root cause of the most common and serious of the sleep disorders is impairment of breathing, and a number of factors predispose a particular individual to hypoventilation during sleep. In turn, obstructive hypopneas and apneas are the most common of the sleep-related respiratory problems and are caused by dysfunction of the upper airway as a conduit for airflow. The overarching principle that underpins the full spectrum of clinical sleep-related breathing disorders is that the sleeping brain modifies respiratory muscle activity and control mechanisms and diminishes the ability to respond to respiratory distress. Depression of upper airway muscle activity and reflex responses, and suppression of arousal (i.e., "waking-up") responses to respiratory disturbance, can also occur with commonly used sedating agents (e.g., hypnotics and anesthetics). Growing evidence indicates that the sometimes critical problems of sleep and sedation-induced depression of breathing and arousal responses may be working through common brain pathways acting on common cellular mechanisms. To identify these state-dependent pathways and reflex mechanisms, as they affect the upper airway, is the focus of this paper. Major emphasis is on the synthesis of established and recent findings. In particular, we specifically focus on 1) the recently defined mechanism of genioglossus muscle inhibition in rapid-eye-movement sleep; 2) convergence of diverse neurotransmitters and signaling pathways onto one root mechanism that may explain pharyngeal motor suppression in sleep and drug-induced brain sedation; 3) the lateral reticular formation as a key hub of respiratory and reflex drives to the upper airway.

Dietary Salt Intake Exaggerates Sympathetic Reflexes and Increases Blood Pressure Variability in Normotensive Rats

Abstract: Previous studies have reported that chronic increases in dietary salt intake enhance sympathetic nerve activity and arterial blood pressure (ABP) responses evoked from brain stem nuclei of normoten...

Modulation of the initial light reflex during affective picture viewing

Abstract: An initial reflexive constriction of the pupil to stimulation-the light reflex-is primarily modulated by brightness, but is attenuated when participants are under threat of shock (i.e., fear-inhibited light reflex). The present study assessed whether the light reflex is similarly attenuated when viewing emotional pictures. Pupil diameter was recorded while participants viewed erotic, violent, and neutral scenes that were matched in brightness; scrambled versions identical in brightness were also presented as an additional control. Compared to viewing neutral scenes, the light reflex was reliably modulated by hedonic content, with significant attenuation both when viewing unpleasant as well as pleasant pictures. No differences in the light reflex were found among scrambled versions. Thus, emotional modulation of the initial light reflex is not confined to a context of fear and is not indicative of brightness differences when viewing pictures of natural scenes.

Locomotor training improves premotoneuronal control after chronic spinal cord injury.

Abstract: Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training The soleus H reflexes evoked at 10, 033, 020, 014, and 011 Hz were normalized to the H reflex evoked at 009 Hz Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest During stepping, presynaptic inhibition was modulated in a phase-dependent manner Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking

Inherent variations in CO-H2S-mediated carotid body O2 sensing mediate hypertension and pulmonary edema.

Abstract: Oxygen (O2) sensing by the carotid body and its chemosensory reflex is critical for homeostatic regulation of breathing and blood pressure Humans and animals exhibit substantial interindividual variation in this chemosensory reflex response, with profound effects on cardiorespiratory functions However, the underlying mechanisms are not known Here, we report that inherent variations in carotid body O2 sensing by carbon monoxide (CO)-sensitive hydrogen sulfide (H2S) signaling contribute to reflex variation in three genetically distinct rat strains Compared with Sprague-Dawley (SD) rats, Brown-Norway (BN) rats exhibit impaired carotid body O2 sensing and develop pulmonary edema as a consequence of poor ventilatory adaptation to hypobaric hypoxia Spontaneous Hypertensive (SH) rat carotid bodies display inherent hypersensitivity to hypoxia and develop hypertension BN rat carotid bodies have naturally higher CO and lower H2S levels than SD rat, whereas SH carotid bodies have reduced CO and greater H2S generation Higher CO levels in BN rats were associated with higher substrate affinity of the enzyme heme oxygenase 2, whereas SH rats present lower substrate affinity and, thus, reduced CO generation Reducing CO levels in BN rat carotid bodies increased H2S generation, restoring O2 sensing and preventing hypoxia-induced pulmonary edema Increasing CO levels in SH carotid bodies reduced H2S generation, preventing hypersensitivity to hypoxia and controlling hypertension in SH rats

Repeated core temperature elevation induces conduit artery adaptation in humans.

Abstract: Shear stress is a known stimulus to vascular adaptation in humans. However, it is not known whether thermoregulatory reflex increases in blood flow and shear can induce conduit artery adaptation. Ten healthy young volunteers therefore underwent 8 weeks of 3 × weekly bouts of 30 min lower limb heating (40 °C) during which the upper body was not directly heated. Throughout each leg heating session, a pneumatic cuff was placed on one forearm and inflated to unilaterally restrict reflex-mediated blood flow responses. Each bout of leg heating significantly increased brachial artery shear rate in the uncuffed arm (96 ± 97 vs 401 ± 96 l/s, P < 0.01), whereas no change was apparent in the cuffed arm (83 ± 69 vs 131 ± 76 l/s, P = 0.67). Repeated episodic exposure to leg heating enhanced brachial artery endothelial function (measured by flow-mediated dilation) in the uncuffed arm from week 0 (5.2 ± 1.9 %) to week 4 (7.7 ± 2.6 %, P < 0.05), before returning to baseline levels by week 8. No adaptation was evident in the cuffed arm. We conclude that repeated increases in core temperature, induced via lower limb heating, resulted in upper limb conduit artery vascular adaptation which was dependent upon increases in shear stress. To our knowledge this is the first study to establish a beneficial systemic impact of thermoregulatory reflexes on conduit artery function in humans.

Generalized versus partial reflex seizures: A review

Abstract: In this review we assess our currently available knowledge about reflex seizures with special emphasis on the difference between "generalized" reflex seizures induced by visual stimuli, thinking, praxis and language tasks, and "focal" seizures induced by startle, eating, music, hot water, somatosensory stimuli and orgasm. We discuss in particular evidence from animal, clinical, neurophysiological and neuroimaging studies supporting the concept that "generalized" reflex seizures, usually occurring in the setting of IGE, should be considered as focal seizures with quick secondary generalization. We also review recent advances in genetic and therapeutic approach of reflex seizures.

Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

Abstract: The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors

Abstract: The neurocirculatory responses to exercise are exaggerated in hypertension, increasing cardiovascular risk, yet the mechanisms remain incompletely understood. The aim of this study was to examine t...

Endothelial nitric oxide synthase mediates the nitric oxide component of reflex cutaneous vasodilatation during dynamic exercise in humans

Abstract: Key points Increases in skin blood flow and sweating also occur during exercise; however, it is not known if the mechanisms controlling these responses are the same during passive heat stress and exercise. The prevailing thought has been that mechanisms of cutaneous vasodilatation during passive heat stress and sustained dynamic exercise are the same, or very similar. Nitric oxide (NO) has been shown to be important for increasing skin blood flow during passive heat stress but it is unknown if this molecule is also involved during sustained dynamic exercise. The findings from our study suggest NO is involved in increasing skin blood flow during sustained dynamic exercise in humans but the NO is produced from a different enzyme compared to passive heat stress. These findings may help us better understand and aid individuals who have difficulty regulating their body temperature during sustained dynamic exercise (e.g. ageing). Abstract Recent data suggests neuronal nitric oxide synthase (nNOS) mediates the NO component of reflex cutaneous vasodilatation with passive heat stress. We tested the hypothesis that nNOS inhibition would attenuate reflex cutaneous vasodilatation during sustained dynamic exercise in young healthy humans. All subjects first performed an incremental VO2, peak test to exhaustion on a custom-built supine cycle ergometer. On a separate day, subjects were instrumented with four intradermal microdialysis fibres on the forearm and each randomly assigned as: (1) lactated Ringer's (control); (2) 20 mm Nω-nitro-l-arginine methyl ester hydrochloride (non-selective NOS inhibitor); (3) 5 mm N-propyl-l-arginine (nNOS inhibitor); and (4) 10 mm N5-(1-iminoethyl)-l-ornithine dihydrochloride [endothelial NOS (eNOS) inhibitor]. Following microdialysis placement, subjects performed supine cycling with the experimental arm at heart level at 60% VO2, peak for a period sufficient to raise core temperature 0.8°C. At the end of cycling, all microdialysis sites were locally heated to 43°C and sodium nitroprusside was perfused to elicit maximal vasodilatation. Mean arterial pressure, skin blood flow via laser-Doppler flowmetry and core temperature via ingestible telemetric pill were measured continuously; cutaneous vascular conductance (CVC) was calculated as laser-Doppler flowmetry/mean arterial pressure and normalized to maximum. There was no significant difference between control (58 ± 2%CVCmax) and nNOS-inhibited (56 ± 3%CVCmax) sites in response to exercise-induced hyperthermia. The increase in CVC at eNOS-inhibited (41 ± 3%CVCmax) and non-selective NOS-inhibited (40 ± 4%CVCmax) sites were significantly attenuated compared to control and nNOS-inhibited (P < 0.001 all conditions) but there was no difference between eNOS-inhibited and non-selective NOS-inhibited sites. These data suggest eNOS, not nNOS, mediate NO synthesis during reflex cutaneous vasodilatation with sustained dynamic exercise.

Pten deletion in RIP-Cre neurons protects against type 2 diabetes by activating the anti-inflammatory reflex.

Abstract: A new study by Minna Woo and colleagues shows that a neuronal relay from the brain to the adipose tissue regulates whole-body insulin sensitivity by affecting macrophage function, and thus inflammation, in the periphery. These results suggest that a centrally mediated anti-inflammatory reflex exists to regulate metabolic health.

Neural mechanisms of peristalsis in the isolated rabbit distal colon: a neuromechanical loop hypothesis

Abstract: Propulsive contractions of circular muscle are largely responsible for the movements of content along the digestive tract. Mechanical and electrophysiological recordings of isolated colonic circular muscle have demonstrated that localized distension activates ascending and descending interneuronal pathways, evoking contraction orally and relaxation anally. These polarised enteric reflex pathways can theoretically be sequentially activated by the mechanical stimulation of the advancing contents. Here, we test the hypothesis that initiation and propagation of peristaltic contractions involves a neuromechanical loop; that is an initial gut distension activates local and oral reflex contraction and anal reflex relaxation, the subsequent movement of content then acts as new mechanical stimulus triggering sequentially reflex contractions/relaxations at each point of the gut resulting in a propulsive peristaltic contraction. In fluid filled isolated rabbit distal colon, we combined spatiotemporal mapping of gut diameter and intraluminal pressure with a new analytical method, allowing us to identify when and where active (neurally-driven) contraction or relaxation occurs. Our data indicate that gut dilation is associated with propagating peristaltic contractions, and that the associated level of dilation is greater than that preceding non-propagating contractions (2.7 ± 1.4mm v 1.6 ± 1.2mm; P < 0.0001). These propagating contractions lead to the formation of boluses that are propelled by oral active neurally driven contractions. The propelled boluses also activate neurally driven anal relaxations, in a diameter dependent manner. These data support the hypothesis that neural peristalsis is the consequence of the activation of a functional loop involving mechanical dilation which activates polarized enteric circuits. These produce propulsion of the bolus which activates further anally, polarized enteric circuits by distension, thus closing the neuromechanical loop.

Contributions to the understanding of gait control.

Abstract: This thesis is based on ten published articles. The experimental work was carried out at the Faculty of Health Sciences, University of Copenhagen. The aim was to investigate and describe a number of basic mechanical and physiological mechanisms behind human walking. The methodologies used were biomechanical movement analysis and electrophysiology. The walking experiments were carried out in a gait lab, where the subjects were video recorded while they walked across two force platforms, which measured the ground reaction forces. Net joint moments about the hip-, knee- and ankle joint were calculated by combining the movement data and the external reaction forces (inverse dynamics). Muscle activity and sensory input to the spinal cord were measured by electromyography (EMG) and electrical stimulation of peripheral nerves. The results showed that the gait pattern varies to a great degree between individuals. Some people choose to exert the highest forces about the ankle joint while others prefer to use the knee joint. By use of a cluster analysis, fifteen healthy subjects could be divided into two groups. The extensor moment about the knee joint was the main factor for separating the two gait patterns, but the group with the highest extensor moments about the knee joint also walked with more flexed knee joints, higher EMG activity in the quadriceps muscle and higher bone-on-bone forces. This may lead to development of osteoarthritis over the years. Walking on high-heeled shoes reduced the ankle joint moment significantly either because of reduced muscle fiber length and/or increased co-contraction about the joint. On the contrary, the extensor moment about the knee joint was almost doubled in the high-heeled condition compared to bare footed walking at the same velocity. Also the EMG activity increased in the leg muscles. This could be an explanation pertaining to the higher incidence of osteoarthritis in women than in men. Patients with a drop-foot cannot put the foot to the ground with the heel first. Moreover, they have to increase flexion of the hip joint during the swing phase because the foot hangs in a plantar flexed position. It was shown that the ankle joint plantar flexor moment increased in the healthy leg and that the knee joint extensor moment increased significantly in both the affected and the healthy leg. The latter is most likely due to the patients trying to avoid an asymmetrical gait pattern. It is recommended to use an orthosis with drop-foot patients in order to keep the ankle joint dorsiflexed prior to touchdown, otherwise bone-on-bone forces in both knee joints will increase and probably lead to osteoarthritis. The hip joint moment varies less between individuals. However, both during walking and running an unexplained hip joint flexor moment is present during the last half of the stance phase. The moment appears to oppose the speed of progression and it has been suggested that it serves to balance the upper body. This was investigated in a group of healthy subjects who were asked to walk with their upper body in a reclined, inclined and normal position, respectively. It was shown that the hip joint flexor moment was similar in the reclined and the normal position but lower when walking in the inclined position and it can be concluded that the upper body is not balanced by hip joint flexor muscles but rather by accelerations of the pelvis and activity in abdominal and back muscles. These experiments also showed that the trailing leg is brought forward during the swing phase without activity in the flexor muscles about the hip joint. This was verified by the absence of EMG activity in the iliacus muscle measured by intramuscular wire electrodes. Instead the strong ligaments restricting hip joint extension are stretched during the first half of the swing phase thereby storing elastic energy, which is released during the last half of the stance phase and accelerating the leg into the swing phase. This is considered an important energy conserving feature of human walking. The gating of sensory input to the spinal cord during walking and running was investigated by use of the Hoffmann (H) reflex in m. soleus and m. gastrocnemius medialis. This reflex expresses the central component of the stretch reflex, i.e. the transmission from Ia afferents to α-motoneurones in the spinal cord. The soleus H-reflex was shown to be strongly modulated during the gait cycle. In general, it was facilitated in the stance phase and suppressed in the swing phase. However, as it was the case with the biomechanical parameters, inter-individual H-reflex modulations were found and they were highly reproducible between days. One group of subjects had an almost completely suppressed H-reflex during the entire swing phase, while another group showed a gradually increasing reflex excitability during the swing phase. This group also walked with a lower extensor moment about the knee joint and higher plantar flexor moment about the ankle joint and it is speculated that this gait pattern highly relies on reflexes to deal with unexpected perturbations. The subjects with the suppressed reflex during the swing phase also showed a higher EMG activity in the anterior tibial muscle, so it is likely that the suppression of the H-reflex was at least partly due to reciprocal antagonist inhibition. All subjects showed complete suppression of the H-reflex at toeoff. This seems necessary to avoid a stretch reflex being elicited in the soleus muscle as the ankle joint undergoes a fast dorsiflexion just after toeoff. The reflex modulation is clearly an integrated part of the human gait pattern and is absolutely necessary for normal gait function with smoothe movements. Furthermore, it is anticipated that the afferent input from the muscle spindles is used to drive the motor output from the α-motoneurones together with descending activity from the motor cortex. During running the H-reflex increased in both the soleus and the gastrocnemius already before heel strike and before the onset of EMG activity in the same two muscles and with a relatively high activity in the anterior tibial muscle, but this was most pronounced in the soleus. The H-reflex was always higher in the soleus also when expressed as percentage of the maximal M-wave. This is due to the difference in muscle fiber type distribution between the two muscles. The H-reflex increased from walking to running in both muscles and further with increasing running speed. Unexpectedly, there were no signs of the faster gastrocnemius becoming more important at higher running speed. During walking it is not possible to observe a stretch reflex in the form of a synchronized activation of a large number of muscle fibers as this would disturb the movement pattern. It is rather likely that the input from Ia afferents directly contributes to activate the α-motoneurones. However, during running the stance phase is much shorter, which enables the possibility of a stretch reflex to contribute to a strong contraction during push-off. EMG peaks in the soleus with an appropriate latency were observed in the soleus during running. This was not the case with the gastrocnemius and the explanation is most likely that the gastrocnemius is biarticular and not stretched to any great extent during running.

Loss of α-calcitonin gene-related peptide (αCGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR).

Abstract: The neuroactive peptide calcitonin-gene related peptide (CGRP) is known to act at efferent synapses and their targets in hair cell organs, including the cochlea and lateral line. CGRP is also expressed in vestibular efferent neurons as well as a number of central vestibular neurons. Although CGRP-null (−/−) mice demonstrate a significant reduction in cochlear nerve sound-evoked activity compared with wild-type mice, it is unknown whether and how the loss of CGRP influence vestibular system function. Vestibular function was assessed by quantifying the vestibulo-ocular reflex (VOR) in alert mice. The loss of CGRP in (−/−) mice was associated with a reduction of the VOR gain of ≈50% without a concomitant change in phase. Using immunohistochemistry, we confirmed that, although CGRP staining was absent in the vestibular end-organs of null (−/−) mice, cholinergic staining appeared normal, suggesting that the overall gross development of vestibular efferent innervation was unaltered. We further confirmed that the observed deficit in vestibular function of null (−/−) mice was not the result of nontargeted effects at the level of the extraocular motor neurons and/or their innervation of extraocular muscles. Analysis of the relationship between vestibular quick phase amplitude and peak velocity revealed that extraocular motor function was unchanged, and immunohistochemistry revealed no abnormalities in motor endplates. Together, our findings show that the neurotransmitter CGRP plays a key role in ensuring VOR efficacy.

Perturbation-evoked responses in primary motor cortex are modulated by behavioral context

Abstract: Corrective responses to external perturbations are sensitive to the behavioral task being performed. It is believed that primary motor cortex (M1) forms part of a transcortical pathway that contrib...

Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy.

Abstract: Sepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play a significant role in modulating the immune response. Thus, similar toall other physiological systems, the immune system is both connected to and regulated by the central nervous system. The efferent arc consists of the activation of the hypothalamic–pituitary–adrenal axis, sympathetic activation, the cholinergic anti-inflammatory reflex, and the local release of physiological neuromodulators. Immunosensory activity is centered on the production of pro-inflammatory cytokines, signals that are conveyed to the brain through different pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve are broadly discussed here. Despite cytokine receptor expression in vagal afferent fibers, pro-inflammatory cytokines have no significant effect on vagus nerve activity. Thus, the CB may be the source of immunosensory inputs and incoming neural signals and, in fact, sense inflammatory mediators, playing a protective role during sepsis. Considering that CB stimulation increases sympathetic activity and adrenal glucocorticoids release, the electrical stimulation of arterial chemoreceptors may be suitable therapeutic approach for regulating systemic inflammation.

The effect of air puff stress on c-Fos expression in rat hypothalamus and brainstem: central circuitry mediating sympathoexcitation and baroreflex resetting.

Abstract: Psychological stress evokes increases in sympathetic activity and blood pressure, which are due at least in part to an upward resetting of the baroreceptor-sympathetic reflex. In this study we determined whether sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), which have a critical role in the reflex control of sympathetic activity, are activated during air puff stress, a moderate psychological stressor. Secondly, we identified neurons that are activated by air puff stress and that also project to the nucleus tractus solitarius (NTS), a key site for modulation of the baroreceptor reflex. Air puff stress resulted in increased c-Fos expression in several hypothalamic and brainstem nuclei, including the paraventricular nucleus (PVN), dorsomedial hypothalamus, perifornical area (PeF), periaqueductal gray (PAG), NTS and rostral ventromedial medulla, but not in the RVLM region that contains sympathetic premotor neurons. In contrast, neurons in this RVLM region, including catecholamine-synthesizing neurons, did express c-Fos following induced hypotension, which reflexly activates RVLM sympathetic premotor neurons. The highest proportion of NTS-projecting neurons that were double-labelled with c-Fos after air puff stress was in the ventrolateral PAG (29.3 ± 5.5%), with smaller but still significant proportions of double-labelled NTS-projecting neurons in the PVN and PeF (6.5 ± 1.8 and 6.4 ± 1.7%, respectively). The results suggest that the increased sympathetic activity during psychological stress is not driven primarily by RVLM sympathetic premotor neurons, and that neurons in the PVN, PeF and ventrolateral PAG may contribute to the resetting of the baroreceptor-sympathetic reflex that is associated with psychological stress.

Projection neurons of the vestibulo-sympathetic reflex pathway

Abstract: Changes in head position and posture are detected by the vestibular system and are normally followed by rapid modifications in blood pressure. These compensatory adjustments, which allow humans to stand up without fainting, are mediated by integration of vestibular system pathways with blood pressure control centers in the ventrolateral medulla. Orthostatic hypotension can reflect altered activity of this neural circuitry. Vestibular sensory input to the vestibulo-sympathetic pathway terminates on cells in the vestibular nuclear complex, which in turn project to brainstem sites involved in the regulation of cardiovascular activity, including the rostral and caudal ventrolateral medullary regions (RVLM and CVLM, respectively). In the present study, sinusoidal galvanic vestibular stimulation was used to activate this pathway, and activated neurons were identified through detection of c-Fos protein. The retrograde tracer FluoroGold was injected into the RVLM or CVLM of these animals, and immunofluorescence studies of vestibular neurons were conducted to visualize c-Fos protein and FluoroGold concomitantly. We observed activated projection neurons of the vestibulo-sympathetic reflex pathway in the caudal half of the spinal, medial and parvocellular medial vestibular nuclei. Approximately two-thirds of the cells were ipsilateral to FluoroGold injection sites in both RVLM and CVLM and the remainders were contralateral. As a group, cells projecting to RVLM were located slightly rostral to those with terminals in CVLM. Individual activated projection neurons were multipolar, globular or fusiform in shape. This study provides the first direct demonstration of the central vestibular neurons that mediate the vestibulo-sympathetic reflex.

Two Strategies for Response to 14°C Cold-Water Immersion: Is there a Difference in the Response of Motor, Cognitive, Immune and Stress Markers?

Abstract: Here, we address the question of why some people have a greater chance of surviving and/or better resistance to cold-related-injuries in prolonged exposure to acute cold environments than do others, despite similar physical characteristics. The main aim of this study was to compare physiological and psychological reactions between people who exhibited fast cooling (FC; n = 20) or slow cooling (SC; n = 20) responses to cold water immersion. Individuals in whom the T(re) decreased to a set point of 35.5 °C before the end of the 170-min cooling time were indicated as the FC group; individuals in whom the T(re) did not decrease to the set point of 35.5 °C before the end of the 170-min cooling time were classified as the SC group. Cold stress was induced using intermittent immersion in bath water at 14 °C. Motor (spinal and supraspinal reflexes, voluntary and electrically induced skeletal muscle contraction force) and cognitive (executive function, short term memory, short term spatial recognition) performance, immune variables (neutrophils, leucocytes, lymphocytes, monocytes, IL-6, TNF-α), markers of hypothalamic-pituitary-adrenal axis activity (cortisol, corticosterone) and autonomic nervous system activity (epinephrine, norepinephrine) were monitored. The data obtained in this study suggest that the response of the FC group to cooling vs the SC group response was more likely an insulative-hypothermic response and that the SC vs the FC group displayed a metabolic-insulative response. The observations that an exposure time to 14 °C cold water--which was nearly twice as short (96-min vs 170-min) with a greater rectal temperature decrease (35.5 °C vs 36.2 °C) in the FC group compared with the SC group--induces similar responses of motor, cognitive, and blood stress markers were novel. The most important finding is that subjects with a lower cold-strain-index (SC group) showed stimulation of some markers of innate immunity and suppression of markers of specific immunity.

Comparison of tear lipid profile among basal, reflex, and flush tear samples.

Abstract: PurposeTo determine whether tear collection by flushing the ocular surface with saline (flush tears) or collection by stimulation (reflex tears) can be used as an alternative to basal tear collection for the identification and quantification of lipids in the tear film.MethodsTear samples wer

Trigeminocardiac reflex: differential behavior and risk factors in the course of the trigeminal nerve

Abstract: ; The trigeminocardiac reflex (TCR) is a brainstem reflex describing the acute hemodynamic perturbations in neurosurgical patients. The roles of different anatomic locations of this reflex arc on end responses have been found to be variable. In this article, we have highlighted the role and importance of different TCR pathway (peripheral vs central) mechanisms, their manifestations and the various risk factors associated with these. In addition, new insights into various other non-neurosurgical conditions, in special relation to neurointerventional procedures, are also presented in this article. This study is a narrative review based on a PubMed/Google search (from 1 January 1970 to 31 March 2013) on this topic. The common manifestations, such as hypotension and bradycardia, are vagal-dominated responses; however, unusual manifestations, such as hypertension and tachycardia, signify the involvement of the sympathetic nervous system. In addition, there is a complex interaction of the various sensor...

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

Abstract: Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5′-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1−/− mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion.

The vestibulo-ocular reflex and subjective balance after vestibular schwannoma surgery.

Abstract: Objectives/Hypothesis To evaluate the vestibulo-ocular reflex and its relationship with subjective balance in a long-term follow-up after vestibular schwannoma surgery. Study Design Retrospective cohorts study in a tertiary referral hospital. Forty-nine consecutive patients on which vestibular schwannoma surgery was performed at least 1 year before. Methods Patients are classified in accordance with the morphology of the vestibulo-ocular reflex (VOR) into two groups: Group A, in which covert and overt saccades always occur in an organized fashion; and group B, in which covert and overt saccades randomly occur during head impulse and once finished. We evaluate the presence of covert and overt saccades and the morphology of the VOR measured by the video head impulse test (vHIT) and its relationship with subjective balance measured by Dizziness Handicap Inventory (DHI). Results The group B patients returned a higher score in total DHI and all three subscales without any predominant subscale (P = 0,0002; t test). Group B patients were older than those in group A (P = 0,024; t test). No differences were found in sex distribution, tumor size, or side or time interval after surgery. Regarding the unaffected side, overt saccades were found to be more frequent in group B patients (P = 0.05; X2). Conclusions Long-term follow-up after vestibular schwannoma surgery has shown that 22% of the patients display a particular abnormality in the VOR because refixation saccades occur in a random fashion after elicitation of the reflex in the HIT test. These patients report the higher level of vestibular disability and handicap. Level of Evidence 2b. Laryngoscope, 124:1431–1435, 2014