Showing papers on "Reflex published in 2012"

Reflex Principles of Immunological Homeostasis

Abstract: The reasoning that neural reflexes maintain homeostasis in other body organs, and that the immune system is innervated, prompted a search for neural circuits that regulate innate and adaptive immunity. This elucidated the inflammatory reflex, a prototypical reflex circuit that maintains immunological homeostasis. Molecular products of infection or injury activate sensory neurons traveling to the brainstem in the vagus nerve. The arrival of these incoming signals generates action potentials that travel from the brainstem to the spleen and other organs. This culminates in T cell release of acetylcholine, which interacts with α7 nicotinic acetylcholine receptors (α7 nAChR) on immunocompetent cells to inhibit cytokine release in macrophages. Herein is reviewed the neurophysiological basis of reflexes that provide stability to the immune system, the neural- and receptor-dependent mechanisms, and the potential opportunities for developing novel therapeutic devices and drugs that target neural pathways to treat inflammatory diseases.

Rethinking inflammation: neural circuits in the regulation of immunity.

Abstract: Neural reflex circuits regulate cytokine release to prevent potentially damaging inflammation and maintain homeostasis. In the inflammatory reflex, sensory input elicited by infection or injury travels through the afferent vagus nerve to integrative regions in the brainstem, and efferent nerves carry outbound signals that terminate in the spleen and other tissues. Neurotransmitters from peripheral autonomic nerves subsequently promote acetylcholine-release from a subset of CD4(+) T cells that relay the neural signal to other immune cells, e.g. through activation of α7 nicotinic acetylcholine receptors on macrophages. Here, we review recent progress in the understanding of the inflammatory reflex and discuss potential therapeutic implications of current findings in this evolving field.

Neural reflexes in inflammation and immunity

Abstract: The mammalian immune system and the nervous system coevolved under the influence of infection and sterile injury. Knowledge of homeostatic mechanisms by which the nervous system controls organ function was originally applied to the cardiovascular, gastrointestinal, musculoskeletal, and other body systems. Development of advanced neurophysiological and immunological techniques recently enabled the study of reflex neural circuits that maintain immunological homeostasis, and are essential for health in mammals. Such reflexes are evolutionarily ancient, dating back to invertebrate nematode worms that possess primitive immune and nervous systems. Failure of these reflex mechanisms in mammals contributes to nonresolving inflammation and disease. It is also possible to target these neural pathways using electrical nerve stimulators and pharmacological agents to hasten the resolution of inflammation and provide therapeutic benefit.

Effects of whole body vibration on motor unit recruitment and threshold.

Abstract: Whole body vibration (WBV) has been suggested to elicit reflex muscle contractions but this has never been verified. We recorded from 32 single motor units (MU) in the vastus lateralis of 7 healthy...

Hiccup: mystery, nature and treatment.

Abstract: Hiccup is the sudden onset of erratic diaphragmatic and intercostal muscle contraction and immediately followed by laryngeal closure. The abrupt air rush into lungs elicits a "hic" sound. Hiccup is usually a self-limited disorder; however, when it is prolonged beyond 48 hours, it is considered persistent whereas episodes longer than 2 months are called intractable. A reflex arc involving peripheral phrenic, vagal and sympathetic pathways and central midbrain modulation is likely responsible for hiccup. Accordingly, any irritant in terms of physical/chemical factors, inflammation, neoplasia invading the arc leads to hiccups. The central causes of hiccup include stroke, space occupying lesions and injury etc, whereas peripheral causes include lesions along the arc such as tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease and applied instrumentations on human body etc. Besides, various drugs (eg, anti-parkinsonism drugs, anesthetic agents, steroids and chemotherapies etc) are the possible etiology. An effective treatment of persistent hiccup may be established upon the correct diagnosis of lesion responsible for the serious event. The pharmacotherapy of hiccup includes chlorpromazine, gabapentin, baclofen, serotonergic agonists, prokinetics and lidocaine. Non-pharmacological approaches such as nerve blockade, pacing, acupuncture and measures to hold breathing are also successful. Finally, alternative medicines and remedies are convenient to treat hiccups with uncertain effect. In conclusions, hiccup is likely to result from lesions involving the hiccup reflex arc. The lesion may need to be localized correctly for ablative treatment in patients with intractable hiccup. Apart from lesion ablation, drugs acting on reflex arc may be effective, while some other conventional measures may also be tried.

Single motor unit activity in human extraocular muscles during the vestibulo-ocular reflex

Abstract: Motor unit activity in human eye muscles during the vestibulo-ocular reflex (VOR) is not well understood, since the associated head and eye movements normally preclude single unit recordings. Therefore we recorded single motor unit activity following bursts of skull vibration and sound, two vestibular otolith stimuli that elicit only small head and eye movements. Inferior oblique (IO) and inferior rectus (IR) muscle activity was measured in healthy humans with concentric needle electrodes. Vibration elicited highly synchronous, short-latency bursts of motor unit activity in the IO (latency: 10.5 ms) and IR (14.5 ms) muscles. The activation patterns of the two muscles were similar, but reciprocal, with delayed activation of the IR muscle. Sound produced short-latency excitation of the IO muscle (13.3 ms) in the eye contralateral to the stimulus. Simultaneous needle and surface recordings identified the IO as the muscle of origin of the vestibular evoked myogenic potential (oVEMP) thus validating the physiological basis of this recently developed clinical test of otolith function. Single extraocular motor unit recordings provide a window into neural activity in humans that can normally only be examined using animal models and help identify the pathways of the translational VOR from otoliths to individual eye muscles.

Significance of Group III and IV muscle afferents for the endurance exercising human

Abstract: 1. With the onset of dynamic whole-body exercise, contraction-induced mechanical and biochemical stimuli within locomotor muscle cause an increase in the discharge frequency of thinly myelinated (Group III) and unmyelinated (Group IV) nerve fibres located within the muscle. 2. These thin fibre muscle afferents project to various sites within the central nervous system and thereby substantially influence the exercising human. 3. First, Group III/IV muscle afferents are the afferent arm of cardiovascular and ventilatory reflex responses that are mediated in the nucleus tractus solitarius and the ventrolateral medulla. Therefore, neural feedback from working skeletal muscle is a vital component in providing a high capacity for endurance exercise because muscle perfusion and O₂ delivery determine the fatigability of skeletal muscle. 4. Second, Group III/IV muscle afferents facilitate 'central fatigue' (failure, or unwillingness, of the central nervous system to 'drive' motoneurons) by exerting inhibitory influences on central motor drive during exercise. 5. Thus, Group III/IV muscle afferents play a substantial role in a human's susceptibility to fatigue and capacity for endurance exercise.

Bronchoconstriction Triggered by Breathing Hot Humid Air in Patients with Asthma: Role of Cholinergic Reflex

Abstract: Rationale: Hyperventilation of hot humid air induces transient bronchoconstriction in patients with asthma; the underlying mechanism is not known. Recent studies showed that an increase in temperature activates vagal bronchopulmonary C-fiber sensory nerves, which upon activation can elicit reflex bronchoconstriction. Objectives: This study was designed to test the hypothesis that the bronchoconstriction induced by increasing airway temperature in patients with asthma is mediated through cholinergic reflex resulting from activation of these airway sensory nerves. Methods: Specific airway resistance (SRaw) and pulmonary function were measured to determine the airway responses to isocapnic hyperventilation of humidified air at hot (49°C; HA) and room temperature (20–22°C; RA) for 4 minutes in six patients with mild asthma and six healthy subjects. A double-blind design was used to compare the effects between pretreatments with ipratropium bromide and placebo aerosols on the airway responses to HA challenge in these patients. Measurements and Main Results: SRaw increased by 112% immediately after hyperventilation of HA and by only 38% after RA in patients with asthma. Breathing HA, but not RA, triggered coughs in these patients. In contrast, hyperventilation of HA did not cause cough and increased SRaw by only 22% in healthy subjects; there was no difference between their SRaw responses to HA and RA challenges. More importantly, pretreatment with ipratropium completely prevented the HA-induced bronchoconstriction in patients with asthma. Conclusions: Bronchoconstriction induced by increasing airway temperature in patients with asthma is mediated through the cholinergic reflex pathway. The concomitant increase in cough response further indicates an involvement of airway sensory nerves, presumably the thermosensitive C-fiber afferents.

Improved postural control after slackline training is accompanied by reduced H-reflexes

Abstract: "Slacklining" represents a modern sports activity where people have to keep balance on a tightened ribbon. The first trials on the slackline result in uncontrollable lateral swing of the supporting leg. Training decreases those oscillations and therefore improves postural control. However, the underlying neural mechanisms are not known. Therefore, the present study aimed to highlight spinal adaptations going along with slackline training. Twenty-four subjects were either assigned to a training or a control group and postural control was assessed before and after the 10 training sessions. Additionally, soleus Hoffmann (H)-reflexes were elicited to evaluate changes in the excitability of the spinal reflex circuitry. Trained subjects were able to maintain balance on the slackline for at least 20 s (P<0.001) and reduced platform movements on the balance board (P<0.05). The H-reflexes were significantly diminished (P<0.05) while no changes occurred in the background electromyography (bEMG). The control group showed no significant changes. From a functional point of view the reflex reduction may serve to suppress uncontrollable reflex mediated joint oscillations. As the bEMG remained unchanged, presynaptic rather than post-synaptic mechanisms are speculated to be responsible for the changes in the Ia-afferent transmission.

Anatomy and neuro-pathophysiology of the cough reflex arc

Abstract: Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. It accounts for a significant number of consultations both at the level of general practitioner and of respiratory specialists. In this review we first analyze the cough reflex under normal conditions; then we analyze the anatomy and the neuro-pathophysiology of the cough reflex arc. The aim of this review is to provide the anatomic and pathophysiologic elements of evaluation of the complex and multiple etiologies of cough.

The Bainbridge and the “Reverse” Bainbridge Reflexes: History, Physiology, and Clinical Relevance

Abstract: Francis A. Bainbridge demonstrated in 1915 that an infusion of saline or blood into the jugular vein of the anesthetized dog produced tachycardia. His findings after transection of the cardiac autonomic nerve supply and injection of the cholinergic blocking drug atropine demonstrated that the tachycardia was reflex in origin, with the vagus nerves constituting the afferent limb and a withdrawal of vagal tone the primary efferent limb. Subsequent investigators demonstrated that the increase in venous return was detected by stretch receptors in the right and left atria. In the 1980s, it was shown convincingly that the Bainbridge reflex was present in primates, including humans, but that the reflex was much less prominent than in the dog. This difference may be due to a more dominant arterial baroreceptor reflex in humans. A "reverse" Bainbridge reflex has been proposed to explain the decreases in heart rate observed under conditions in which venous return is reduced, such as during spinal and epidural anesthesia, controlled hypotension, and severe hemorrhage. The Bainbridge reflex is invoked throughout the anesthesia literature to describe the effect of changes in venous return on heart rate in patients in the surgical and critical care settings, but a critical analysis of the experimental and clinical evidence is lacking. Our main objectives in this review are to summarize the history of the Bainbridge reflex, to describe its anatomy and physiology, and to discuss the evidence for and against it having an influence on heart rate changes observed clinically. The interaction of the Bainbridge reflex with the arterial baroreceptor and Bezold-Jarisch reflexes is discussed.

Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats

Abstract: It has been reported that the P2Y12 receptor (P2Y12R) is involved in satellite glial cells (SGCs) activation, indicating that P2Y12R expressed in SGCs may play functional roles in orofacial neuropathic pain mechanisms. However, the involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown. We therefore studied the reflex to noxious mechanical or heat stimulation of the tongue, P2Y12R and glial fibrillary acidic protein (GFAP) immunohistochemistries in the trigeminal ganglion (TG) in a rat model of unilateral lingual nerve crush (LNC) to evaluate role of P2Y12R in SGC in lingual neuropathic pain. The head-withdrawal reflex thresholds to mechanical and heat stimulation of the lateral tongue were significantly decreased in LNC-rats compared to sham-rats. These nocifensive effects were apparent on day 1 after LNC and lasted for 17 days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons encircled with GFAP-immunoreactive (IR) cells significantly increased in the ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC, P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN)-IR cells (i.e. neurons) in TG. After 3 days of successive administration of the P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly decreased coincident with a significant reversal of the lowered head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue compared to vehicle-injected rats. Furthermore, after 3 days of successive administration of the P2YR agonist 2-MeSADP into the TG in naive rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly increased and head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue were significantly decreased in a dose-dependent manner compared to vehicle-injected rats. The present findings provide the first evidence that the activation of P2Y12R in SGCs of TG following lingual nerve injury is involved in the enhancement of TG neuron activity and nocifensive reflex behavior, resulting in neuropathic pain in the tongue.

The exercise pressor reflex in animals.

Abstract: This report summarizes work concerning the exercise pressor reflex performed in my laboratory over the past 20 years or so. It is part of a symposium held to celebrate the 40th anniversary of two publications by Dr Jere Mitchell that appeared in The Journal of Physiology. For the most part, this report concerns itself with the discharge properties of group III and IV muscle afferents. Particular attention has been paid to their responses to arterial injection of putative metabolic byproducts of muscular contraction as well as their responses to both static contraction and dynamic exercise.

Age-related influence of vision and proprioception on Ia presynaptic inhibition in soleus muscle during upright stance

Abstract: This study investigated the modulation of Ia afferent input in young and elderly adults during quiet upright stance in normal and modified visual and proprioceptive conditions. The surface EMG of leg muscles, recruitment curve of the soleus (SOL) Hoffmann (H) reflex and presynaptic inhibition of Ia afferents from SOL, assessed with the D1 inhibition and single motor unit methods, were recorded when young and elderly adults stood with eyes open or closed on two surfaces (rigid vs. foam) placed over a force platform. The results showed that elderly adults had a longer path length for the centre of pressure and larger antero-posterior body sway across balance conditions (P < 0.05). Muscle EMG activities were greater in elderly compared with young adults (P < 0.05), whereas the H(max) expressed as a percentage of the H(max) was lower (P = 0.048) in elderly (38 ± 16%) than young adults (58 ± 16%). The conditioned H reflex/test H reflex ratio (D1 inhibition method) increased with eye closure and when standing on foam (P < 0.05), with greater increases for elderly adults (P = 0.019). These changes were accompanied by a reduced peak motor unit discharge probability when standing on rigid and foam surfaces (P 0.001), with a greater effect for elderly adults (P = 0.026). Based on these latter results, the increased conditioned H reflex/test H reflex ratio in similar sensory conditions is likely to reflect occlusion at the level of presynaptic inhibitory interneurones. Together, these findings indicate that elderly adults exhibit greater modulation of Ia presynaptic inhibition than young adults with variation in the sensory conditions during upright standing.

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals

Abstract: Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Volitional control of reflex cough.

Abstract: Multiple studies suggest a role for the cerebral cortex in the generation of reflex cough in awake humans. Reflex cough is preceded by detection of an urge to cough; strokes specifically within the...

Planning of ballistic movement following stroke: insights from the startle reflex.

Abstract: Following stroke, reaching movements are slow, segmented, and variable It is unclear if these deficits result from a poorly constructed movement plan or an inability to voluntarily execute an appropriate plan The acoustic startle reflex provides a means to initiate a motor plan involuntarily In the presence of a movement plan, startling acoustic stimulus triggers non-voluntary early execution of planned movement, a phenomenon known as the startReact response In unimpaired individuals, the startReact response is identical to a voluntarily initiated movement, except that it is elicited 30–40 ms As the startReact response is thought to be mediated by brainstem pathways, we hypothesized that the startReact response is intact in stroke subjects If startReact is intact, it may be possible to elicit more task-appropriate patterns of muscle activation than can be elicited voluntarily We found that startReact responses were intact following stroke Responses were initiated as rapidly as those in unimpaired subjects, and with muscle coordination patterns resembling those seen during unimpaired volitional movements Results were striking for elbow flexion movements, which demonstrated no significant differences between the startReact responses elicited in our stroke and unimpaired subject groups The results during planned extension movements were less straightforward for stroke subjects, since the startReact response exhibited task inappropriate activity in the flexors This inappropriate activity diminished over time This adaptation suggests that the inappropriate activity was transient in nature and not related to the underlying movement plan We hypothesize that the task-inappropriate flexor activity during extension results from an inability to suppress the classic startle reflex, which primarily influences flexor muscles and adapts rapidly with successive stimuli These results indicate that stroke subjects are capable of planning ballistic elbow movements, and that when these planned movements are involuntarily executed they can be as rapid and appropriate as those in unimpaired individuals

Brain activity underlying impaired continence control in older women with overactive bladder

Abstract: The overactive bladder syndrome (OAB) is a prevalent problem in clinical practice, diagnosed and managed mainly by patients’ reports1. Pharmacological or conservative treatment has only moderate success, perhaps because the underlying causes or phenotypes are heterogeneous and require different therapies. The central symptom of OAB is urgency2, sometimes accompanied by urine leakage episodes (urgency urinary incontinence – UUI), believed to be associated with or caused by involuntary detrusor contractions2,3. Such contractions, observed during urodynamic examination and either spontaneous or provoked 1, are known as detrusor overactivity (DO). Although the etiology of DO and OAB is frequently unknown and although DO is not always observed in patients with OAB, it is the only unambiguous physiological sign of the lower urinary tract (LUT) dysfunction underlying OAB. Its involuntary character implies, at least in part, an abnormality in CNS function, since the CNS is essential for the regulation of voluntary micturition and continence.4, 5,6 Failure to elicit DO during urodynamics in some patients with OAB may suggest that the underlying functional disorder of continence control is different or less severe than in those with more easily elicitable DO. Recent urodynamic studies support this idea by demonstrating physiological differences at LUT level between OAB patients who exhibit DO on urodynamic study and those who do not.7,8 In a group of 144 such women7, those with urodynamically elicitable DO reported strong desire to void and urgency at smaller volumes. These findings suggested elicitability of DO as a marker of the severity of impairment of continence control within the spectrum of OAB symptoms. Elicitability may differ according to circumstances; e.g. it may be more difficult to elicit DO in the scanner than during regular urodynamics, and more difficult during urodynamics than in daily life. The underlying mechanism of elicitability remains unknown: information about brain activity during DO or during urgency preceding DO would shed light on mechanisms involving the CNS. Functional brain-imaging studies 9,10,11 have identified a group of brain regions believed to be a part of a network that regulates all phases of the micturition cycle (the ‘brain-bladder control network’) (see provisional working model, Fig. 1). Neuroanatomical and neurophysiological observations6,12 show that voiding is fundamentally regulated by a long-loop, spinobulbospinal (brainstem) reflex. During urine storage bladder afferents ascend via the sacral spinal cord to the midbrain periaqueductal gray (PAG). If they exceed a certain threshold, the reflex is triggered and a signal is sent to the micturition center in the pons (PMC). Thence an efferent signal passes to the sacral cord, where it stimulates both detrusor contraction and, via inhibitory interneurons, striated sphincter relaxation, so that voiding ensues. This voiding reflex thus switches back and forth between the storage and voiding phases 4,6. Figure 1 Provisional working model of brain/bladder control4,6,9,12,13,15. Voiding is triggered and coordinated by the voiding reflex shown in simplified form at the bottom of the diagram. Cerebral control is exercised by suppressing the reflex at the PAG during ... Normally however the reflex does not operate in isolation. During storage an ascending afferent signal is relayed from the PAG to higher regions of the brain, which assess whether voiding is safe and appropriate, generate bladder sensations, and in return provide output that promotes or suppresses voiding, probably at the PAG13,6. Thus the PAG is the pivotal region via which the reflex influences and is influenced by the cortical parts of the control network. As suggested in Fig. 1 (and elsewhere13), the primary target of the signal ascending from the PAG is the insula and nearby lateral prefrontal cortex (especially on the right), where it evokes normal bladder sensation (desire to void). Desire to void is a homeostatic emotion 14 that provides motivation as well as appropriate motor output to maintain continence (homeostasis). This appears to be a normal continence mechanism, activated when there is desire to void. Fig. 1 suggests that the insular activity is propagated to the lateral (dlPFC) and medial (mPFC) prefrontal cortex (concerned with executive decision-making and social context) and thence back to the PAG, where it suppresses the voiding reflex. The medial – particularly the ventromedial (vmPFC) – prefrontal cortex appears to be deactivated as part of this mechanism15. In UUI subjects, the signal ascending from the PAG (provoked in the scanner by further filling of a well-filled bladder) is also relayed to dorsal anterior cingulate gyrus (dACG) and nearby regions such as the supplementary motor area, SMA (Fig. 1). It evokes the abnormal sensation of ‘urgency’ 15–18, a homeostatic emotion. Activation of SMA is known to tighten the pelvic floor and urethral sphincter. This appears to be a back-up continence mechanism, used if the normal mechanism is inadequate. Finally, bladder filling provokes deactivations in parahippocampal or paralimbic areas19, subcortical changes that suggest evaluation of the safety of voiding, and may provide a third continence mechanism (Fig. 1). The presence or absence of all these activations and deactivations presumably reflects the ability or inability of the CNS to suppress DO (i.e. reduce DO elicitability) and thus prevent incontinence. To test this assumption, we here present a cohort of older women with OAB/UUI who underwent an experimental protocol set up in the brain imaging scanner, which included bladder filling coupled with simultaneous measurement of regional brain activity (via functional magnetic resonance imaging - fMRI) and urodynamic monitoring. Despite clear signs and symptoms of UUI in all subjects, only one-third of the cohort developed DO and lost continence in the scanner (the ‘DO group’). We therefore set up a secondary analysis to compare brain activity in the DO group with the group that maintained full control of the bladder in the scanner (the ‘no DO group’). These 2 groups apparently differed in DO elicitability and we postulated, a priori, that they would display different patterns of regional brain activity during urgency. Specifically, we made the postulate that the brain responses involved in maintaining continence (see Fig. 1) would be diminished in the DO group, implying: less activation in SMA/dACG (Hypothesis 1a) and less prominent deactivation in vmPFC/mPFC and parahippocampal complex (Hypothesis 1b). We also explored possible phenotypic differences by analyzing: a) differences between the groups in their response to bladder filling during standard urodynamics (e.g. sensation of filling, desire to void and urgency), and, b) differences in clinical covariates associated with urgency, UUI and continence control such as: age, extent of structural brain changes (white-matter hyperintensities - WMH), cognition, depression history and psychological burden of the disease. In addition, without making specific hypotheses, we planned to look for differences in brain activity between those with and without elicitable DO when the bladder was nearly empty and sensation relatively weak and, thus, without reported urgency.

Task-dependent coordination of rapid bimanual motor responses.

Abstract: Optimal feedback control postulates that feedback responses depend on the task relevance of any perturbations. We test this prediction in a bimanual task, conceptually similar to balancing a laden tray, in which each hand could be perturbed up or down. Single-limb mechanical perturbations produced long-latency reflex responses (“rapid motor responses”) in the contralateral limb of appropriate direction and magnitude to maintain the tray horizontal. During bimanual perturbations, rapid motor responses modulated appropriately depending on the extent to which perturbations affected tray orientation. Specifically, despite receiving the same mechanical perturbation causing muscle stretch, the strongest responses were produced when the contralateral arm was perturbed in the opposite direction (large tray tilt) rather than in the same direction or not perturbed at all. Rapid responses from shortening extensors depended on a nonlinear summation of the sensory information from the arms, with the response to a bimanual same-direction perturbation (orientation maintained) being less than the sum of the component unimanual perturbations (task relevant). We conclude that task-dependent tuning of reflexes can be modulated online within a single trial based on a complex interaction across the arms.

Neuroanatomical evidence demonstrating the existence of the vagal anti-inflammatory reflex in the intestine.

Abstract: Background The cholinergic anti-inflammatory pathway is proposed to be part of the so-called vago-vagal ‘inflammatory reflex’. The aim of this study is to provide neuro-anatomical evidence to support the existence of a functional neuronal circuit and its activation in response to intestinal inflammation. Methods The expression of c-fos was evaluated at different levels of the neurocircuitry in the course of postoperative ileus (POI) in a mouse model. Specific activation of the motor neurons innervating the inflamed intestine and the spleen was monitored by retrograde tracing using cholera toxin-b. The role of the vagal afferent pathway nerve was evaluated by selective vagal denervation of the intestine. Key Results Abdominal surgery resulted in subtle inflammation of the manipulated intestine at 24 h (late phase), but not after 2 and 6 h (early) after surgery. This local inflammation was associated with activation of neurons in the nucleus of the solitary tract and in the dorsal nucleus of the vagus. The vagal output mainly targeted the inflamed zone: 42% of motor neurons innervating the intestine expressed c-fos IR in contrast to 7% of those innervating the spleen. Vagal denervation of the intestine abolished c-fos expression in the brain nuclei involved in the neuronal network activated by intestinal inflammation. Conclusions & Inferences Our data demonstrate that intestinal inflammation triggers a vagally mediated circuit leading mainly to activation of vagal motor neurons connected to the inflamed intestine. These findings for the first time provide neuro-anatomical evidence for the existence of the endogenous ‘inflammatory reflex’ and its activation during inflammation.

Modulation of physiological reflexes by pain: role of the locus coeruleus.

Abstract: The locus coeruleus is activated by noxious stimuli, and this activation leads to inhibition of perceived pain. As two physiological reflexes, the acoustic startle reflex and the pupillary light reflex, are sensitive to noxious stimuli, this sensitivity, at least to some extent, may be mediated by the locus coeruleus. The acoustic startle reflex, contraction of a large body of skeletal muscles in response to a sudden loud acoustic stimulus, can be enhanced by both directly (“sensitization”) and indirectly (“fear conditioning”) applied noxious stimuli. The enhancement of the startle response by conditioned fear (“fear-potentiated startle”) involves the activation of the amygdala. The locus coeruleus may also be involved in both sensitization and fear potentiation: pain signals activate the locus coeruleus both directly and indirectly via the amygdala, which results in enhanced motoneurone activity, leading to an enhanced muscular response. The light reflex response is constriction of the pupil evoked by a light stimulus. The pupil is dilated by the sympathetic and constricted by the parasympathetic output to the iris. The locus coeruleus contributes to the sympathetic outflow to the iris and attenuates the parasympathetic output by inhibiting the Edinger-Westphal nucleus, the preganglionic cholinergic nucleus in the light reflex pathway. Noxious stimulation results in pupil dilation (“reflex dilation”), without any change in the light reflex response, consistent with sympathetic activation via the locus coeruleus. Conditioned fear, on the other hand, results in the attenuation of the light reflex response (“fear-inhibited light reflex”), consistent with the inhibition of the parasympathetic light reflex via the locus coeruleus. Directly applied pain and fear conditioning may affect different populations of autonomic neurones in the locus coeruleus, directly applied pain activating sympathetic and fear conditioning parasympathetic premotor neurones.

Genioglossus activity available via non-arousal mechanisms vs. that required for opening the airway in obstructive apnea patients.

Abstract: It is generally believed that reflex recruitment of pharyngeal dilator muscles is insufficient to open the airway of obstructive apnea (OSA) patients once it is closed and, therefore, that arousal ...

A critical period in the supraspinal control of pain: opioid-dependent changes in brainstem rostroventral medulla function in preadolescence

Abstract: We have previously shown that the balance of electrically evoked descending brainstem control of spinal nociceptive reflexes undergoes a switch from excitation to inhibition in preadolescent rats. Here we show that the same developmental switch occurs when μ-opioid receptor agonists are microinjected into the rostroventral medulla (RVM). Microinjections of the μ-opioid receptor agonist [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin (DAMGO) into the RVM of lightly anaesthetised adult rats produced a dose-dependent decrease in mechanical nociceptive hindlimb reflex electromyographic activity. However, in preadolescent (postnatal day 21 [P21]) rats, the same doses of DAMGO produced reflex facilitation. RVM microinjection of δ-opioid receptor or GABA(A) receptor agonists, on the other hand, caused reflex depression at both ages. The μ-opioid receptor-mediated descending facilitation is tonically active in naive preadolescent rats, as microinjection of the μ-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) into the RVM at this age decreases spinal nociceptive reflexes while having no effect in adults. To test whether tonic opioid central activity is required for the preadolescent switch in RVM descending control, naloxone hydrochloride was delivered continuously from subcutaneous osmotic mini-pumps for 7-day periods, at various postnatal stages. Blockade of tonic opioidergic activity from P21 to P28, but not at earlier or later ages, prevented the normal development of descending RVM inhibitory control of spinal nociceptive reflexes. Enhancing opioidergic activity with chronic morphine over P7 to P14 accelerated this development. These results show that descending facilitation of spinal nociception in young animals is mediated by μ-opioid receptor pathways in the RVM. Furthermore, the developmental transition from RVM descending facilitation to inhibition of pain is determined by activity in central opioid networks at a critical period of periadolescence.

Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation through nitric oxide-dependent mechanisms in aged human skin.

Abstract: Functional constitutive nitric oxide synthase (NOS) is required for full expression of reflex cutaneous vasodilation that is attenuated in aged skin. Both the essential cofactor tetrahydrobiopterin...

Effect of percutaneous stimulation at different spinal levels on the activation of sensory and motor roots.

Abstract: Percutaneous spinal stimulation is a promising new technique for understanding human spinal reflexes and for evaluating the pathophysiology of motor roots. Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral junctions, sites that overlie the lumbosacral enlargement. The present study sought to determine the best location for targeting sensory and motor roots during sitting. We used paired stimuli, 50 ms apart, to distinguish the contribution of the reflex and motor components which make up the root evoked potential. This assumed that post-stimulation attenuation, primarily through homosynaptic depression, would abolish the second potential if it was trans-synaptic in origin. Conversely, successive responses would be unchanged if motor roots were being stimulated. Here, we show that sensory root reflexes were optimally elicited with percutaneous stimulation over the L1-L3 vertebrae. However, the optimal position varied between subjects and depended on the target muscle being studied. A collision test showed that the reflex recorded in pre-tibial flexors was low in amplitude and was prone to crosstalk from neighbouring muscles. In contrast to the reflex response, direct motor root activation was optimal with stimulation over the more caudal L5-S1 vertebrae. The present results support the utility of paired stimulation for evaluating the topographical recruitment of sensory and motor roots to human leg muscles.

Control of reflex reversal in stick insect walking: effects of intersegmental signals, changes in direction, and optomotor-induced turning

Abstract: In many animals, the effects of sensory feedback on motor output change during locomotion. These changes can occur as reflex reversals in which sense organs that activate muscles to counter perturb...