Respiratory Component of the Orienting Reflex: A Novel Sensitive Index of Sensory-Induced Arousal in Rats

In humans, the integrated response to a novel stimulus (orienting reflex, OR) includes behavioral (head turning etc.) and well-characterized physiological components (changes in heart rate, respiration, skin conductance, and EEG patterns). In rodents, the physiological components of the OR include changes in heart rate and cutaneous vasoconstrictor tone, but respiratory changes have so far not been systematically documented. In the present study conducted in adult male Wistar rats, the OR was elicited by 60-dB acoustic tones while animals were in a whole-body plethysmograph for respiratory recordings. In addition to respiration, in different groups of animals we concurrently recorded either EEG, or heart rate (both by biotelemetry), or tail blood flow (using ultrasound Doppler). Acoustic stimuli provoked vigorous tachypneic responses with respiratory rate rising from 80–100 to 450–650 cpm, and with small and variable changes in tidal volume. This respiratory arousal response was often, but not always, accompanied by EEG desynchronization and by variable tail vasoconstriction, and by small and inconsistent changes in the heart rate. We conclude that tachypneic responses are a new highly sensitive index of sensory-induced arousal

Autonomic changes induced by provocative motion in rats bred for high (HAB) and low (LAB) anxiety-related behavior: Paradoxical responses in LAB animals.

In humans, associations between anxiety and nausea (including motion-induced) are reported but the underlying mechanisms are not known. Hypothermia is proposed to be an index of nausea in rats. Utilising hypothermia and heart rate as outcome measures we investigated the response to provocative motion in rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviors and in non-selected (NAB) rats to further elucidate the potential relationship between hypothermia and nausea-like state. Core temperature and electrocardiogram were monitored in each group (n=10 per group) using telemetry, with or without circular motion (40min; 0.75Hz) and vehicle or diazepam (2mg/kg, i.p.) pre-treatment. Heart rate and time- and frequency-domain parameters of heart rate variability were derived from the electrocardiogram. There was no baseline difference in core temperature between the three groups (mean 38.0±0.1°C), but HAB animals had a significantly lower resting heart rate (330±7bpm) compared to LAB (402±5bpm) and NAB (401±9bpm). Animals in all groups exhibited hypothermia during motion (HAB: 36.3±0.1°C; NAB: 36.4±0.1°C; LAB: 34.9±0.2°C) with the magnitude (area under the curve, AUC) of the response during 40-min motion being greater in LAB compared to NAB and HAB rats, and this was also the case for the motion-induced bradycardia. Diazepam had minimal effects on baseline temperature and heart rate in all groups, but significantly reduced the hypothermia response (AUC) to motion in all groups by ~30%. Breeding for extremes in anxiety-related behavior unexpectedly selects animals with low trait anxiety that have enhanced bradycardia and hypothermic responses to motion; consequently, this animal model appears to be not suitable for exploring relationships between anxiety and autonomic correlates of nausea. Thermal and cardiovascular responses to motion were little different between HAB and NAB rats indicating that either hypothermia is not an index of a nausea-like state in rats, or that the positive correlation between anxiety and nausea demonstrated in humans does not exist in rats. The mechanism underlying the enhanced physiological responses in LAB requires more detailed study and may provide a novel model to investigate factors modulating motion sensitivity

Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew).

Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant), and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pK b values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain areas regulating emesis control, and caused hypothermia; it also appeared to cause sedation and reduced the dominant frequency of slow waves. In conclusion, motion-induced emesis was associated with a disruption of GMA, respiration, and hypothermia. Mepyramine was a more efficacious anti-emetic than cetirizine, suggesting an important role of centrally-located H1 receptors. The ability of mepyramine to elevate c-fos provides a new perspective on how H1 receptors are involved in mechanisms of emesis control

Cardiorespiratory Phase-Coupling Is Reduced in Patients with Obstructive Sleep Apnea

Cardiac and respiratory rhythms reveal transient phases of phase-locking which were proposed to be an important aspect of cardiorespiratory interaction. The aim of this study was to quantify cardio-respiratory phase-locking in obstructive sleep apnea (OSA). We investigated overnight polysomnography data of 248 subjects with suspected OSA. Cardiorespiratory phase-coupling was computed from the R-R intervals of body surface ECG and respiratory rate, calculated from abdominal and thoracic sensors, using Hilbert transform. A significant reduction in phase-coupling was observed in patients with severe OSA compared to patients with no or mild OSA. Cardiorespiratory phase-coupling was also associated with sleep stages and was significantly reduced during rapid-eye-movement (REM) sleep compared to slow-wave (SW) sleep. There was, however, no effect of age and BMI on phase coupling. Our study suggests that the assessment of cardiorespiratory phase coupling may be used as an ECG based screening tool for determining the severity of OSA

Building a transdisciplinary expert consensus on the cognitive drivers of performance under pressure: An international multi-panel Delphi study

IntroductionThe ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport. Despite recognition that such performance depends on a range of cognitive factors, how common these factors are across performance domains remains unclear. The current study sought to integrate existing knowledge in the performance field in the form of a transdisciplinary expert consensus on the cognitive mechanisms that underlie performance under pressure.MethodsInternational experts were recruited from four performance domains [(i) Defense; (ii) Competitive Sport; (iii) Civilian High-stakes; and (iv) Performance Neuroscience]. Experts rated constructs from the Research Domain Criteria (RDoC) framework (and several expert-suggested constructs) across successive rounds, until all constructs reached consensus for inclusion or were eliminated. Finally, included constructs were ranked for their relative importance.ResultsSixty-eight experts completed the first Delphi round, with 94% of experts retained by the end of the Delphi process. The following 10 constructs reached consensus across all four panels (in order of overall ranking): (1) Attention; (2) Cognitive Control—Performance Monitoring; (3) Arousal and Regulatory Systems—Arousal; (4) Cognitive Control—Goal Selection, Updating, Representation, and Maintenance; (5) Cognitive Control—Response Selection and Inhibition/Suppression; (6) Working memory—Flexible Updating; (7) Working memory—Active Maintenance; (8) Perception and Understanding of Self—Self-knowledge; (9) Working memory—Interference Control, and (10) Expert-suggested—Shifting.DiscussionOur results identify a set of transdisciplinary neuroscience-informed constructs, validated through expert consensus. This expert consensus is critical to standardizing cognitive assessment and informing mechanism-targeted interventions in the broader field of human performance optimization

Animal models of psychogenic cardiovascular disorders: what we can learn from them and what we cannot

1. Epidemiological and clinical studies from the past 50 years provide unequivocal evidence for a close association and causative links between psychological stresses and cardiovascular dysfunction in humans. Not surprisingly, numerous animal experiments have been undertaken in an attempt to clarify underlying pathophysiological mechanisms. The present review focuses on animal models that provide insight into the mechanisms of stress-induced cardiovascular dysfunction. 2. Great success was achieved in elucidating the neural pathways and neurotransmitters responsible for the cardiac consequences of acute stressors, such as stress-induced ventricular arrhythmias and stress cardiomyopathy. These disturbances were reproduced successfully in canine and rodent models. The most important finding from these animal models is that these disturbances are mediated by elevated sympathetic outflow to the ventricular myocardium. 3. In contrast, attempts to induce psychogenic hypertension in rodents produced inconsistent and contentious results. More recent studies using biotelemetry raised serious doubts regarding the validity of earlier results obtained with the tail-cuff method and it remains unclear whether chronic stress can lead to sustained hypertension in animal models

Central 5-HT receptors in cardiovascular control during stress

Our aim is to consolidate recent data on relationship between central serotonergic neurotransmission and stress-elicited cardiovascular changes. Activation of central of 5-HT1A receptors attenuates tachycardic and pressor changes elicited by a wide range of stressors (airjet, restraint, open field, fear conditioning, social defeat), supporting the previous view of these receptors as “sympathoinhibitory”. Their likely location is the medullary raphe. It is still unknown whether 5-TH1A receptors are sympathoinhibitory in physiological condition, as 5-HT1A antagonists do not affect basal or stress-altered cardiovascular parameters. In contrast to the established view that central 5-HT2A receptors are “sympathoexcitatory”, experiments with new selective antagonists indicate that these receptors do not mediate stress-induced pressor and tachycardic responses, and are not involved in cardiovascular control at rest. The exception is control of cutaneous vascular bed, both at rest and during stress, likely at the spinal level. 5-HT3 receptors located in the nucleus tractus silitarius (NTS) contribute to stress-induced suppression of the baroreflex. 5-HT3 receptors located in sympathetic ganglia possibly contribute to the development of sustained hypertension in chronically stressed rats