Associate Professor Eugene Nalivaiko

Introduction: The 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. Methods: International 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. Results: Sixty-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. Discussion: Our 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.

This paper describes the conceptual design of a virtual reality-based stress management training tool and evaluation of the initial prototype in a pilot efficacy study. Performance Edge virtual-reality (VR) was co-developed with the Australian Defence Force (ADF) to address the need for practical stress management training for ADF personnel. The VR application is biofeedback-enabled and contains key stress management techniques derived from acceptance and commitment and cognitive behavioural therapy in a modular framework. End-user-provided feedback on usability, design, and user experience was positive, and particularly complimentary of the respiratory biofeedback functionality. Training of controlled breathing delivered across 3 sessions increased participants¿ self-reported use of breath control in everyday life and progressively improved controlled breathing skills (objectively assessed as a reduction in breathing rate and variability). Thus the data show that a biofeedback-enabled controlled breathing protocol delivered through Performance Edge VR can produce both behaviour change and objective improvement in breathing metrics. These results confirm the validity of Performance Edge VR platform, and its Controlled Breathing module, as a novel approach to tailoring VR-based applications to train stress management skills in a workplace setting.

Existing evidence suggests that cybersickness may be clinically different from ¿classic,¿ motion-induced sickness; this evidence was, however, obtained in separate studies that focused on just one of the two conditions. Our aim was to bring clarity to this issue by directly comparing subjective symptoms and physiological effects of motion sickness induced by physical motion (Coriolis cross-coupling) and by immersion in virtual reality (ride on a roller coaster) in the same subjects. A cohort of 30 young, healthy volunteers was exposed to both stimulations in a counterbalanced order on 2 separate days =1 wk apart. Nausea scores were recorded during the exposure, and the Motion Sickness Assessment Questionnaire (MSAQ) was used to profile subjective symptoms postexperiment. Tonic and phasic forehead skin conductance level (SCL) was measured before and during exposure in both stimulation methods. We found that the nausea onset times were significantly correlated in both tests (r 0.40, P 0.03). Similarly, the maximum nausea ratings were significantly correlated during both provocations (r 0.58, P 0.0012). Symptom-profiling with the MSAQ revealed substantial and significant correlations between total symptom scores (r 0.69, P < 0.0001) between each of 4 symptom clusters and between 15/18 individual symptoms assessed in both conditions. Both virtual reality and Coriolis cross-coupling provocations caused an increase in tonic SCL associated with nausea [mean difference (mean diff) 5.1, confidence interval (CI) (2.59, 6.97), P 0.007 and mean diff 1.49, CI (0.47, 7.08), P 0.0001, respectively], with a close correlation between the conditions (r 0.48, P 0.04). This was accompanied by a significant increase in the amplitude of phasic skin conductance transients in both visual stimulation and Coriolis cross-coupling when participants reported maximum nausea compared with no nausea [mean diff 0.27, CI (0.091, 0.63), P < 0.001 and mean diff 0.235, CI (0.053, 0.851), P < 0.006, respectively]. We conclude that symptoms and physiological changes occurring during cybersickness and classic motion sickness are quite similar, at least during advanced stages of these malaises.

The human vestibular system is a sensory and equilibrium system that manages and controls the human sense of balance and movement. It is the main sensor humans use to perceive rotational and linear motions. Determining an accurate mathematical model of the human vestibular system is significant for research pertaining to motion perception, as the quality and effectiveness of the motion cueing algorithm (MCA) directly depends on the mathematical model used in its design. This paper describes the history and analyses the development process of mathematical semicircular canal models. The aim of this review is to determine the most consistent and reliable mathematical semicircular canal models that agree with experimental results and theoretical analyses, and offer reliable approximations for the semicircular canal functions based on the existing studies. Selecting and formulating accurate mathematical models of semicircular canals are essential for implementation into the MCA and for ensuring effective human motion perception modeling.

Motion sickness is associated with a variety of autonomic symptoms, presumably due to proximity or functional interconnectivity between the autonomic centers in the brainstem and the vestibular system. A direct influence of the vestibular system on cardiovascular variables, defined as the vestibulo-sympathetic reflex, has been reported previously. Our aim was to investigate the sudomotor components of the autonomic responses associated with motion sickness during passive cross-coupling stimulation (¿roll while rotating¿). Healthy subjects (n¿=¿17) were rotated at 40°/s around an earth-vertical yaw axis alone and in combination with sinusoidal roll oscillations (0.2¿Hz). Motion sickness was assessed verbally every minute using a 1¿10 scale, while recording DC and AC skin conductance levels (SCL) from the forehead. Yaw rotation alone provoked neither motion sickness nor variations of forehead sweating. Yet during cross-coupling stimulation all subjects reported motion sickness. Higher motion sickness scores (>5) were associated with significantly higher amplitudes of AC-SCL events compared to the lower scores (0.22¿±¿0.01 vs. 0.11¿±¿0.01¿µS, respectively). Frequency domain analysis of the AC-SCL events revealed a peak at 0.2¿Hz, coinciding with the frequency of the chair rolls. The total power of AC-SCL signals did not match the trend of motion sickness scores across conditions. We conclude that: (1) although SCL is related to motion sickness, it does not follow the perceived sickness closely; (2) the discrepancy between SCL and motion sickness and the rhythmic AC-SCL events could reflect a sudomotor component of the vestibulo-sympathetic reflex.

Hypothermic responses accompany motion sickness in humans and can be elicited by provocative motion in rats. We aimed to determine the potential role in these responses of the efferent cholinergic vestibular innervation. To this end, we used knockout (KO) mice lacking a9 cholinoreceptor subunit predominantly expressed in the vestibular hair cells and CBA strain as a wild-type (WT) control. In WT mice, circular horizontal motion (1¿Hz, 4¿cm radius, 20¿min) caused rapid and dramatic falls in core body temperature and surface head temperature associated with a transient rise in the tail temperature; these responses were substantially attenuated in KO mice; changes were (WT vs. KO): for the core body temperature¿-¿5.2¿±¿0.3 vs. -¿2.9¿±¿0.3¿°C; for the head skin temperature¿-¿3.3¿±¿0.2 vs. -¿1.7¿±¿0.2¿°C; for the tail skin temperature¿+¿3.9¿±¿1.1 vs¿+¿1.1¿±¿1.2¿°C. There was a close correlation in the time course of cooling the body and the surface of the head. KO mice also required 25% more time to complete a balance test. We conclude: i) that the integrity of cholinergic efferent vestibular system is essential for the full expression of motion-induced hypothermia in mice, and that the role of this system is likely facilitatory; ii) that the system is involvement in control of balance, but the involvement is not major; iii) that in mice, motion-induced body cooling is mediated via increased heat flow through vasodilated tail vasculature and (likely) via reduced thermogenesis. Our results support the idea that hypothermia is a biological correlate of a nausea-like state in animals.

Psychological resilience can be defined as individual's ability to withstand and adapt to adverse and traumatic events. Resilience is traditionally assessed by subjective reports, a method that is susceptible to self-report bias. An ideal solution to this challenge is the introduction of standardised and validated physiological and/or biological predictors of resilience. We provide a summary of the major concepts in the field of resilience followed by a detailed critical review of the literature around physiological, neurochemical and immune markers of resilience. We conclude that in future experimental protocols, biological markers of resilience should be assesses both during baseline and during laboratory stressors. In the former case the most promising candidates are represented by heart rate variability and by in vitro immune cells assay; in the latter case¿by startle responses (especially their habituation) during stress challenge and by cardiovascular recovery after stress, and by cortisol, DHEA and cytokine responses. Importantly, they should be used in combination to enhance predictive power.

This study assessed the¿effects of resveratrol, a polyphenol¿found in grapes and red wine¿on non-pregnant murine uteri under hypoxia. Resveratrol at 1, 3, 10, 30 and 100¿µM promoted uterine relaxation and decreased the amplitude and frequency of spontaneous uterine contractions. Assayed at 3, 10, 30¿µM, resveratrol inhibited the oxytocin-induced cumulative contractions reducing the maximum effect in a dose-dependent manner. In hypoxic uteri, resveratrol at 100¿µM restored the uterine contractions compromised by hypoxia. In addition, under hypoxia, resveratrol prevented the decrease in uterine contractions maintaining >75% of its contraction capability. The effects of resveratrol on uterine contractions under hypoxia were attenuated by tetraethylammonium (10¿mM) and almost abolished by glibenclamide (10¿µM). Our¿results show regenerative and protective effects of resveratrol in non-pregnant murine uteri under hypoxia and describes for the first time that these effects are mediated by blockade of ATP-sensitive potassium channels.

Periaqueductal grey is believed to be one of the key structures of the central respiratory stress network. Previous studies established that stimulation of the periaqueductal grey, especially its dorsolateral division (dlPAG), evokes tachypnea as well as increases in other autonomic parameters and motor activity. We investigated the effects of blockade of the dlPAG with GABAA agonist muscimol on respiration during stress and presentation of brief alerting stimuli in conscious unrestrained rats. We found that integrity of the dlPAG is not essential for stress-induced increase in basal/resting respiratory rate or for generation of respiratory responses to brief alerting stimuli. However, blockade of the dlPAG reduced the amount of motor activity and concomitant high-frequency respiratory activity during restraint and the first 5 min of novelty stress. We conclude that the integrity of the dlPAG is not essential for generation of respiratory component of the defense reaction, but it mediates expression of the fight-or-flight response including its respiratory component.

Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n. =. 8) having values of 23-29. °C, and high-temperature group (n. =. 18) having values of 32-36. °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4. °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2. °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50. ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology.

Objective: Heartbeat-evoked potentials (HEPs) in electroencephalogram (EEG) provide a quantitative measure of cardiac interoception during sleep. We previously reported reduced HEPs in children with sleep-disordered breathing (SDB), indicative of attenuated cardiac information processing. The objective of this study was to investigate the link between HEP and respiration. Patients/Methods: From the overnight polysomnograms of 40 healthy children and 40 children with SDB, we measured HEPs during epochs of stage 2, slow-wave and rapid eye movement (REM) sleep free of abnormal respiratory events. HEPs were analysed with respect to respiratory phase. Results: We observed a marked association between respiratory phase and HEP in children with SDB during REM sleep, but not in normal children. In children with SDB, HEP waveforms were attenuated during expiration compared to inspiration. Following adenotonsillectomy, expiratory HEP peak amplitude increased in the SDB children and was no longer different from those of normal children. Conclusions: The expiratory phase of respiration is primarily associated with attenuated cardiac information processing in children with SDB, establishing a pathophysiological link between breathing and HEP attenuation.

Nausea is a prominent symptom and major cause of complaint for patients receiving anticancer chemo- or radiation therapy. The arsenal of anti-nausea drugs is limited, and their efficacy is questionable. Currently, the development of new compounds with anti-nausea activity is hampered by the lack of physiological correlates of nausea. Physiological correlates are needed because common laboratory rodents lack the vomiting reflex. Furthermore, nausea does not always lead to vomiting. Here, we report the results of studies conducted in four research centers to investigate whether nausea is associated with any specific thermoregulatory symptoms. Two species were studied: the laboratory rat, which has no vomiting reflex, and the house musk shrew (Suncus murinus), which does have a vomiting reflex. In rats, motion sickness was induced by rotating them in their individual cages in the horizontal plane (0.75 Hz, 40 min) and confirmed by reduced food consumption at the onset of dark (active) phase. In 100% of rats tested at three centers, postrotational sickness was associated with marked (~1.5°C) hypothermia, which was associated with a short-lasting tail-skin vasodilation (skin temperature increased by ~4°C). Pretreatment with ondansetron, a serotonin 5-HT3 receptor antagonist, which is used to treat nausea in patients in chemo- or radiation therapy, attenuated hypothermia by ~30%. In shrews, motion sickness was induced by a cyclical backand-forth motion (4 cm, 1 Hz, 15 min) and confirmed by the presence of retching and vomiting. In this model, sickness was also accompanied by marked hypothermia (~2°C). Like in rats, the hypothermic response was preceded by transient tail-skin vasodilation. In conclusion, motion sickness is accompanied by hypothermia that involves both autonomic and thermoeffector mechanisms: tail-skin vasodilation and possibly reduction of the interscapular brown adipose tissue activity. These thermoregulatory symptoms may serve as physiological correlates of nausea.

The dorsomedial hypothalamus (DMH) and lateral/dorsolateral periaqueductal gray (PAG) are anatomically and functionally connected. Both the DMH and PAG depend on glutamatergic inputs for activation. We recently reported that removal of GABA-ergic tone in the unilateral DMH produces: asymmetry, that is, a right- (R-) sided predominance in cardiac chronotropism, and lateralization, that is, a greater increase in ipsilateral renal sympathetic activity (RSNA). In the current study, we investigated whether excitatory amino acid (EAA) receptors in the DMH-PAG pathway contribute to the functional interhemispheric difference. In urethane (1.2 to 1.4 g/kg, i.p.) anesthetized rats, we observed that: (i) nanoinjections of N-methyl D-aspartate (NMDA 100 pmol/100 nl) into the unilateral DMH produced the same right-sided predominance in the control of cardiac chronotropy, (ii) nanoinjections of NMDA into the ipsilateral DMH or PAG evoked lateralized RSNA responses, and (iii) blockade of EAA receptors in the unilateral DMH attenuated the cardiovascular responses evoked by injection of NMDA into either the R- or left- (L-) PAG. In awake rats, nanoinjection of kynurenic acid (1 nmol/100 nL) into the L-DMH or R- or L-PAG attenuated the tachycardia evoked by air stress. However, the magnitude of stress-evoked tachycardia was smallest when the EAA receptors of the R-DMH were blocked. We conclude that EAA receptors contribute to the right-sided predominance in cardiac chronotropism. This interhemispheric difference that involves EAA receptors was observed in the DMH but not in the PAG.

Maintenance of homeostasis in normal or stressful situations depends upon mechanisms controlling autonomic activity. Central requirement for changes in sympathetic output resulting from emotional stress must be adjusted to the input signals from visceral sensory afferent (feedback response) for an optimum cardiovascular performance. There is a large body of evidence indicating that emotional stress can lead to cardiovascular disease. Reviewing the descending pathways from dorsomedial hypothalamus, a key region involved in the cardiovascular response to emotional stress, we discuss the interactions between mechanisms controlling the sympathetic output to the cardiovascular system and the possible implications in cardiovascular disease. © 2014 Elsevier B.V.

Neural substrate of nausea is poorly understood, contrasting the wealth of knowledge about the emetic reflex. One of the reasons for this knowledge deficit is limited number and face validity of animal models of nausea. Our aim was to search for new physiological correlates of nausea in rats. Specifically, we addressed the question whether provocative motion (40-min rotation at 0.5 Hz) affects sleep architecture, brain temperature, heart rate (HR) and arterial pressure. Six adult male Sprague-Dawley rats were instrumented for recordings of EEG, nuchal electromyographic, hypothalamic temperature and arterial pressure. Provocative motion had the following effects: (1) total abolition of REM sleep during rotation and its substantial reduction during the first hour post-rotation (from 20 ± 3 to 5 ± 1.5 %); (2) reduction in NREM sleep, both during rotation (from 57 ± 6 to 19 ± 5 %) and during the first hour post-rotation (from 56 ± 3 to 41 ± 9 %); (3) fall in the brain temperature (from 37.1 ± 0.1 to 36.0 ± 0.1°C); and (4) reduction in HR (from 375 ± 6 to 327 ± 7 bpm); arterial pressure was not affected. Ondansetron, a 5-HT3 antagonist, had no major effect on all observed parameters during both baseline and provocative motion. We conclude that in rats, provocative motion causes prolonged arousing effects, however without evidence of sympathetic activation that usually accompanies heightened arousal. Motion-induced fall in the brain temperature complements and extends our previous observations in rats and suggests that similar to humans, provocative motion triggers coordinated thermoregulatory response, leading to hypothermia in this species. © 2014 Springer-Verlag.

Respiratory patterns represent a promising physiological index for assessing emotional states in preclinical studies. Since disturbed emotional regulation may lead to forms of excessive aggressiveness, in this study we investigated the hypothesis that rats that differ largely in their level of aggressive behavior display matching alterations in respiration. Respiration was recorded in male high-aggressive (HA, n=. 8) and non-aggressive (NA, n=. 8) Wild-type Groningen rats using whole-body plethysmography. Subsequently, anxiety-related behaviors were evaluated in the elevated plus maze and social avoidance-approach tests. During respiratory testing, HA rats showed elevated basal respiratory rate, reduced sniffing, exaggerated tachypnoeic response to an acoustic stimulus and a larger incidence of sighs. In addition, HA rats spent less time in the open arms of the plus maze and displayed higher levels of social avoidance behavior compared to NA rats. These findings indicate that HA rats are characterized by alterations in respiratory functioning and behavior that are overall indicative of an anxiety-like phenotype.

There are a limited number of biological indices for assessing pro-emetic states in laboratory rodents as they do not possess the vomiting response. In the present study we tested the hypothesis that in rats, pro-emetic intervention would affect the respiratory pattern. To this end, using whole-body plethysmography, in adult male Wistar rats we recorded respiration after i.p. administration of either the emetic agent LiCl or Ringer. Quantification of respiratory signals (from 5 to 35min post-injection) revealed that post-LiCl, mean respiratory rate was significantly lower (126±9 vs. 178±10cpm, p<0.005) and less variable (Kvar 59±8% vs. 73±3%; p<0.05) compared to the post-Ringer condition. Furthermore, while mode values of respiratory rate histograms did not differ between the treatments (indicating that the dominant respiratory frequency remained unchanged), LiCl reduced the fraction of time spent at high respiratory rate (>200cpm) from 25±3% to 9±2% (p=0.004). Thus, reduction of the mean respiratory rate by LiCl was predominantly due to reduced contribution of high-frequency breathing that is normally associated with motor activity and/or arousal. Non-linear multifractal analysis of respiratory signals revealed that post-LiCl, respiration becomes less random and more orderly. 5-HT3 antagonist ondansetron prevented respiratory changes elicited by LiCl. We conclude that the observed changes likely reflect effects of LiCl on animals' motion, and that this effect is mediated via 5-HT3 receptors. Providing that the effects observed in our study were quite robust, we suggest that simple and non-invasive respiratory monitoring may be a promising approach for studying emesis in rodents. © 2013 IBRO.