Fatigue and vigilance in medical experts detecting breast cancer.

An abundance of laboratory-based experiments has described a vigilance decrement of reducing accuracy to detect targets with time on task, but there are few real-world studies, none of which have previously controlled the environment to control for bias. We describe accuracy in clinical practice for 360 experts who examined >1 million women's mammograms for signs of cancer, whilst controlling for potential biases. The vigilance decrement pattern was not observed. Instead, test accuracy improved over time, through a reduction in false alarms and an increase in speed, with no significant change in sensitivity. The multiple-decision model explains why experts miss targets in low prevalence settings through a change in decision threshold and search quit threshold and propose it should be adapted to explain these observed patterns of accuracy with time on task. What is typically thought of as standard and robust research findings in controlled laboratory settings may not directly apply to real-world environments and instead large, controlled studies in relevant environments are needed.

Edge-Based General Linear Models Capture Moment-to-Moment Fluctuations in Attention.

Although we must prioritize the processing of task-relevant information to navigate life, our ability to do so fluctuates across time. Previous work has identified fMRI functional connectivity (FC) networks that predict an individual's ability to sustain attention and vary with attentional state from 1 min to the next. However, traditional dynamic FC approaches typically lack the temporal precision to capture moment-to-moment network fluctuations. Recently, researchers have "unfurled" traditional FC matrices in "edge cofluctuation time series" which measure timepoint-by-timepoint cofluctuations between regions. Here we apply event-based and parametric fMRI analyses to edge time series to capture moment-to-moment fluctuations in networks related to attention. In two independent fMRI datasets examining young adults of both sexes in which participants performed a sustained attention task, we identified a reliable set of edges that rapidly deflects in response to rare task events. Another set of edges varies with continuous fluctuations in attention and overlaps with a previously defined set of edges associated with individual differences in sustained attention. Demonstrating that edge-based analyses are not simply redundant with traditional regions-of-interest-based approaches, up to one-third of reliably deflected edges were not predicted from univariate activity patterns alone. These results reveal the large potential in combining traditional fMRI analyses with edge time series to identify rapid reconfigurations in networks across the brain.

Functional near-infrared spectroscopy-based neurofeedback training regulates time-on-task effects and enhances sustained cognitive performance.

Time-on-task effect is a common consequence of long-term cognitive demand work, which reflects reduced behavioral performance and increases the risk of accidents. Neurofeedback is a neuromodulation method that can guide individuals to regulate their brain activity and manifest as changes in related symptoms and cognitive behaviors. This study aimed to examine the effects of functional near-infrared spectroscopy-based neurofeedback training on time-on-task effects and sustained cognitive performance. A randomized, single-blind, sham-controlled study was performed: 17 participants received feedback signals of their own dorsolateral prefrontal cortex activity (neurofeedback group), and 16 participants received feedback signals of dorsolateral prefrontal cortex activity from the neurofeedback group (sham-neurofeedback group). All participants received 5 neurofeedback training sessions and completed 2 sustained cognitive tasks, including a 2-back task and a psychomotor vigilance task, to evaluate behavioral performance changes following neurofeedback training. Results showed that neurofeedback relative to the sham-neurofeedback group exhibited increased dorsolateral prefrontal cortex activation, increased accuracy in the 2-back task, and decreased mean response time in the psychomotor vigilance task after neurofeedback training. In addition, the neurofeedback group showed slower decline performance during the sustained 2-back task after neurofeedback training compared with sham-neurofeedback group. These findings demonstrate that neurofeedback training could regulate time-on-task effects on difficult task and enhance performance on sustained cognitive tasks by increasing dorsolateral prefrontal cortex activity.

Fluctuation in cortical excitation/inhibition modulates capability of attention across time scales ranging from hours to seconds.

Sustained attention, as the basis of general cognitive ability, naturally varies across different time scales, spanning from hours, e.g. from wakefulness to drowsiness state, to seconds, e.g. trial-by-trail fluctuation in a task session. Whether there is a unified mechanism underneath such trans-scale variability remains unclear. Here we show that fluctuation of cortical excitation/inhibition (E/I) is a strong modulator to sustained attention in humans across time scales. First, we observed the ability to attend varied across different brain states (wakefulness, postprandial somnolence, sleep deprived), as well as within any single state with larger swings. Second, regardless of the time scale involved, we found highly attentive state was always linked to more balanced cortical E/I characterized by electroencephalography (EEG) features, while deviations from the balanced state led to temporal decline in attention, suggesting the fluctuation of cortical E/I as a common mechanism underneath trans-scale attentional variability. Furthermore, we found the variations of both sustained attention and cortical E/I indices exhibited fractal structure in the temporal domain, exhibiting features of self-similarity. Taken together, these results demonstrate that sustained attention naturally varies across different time scales in a more complex way than previously appreciated, with the cortical E/I as a shared neurophysiological modulator.

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation. In this study, we investigate whether LC microstructural integrity, assessed by fractional anisotropy (FA) through diffusion tensor imaging (DTI) at baseline before sleep deprivation, can predict impaired psychomotor vigilance test (PVT) performance during sleep deprivation in a cohort of 60 healthy individuals subjected to a rigorously controlled in-laboratory sleep study. The findings indicate that individuals with high LC FA experience less vigilance impairment from sleep deprivation compared with those with low LC FA. LC FA accounts for 10.8% of the variance in sleep-deprived PVT lapses. Importantly, the relationship between LC FA and impaired PVT performance during sleep deprivation is anatomically specific, suggesting that LC microstructural integrity may serve as a biomarker for vigilance vulnerability to sleep loss.

Electrodermal lability and sensorimotor preparation: effects on reaction time, contingent negative variation, and heart rate.

Electrodermal lability is a trait-like measure of spontaneous sympathetic resting activity. In the present study, we addressed whether interindividual differences in this lability have an impact on the reaction time (RT) and on two physiological indicators of a goal-oriented sensorimotor preparation in a long-running, forewarned RT task (S1-S2 paradigm). The two indicators were the brain's contingent negative variation (CNV) and a heart rate deceleration (HRD). The interindividual differences were determined by counting spontaneous skin conductance fluctuations during a 5-min resting phase and dividing the subjects into two groups: individuals below (stable) and above (labile) the median of these fluctuations. In the task, labile individuals had a shorter RT compared with stable individuals and showed in the final phase of preparation in both physiological indicators the stronger response. Thus, lability-dependent effects in forewarned RT tasks cannot be explained by differences in stimulus-driven or passively controlled processes alone. Rather, goal-oriented, deliberately controlled processes that serve to adequately prepare for an imperative stimulus-the S2 in our paradigm-also must be considered to explain them. Labile individuals not only react faster than stable ones but also intentionally prepare themselves more appropriately for the imperative stimulus. A norepinephrine hypothesis focusing on the tonic activity of the locus coeruleus (LC) is proposed as an explanation for these and other lability-dependent effects. The frequency of spontaneous electrodermal fluctuations at rest may represent a peripheral, noninvasive, and easily measurable indicator of the baseline LC activity during wakefulness.

Resting-State fMRI Study of Vigilance Under Circadian and Homeostatic Modulation Based on Fractional Amplitude of Low-Frequency Fluctuation and Regional Homogeneity in Humans Under Normal Entrained Conditions.

BACKGROUND: How brain neural activity changes at multiple time points throughout the day and the neural mechanisms underlying time-dependent modulation of vigilance are less clear. PURPOSE: To explore the effect of circadian rhythms and homeostasis on brain neural activity and the potential neural basis of time-dependent modulation of vigilance. STUDY TYPE: Prospective. SUBJECTS: A total of 30 healthy participants (22-27 years old). FIELD STRENGTH/SEQUENCE: A 3.0 T, T1-weighted imaging, echo-planar functional MRI (fMRI). ASSESSMENT: Six resting-state fMRI (rs-fMRI) scanning sessions were performed at fixed times (9:00 h, 13:00 h, 17:00 h, 21:00 h, 1:00 h, and 5:00 h) to investigate fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) diurnal variation. The fALFF/ReHo and the result of the psychomotor vigilance task were used to assess local neural activity and vigilance. STATISTICAL TESTS: One-way repeated measures analysis of variance (ANOVA) was used to assess changes in vigilance (P < 0.05) and neural activity in the whole brain (P < 0.001 at the voxel level and P < 0.01 at the cluster level, Gaussian random field [GRF] corrected). Correlation analysis was used to examine the relationship between neural activity and vigilance at all-time points of the day. RESULTS: The fALFF/ReHo in the thalamus and some perceptual cortices tended to increase from 9:00 h to 13:00 h and from 21:00 h to 5:00 h, whereas the key nodes of the default mode network (DMN) tended to decrease from 21:00 h to 5:00 h. The vigilance tended to decrease from 21:00 h to 5:00 h. The fALFF/ReHo in the thalamus and some perceptual cortices was negatively correlated with vigilance at all-time points of the day, whereas the fALFF/ReHo in the key nodes of the DMN was positively correlated with vigilance. DATA CONCLUSION: Neural activities in the thalamus and some perceptual cortices show similar trends throughout the day, whereas the key nodes of the DMN show roughly opposite trends. Notably, diurnal variation of the neural activity in these brain regions may be an adaptive or compensatory response to changes in vigilance. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: 1.

Activation of androgen receptor-expressing neurons in the posterior medial amygdala is associated with stress resistance in dominant male hamsters.

Social stress is a negative emotional experience that can increase fear and anxiety. Dominance status can alter the way individuals react to and cope with stressful events. The underlying neurobiology of how social dominance produces stress resistance remains elusive, although experience-dependent changes in androgen receptor (AR) expression is thought to play an essential role. Using a Syrian hamster (Mesocricetus auratus) model, we investigated whether dominant individuals activate more AR-expressing neurons in the posterior dorsal and posterior ventral regions of the medial amygdala (MePD, MePV), and display less social anxiety-like behavior following social defeat stress compared to subordinate counterparts. We allowed male hamsters to form and maintain a dyadic dominance relationship for 12 days, exposed them to social defeat stress, and then tested their approach-avoidance behavior using a social avoidance test. During social defeat stress, dominant subjects showed a longer latency to submit and greater c-Fos expression in AR+ cells in the MePD/MePV compared to subordinates. We found that social defeat exposure reduced the amount of time animals spent interacting with a novel conspecific 24 h later, although there was no effect of dominance status. The amount of social vigilance shown by dominants during social avoidance testing was positively correlated with c-Fos expression in AR+ cells in the MePV. These findings indicate that dominant hamsters show greater neural activity in AR+ cells in the MePV during social defeat compared to their subordinate counterparts, and this pattern of neural activity correlates with their proactive coping response. Consistent with the central role of androgens in experience-dependent changes in aggression, activation of AR+ cells in the MePD/MePV contributes to experience-dependent changes in stress-related behavior.

The effect of sleep restriction, with or without high-intensity interval exercise, on behavioural alertness and mood state in young healthy males.

Mood state and alertness are negatively affected by sleep loss, and can be positively influenced by exercise. However, the potential mitigating effects of exercise on sleep-loss-induced changes in mood state and alertness have not been studied comprehensively. Twenty-four healthy young males were matched into one of three, 5-night sleep interventions: normal sleep (NS; total sleep time (TST) per night = 449 ± 22 min), sleep restriction (SR; TST = 230 ± 5 min), or sleep restriction and exercise (SR + EX; TST = 235 ± 5 min, plus three sessions of high-intensity interval exercise (HIIE)). Mood state was assessed using the profile of mood states (POMS) and a daily well-being questionnaire. Alertness was assessed using psychomotor vigilance testing (PVT). Following the intervention, POMS total mood disturbance scores significantly increased for both the SR and SR + EX groups, and were greater than the NS group (SR vs NS; 31.0 ± 10.7 A.U., [4.4-57.7 A.U.], p = 0.020; SR + EX vs NS; 38.6 ± 14.9 A.U., [11.1-66.1 A.U.], p = 0.004). The PVT reaction times increased in the SR (p = 0.049) and SR + EX groups (p = 0.033) and the daily well-being questionnaire revealed increased levels of fatigue in both groups (SR; p = 0.041, SR + EX; p = 0.026) during the intervention. Despite previously demonstrated physiological benefits of performing three sessions of HIIE during five nights of sleep restriction, the detriments to mood, wellness, and alertness were not mitigated by exercise in this study. Whether alternatively timed exercise sessions or other exercise protocols could promote more positive outcomes on these factors during sleep restriction requires further research.

Crosstalk between the subiculum and sleep-wake regulation: A review.

The circuitry underlying the initiation, maintenance, and coordination of wakefulness, rapid eye movement sleep, and non-rapid eye movement sleep is not thoroughly understood. Sleep is thought to arise due to decreased activity in the ascending reticular arousal system, which originates in the brainstem and awakens the thalamus and cortex during wakefulness. Despite the conventional association of sleep-wake states with hippocampal rhythms, the mutual influence of the hippocampal formation in regulating vigilance states has been largely neglected. Here, we focus on the subiculum, the main output region of the hippocampal formation. The subiculum, particulary the ventral part, sends extensive monosynaptic projections to crucial regions implicated in sleep-wake regulation, including the thalamus, lateral hypothalamus, tuberomammillary nucleus, basal forebrain, ventrolateral preoptic nucleus, ventrolateral tegmental area, and suprachiasmatic nucleus. Additionally, second-order projections from the subiculum are received by the laterodorsal tegmental nucleus, locus coeruleus, and median raphe nucleus, suggesting the potential involvement of the subiculum in the regulation of the sleep-wake cycle. We also discuss alterations in the subiculum observed in individuals with sleep disorders and in sleep-deprived mice, underscoring the significance of investigating neuronal communication between the subiculum and pathways promoting both sleep and wakefulness.

Alteration in neural oscillatory activity and phase-amplitude coupling after sleep deprivation: Evidence for impairment and compensation effects.

Insufficient sleep can significantly affect vigilance and increase slow-wave electroencephalographic power as homeostatic sleep pressure accumulates. Phase-amplitude coupling is involved in regulating the spatiotemporal integration of physiological processes. This study aimed to examine the functional associations of resting-state electroencephalographic power and delta/theta-gamma phase-amplitude coupling from the prefrontal cortex (PFC) to posterior regions with vigilance performance after sleep deprivation. Forty-six healthy adults underwent 24-hr sleep deprivation with resting-state electroencephalographic recordings, and vigilant attention was measured using the Psychomotor Vigilance Task. Power spectral and phase-amplitude coupling analyses were conducted, and correlation analysis was utilized to reveal the relationship between electroencephalographic patterns and changes in vigilance resulting from sleep deprivation. Sleep deprivation significantly declined vigilance performance, accompanied by increased resting-state electroencephalographic power in all bands and delta/theta-gamma phase-amplitude coupling. The increased theta activity in centro-parieto-occipital areas significantly correlated with decreased mean and slowest response speed. Conversely, the increased delta-low gamma and theta-high gamma phase-amplitude couplings negatively correlated with the deceleration of the fastest Psychomotor Vigilance Task reaction times. These findings suggest that sleep deprivation affects vigilance by altering electroencephalographic spectral power and information communication across frequency bands in different brain regions. The distinct effects of increased theta power and delta/theta-gamma phase-amplitude coupling might reflect the impairment and compensation of sleep deprivation on vigilance performance, respectively.

Reaction time in psychomotor vigilance task is related to hypoxic load in males with sleep apnea.

Oxygen saturation (SpO2 )-based parameters are more strongly linked to impaired daytime vigilance than the conventional diagnostic metrics in patients with obstructive sleep apnea (OSA). However, whether the association between SpO2 -based parameters and impaired daytime vigilance is modulated by sex, remains unknown. Hence, we investigated the interplay between sex and detailed SpO2 -based metrics and their association with impaired vigilance in patients with OSA. The study population consisted of 855 (473 males, 382 females) patients with suspected OSA who underwent overnight polysomnography and psychomotor vigilance task (PVT). The population was grouped by sex and divided into quartiles (Q1-Q4) based on median reaction times (RTs) in the PVT. In addition to conventional diagnostic metrics, desaturation severity (DesSev), fall severity (FallSev), and recovery severity (RecovSev) were compared between the sexes and between the best (Q1) and worst (Q4) performing quartiles by using cumulative distribution functions (CDFs). Additionally, sex-specific covariate-adjusted linear regression models were used to investigate the connection between the parameters and RTs. The CDFs showed significantly higher hypoxic load in Q4 in males compared to females. In addition, the DesSev (ß = 8.05, p < 0.01), FallSev (ß = 6.48, p = 0.02), RecovSev (ß = 9.13, p < 0.01), and Oxygen Desaturation Index (ß = 12.29, p < 0.01) were associated with increased RTs only in males. Conversely, the Arousal Index (ß = 10.75-11.04, p < 0.01) was associated with impaired vigilance in females. The severity of intermittent hypoxaemia was strongly associated with longer RTs in males whereas the Arousal Index had the strongest association in females. Thus, the impact of hypoxic load on impaired vigilance seems to be stronger in males than females.

Cognitive performance of air personnel following sleep deprivation.

Air forces have developed several methods for reducing fatigue-related accidents. In the Israeli Air Force, the "Dead Tired" workshop was developed with the purpose of presenting aircrew with their objective performance under sleep deprivation conditions. The aim of this study was to examine the cognitive abilities of both aircrew and unmanned aerial vehicle operators, both objectively and subjectively. All Israeli aircrew and unmanned aerial vehicle operators participated in a "Dead Tired" workshop. During the workshop, the participants performed the Psychomotor Vigilance Task, a task that tests their attention abilities, while gathering information on their subjective sleepiness in the form of a Karolinska Sleepiness Scale. Data of 366 participants (25 females), of whom 187 were unmanned aerial vehicle operators and 179 were aircrew, were obtained; and the mean age was 21.8 ± 1.2 years (range 19-26 years). A significant decline in task performance was seen following 20 hr of wakefulness in both unmanned aerial vehicle operators and aircrew (p < 0.001). Unmanned aerial vehicle operators' performance was significantly better throughout the majority of the workshop (p < 0.001). Recovery after the full-night's sleep was seen for unmanned aerial vehicle operators, but not for aircrew (p = 0.008). A high correlation was seen between Psychomotor Vigilance Task performance and Karolinska Sleepiness Scale responses (correlation coefficient = 0.93). Sleep deprivation negatively impacted the performance of both groups of participants. Unmanned aerial vehicle operators were found to be more resilient to the effects of sleep deprivation and were quicker to recover in comparison to aircrew.

The Ultra-Long-Term Sleep study: Design, rationale, data stability and user perspective.

Sleep deprivation and poor sleep quality are significant societal challenges that negatively impact individuals' health. The interaction between subjective sleep quality, objective sleep measures, physical and cognitive performance, and their day-to-day variations remains poorly understood. Our year-long study of 20 healthy individuals, using subcutaneous electroencephalography, aimed to elucidate these interactions, assessing data stability and participant satisfaction, usability, well-being and adherence. In the study, 25 participants were fitted with a minimally invasive subcutaneous electroencephalography lead, with 20 completing the year of subcutaneous electroencephalography recording. Signal stability was measured using covariance of variation. Participant satisfaction, usability and well-being were measured with questionnaires: Perceived Ease of Use questionnaire, System Usability Scale, Headache questionnaire, Major Depression Inventory, World Health Organization 5-item Well-Being Index, and interviews. The subcutaneous electroencephalography signals remained stable for the entire year, with an average participant adherence rate of 91%. Participants rated their satisfaction with the subcutaneous electroencephalography device as easy to use with minimal or no discomfort. The System Usability Scale score was high at 86.3 ± 10.1, and interviews highlighted that participants understood how to use the subcutaneous electroencephalography device and described a period of acclimatization to sleeping with the device. This study provides compelling evidence for the feasibility of longitudinal sleep monitoring during everyday life utilizing subcutaneous electroencephalography in healthy subjects, showcasing excellent signal stability, adherence and user experience. The amassed subcutaneous electroencephalography data constitutes the largest dataset of its kind, and is poised to significantly advance our understanding of day-to-day variations in normal sleep and provide key insights into subjective and objective sleep quality.

Can transcutaneous auricular vagus nerve stimulation mitigate vigilance loss? Examining the effects of stimulation at individualized versus constant current intensity.

According to the arousal model of vigilance, the locus coeruleus-norepinephrine (LC-NE) system modulates sustained attention over long periods by regulating physiological arousal. Recent research has proposed that transcutaneous auricular vagus nerve stimulation (taVNS) modulates indirect physiological markers of LC-NE activity, although its effects on vigilance have not yet been examined. Aiming to develop a safe and noninvasive procedure to prevent vigilance failures in prolonged tasks, the present study examined whether taVNS can mitigate vigilance loss while modulating indirect markers of LC-NE activity. Following a preregistered protocol (https://osf.io/tu2xy/), 50 participants completed three repeated sessions in a randomized order, in which either active taVNS at individualized intensity set by participant, active taVNS set at 0.5 mA for all participants, or sham taVNS, was delivered while performing an attentional and vigilance task (i.e., ANTI-Vea). Changes in salivary alpha-amylase and cortisol concentrations were measured as markers of LC-NE activity. Self-reports of feelings associated with stimulation and guessing rate of active/sham conditions supported the efficacy of the single-blind procedure. Contrary to our predictions, the observed vigilance decrement was not modulated by active taVNS. Pairwise comparisons showed a mitigation by active taVNS on cortisol reduction across time. Interestingly, Spearman's correlational analyses showed some interindividual effects of taVNS on indirect markers of LC-NE, evidenced by positive associations between changes in salivary alpha-amylase and cortisol in active but not sham taVNS. We highlight the relevance of replicating and extending the present outcomes, investigating further parameters of stimulation and its effects on other indirect markers of LC-NE activity.

Auditory vigilance task performance and cerebral hemodynamics: effects of spatial uncertainty.

The vigilance decrement, a temporal decline in detection performance, has been observed across multiple sensory modalities. Spatial uncertainty about the location of task-relevant stimuli has been demonstrated to increase the demands of vigilance and increase the severity of the vigilance decrement when attending to visual displays. The current study investigated whether spatial uncertainty also increases the severity of the vigilance decrement and task demands when an auditory display is used. Individuals monitored an auditory display to detect critical signals that were shorter in duration than non-target stimuli. These auditory stimuli were presented in either a consistent, predictable pattern that alternated sound presentation from left to right (spatial certainty) or an inconsistent, unpredictable pattern that randomly presented sounds from the left or right (spatial uncertainty). Cerebral blood flow velocity (CBFV) was measured to assess the neurophysiological demands of the task. A decline in performance and CBFV was observed in both the spatially certain and spatially uncertain conditions, suggesting that spatial auditory vigilance tasks are demanding and can result in a vigilance decrement. Spatial uncertainty resulted in a more severe vigilance decrement in correct detections compared to spatial certainty. Reduced right-hemispheric CBFV was also observed during spatial uncertainty compared to spatial certainty. Together, these results suggest that auditory spatial uncertainty hindered performance and required greater attentional demands compared to spatial certainty. These results concur with previous research showing the negative impact of spatial uncertainty in visual vigilance tasks, but the current results contrast recent research showing no effect of spatial uncertainty on tactile vigilance.

Surveillance for donor-derived infections in Australia.

BACKGROUND: Systems for quality and safety assurance in organ donation and transplantation are vital, especially those that seek to minimize donor disease transmission. Australia has developed a national vigilance and surveillance system to identify, review, and analyze actual and potential donor-derived infections and other disease transmissions. METHODS: The system involves notification of incidents to the Australian Organ and Tissue Authority for review by a Vigilance and Surveillance Expert Advisory Committee (VSEAC). The VSEAC grades incidents, O makes recommendations, and issues communications both publicly and to the clinical donation and transplant sector. RESULTS: Annual notifications have increased since the inception of the system in 2012 until 2022. The vast majority relate to procedural aspects including donor assessment, information/data issues, and the recovery, offer, allocation, preservation and transportation of organs. Possible donor-derived disease accounted for 19% of all notifications, and those related to possible donor-derived infection only 12%. The VSEAC, as a result of reviewing these incidents, has made recommendations resulting in revisions to donor screening, organ allocation, packaging and transportation. The review of incidents has led to changes in clinical guidance for increased viral risk donor assessment, testing, and ensuing organ utilization and recipient surveillance. Guidance has also been reviewed for other infectious risks including strongyloides, human T-lymphotropic virus, and HEV. CONCLUSION: The Australian vigilance and surveillance system has enabled national retrospective reporting and evaluation of serious adverse events or reactions to identify trends and inform processes and guidelines, therefore improving the safety of donation and transplantation.

Chronic pain recruits hypothalamic dynorphin/kappa opioid receptor signalling to promote wakefulness and vigilance.

Increased vigilance in settings of potential threats or in states of vulnerability related to pain is important for survival. Pain disrupts sleep and conversely, sleep disruption enhances pain, but the underlying mechanisms remain unknown. Chronic pain engages brain stress circuits and increases secretion of dynorphin, an endogenous ligand of the kappa opioid receptor (KOR). We therefore hypothesized that hypothalamic dynorphin/KOR signalling may be a previously unknown mechanism that is recruited in pathological conditions requiring increased vigilance. We investigated the role of KOR in wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep in freely moving naïve mice and in mice with neuropathic pain induced by partial sciatic nerve ligation using EEG/EMG recordings. Systemic continuous administration of U69,593, a KOR agonist, over 5 days through an osmotic minipump decreased the amount of NREM and REM sleep and increased sleep fragmentation in naïve mice throughout the light-dark sleep cycle. We used KORcre mice to selectively express a Gi-coupled designer receptor activated by designer drugs (Gi-DREADD) in KORcre neurons of the hypothalamic paraventricular nucleus, a key node of the hypothalamic-pituitary-adrenal stress response. Sustained activation of Gi-DREADD with clozapine-N-oxide delivered in drinking water over 4 days, disrupted sleep in these mice in a similar way as systemic U69,593. Mice with chronic neuropathic pain also showed disrupted NREM and total sleep that was normalized by systemic administration of two structurally different KOR antagonists, norbinaltorphimine and NMRA-140, currently in phase II clinical development, or by CRISPR/Cas9 editing of paraventricular nucleus KOR, consistent with endogenous KOR activation disrupting sleep in chronic pain. Unexpectedly, REM sleep was diminished by either systemic KOR antagonist or by CRISPR/Cas9 editing of paraventricular nucleus KOR in sham-operated mice. Our findings reveal previously unknown physiological and pathophysiological roles of dynorphin/KOR in eliciting arousal. Physiologically, dynorphin/KOR signalling affects transitions between sleep stages that promote REM sleep. Furthermore, while KOR antagonists do not promote somnolence in the absence of pain, they normalized disrupted sleep in chronic pain, revealing a pathophysiological role of KOR signalling that is selectively recruited to promote vigilance, increasing chances of survival. Notably, while this mechanism is likely beneficial in the short-term, disruption of the homeostatic need for sleep over longer periods may become maladaptive resulting in sustained pain chronicity. A novel approach for treatment of chronic pain may thus result from normalization of chronic pain-related sleep disruption by KOR antagonism.

Longitudinal point-of-care assessment of psychomotor vigilance in children in the epilepsy monitoring unit.

The epilepsy monitoring unit (EMU) is a complex and dynamic operational environment, where the cognitive and behavioural consequences of medical and environmental changes often go unnoticed. The psychomotor vigilance task (PVT) has been used to detect changes in cognition and behaviour in numerous contexts, including among astronauts on spaceflight missions, pilots, and commercial drivers. Here, we piloted serial point-of-care administration of the PVT in children undergoing invasive monitoring in the EMU. Seven children completed the PVT throughout their hospital admission and their performance was associated with daily seizure counts, interictal epileptiform discharges, number of antiseizure medications (ASMs) administered, and sleep quality metrics. Using mixed-effects models, we found that PVT reaction time and accuracy were adversely affected by greater number of ASMs and interictal epileptiform activity. We show that serial point-of-care PVT is simple and feasible in the EMU and may enable greater understanding of individual patient responses to medical and environmental alterations, inform clinical decision-making, and support quality-improvement and research initiatives.

Mapping between cognitive theories and psycho-physiological models of attention system performance.

Declines in the capacity to sustain attention to repetitive, monotonous tasks is a phenomenon known as vigilance decrement (Endsley M, Kiris E. The out-of-the-loop performance problem and level of control in automation. 1995. Hum Factors. 37:32-64). This review compares cognitive theories with psycho-physiological models of vigilance decrement, and a gap is identified in mapping between the 2. That is, theories of vigilance decrement refer to "cognitive" resources; by contrast, psychophysiological models of the cerebral systems associated with attention explain performance functions according to neurochemical resources. A map does not currently exist in the literature that bridges the gap between cognitive theories of vigilance decrement and psychophysiological models of the human attention system. The link between "cognitive resource" theories of vigilance decrement and the psychophysiological models of attention performance is a gap in the literature that this review fills. This comprehensive review provides an expanded psychophysiological understanding of vigilance decrement that could help inform the management of declines in sustained attention capacity in operational settings. In addition, elucidating the link between cognitive theories of vigilance decrement and psychophysiological models of the human attention system might be used to treat and better understand pathologies such as attention-deficit hyperactivity disorder.