Arousal State Research Articles

Involvement of Melatonin, Oxidative Stress, and Inflammation in the Protective Mechanism of the Carotid Artery over the Torpor–Arousal Cycle of Ground Squirrels

Hibernating mammals experience severe hemodynamic changes over the torpor–arousal cycle, with oxygen consumption reaching peaks during the early stage of torpor to re-enter arousal. Melatonin (MT) can improve mitochondrial function and reduce oxidative stress and inflammation. However, the regulatory mechanisms of MT action on the vascular protective function of hibernators are still unclear. Morphology, hemodynamic, mitochondrial oxidative stress, and inflammatory factors of the carotid artery were assessed in ground squirrels who were sampled during summer active (SA), late torpor (LT), and interbout arousal (IBA) conditions. Changes were assessed by methods including hematoxylin and eosin staining, color Doppler ultrasound, ELISA, Western blots, and qPCR. Changes in arterial blood and serum melatonin were also measured by blood gas analyzer and ELISA, whereas mitochondrial oxidative stress and inflammation factors of primary vascular smooth muscle cells (VSMCs) were assessed by qPCR. (1) Intima-media carotid thickness, peak systolic velocity (PSV), end diastolic blood flow velocity (EDV), maximal blood flow rate (Vmax) and pulsatility index (PI) were significantly decreased in the LT group as compared with the SA group, whereas there were no difference between the SA and IBA groups. (2) PO2, oxygen saturation, hematocrit and PCO2 in the arterial blood were significantly increased, and pH was significantly decreased in the LT group as compared with the SA and IBA groups. (3) The serum melatonin concentration was significantly increased in the LT group as compared with the SA and IBA groups. (4) MT treatment significantly reduced the elevated levels of LONP1, NF-κB, NLRP3 and IL-6 mRNA expression of VSMCs under hypoxic conditions. (5) Protein expression of HSP60 and LONP1 in the carotid artery were significantly reduced in the LT and IBA groups as compared with the SA group. (6) The proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the carotid artery of the LT group as compared with the SA and IBA groups. The carotid artery experiences no oxidative stress or inflammatory response during the torpor–arousal cycle. In addition, melatonin accumulates during torpor and alleviates oxidative stress and inflammatory responses caused by hypoxia in vitro in VSMCs from ground squirrels.

Infraslow noradrenergic locus coeruleus activity fluctuations are gatekeepers of the NREM-REM sleep cycle.

The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear. Here, we show in mice that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two brain-autonomic states that govern the NREMS-REMS cycle over ~50-s periods; high LC activity induces a subcortical-autonomic arousal state that facilitates cortical microarousals, whereas low LC activity is required for NREMS-to-REMS transitions. This functional alternation regulates the duration of the NREMS-REMS cycle by setting permissive windows for REMS entries during undisturbed sleep while limiting these entries to maximally one per ~50-s period during REMS restriction. A stimulus-enriched, stress-promoting wakefulness was associated with longer and shorter levels of high and low LC activity, respectively, during subsequent NREMS, resulting in more microarousal-induced NREMS fragmentation and delayed REMS onset. We conclude that LC activity fluctuations are gatekeepers of the NREMS-REMS cycle and that this role is influenced by adverse wake experiences.

Brain state and cortical layer-specific mechanisms underlying perception at threshold

Identical stimuli can be perceived or go unnoticed across successive presentations, producing divergent behavioral outcomes despite similarities in sensory input. We sought to understand how fluctuations in behavioral state and cortical layer and cell class-specific neural activity underlie this perceptual variability. We analyzed physiological measurements of state and laminar electrophysiological activity in visual area V4 while monkeys were rewarded for correctly reporting a stimulus change at perceptual threshold. Hit trials were characterized by a behavioral state with heightened arousal, greater eye position stability, and enhanced decoding performance of stimulus identity from neural activity. Target stimuli evoked stronger responses in V4 in hit trials, and excitatory neurons in the superficial layers, the primary feed-forward output of the cortical column, exhibited lower variability. Feed-forward interlaminar population correlations were stronger on hits. Hit trials were further characterized by greater synchrony between the output layers of the cortex during spontaneous activity, while the stimulus-evoked period showed elevated synchrony in the feed-forward pathway. Taken together, these results suggest that a state of elevated arousal and stable retinal images allow enhanced processing of sensory stimuli, which contributes to hits at perceptual threshold.

Brain state and cortical layer-specific mechanisms underlying perception at threshold

Identical stimuli can be perceived or go unnoticed across successive presentations, producing divergent behavioral outcomes despite similarities in sensory input. We sought to understand how fluctuations in behavioral state and cortical layer and cell class-specific neural activity underlie this perceptual variability. We analyzed physiological measurements of state and laminar electrophysiological activity in visual area V4 while monkeys were rewarded for correctly reporting a stimulus change at perceptual threshold. Hit trials were characterized by a behavioral state with heightened arousal, greater eye position stability, and enhanced decoding performance of stimulus identity from neural activity. Target stimuli evoked stronger responses in V4 in hit trials, and excitatory neurons in the superficial layers, the primary feed-forward output of the cortical column, exhibited lower variability. Feed-forward interlaminar population correlations were stronger on hits. Hit trials were further characterized by greater synchrony between the output layers of the cortex during spontaneous activity, while the stimulus-evoked period showed elevated synchrony in the feed-forward pathway. Taken together, these results suggest that a state of elevated arousal and stable retinal images allow enhanced processing of sensory stimuli, which contributes to hits at perceptual threshold.

Interactions between arousal state and CO₂ determine the activity of central chemoreceptor neurons that drive breathing.

The homeostatic regulation of pulmonary ventilation, and ultimately arterial PCO2, depends on interactions between respiratory chemoreflexes and arousal state. The ventilatory response to CO2 is triggered by neurons in the retrotrapezoid nucleus (RTN) that function as sensors of central pH, which can be identified in adulthood by expression of Phox2b and Neuromedin B. Here we examine the dynamic response of genetically-defined RTN neurons to hypercapnia and arousal state in freely-behaving adult male and female mice using the calcium indicator jGCaMP7 and fiber photometry. We found that hypercapnia vigorously activates RTN neurons with a low CO2 recruitment threshold and with response kinetics that match respiratory activity whereas hypoxia had little effect. RTN activity increased transiently during wakefulness and respiratory-related arousals, rose persistently during REM sleep and their CO2 response persisted under anesthesia. Complementary studies using inhibitory optogenetics show that RTN activity supports eupneic breathing under anesthesia as well as during states of high arousal, but their activity is redundant for voluntary breathing patterns. Collectively, this study demonstrates that CO2-activated RTN neurons are exquisitely sensitive to arousal state, which determines their contribution to alveolar ventilation in relation to arterial PCO2 Significance statement Respiratory chemoreceptors stimulate neural respiratory motor output to regulate arterial PCO2 and PO2, thereby maintaining optimal gas exchange. Central chemoreceptor neurons expressing Phox2b and Neuromedin B in the Retrotrapezoid Nucleus (RTN) are required for the hypercapnia ventilatory response. However, the dynamic activity of RTN neurons in conditions of normal and elevated carbon dioxide has not been described in unanesthetized conditions. Here, we use a genetically-encoded calcium indicator to demonstrate that RTN neurons exquisitely sensitivity to hypercapnia and variations in arousal and sleep-state in freely-behaving mice. This work has implications for understanding the central control of breathing across arousal-states, particularly during sleep and anesthesia.

A database of naturalistic expressive faces for studying high arousal states

Recent studies comparing behavior to different sets of facial stimuli have highlighted a need to employ more naturalistic, genuine facial expressions in cognitive research. To address this need, we identified and selected a large set of highly expressive face stimuli from the public domain, and used these stimuli to test whether participants can recognise when others are experiencing pain from their facial behaviour. After identifying 315 expressive faces to represent the kinds of facial behaviours often seen in three distinct contexts (i.e., injury-related, loss-related and victory-related), we ran six behavioural ratings tasks to characterise these faces along six dimensions; level of arousal, emotional valence, level of physical pain, attractiveness, familiarity, and perceived gender. The results indicate that injury-related expressions are recognised as lower in emotional valence than victory-related expressions, and higher in psychological arousal than both victory- and loss-related expressions. Overall, these findings suggest that the intense, energetic expressions of people in competitive situations are not rendered ambiguous to third parties by increased arousal. These results validate the use of naturalistic facial expressions in studies of non-verbal, injury-related behaviours and their recognition in forensic and clinical settings. PerspectiveHere we created and validated a large set of visual stimuli, which have been made available to the scientific community. Our results demonstrate that among high-arousal states, expressions related to feelings of intense pain and injury are visually distinct from expressions related to loss or triumph. Thus, the Wild Faces Database – High Arousal States (WFD-HAS) extension provides an important tool for understanding how we recognise injury-related facial expressions in the real world.

Influence of rhythmic contexts on perception: No behavioral and eye-tracker evidence for rhythmic entrainment

Entrainment theories propose that attention inherently oscillates between moments of attentional enhancement and disengagement. Consequently, perceptual and response benefits have been reported in tasks with a rhythmic structure. In the present study, we report two preregistered auditory experiments attempting to replicate previous supporting behavioral evidence of entrainment theories. In addition, we incorporated eye-tracker measures. Both Experiment 1 (duration discrimination task) and Experiment 2 (pitch discrimination task) showed no phase-specific benefit of rhythmic sequences compared to arrhythmic ones. Importantly, a tonic larger pupil size for arrhythmic conditions was observed irrespective of target phase, suggesting higher processing demands or arousal state imposed by a sustained uncertain context. Overall, the present results call into question whether the perceptual benefits predicted by entrainment theories are generalizable across all experimental designs and paradigms. On the contrary, our findings join a large group of studies that have failed to replicate the foundational results of attentional entrainment.

A human brain network linked to restoration of consciousness after deep brain stimulation.

Disorders of consciousness (DoC) are states of impaired arousal or awareness. Deep brain stimulation (DBS) is a potential treatment, but outcomes vary, possibly due to differences in patient characteristics, electrode placement, or stimulation of specific brain networks. We studied 40 patients with DoC who underwent DBS targeting the thalamic centromedian-parafascicular complex. Better-preserved gray matter, especially in the striatum, correlated with consciousness improvement. Stimulation was most effective when electric fields extended into parafascicular and subparafascicular nuclei-ventral to the centromedian nucleus, near the midbrain-and when it engaged projection pathways of the ascending arousal network, including the hypothalamus, brainstem, and frontal lobe. Moreover, effective DBS sites were connected to networks similar to those underlying impaired consciousness due to generalized absence seizures and acquired lesions. These findings support the therapeutic potential of DBS for DoC, emphasizing the importance of precise targeting and revealing a broader link between effective DoC treatment and mechanisms underlying other conscciousness-impairing conditions.

Regularizing hyperparameters of interacting neural signals in the mouse cortex reflect states of arousal.

In natural behaviors, multiple neural signals simultaneously drive activation across overlapping brain networks. Due to limitations in the amount of data that can be acquired in common experimental designs, the determination of these interactions is commonly inferred via modeling approaches, which reduce overfitting by finding appropriate regularizing hyperparameters. However, it is unclear whether these hyperparameters can also be related to any aspect of the underlying biological phenomena and help interpret them. We applied a state-of-the-art regularization procedure-automatic locality determination-to interacting neural activations in the mouse posterior cortex associated with movements of the body and eyes. As expected, regularization significantly improved the determination and interpretability of the response interactions. However, regularizing hyperparameters also changed considerably, and seemingly unpredictably, from animal to animal. We found that these variations were not random; rather, they correlated with the variability in visually evoked responses and with the variability in the state of arousal of the animals measured by pupillometry-both pieces of information that were not included in the modeling framework. These observations could be generalized to another commonly used-but potentially less informative-regularization method, ridge regression. Our findings demonstrate that optimal model hyperparameters can be discovery tools that are informative of factors not a priori included in the model's design.

Locus coeruleus co-activation patterns at rest show higher state persistence in patients with dissociative seizures: A Pilot Study.

Dissociative seizures are paroxysmal disruptions of awareness and behavioral control in the context of affective arousal. Alterations in stress-related endocrine function have been demonstrated, but the timescale of dissociation suggests that the central locus coeruleus (LC) noradrenergic system is likely pivotal. Here, we investigate whether LC activation at rest is associated with altered brain network dynamics. A preliminary co-activation pattern (CAP) analysis of resting-state functional magnetic resonance imaging (fMRI) in 14 patients with dissociative seizures and 14 healthy controls was performed by using the LC as a seeding region. The red nucleus served as a control condition. Entry rates, durations, and state transition probabilities of identified CAPs were calculated. Analyses were corrected for demographic, technical, and clinical confounders including depression and anxiety. Three LC-related CAPs were identified, with the dominant two showing inverse activations and deactivations of the default mode network and the attention networks, respectively. Analysis of transition probabilities between and within the three CAPs revealed higher state persistence in patients compared to healthy controls for both CAP2LC (Cohen's d = -0.55; p = 0.01) and CAP3LC (Cohen's d = -0.57; p = 0.01). The control analysis using the red nucleus as a seed yielded similar CAPs, but no significant between-group differences in transition probabilities. Higher state persistence of LC-CAPs in patients with dissociative seizures generates the novel hypothesis that arousal-related impairments of network switching might be a candidate neural mechanism of dissociation. Dissociative seizures often arise during high affective arousal. The locus coeruleus is a brain structure involved in managing such acute arousal states. We investigated whether the activity of the locus coeruleus correlates with activity in other regions of the brain (which we refer to as "brain states"), and whether those brain states were different between patients with dissociative seizures and healthy controls. We found that patients tended to stay in certain locus coeruleus-dependent brain states instead of switching between them. This might be related to the loss of awareness and disruptions of brain functions ("dissociation") that patients experience during seizures.

Linear and nonlinear analysis of multimodal physiological data for affective arousal recognition.

In this work we intend to design a system to classify human arousal at five levels (i.e., five stress levels) using four peripheral bio signals including photo-plethysmography measurements (PPG), galvanic skin response (GSR), thorax respiration (TR) and abdominal respiration (AR). A total of 98 young people voluntarily participated in this study, including 65 men and 33 women with an average age of 24.48 ± 4.26 years. We induced five levels of mental stress in subjects through the Stroop test. A range of physiological features from different analysis domains, including statistical, frequency, and geometrical analyzes, as well as recurrence quantification analysis (RQA) and detrended fluctuation analysis (DFA) were extracted to find out the best arousal-related features and to correlate them with arousal states. Classification of the five arousal levels is performed by a simple naïve Bayes classifier. Accuracies of 58.45%, 57.1% and 69.13% were obtained using linear features, nonlinear features and a combination of them, respectively. The combination of linear and nonlinear features resulted in the largest average accuracy of 69.13%, ICC of 88.12% and F1 of 69.43% values in the classification of five levels of mental stress. This paper suggested that combining linear and nonlinear dynamic methods for the analysis of physiological data could help improve the accuracy of the recognition of arousal levels. However, it should be noted that combining multiple modalities (here, PPG, GSR and respiration modalities) by equally weighting them may not always be a good approach to improve accuracy.

The effects of emotional arousal on pupil size depend on luminance

Pupillometry is widely used to measure arousal states. The primary functional role of the pupil, however, is to respond to the luminance of visual inputs. We previously demonstrated that cognitive effort-related arousal interacted multiplicatively with luminance, with the strongest pupillary effects of arousal occurring at low-to-mid luminances (< 37 cd/m2), implying a narrow range of conditions ideal for assessing cognitive arousal-driven pupillary differences. Does this generalize to other forms of arousal? To answer this, we assessed luminance-driven pupillary response functions while manipulating emotional arousal, using well-established visual and auditory stimulus sets. At the group level, emotional arousal interacted with the pupillary light response differently from cognitive arousal: the effects occurred primarily at much lower luminances (< 20 cd/m2). Analyses at the individual-participant level revealed qualitatively distinct patterns of modulation, with a sizable number of individuals displaying no arousal response to the visual or auditory stimuli, regardless of luminance. Together, our results suggest that effects of arousal on pupil size are not monolithic: different forms of arousal exert different patterns of effects. More practically, our findings suggest that lower luminances create better conditions for measuring pupil-linked arousal, and when selecting ambient luminance levels, consideration of the arousal manipulation and individual differences is critical.

Context or arousal? Function of drumming in Mongolian gerbils (Meriones unguiculatus)

Drumming is a non-vocal auditory display producing airborne as well as seismic vibrations by tapping body extremities on a surface. It is mostly described as an alarm signal but is also discussed to signal dominance or mating quality. To clarify the function of drumming in Mongolian gerbils (Meriones unguiculatus), we compared the occurrence of drumming during predator, opposite-sex and same-sex encounters. We tested 48 captive Mongolian gerbils (Meriones unguiculatus) in three experiments. In predator experiments, subjects were exposed alone or with their cagemate to aerial and terrestrial predator dummies. In social encounter experiments, familiar and unfamiliar male–female dyads and same-sex dyads were confronted. For the same-sex encounters, a dominance index was calculated for each subject based on the number of won and lost conflicts. Drumming and drumming-call combinations were counted, and a multi-parametric sound analysis was performed. In all experiments drumming and drumming-call combinations occurred. In predator experiments, more subjects drummed when confronted with the predator stimulus than in the habituation phase. In social encounter experiments, more subjects drummed when facing an unfamiliar than a familiar conspecific. In addition, the accompanying call type and body posture of the sender differed between experiments. Thus, we suggest that whereas drumming signals an increased arousal state of the sender, the accompanying call type and the body posture signal context specific information.

Feeling tired versus feeling relaxed: Two faces of low physiological arousal.

Human well-being and functioning depend on two fundamental mental states: Relaxation and sleepiness. Relaxation and sleepiness are both assumed to be states of low physiological arousal and negatively correlated. However, it is still unclear how consistent this negative relationship is across different settings and whether it changes before and after an intervention. Here we investigated this intricate relationship between subjective momentary sleepiness and relaxation states by meta-analytically analyzing several data sets from studies using the Relaxation State Questionnaire. We discovered that subjective sleepiness and relaxation were in fact anti-correlated pre-intervention. This anti-correlation provides a quantitative dissociation between sleepiness and relaxation. Thus, even though sleepiness and relaxation both implicate a low arousal level, the two mental states are subjectively experienced in a qualitatively different fashion, and thus reflect distinct underlying constructs. For the post-intervention relationship, this negative correlation could not be consistently found. This indicates that there are aspects of the experimental setting or intervention that introduce changes in the dynamics of the relationship of the two constructs.

Changes in electrophysiological aperiodic activity during cognitive control in Parkinson’s disease

Abstract Cognitive symptoms in Parkinson’s disease are common and can significantly affect patients’ quality of life. Therefore, there is an urgent clinical need to identify a signature derived from behavioural and/or neuroimaging indicators that could predict which patients are at increased risk for early and rapid cognitive decline. Recently, converging evidence identified that aperiodic activity of the EEG reflects meaningful physiological information associated with age, development, cognitive and perceptual states or pathologies. In this study, we aimed to investigate aperiodic activity in Parkinson’s disease during cognitive control and characterize its possible association with behaviour. Here, we recorded high-density EEG in 30 healthy controls and 30 Parkinson’s disease patients during a Simon task. We analysed task-related behavioural data in the context of the activation–suppression model and extracted aperiodic parameters (offset, exponent) at both scalp and source levels. Our results showed lower behavioural performances in cognitive control as well as higher offsets in patients in the parieto-occipital areas, suggesting increased excitability in Parkinson’s disease. A small congruence effect on aperiodic parameters in pre- and post-central brain areas was also found, possibly associated with task execution. Significant differences in aperiodic parameters between the resting-state, pre- and post-stimulus phases were seen across the whole brain, which confirmed that the observed changes in aperiodic activity are linked to task execution. No correlation was found between aperiodic activity and behaviour or clinical features. Our findings provide evidence that EEG aperiodic activity in Parkinson’s disease is characterized by greater offsets, and that aperiodic parameters differ depending on arousal state. However, our results do not support the hypothesis that the behaviour-related differences observed in Parkinson’s disease are related to aperiodic changes. Overall, this study highlights the importance of considering aperiodic activity contributions in brain disorders and further investigating the relationship between aperiodic activity and behaviour.

Resisting to Exist and the Subtle Invisible Protest: Six Solution Focused Tactics about Challenging Behaviour

According to Young Minds, ‘everyone gets angry sometimes’. Their website offers a number of de-escalating strategies, including staying calm, managing responses, and setting limits to help young people who most deem resistive. Yet, Young Minds are not alone because such logical advice is ubiquitous in the literature about challenging behaviour despite the fact that in our experience when faced with high states of arousal, most young people tend to act first and deal with the consequences later. It is not that they are stupid or non-caring, but they are human, capable of great feats as well as stupidity. The same is true for any claims that solution focused (SF) conversations can put right the several decades of psychological theory suggesting resistance requires logic and better cognition. By giving the correct thinking skills, young people will walk away from risk, avoid physical confrontation, handle challenging situations like logical thinkers, and generally discount that the process of growing up is part of the challenge. It is with this in mind that over recent years in our current SF practice (with staff group supervision), we have examined the concept of ‘resistance’ and how it can be put to use as a process of collaboration. To do this, we have revisited SF theory that preoccupied many of its pioneers during the 1980s and 1990s and attempted to make it useful for the early 2020s for professionals having conversations with young people, who, in traditional models, are labelled challenging. We want to introduce key differences of solution focused practice and how our research started to formulate a 6D-SF model (details, dynamics, dimensions, dispositions, dislocations, descriptions) for contemplating how groups of professionals relate to each other and are triggered by challenging behaviour. We do not claim to have proof, logic, or exactness on our side, but we are happy to suggest how our resistance mirrors what many of the staff teams feel and describe when working through their work.

Complex housing in adulthood state-dependently affects the excitation-inhibition balance in the infralimbic prefrontal cortex of male C57Bl/6 mice

The prefrontal cortex (PFC) plays an important role in social behavior and is sensitive to stressful circumstances. Challenging life conditions might change PFC function and put individuals at risk for maladaptive social behavior. The excitation-inhibition (EI) balance of prefrontal neurons appears to play a crucial role in this process. Here, we examined how a challenging life condition in C57BL/6JolaHsd mice, i.e. group-housing 6 mice in a complex environment for 10 days in adulthood, changes the EI-balance of infralimbic prefrontal neurons in layer 2/3, compared to standard pair-housing. Slices were prepared from “undisturbed” mice, i.e. the first mouse taken from the cage, or mice taken ∼15 min later, who were mildly aroused after removal of the first mouse. We observed a housing-condition by arousal-state interaction, with in the complex housing group an elevated EI-balance in undisturbed and reduced EI-balance in mildly aroused animals, while no differences were observed in standard housed animals. The change was explained by a shift in mIPSC and mEPSC frequency, while amplitudes remained unaffected. Female mice showed no housing-by-state interaction, but a main effect of housing was found for mIPSCs, with a higher frequency in complex- versus standard-housed females. No effects were observed in males who were complex-housed from a young age onwards. Explorative investigations support a potential mediating role of corticosterone in housing effects on the EI-balance of males. We argue that taking the arousal state of individuals into account is necessary to better understand the consequences of exposure to challenging life conditions for prefrontal function.

Sexual Excitation in Young Women with Different Levels of Sexual Satisfaction in Relationships: A Laboratory Study.

Sexual satisfaction is an important dimension of sexual health. Despite there being evidence about its relations with sexual arousal, this association has not been addressed considering arousal as a trait and as a state. Therefore, the goal of this laboratory study was to examine, in young women with different levels of sexual satisfaction in their relationships, sexual arousal as a trait (i.e., propensity for sexual excitation/inhibition) and as a state (i.e., genital response and self-reported sexual arousal to a video with explicit sexual content). The sample was composed of 45 Spanish heterosexual women with a partner, from 18 to 25 years old. In the first phase, we evaluated the propensity for sexual inhibition/excitation and sexual satisfaction of the participants. In the second phase-in the context of a sexuality laboratory-the vaginal pulse amplitude, the rating of sexual arousal, and the rating of genital sensations were evaluated. The participants, distributed in three groups with different levels of sexual satisfaction (p < 0.001), were compared based on the different measures of sexual arousal. The results indicated that the group with lower sexual satisfaction, compared to the group with higher sexual satisfaction, reported more sexual inhibition due to the threat of performance failure (p = 0.011) and due to the threat of performance consequences (p = 0.038). However, no significant differences in sexual arousal status were found between the three groups. In conclusion, the negative association between sexual satisfaction and propensity for sexual inhibition in young women with a partner is supported, but not the positive association between trait/state sexual arousal and sexual satisfaction.

Dopamine and Norepinephrine Differentially Mediate the Exploration-Exploitation Tradeoff.

Dopamine (DA) and norepinephrine (NE) have been repeatedly implicated in neuropsychiatric vulnerability, in part via their roles in mediating the decision-making processes. Although two neuromodulators share a synthesis pathway and are coactivated under states of arousal, they engage in distinct circuits and modulatory roles. However, the specific role of each neuromodulator in decision-making, in particular the exploration-exploitation tradeoff, remains unclear. Revealing how each neuromodulator contributes to exploration-exploitation tradeoff is important in guiding mechanistic hypotheses emerging from computational psychiatric approaches. To understand the differences and overlaps of the roles of these two catecholamine systems in regulating exploration, a direct comparison using the same dynamic decision-making task is needed. Here, we ran male and female mice in a restless two-armed bandit task, which encourages both exploration and exploitation. We systemically administered a nonselective DA antagonist (flupenthixol), a nonselective DA agonist (apomorphine), a NE beta-receptor antagonist (propranolol), and a NE beta-receptor agonist (isoproterenol) and examined changes in exploration within subjects across sessions. We found a bidirectional modulatory effect of dopamine on exploration. Increasing dopamine activity decreased exploration and decreasing dopamine activity increased exploration. The modulatory effect of beta-noradrenergic receptor activity on exploration was mediated by sex. Reinforcement learning model parameters suggested that dopamine modulation affected exploration via decision noise and norepinephrine modulation affected exploration via sensitivity to outcome. Together, these findings suggested that the mechanisms that govern the exploration-exploitation transition are sensitive to changes in both catecholamine functions and revealed differential roles for NE and DA in mediating exploration.

Differences in Self-Rated Worker Outcomes Across Stress States: An Interim Analysis of Hybrid Worker Data

Stress experiences can have dire consequences for worker performance and well-being, and the social environment of the workplace is a key contributor to worker experience. This study investigated the relationship between hybrid workers’ self-ratings of productivity, mood, and stress with perceptions of positive (eustress) and negative (distress) stress states. We hypothesized that self-ratings would vary across combinations of eustress and distress experiences and that these differences would differ based on the social context. Ecological momentary assessments (EMA) were used to obtain ecologically valid data at four data points each workday across a 4-month study period in a cohort of seven office workers. Findings aligned with the Yerkes–Dodson law, such that higher states of arousal were associated with greater self-perceived productivity, and higher stress magnitudes were found when distress existed. Compared to other states, eustress was associated with higher productivity in work-related activities and better mood across all activity types.