Renewal of instrumental avoidance in humans.

The ABA renewal effect occurs when behavior is trained in one context (A), extinguished in a second context (B), and the test occurs in the training context (A). Two mechanisms that explain ABA renewal are context summation at the test and contextual modulation of extinction learning, with the former being unlikely if both contexts have a similar associative history. In two experiments, we used within-subjects designs in which participants learned to avoid a loud noise (unconditioned stimulus) signaled by discrete visual stimuli (conditioned stimuli [CSs]), by pressing the space bar on the computer keyboard. The training was conducted in two contexts, with a different pair of CSs (CS+ and CS-) trained in each context. During extinction, CS+ and CS- stimuli were presented in the alternative context from that of training, and participants were allowed to freely respond, but no loud noise was presented. Finally, all CSs were tested in both contexts, resulting in a within-subjects ABA versus ABB comparison. Across experiments, participants increased avoidance responses during training and decreased them during extinction, although Experiment 2 revealed less extinction. During the test, responding was higher when CS+ were tested in the training context (ABA) versus the extinction context (ABB), revealing the renewal of instrumental avoidance. Experiment 2 also measured expectancy after the avoidance test and revealed a remarkable similarity between avoidance responses and expectancy ratings. This study shows the renewal of instrumental avoidance in humans, and the results suggest the operation of a modulatory role for the context in renewal, similar to the occasion setting of extinction learning by the context. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Direct serotonin release in humans shapes aversive learning and inhibition.

The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.

Thirst-driven hygrosensory suppression promotes water seeking in Drosophila.

Survival in animals relies on navigating environments aligned with physiological needs. In Drosophila melanogaster, antennal ionotropic receptors (IRs) sensing humidity changes govern hygrotaxis behavior. This study sheds light on the crucial role of IR8a neurons in the transition from high humidity avoidance to water-seeking behavior when the flies become thirsty. These neurons demonstrate a heightened calcium response toward high humidity stimuli in satiated flies and a reduced response in thirsty flies, modulated by fluctuating levels of the neuropeptide leucokinin, which monitors the internal water balance. Optogenetic activation of IR8a neurons in thirsty flies triggers an avoidance response similar to the moisture aversion in adequately hydrated flies. Furthermore, our study identifies IR40a neurons as associated with dry avoidance, while IR68a neurons are linked to moist attraction. The dynamic interplay among these neurons, each with opposing valences, establishes a preference for approximately 30% relative humidity in well-hydrated flies and facilitates water-seeking behavior in thirsty individuals. This research unveils the intricate interplay between sensory perception, neuronal plasticity, and internal states, providing valuable insights into the adaptive mechanisms governing hygrotaxis in Drosophila.

Convergent direct and indirect cortical streams shape avoidance decisions in mice via the midline thalamus.

Current concepts of corticothalamic organization in the mammalian brain are mainly based on sensory systems, with less focus on circuits for higher-order cognitive functions. In sensory systems, first-order thalamic relays are driven by subcortical inputs and modulated by cortical feedback, while higher-order relays receive strong excitatory cortical inputs. The applicability of these principles beyond sensory systems is uncertain. We investigated mouse prefronto-thalamic projections to the midline thalamus, revealing distinct top-down control. Unlike sensory systems, this pathway relies on indirect modulation via the thalamic reticular nucleus (TRN). Specifically, the prelimbic area, which influences emotional and motivated behaviors, impacts instrumental avoidance responses through direct and indirect projections to the paraventricular thalamus. Both pathways promote defensive states, but the indirect pathway via the TRN is essential for organizing avoidance decisions through disinhibition. Our findings highlight intra-thalamic circuit dynamics that integrate cortical cognitive signals and their role in shaping complex behaviors.

Compulsive avoidance in youths and adults with OCD: an aversive pavlovian-to-instrumental transfer study.

Compulsive behaviour may often be triggered by Pavlovian cues. Assessing how Pavlovian cues drive instrumental behaviour in obsessive-compulsive disorder (OCD) is therefore crucial to understand how compulsions develop and are maintained. An aversive Pavlovian-to-Instrumental transfer (PIT) paradigm, particularly one involving avoidance/cancellation of negative outcomes, can enable such investigation and has not previously been studied in clinical-OCD. Forty-one participants diagnosed with OCD (21 adults; 20 youths) and 44 controls (21 adults; 23 youths) completed an aversive PIT task. Participants had to prevent the delivery of unpleasant noises by moving a joystick in the correct direction. They could infer these correct responses by learning appropriate response-outcome (instrumental) and stimulus-outcome (Pavlovian) associations. We then assessed whether Pavlovian cues elicited specific instrumental avoidance responses (specific PIT) and induced general instrumental avoidance (general PIT). We investigated whether task learning and confidence indices influenced PIT strength differentially between groups. There was no overall group difference in PIT performance, although youths with OCD showed weaker specific PIT than youth controls. However, urge to avoid unpleasant noises and preference for safe over unsafe stimuli influenced specific and general PIT respectively in OCD, while PIT in controls was more influenced by confidence in instrumental and Pavlovian learning. Thus, in OCD, implicit motivational factors, but not learnt knowledge, may contribute to the successful integration of aversive Pavlovian and instrumental cues. This implies that compulsive avoidance may be driven by these automatic processes. Youths with OCD show deficits in specific PIT, suggesting cue integration impairments are only apparent in adolescence. These findings may be clinically relevant as they emphasise the importance of targeting such implicit motivational processes when treating OCD.

Learning obstacle avoidance and predation in complex reef environments with deep reinforcement learning.

The reef ecosystem plays a vital role as a habitat for fish species with limited swimming capabilities, serving not only as a sanctuary and food source but also influencing their behavioral tendencies. Understanding the intricate mechanism through which fish adeptly navigate the moving targets within reef environments within complex water flow, all while evading obstacles and maintaining stable postures, has remained a challenging and prominent subject in the realms of fish behavior, ecology, and biomimetics alike. An integrated simulation framework is used to investigate fish predation problems within intricate environments, combining deep reinforcement learning algorithms (DRL) with high-precision fluid-structure interaction numerical methods-immersed boundary lattice Boltzmann method (lB-LBM). The Soft Actor-Critic (SAC) algorithm is used to improve the intelligent fish's capacity for random exploration, tackling the multi-objective sparse reward challenge inherent in real-world scenarios. Additionally, a reward shaping method tailored to its action purposes has been developed, capable of capturing outcomes and trend characteristics effectively. The convergence and robustness advantages of the method elucidated in this paper are showcased through two case studies: one addressing fish capturing randomly moving targets in hydrostatic flow field, and the other focusing on fish counter-current foraging in reef environments to capture drifting food. A comprehensive analysis was conducted of the influence and significance of various reward types on the decision-making processes of intelligent fish within intricate environments.

Observational threat learning influences costly avoidance behaviour in healthy humans.

Avoidance is an essential behaviour for ensuring safety in uncertain and dangerous environments. One way to learn what is dangerous and must be avoided is through observational threat learning. This online study explored the behavioural implications of observed threat learning, examining how participants avoided or approached a learned threat and how this affected their movement patterns. Participants (n = 89) completed an observational threat learning task, rating their fear, discomfort, and physical arousal in response to conditioned stimuli. The retrieval of learned threat was reassessed 24 h later, followed by a reminder of the observed threat associations. Participants subsequently completed a computerised avoidance task, in which they navigated from a starting point to an endpoint by selecting one of two doors, each associated with either safety or danger, relying on observed information. Opting for the safe door entailed increased effort to attain the goal. Results demonstrated that observational threat learning influenced avoidance behaviour and decision-making dependent on baseline effort level. Participants tended to exhibit thigmotaxis, staying close to walls and taking extra steps to reach their goal. This behaviour indirectly mediated the number of steps taken. This study provides valuable insights into avoidance behaviour following observational threat learning in healthy humans.

Dissociable hindbrain GLP1R circuits for satiety and aversion.

The most successful obesity therapeutics, glucagon-like peptide-1 receptor (GLP1R) agonists, cause aversive responses such as nausea and vomiting1,2, effects that may contribute to their efficacy. Here, we investigated the brain circuits that link satiety to aversion, and unexpectedly discovered that the neural circuits mediating these effects are functionally separable. Systematic investigation across drug-accessible GLP1R populations revealed that only hindbrain neurons are required for the efficacy of GLP1-based obesity drugs. In vivo two-photon imaging of hindbrain GLP1R neurons demonstrated that most neurons are tuned to either nutritive or aversive stimuli, but not both. Furthermore, simultaneous imaging of hindbrain subregions indicated that area postrema (AP) GLP1R neurons are broadly responsive, whereas nucleus of the solitary tract (NTS) GLP1R neurons are biased towards nutritive stimuli. Strikingly, separate manipulation of these populations demonstrated that activation of NTSGLP1R neurons triggers satiety in the absence of aversion, whereas activation of APGLP1R neurons triggers strong aversion with food intake reduction. Anatomical and behavioural analyses revealed that NTSGLP1R and APGLP1R neurons send projections to different downstream brain regions to drive satiety and aversion, respectively. Importantly, GLP1R agonists reduce food intake even when the aversion pathway is inhibited. Overall, these findings highlight NTSGLP1R neurons as a population that could be selectively targeted to promote weight loss while avoiding the adverse side effects that limit treatment adherence.

Intense training prevents the amnestic effect of inactivation of dorsomedial striatum and induces high resistance to extinction.

A large body of evidence has shown that treatments that interfere with memory consolidation become ineffective when animals are subjected to an intense learning experience; this effect has been observed after systemic and local administration of amnestic drugs into several brain areas, including the striatum. However, the effects of amnestic treatments on the process of extinction after intense training have not been studied. Previous research demonstrated increased spinogenesis in the dorsomedial striatum, but not in the dorsolateral striatum after intense training, indicating that the dorsomedial striatum is involved in the protective effect of intense training. To investigate this issue, male Wistar rats, previously trained with low, moderate, or high levels of foot shock, were used to study the effect of tetrodotoxin inactivation of dorsomedial striatum on memory consolidation and subsequent extinction of inhibitory avoidance. Performance of the task was evaluated during seven extinction sessions. Tetrodotoxin produced a marked deficit of memory consolidation of inhibitory avoidance trained with low and moderate intensities of foot shock, but normal consolidation occurred when a relatively high foot shock was used. The protective effect of intense training was long-lasting, as evidenced by the high resistance to extinction exhibited throughout the extinction sessions. We discuss the possibility that increased dendritic spinogenesis in dorsomedial striatum may underly this protective effect, and how this mechanism may be related to the resilient memory typical of post-traumatic stress disorder (PTSD).

The generalization of threat beliefs to novel safety stimuli induced by safety behaviors.

Safety behaviors are responses that can reduce or even prevent an expected threat. Moreover, empirical studies have shown that using safety behaviors to a learnt safety stimulus can induce threat beliefs to it. No research so far has examined whether threat beliefs induced this way generalize to other novel stimuli related to the safety stimulus. Using a fear and avoidance conditioning model, the current study (n=116) examined whether threat beliefs induced by safety behaviors generalize to other novel generalization stimuli (GSs). Participants first acquired safety behaviors to a threat predicting conditioned stimulus (CSthreat). Safety behaviors could then be performed in response to one safe stimulus (CSsafeShift) but not to another (CSsafe). In a following generalization test, participants showed a significant but small increase in threat expectancies to GSs related to CSsafeShift compared to GSs related to CSsafe. Interestingly, the degree of safety behaviors used to the CSsafeShift predicted the subsequent increase in generalized threat expectancies, and this link was elevated in trait anxious individuals. The findings suggest that threat beliefs induced by unnecessary safety behaviors generalize to other related stimuli. This study provides a potential explanation for the root of threat belief acquisition to a wide range of stimuli or situations.

Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.

Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.

Approach-avoidance tendencies in proactive and reactive aggression.

Aggressive behaviors have been related to approach/avoidance tendencies. In our current study, we investigated whether approach/avoidance tendencies for angry versus fearful emotional expressions were differentially predictive of children's reactive and proactive aggression. A total of 116 children (58 girls, Mage = 10.90, standard deviation SDage = 0.98) completed an approach/avoidance task (AAT) and a stimulus-response compatibility task (SRCT), both measuring the extent to which they tended to approach or avoid angry and fearful facial expressions relative to neutral facial expressions. Children also completed a self-report scale of reactive and proactive aggression. Although none of the approach/avoidance tendency scores correlated significantly with either of the aggression scores, stronger approach tendencies for angry faces and stronger avoidance tendencies for fearful faces in the AAT predicted more reactive aggression. Similar yet nonsignificant results were found for proactive aggression, but no effects were replicated in the SRCT. Our results thus invite the conclusion that reactive aggression is characterized by a tendency to approach angry faces and a tendency to avoid fearful faces. However, the poor discrimination between both types of aggression as well as the lack of convergence between the results of our two measures of approach/avoidance tendencies indicates that further research is needed to establish the role of approach/avoidance tendencies for emotional faces as markers for childhood aggression.

The effect of typicality training on costly safety behavior generalization.

BACKGROUND AND OBJECTIVES: Typicality asymmetry in generalization refers to enhanced fear generalization when trained with typical compared to atypical exemplars. Typical exemplars are highly representative of their category, whereas atypical exemplars are less representative. Individual risk factors, such as trait anxiety, attenuate this effect, due to the high level of threat ambiguity of atypical exemplars. Although recent research provided evidence for generalization of safety behavior, it is unclear whether this generalization also follows typicality asymmetry. This study examined (1) whether participants exhibited typicality asymmetry in the generalization of safety behavior and (2) whether this effect would be attenuated by individual risk factors, such as intolerance of uncertainty and trait anxiety. METHODS: Participants were trained with either typical (Typical group, n = 53) or atypical (Atypical group, n = 55) exemplars in a fear and avoidance conditioning procedure. Participants acquired differential conditioned fear and costly safety behavior to the threat- and safety-related exemplars. In a following Generalization Test, the degree of safety behavior to novel exemplars of the same categories was tested. RESULTS: The Atypical group showed greater differential safety behavior responses compared to the Typical group. Higher trait anxiety was associated with lower differential safety behavior generalization, driven by an increase in generalized responding to novel safety-related exemplars. LIMITATIONS: This study used hypothetical cost instead of real cost. CONCLUSIONS: Training with atypical exemplars led to greater safety behavior generalization. Moreover, individuals with high trait anxiety show impaired safety behavior generalization.

Health correlates of experiential and behavioral avoidance among trauma-exposed veterans.

INTRODUCTION: Avoidance is a well-documented risk factor for poor mental and physical health outcomes. However, limited research has explored this relationship specifically among trauma-exposed veterans, a population known to be particularly prone to avoidance behavior. Conceptually, avoidance is often divided into two distinct but overlapping constructs - experiential avoidance (resisting distressing internal states) and behavioral avoidance (avoiding or changing experiences that elicit distress). In this exploratory survey study, we examined associations between behavioral and experiential avoidance and mental, physical, and cognitive functioning, as well as quality of life. METHODS: Veterans with a trauma history (N = 89) completed a 121-item survey containing validated assessments to examine several mental and physical health and wellness-related variables. Correlations between experiential avoidance and outcome measures, and behavioral avoidance and outcome measures, were explored. Multivariable linear regression analyses were conducted to explore the association between experiential and behavioral avoidance on mental health outcomes. In addition, we conducted exploratory analyses in which we investigated these correlations in those who screened positive for PTSD versus those who did not, and between different types of behavioral avoidance and major outcomes. RESULTS: Experiential avoidance was moderately correlated with distress from depressive symptoms, distress related to past trauma, and health-related and cognitive dysfunction. Experiential Avoidance was weakly correlated with distress from anxiety symptoms and poorer quality of life. Behavioral avoidance was moderately correlated with distress from depressive and anxiety symptoms, distress related to past trauma, and cognitive dysfunction, and was weakly correlated with health-related dysfunction and poorer quality of life. Results from multivariable analyses revealed that experiential avoidance was associated with greater distress related to depressive symptoms and past trauma, and behavioral avoidance was associated with greater distress related to anxiety symptoms, depressive symptoms, and past trauma. CONCLUSIONS: Results suggest that avoidance negatively influences major domains of mental and physical health as well as functioning and health-related quality of life in trauma-exposed veterans. They further indicate that behavioral and experiential avoidance may be differentially linked to mental health outcomes. The results support the idea that avoidance may be an important marker for psychosocial functioning and may serve as a treatment target in trauma-exposed veterans.

Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice.

Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments-a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD.

Mechanosensory bristles mediate avoidance behavior by triggering sustained local motor activity in Drosophila melanogaster.

During locomotion, most vertebrates-and invertebrates such as Drosophila melanogaster-are able to quickly adapt to terrain irregularities or avoid physical threats by integrating sensory information along with motor commands. Key to this adaptability are leg mechanosensory structures, which assist in motor coordination by transmitting external cues and proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers remains poorly understood. Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg mechanosensory bristles (MsBs) and the femoral chordotonal organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsBs triggered a fast response and sustained motor activity dependent only on the ventral nerve cord (VNC). Moreover, this leg-MsB-mediated movement lacked inter- and intra-leg coordination but preserved antagonistic muscle activity within joints. Finally, we show that leg-MsB activation mediates strong avoidance behavior away from the stimulus source, which is preserved even in the absence of a central brain. Overall, our data show that mechanosensory stimulation can elicit a fast motor response, independently of central brain commands, to evade potentially harmful stimuli. In addition, it sheds light on how specific sensory circuits modulate motor control, including initiation of movement, allowing a better understanding of how different levels of coordination are controlled by the VNC and central brain locomotor circuits.

Anandamide Modulates Thermal Avoidance in Caenorhabditis elegans Through Vanilloid and Cannabinoid Receptor Interplay.

Understanding the endocannabinoid system in C. elegans may offer insights into basic biological processes and potential therapeutic targets for managing pain and inflammation in human. It is well established that anandamide modulates pain perception by binding to cannabinoid and vanilloid receptors, regulating neurotransmitter release and neuronal activity. One objective of this study was to demonstrate the suitability of C. elegans as a model organism for assessing the antinociceptive properties of bioactive compounds and learning about the role of endocannabinoid system in C. elegans. The evaluation of the compound anandamide (AEA) revealed antinociceptive activity by impeding C. elegans nocifensive response to noxious heat. Proteomic and bioinformatic investigations uncovered several pathways activated by AEA. Enrichment analysis unveiled significant involvement of ion homeostasis pathways, which are crucial for maintaining neuronal function and synaptic transmission, suggesting AEA's impact on neurotransmitter release and synaptic plasticity. Additionally, pathways related to translation, protein synthesis, and mTORC1 signaling were enriched, highlighting potential mechanisms underlying AEA's antinociceptive effects. Thermal proteome profiling identified NPR-32 and NPR-19 as primary targets of AEA, along with OCR-2, Cathepsin B, Progranulin, Transthyretin, and ribosomal proteins. These findings suggest a complex interplay between AEA and various cellular processes implicated in nociceptive pathways and inflammation modulation. Further investigation into these interactions could provide valuable insights into the therapeutic potential of AEA and its targets for the management of pain-related conditions.

Reduced threat avoidance but increased stress induced approach bias in women taking oral contraceptives.

Recent research has increasingly acknowledged the impact of oral contraceptives on affective behavior and stress responses; however, the underlying mechanisms are still not well understood. Studies have previously shown that steroid hormones modulate automatic approach and avoidance behavior. Here, we thus investigated the effects of oral contraceptives on approach and avoidance behavior and whether these effects are modulated by stress. The study comprised 130 female participants, half of whom were using oral contraceptives, while the other half were not using any hormonal contraception (NC). The participants completed the Approach Avoidance Task (AAT), which measures automatic approach and avoidance behavior to socio-affective signals. The AAT was run once before and once after a stress manipulation using the Socially Evaluated Cold Pressor Test. OC users showed absent avoidance behavior to social threat signals and a stress-induced increase in approach behavior to positive social signals. The latter was found in particular in women taking androgenic acting OC, demonstrating that different OC preparations need to be taken into account in research on OC effects. However, OC and NC group did not differ in their cortisol stress response. Overall, the results suggest that OC usage impacts on approach and avoidance behavior to social signals, which might also contribute to the development of affective side effects.

The neurocomputational link between defensive cardiac states and approach-avoidance arbitration under threat.

Avoidance, a hallmark of anxiety-related psychopathology, often comes at a cost; avoiding threat may forgo the possibility of a reward. Theories predict that optimal approach-avoidance arbitration depends on threat-induced psychophysiological states, like freezing-related bradycardia. Here we used model-based fMRI analyses to investigate whether and how bradycardia states are linked to the neurocomputational underpinnings of approach-avoidance arbitration under varying reward and threat magnitudes. We show that bradycardia states are associated with increased threat-induced avoidance and more pronounced reward-threat value comparison (i.e., a stronger tendency to approach vs. avoid when expected reward outweighs threat). An amygdala-striatal-prefrontal circuit supports approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating reward-threat value and bradycardia states. These findings highlight the role of human freezing states in value-based decision making, relevant for optimal threat coping. They point to a specific role for amygdala/dACC in state-value integration under threat.

Pain experience reduces social avoidance to others in pain: a c-Fos-based functional connectivity network study in mice.

Pain experience increases individuals' perception and contagion of others' pain, but whether pain experience affects individuals' affiliative or antagonistic responses to others' pain is largely unknown. Additionally, the neural mechanisms underlying how pain experience modulates individuals' responses to others' pain remain unclear. In this study, we explored the effects of pain experience on individuals' responses to others' pain and the underlying neural mechanisms. By comparing locomotion, social, exploration, stereotyped, and anxiety-like behaviors of mice without any pain experience (naïve observers) and mice with a similar pain experience (experienced observers) when they observed the pain-free demonstrator with intraperitoneal injection of normal saline and the painful demonstrator with intraperitoneal injection of acetic acid, we found that pain experience of the observers led to decreased social avoidance to the painful demonstrator. Through whole-brain c-Fos quantification, we discovered that pain experience altered neuronal activity and enhanced functional connectivity in the mouse brain. The analysis of complex network and graph theory exhibited that functional connectivity networks and activated hub regions were altered by pain experience. Together, these findings reveal that neuronal activity and functional connectivity networks are involved in the modulation of individuals' responses to others' pain by pain experience.