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Rationale: Alcohol consumption despite negative consequences is a core symptom of Alcohol Use Disorder. In animal models, this is studied by pairing aversive stimuli with alcohol access, and continuation of drinking under these conditions is known as aversion resistance. Previously, we found that female mice are more aversion resistant than males. Corticotropin releasing hormone (Crh) and the Crh receptor 1 (Crhr1) regulate stress-induced reinstatement, alcohol dependence, and binge-like drinking. However, the role of the Crh system in aversion resistance has not been assessed. Objectives: We aimed to identify sex differences in the Crh system during quinine-adulterated alcohol intake. Methods: We used two-bottle choice and adulterated the alcohol solution with quinine. Next, we measured Crh and Crhr1 levels in brain tissue using real-time polymerase chain reaction (RT-qPCR) and RNAscope in situ hybridization. We then infused a Crhr1 antagonist into the medial prefrontal cortex (mPFC) prior to quinine-alcohol intake. Results: After quinine-alcohol consumption, females exhibited increased mPFC Crhr1 mRNA levels as measured by RT-qPCR. This was confirmed with greater anatomical specificity using RNAscope, with females exhibiting an increased number of Crhr1 + cells in the dorsomedial PFC and the ventromedial PFC. mPFC Crhr1 antagonist treatment reduced quinine-alcohol consumption in females but did not impact consumption in males. Quinine-free alcohol intake was unaffected by Crhr1 antagonist treatment. Conclusions: Our findings suggest that Crhr1 in mPFC plays a role in aversion resistant alcohol intake in females. Future experiments will examine the sources of Crh innervation to the mPFC and their distinct roles in alcohol seeking. [ABSTRACT FROM AUTHOR]

Reward processing involves evaluation of stimuli to inform what an individual works to pursue or avoid. Patients with behavioral variant frontotemporal dementia (bvFTD) often display reward processing changes, including insensitivity to aversive stimuli. It is unknown how early in the disease course reward changes are detectable. We recruited mutation positive (symptomatic and asymptomatic) and negative members of families with known mutations in progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72). The sample included 4 groups: asymptomatic non-carriers (n = 34), asymptomatic carriers [Clinical Dementia Rating (CDR) 0, n = 16], mildly symptomatic carriers (CDR 0.5, n = 10) and bvFTD (sporadic and genetic, n = 45). A series of tasks utilized pleasant, unpleasant, and neutral olfactants to probe reward consumption and effort to obtain reward. A group by valence interaction showed unpleasant scent ratings were more positive in groups with greater disease severity [χ2(6) = 87.983, p < 0.001]. Mildly symptomatic carriers showed a small difference in ratings of pleasant and unpleasant stimuli, similar to bvFTD. In an effort task, where participants chose to avoid or receive scents, mildly symptomatic carriers and bvFTD chose to smell unpleasant scents more frequently than asymptomatic groups, with mildly symptomatic carriers exceeding bvFTD in their frequency of choosing to smell unpleasant scents. In this same task, motivated effort, determined by rate of button press, determined success at obtaining or avoiding scents. Success rate, calculated based on the number of responses where participants' button presses exceeded an individual threshold set in a practice trial, differed across groups (p = 0.048), driven by mildly symptomatic carriers, who were consistently unsuccessful. There was a group difference in variability in button press rate across trials (p = 0.007), driven by mildly symptomatic carriers who showed less varied effort between scents. These findings suggest alterations to reward functioning can be detected early in bvFTD, even before meeting diagnostic criteria. These results may aid in identifying distinctive, initial reward changes in bvFTD that can facilitate early and accurate diagnosis and inspire efforts to identify anatomic underpinnings of early symptomatic changes. [ABSTRACT FROM AUTHOR]

Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the taste bud) stemming from Penk+ neurons displayed diverse branching patterns and lacked stereotypical endings. The range in complexity observed for individual taste arbors from Penk+ neuronsmirrored the entire population, suggesting that taste arbor morphologies are not primarily regulated by the neuron type. Notably, the distinguishing feature of arbors from Penk+ neurons was their propensity to come within 110 nm (in apposition with) different types of taste-transducing cells within the taste bud. This finding is contrary to the expectation of genetically defined taste neuron types that functionally represent a single stimulus. Consistently, further investigation of Penk+ neuron function revealed that they are more likely to respond to innately aversive stimuli--sour, bitter, and high salt concentrations-- as compared with the full taste population. Penk+ neurons are less likely to respond to nonaversive stimuli--sucrose, umami, and low salt--compared with the full population. Our data support the presence of a genetically defined neuron type in the geniculate ganglion that is responsive to innately aversive stimuli. This implies that genetic expression might categorize peripheral taste neurons into hedonic groups, rather than simply identifying neurons that respond to a single stimulus. [ABSTRACT FROM AUTHOR]

Dynamic gain control of aversive signals enables adaptive behavioral responses. Although the role of amygdalar circuits in aversive processing is well established, the neural pathway for amplifying aversion remains elusive. Here, we show that the brainstem circuit linking the interpeduncular nucleus (IPN) with the nucleus incertus (NI) amplifies aversion and promotes avoidant behaviors. IPN GABA neurons are activated by aversive stimuli and their predicting cues, with their response intensity closely tracking aversive values. Activating these neurons does not trigger aversive behavior on its own but rather amplifies responses to aversive stimuli, whereas their ablation or inhibition suppresses such responses. Detailed circuit dissection revealed anatomically distinct subgroups within the IPN GABA neuron population, highlighting the NI-projecting subgroup as the modulator of aversiveness related to fear and opioid withdrawal. These findings unveil the IPN-NI circuit as an aversion amplifier and suggest potential targets for interventions against affective disorders and opioid relapse. • IPN GABA neurons encode aversive value • The activity of these neurons amplifies aversive responses • The IPN-NI pathway controls aversive evaluation and fear learning • This pathway strengthens the aversive response to opioid withdrawal Liang et al. demonstrate that the brainstem circuit from the interpeduncular nucleus (IPN) to the nucleus incertus (NI) is an aversion amplifier, offering potential therapeutic targets for affective disorders and opioid relapse prevention. [ABSTRACT FROM AUTHOR]

First impressions based on facial appearance affect our behaviour towards others. Since the same face will appear different across images, over time, and so on, our impressions may not be equally weighted across exposures but are instead disproportionately influenced by earlier or later instances. Here, we followed up on previous work which identified an anchoring effect, whereby higher attractiveness ratings were given to a person after viewing naturally varying images of their face presented in descending (high-to-low), rather than ascending (low-to-high), order of attractiveness of these images. In Experiment 1 (n = 301), we compared these 'descending' and 'ascending' conditions for unfamiliar identities by presenting six-image sequences. Although we found higher attractiveness ratings for the 'descending' condition, this small effect equated to only 0.22 points on a 1–7 response scale. In Experiment 2 (n = 307), we presented these six-image sequences in a random order and found no difference in attractiveness ratings given to these randomly ordered sequences when compared with those resulting from both our 'descending' and 'ascending' conditions. Further, we failed to detect an influence of the earlier images in these random sequences on attractiveness ratings. Taken together, we found no compelling evidence that anchoring could have an effect on real-world impression formation. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the spatial frequency (SF) of visual stimuli alters the perceived timing of subjective simultaneity. However, these studies have been limited to the effects of a single SF component. In this study, I measured and compared the points of subjective simultaneity (PSS) for audiovisual stimuli among low, high, and composited SF components. This experiment comprised a dual-presentation timing task and a ternary response format to eliminate response bias. The results indicated that the PSS value of the composition-SF stimuli was more toward visual-lead timing than the low-SF stimuli and did not differ significantly from that of the high-SF stimuli. The correlation coefficients showed that the PSS in composition-SF stimuli marginally approximated that of high-SF stimuli higher than that of low-SF stimuli. Future studies are needed to confirm these findings using visual stimuli with a wider range of SF components and with a modulated contrast. [ABSTRACT FROM AUTHOR]

The hegemonic use of electric shock as an aversive stimulus limits what is known about the generality of avoidance behavior and related phenomena. The purpose of this study was to investigate the effects of using the hot air blast (HAB) instead of electric shock as an aversive stimulus in avoidance conditioning. Four male Wistar rats were exposed to a discrete‐trial procedure. In the first phase, the emission of a lever‐press response during a trial was positively reinforced. In the second phase, the same contingency was employed, but an escapable HAB was presented at the end of a trial when no response was emitted. In the third phase, positive reinforcement was suspended and a discrete‐trial avoidance procedure was employed. In the fourth phase, HAB presentation was completely suspended. As a result, all subjects learned the avoidance response and showed a marked reduction in its frequency during HAB suspension. These results offer evidence indicating that avoidance behavior is controlled by the HAB, thereby advancing the understanding of the generality of this stimulus as being aversive. [ABSTRACT FROM AUTHOR]

Learning safe versus dangerous cues is crucial for survival. During development, parents can influence fear learning by buffering their children's stress response and increasing exploration of potentially aversive stimuli. Rodent findings suggest that these behavioral effects are mediated through parental presence modulation of the amygdala and medial prefrontal cortex (mPFC). Here, we investigated whether similar parental modulation of amygdala and mPFC during fear learning occurs in humans. Using a within‐subjects design, behavioral (final N = 48, 6–17 years, mean = 11.61, SD = 2.84, 60% females/40% males) and neuroimaging data (final N = 39, 6–17 years, mean = 12.03, SD = 2.98, 59% females/41% males) were acquired during a classical fear conditioning task, which included a CS+ followed by an aversive noise (US; 75% reinforcement rate) and a CS−. Conditioning occurred once in physical contact with the participant's parent and once alone (order counterbalanced). Region of interest analyses examined the unconditioned stress response by BOLD activation to the US (vs. implicit baseline) and learning by activation to the CS+ (vs. CS−). Results showed that during US presentation, parental presence reduced the centromedial amygdala activity, suggesting buffering of the unconditioned stress response. In response to learned stimuli, parental presence reduced mPFC activity to the CS+ (relative to the CS−), although this result did not survive multiple comparisons' correction. These preliminary findings indicate that parents modulate amygdala and mPFC activity during exposure to unconditioned and conditioned fear stimuli, potentially providing insight into the neural mechanisms by which parents act as a social buffer during fear learning. Research Highlights: This study used a within‐participant experimental design to investigate how parental presence (vs. absence) affects youth's neural responses in a classical fear conditioning task.Parental presence reduced the youth's centromedial amygdala activation to the unconditioned stimulus (US), suggesting parental buffering of the neural unconditioned response (UR).Parental presence reduced the youth's mPFC activation to a conditioned threat cue (CS+) compared to a safety cue (CS−), suggesting possible parental modulation of fear learning. [ABSTRACT FROM AUTHOR]

Depression is closely related to suicidal ideation (SI); however, it is unclear who is most vulnerable to SI within the context of depression. Research suggests that individual differences in emotion reactivity and regulation may be potential moderators of the link between depression and SI. Therefore, the current study tested this hypothesis using objective markers of emotion reactivity and volitional cognitive regulation capacity during functional magnetic resonance imaging (fMRI). Adults (n = 91) with active SI completed validated self-report measures of current depressive symptoms and SI severity. Participants completed an fMRI task designed to probe neural response to aversive stimuli and during cognitive reappraisal – a form of volitional emotion regulation. Activation of the amygdala during aversive emotion reactivity was measured. Activation of ventrolateral, dorsolateral, and dorsomedial prefrontal cortex (vlPFC, dlPFC, and dmPFC) during cognitive reappraisal were also measured. A series of hierarchical linear regressions testing the unique and interactive effects of depression symptoms and neural activation on severity of SI were conducted. Analyses revealed a depression x amygdala activation interaction. The positive association between depression and SI severity was more robust in the context of high amygdala reactivity than low amygdala reactivity. Analyses also indicated there was no PFC activity (neural cognitive reappraisal) by depression interaction. Psychoactive medications were allowed and all participants endorsed suicidal intent. Strategies aimed at targeting exaggerated emotion reactivity within the context of depression may be beneficial. • Emotion processing may impact the link between depression and suicide. • We tested neural markers of emotion reactivity and regulation as moderators. • Depression coupled with high emotion reactivity may increase suicide risk. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does antidepressant discontinuation increase amygdala reactivity to aversive stimuli, and is this increase associated with a risk of depression relapse? Findings: In this study, discontinuation of antidepressant medication increased amygdala response to negative facial expressions in individuals who eventually relapsed. The increase was associated with the risk of relapse. Meaning: The findings suggest that modulation of amygdala reactivity by antidepressant medications may represent a mechanism by which antidepressant medications help maintain remission and that how antidepressant discontinuation increases may affect relapse risk. This study evaluates the association of amygdala reactivity with negative facial emotions, antidepressant discontinuation, and relapse. Importance: Antidepressant discontinuation substantially increases the risk of a depression relapse, but the neurobiological mechanisms through which this happens are not known. Amygdala reactivity to negative information is a marker of negative affective processes in depression that is reduced by antidepressant medication, but it is unknown whether amygdala reactivity is sensitive to antidepressant discontinuation or whether any change is related to the risk of relapse after antidepressant discontinuation. Objective: To investigate whether amygdala reactivity to negative facial emotions changes with antidepressant discontinuation and is associated with subsequent relapse. Design, Setting, and Participants: The Antidepressiva Absetzstudie (AIDA) study was a longitudinal, observational study in which adult patients with remitted major depressive disorder (MDD) and currently taking antidepressants underwent 2 task-based functional magnetic resonance imaging (fMRI) measurements of amygdala reactivity. Patients were randomized to discontinuing antidepressants either before or after the second fMRI measurement. Relapse was monitored over a 6-month follow-up period. Study recruitment took place from June 2015 to January 2018. Data were collected between July 1, 2015, and January 31, 2019, and statistical analyses were conducted between June 2021 and December 2023. The study took place in a university setting in Zurich, Switzerland, and Berlin, Germany. Of 123 recruited patients, 83 were included in analyses. Of 66 recruited healthy control individuals matched for age, sex, and education, 53 were included in analyses. Exposure: Discontinuation of antidepressant medication. Outcomes: Task-based fMRI measurement of amygdala reactivity and MDD relapse within 6 months after discontinuation. Results: Among patients with MDD, the mean (SD) age was 35.42 (11.41) years, and 62 (75%) were women. Among control individuals, the mean (SD) age was 33.57 (10.70) years, and 37 (70%) were women. Amygdala reactivity of patients with remitted MDD and taking medication did not initially differ from that of control individuals (t125.136 = 0.33; P =.74). An increase in amygdala reactivity after antidepressant discontinuation was associated with depression relapse (3-way interaction between group [12W (waited) vs 1W2 (discontinued)], time point [MA1 (first scan) vs MA2 (second scan)], and relapse: β, 18.9; 95% CI, 0.8-37.1; P =.04). Amygdala reactivity change was associated with shorter times to relapse (hazard ratio, 1.05; 95% CI, 1.01-1.09; P =.01) and predictive of relapse (leave-one-out cross-validation balanced accuracy, 67%; 95% posterior predictive interval, 53-80; P =.02). Conclusions and Relevance: An increase in amygdala reactivity was associated with risk of relapse after antidepressant discontinuation and may represent a functional neuroimaging marker that could inform clinical decisions around antidepressant discontinuation. [ABSTRACT FROM AUTHOR]

Parental behavior comprises a set of crucial actions essential for offspring survival. In this study, a double transgenic mouse model engineered to specifically express channelrhodopsin-2 (ChR2) in paraventricular hypothalamic nucleus (PVN)–oxytocin neurons and ablate lateral hypothalamic area (LHA)–melanin-concentrating hormone (MCH) neurons was used to determine the relationship between PVN–oxytocin neurons and LHA–MCH neurons associated with parental behavior. Optogenetic stimulation of ChR2-expressing PVN–oxytocin neurons induces typical parental behavior with intact LHA–MCH neurons. However, after the partial ablation of LHA–MCH neurons, even optogenetic stimulation of PVN–oxytocin neurons failed to induce parental behavior in virgin male mice, resulting in neglect rather than parental behavior. Furthermore, approximately half of the subjects exhibited burying behavior toward pups, suggesting that pups became aversive stimuli, and male mice actively performed burying behavior to avoid these aversive stimuli. This study emphasizes the novel aspect of oxytocin neurons that could result in neglect in the absence of LHA–MCH neurons regulation. [ABSTRACT FROM AUTHOR]

Safety learning allows the identification of non-threatening situations, a learning process instrumental for survival and psychic health. In contrast to fear learning, in which a sensory cue (conditioned stimulus, CS) is temporally linked to a mildly aversive stimulus (US), safety learning is studied by presenting the CS and US in an explicitly unpaired fashion. This leads to conditioned inhibition of fear responses, in which sensory cues can acquire a safety meaning (CS-). In one variant of safety learning, an auditory CS- was shown to reduce contextual fear responses during recall, as measured by freezing of mice. Here, we performed control experiments to test whether auditory stimuli might interfere with freezing by mechanisms other than safety learning, a phenomenon also called external inhibition. Surprisingly, when auditory stimulation was omitted during training (US-only controls), such stimuli still significantly suppressed contextual freezing during recall, indistinguishable from the reduction of freezing after regular safety training. The degree of this external inhibition was positively correlated with the levels of contextual freezing preceding the auditory stimulation. Correspondingly, in fear learning protocols which employ a new context during recall and therefore induce lower contextual freezing, auditory stimuli did not induce significant external inhibition. These experiments show that in safety learning protocols that employ contextual freezing, the freezing reduction caused by auditory stimuli during recall is dominated by external inhibition, rather than by learned safety. Thus, in safety learning experiments extensive controls should be performed to rule out possible intrinsic effects of sensory cues on freezing behavior. [ABSTRACT FROM AUTHOR]

Introduction: Altered subjective visual sensitivity manifests as feelings of discomfort or overload elicited by intense and irritative visual stimuli. This can result in a host of visual aberrations including visual distortions, elementary visual hallucinations and visceral responses like dizziness and nausea, collectively referred to as "pattern glare." Current knowledge of the underlying neural mechanisms has focused on overall excitability of the visual cortex, but the individual contribution of excitatory and inhibitory systems has not yet been quantified. Methods: In this study, we focus on the role of glutamate and ?-aminobutyric acid (GABA) as potential mediators of individual differences in subjective visual sensitivity, measured by a computerized Pattern Glare Test--a series of monochromatic square-wave gratings with three different spatial frequencies, while controlling for psychological variables related to sensory sensitivity with multiple questionnaires. Resting neurotransmitter concentrations in primary visual cortex (V1) and right anterior insula were studied in 160 healthy participants using magnetic resonance spectroscopy. Results: Data showed significant differences in the perception of visual distortions (VD) and comfort scores between men and women, with women generally reporting more VD, and therefore the modulatory effect of sex was considered in a further examination. A general linear model analysis showed a negative effect of occipital glutamate on a number of reported visual distortions, but also a significant role of several background psychological traits. When assessing comfort scores in women, an important intervening variable was the menstrual cycle. Discussion: Our findings do not support that baseline neurotransmitter levels have a significant role in overreactivity to aversive stimuli in neurotypical population. However, we demonstrated that biological sex can have a significant impact on subjective responses. Based on this additional finding, we suggest that future studies investigate aversive visual stimuli while examining the role of biological sex. [ABSTRACT FROM AUTHOR]

Objective: The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB1), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB1 have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB1 receptors and TRPV1 channels in learned fear processing. Methods: We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning. Results: TRPV1 and CB1 receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB1 restrains fear responses. Conclusion: TRPV1 and CB1 seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to take blood from pigs or minipigs, they are often secured using a maxillary sling. The animals express strong vocalisations, and the procedure subjectively appears to be stressful for the animals. In the present study, 12 Ellegaard minipigs were operantly conditioned to tolerate blood sampling from the neck without restraint by using positive reinforcement. The aim was to initially quantify the extent of stress during blood sampling; to prove whether minipigs can be trained to tolerate aversive stimuli, such as the insertion of a cannula without fixation; and to prove whether stress can be reduced through training. After an initial blood sample with fixation in the maxillary sling, the animals were trained for 3 weeks, and then blood was taken again, but without fixation. Blood and saliva samples were taken to determine cortisol concentration. Heart rate was measured before and during blood sampling. The results showed no difference in the cortisol concentration in serum between trained and untrained animals, while it was significantly lower in saliva after blood sampling in the trained animals, as was the heart rate. The training proved to be a suitable method to reduce stress when taking blood from pigs. Pigs (and minipigs) are often restrained with a maxillary sling for blood collection. They mainly produce strong vocalisations and show resistance to the procedure, which subjectively appears to be stressful for the animals. The present study investigated whether minipigs can be trained to tolerate aversive stimuli and whether training can reduce stress during blood collection. Blood was taken from 12 Ellegaard minipigs with fixation; thereafter, the animals were trained for 3 weeks using clicker training. Then, blood was taken again, but without fixation. Before and after each blood sample, saliva samples were taken. The cortisol concentration was determined using ELISAs. Serum cortisol was not significantly different before and after training (paired-sample t-test, t (9) = 2.052, p = 0.07). However, salivary cortisol was significantly lower after training (ANOVA (analysis of variance), p-value < 0.001, F-value 6.181). In addition, trained minipigs showed a significantly lower heart rate after blood sampling (paired-sample t-test, t (11) = 4.678, p = 0.001) as well as significantly lower heart rate variability (t (11) = 3.704, p = 0.003) compared to before training. The minipigs could be trained to tolerate aversive stimuli. This contributed to stress reduction when taking blood samples. [ABSTRACT FROM AUTHOR]

The ability to flexibly transition between defensive states is crucial for adaptive responding in life‐threatening situations. Potentially threatening situations typically induce a sustained feeling of apprehension in association with hypervigilance, while acute threat is usually characterized by an intense and transient response to cope with the imminent danger. While potential and acute threat states have traditionally been viewed as mutually exclusive, this distinction is being challenged by a growing body of evidence suggesting a more complex interplay during simultaneous activation of these states. However, the interaction between potential and acute threat on a psychophysiological level remains elusive. To fill this gap, 94 healthy individuals participated in one of two contextual fear‐conditioning paradigms. In both paradigms, a differential fear‐learning phase was conducted, followed by a test phase in which the conditioned stimuli were presented in front of either conditioned or inherently aversive contextual images compared to neutral contexts. To capture defensive responses, we recorded subjective (threat and expectancy ratings) and physiological (electrodermal and cardiovascular) activity to the conditioned stimuli as a function of contextual threat. Besides indices of successful fear conditioning, our results revealed stronger threat and unconditioned stimulus expectancy ratings, cardiac deceleration, and skin conductance responses for threat and safety cues presented in inherently aversive compared to neutral contexts. Conditioned contexts had less impact on physiological responses to threat and safety cues than inherently aversive contexts. These findings provide new insights into the additive nature of defensive responses to fear cues and situations of contextual threat. Recent research challenges the idea that defensive states induced by potential and acute threat are mutually exclusive. In this study, we observed enhanced defensive responses to acute threat stimuli during aversive contexts as indexed by heart rate and skin conductance responses, indicating an interplay between potential and acute threat states that is influenced by contextual threat levels. [ABSTRACT FROM AUTHOR]

Research on media's effects on body perception has mainly focused on the role of vision of extreme body types. However, haptics is a major part of the way children experience bodies. Playing with unrealistically thin dolls has been linked to the emergence of body image concerns, but the perceptual mechanisms remain unknown. We explore the effects of haptic experience of extreme body types on body perception, using adaptation aftereffects. Blindfolded participants judged whether the doll-like stimuli explored haptically were thinner or fatter than the average body before and after adaptation to an underweight or overweight doll. In a second experiment, participants underwent a traditional visual adaptation paradigm to extreme bodies, using stimuli matched to those in Experiment 1. For both modalities, after adaptation to an underweight body test bodies were judged as fatter. Adaptation to an overweight body produced opposite results. For the first time, we show adiposity aftereffects in haptic modality, analogous to those established in vision, using matched stimuli across visual and haptic paradigms. [ABSTRACT FROM AUTHOR]

Psychopathy in women has gained the attention of the scientific community, but research on the emotional processing in individuals with psychopathic traits and its role in criminal behavior is still scarce. The present systematic review aims to aggregate existing literature that analyze emotional processing in women with psychopathy traits. The search terms, conducted in six databases, identified 13 relevant studies, meeting the following criteria: women, 18 years or older, prison or community contexts, and written in English, Spanish, or Portuguese. Studies pointed to a compromise in the understanding, management, and categorization of emotions, especially those with negative valence, and the presence of alexithymia in women with higher scores of psychopathic traits. Some studies revealed that women with psychopathy had reduced limbic activation, cortical deficits in emotional processing, and an absence of aversive startle response when exposed to aversive stimuli. Significant relationships between psychopathic traits, heart rate, and skin conductance response were documented. Additionally, the interpersonal-affective facet of psychopathy was linked to emotion management difficulties, while the antisocial-impulsive dimension seems linked to alexithymia and deficits in the processing of negatively valenced emotions. These findings carry practical implications for interventions with psychopathic women. [ABSTRACT FROM AUTHOR]

The role of the cerebellum in emotional control has gained increasing interest, with studies showing it is involved in fear learning and memory in both humans and rodents. This review will focus on the contributions of the cerebellum to the extinction of learned fear responses. Extinction of fearful memories is critical for adaptive behaviour, and is clinically relevant to anxiety disorders such as post-traumatic stress disorder, in which deficits in extinction processes are thought to occur. We present evidence that supports cerebellar involvement in fear extinction, from rodent studies that investigate molecular mechanisms and functional connectivity with other brain regions of the known fear extinction network, to fMRI studies in humans. This evidence is considered in relation to the theoretical framework that the cerebellum is involved in the formation and updating of internal models of the inner and outer world by detecting errors between predicted and actual outcomes. In the case of fear conditioning, these internal models are thought to predict the occurrence of an aversive unconditioned stimulus (US), and when the aversive US is unexpectedly omitted during extinction learning the cerebellum uses prediction errors to update the internal model. Differences between human and rodent studies are highlighted to help inform future work. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterials and methodsResultsConclusionsTo evaluate the efficacy of an immersive movement visualization intervention in patients with hemophilia and hemophilic knee arthropathy.Randomized, single-blind clinical study. Twenty-eight patients with hemophilia were recruited. Patients were randomized to an experimental group (four weeks of immersive movement visualization) and a control group (no intervention). The intensity of pain, pressure pain threshold in the knee, tibialis anterior muscle, lower back level, conditioned pain modulation, range of knee motion, and lower limb functionality were evaluated.There were statistically significant differences in the intergroup effect on knee pain intensity (F = 23.71; p < 0.001) and lower limb functionality (F = 7.11; p = 0.003). 42.86% of the patients in the experimental group exhibited changes greater than the minimum detectable change (MDC) in functionality. 39.29% of the patients subject to the intervention experienced changes greater than the MDC in the knee pressure pain threshold.Immersive motion visualization can improve the intensity of joint pain and functionality in patients with hemophilic knee arthropathy. Functionality, pressure pain threshold, and pain intensity improved in those patients who conducted immersive movement visualization.Implications for rehabilitationImmersive visualization of movement significantly improves intensity of joint pain, functionality, pressure pain threshold, joint health, and conditioned pain modulation in patients with hemophilic knee arthropathy.The fact that it is a therapy without potential aversive stimuli makes it a possible access pathway for patients with high levels of kinesiophobia and/or catastrophism.This low-cost, home-based technology allows its use in patients far from hemophilia reference centers or with difficult access to physiotherapy treatments.The immersive visualization of movement influences the democratization of treatment, in accordance with the WHO's Sustainable Development Goal 3 (health and well-being for all).Immersive visualization of movement significantly improves intensity of joint pain, functionality, pressure pain threshold, joint health, and conditioned pain modulation in patients with hemophilic knee arthropathy.The fact that it is a therapy without potential aversive stimuli makes it a possible access pathway for patients with high levels of kinesiophobia and/or catastrophism.This low-cost, home-based technology allows its use in patients far from hemophilia reference centers or with difficult access to physiotherapy treatments.The immersive visualization of movement influences the democratization of treatment, in accordance with the WHO's Sustainable Development Goal 3 (health and well-being for all). [ABSTRACT FROM AUTHOR]

Background: Parasympathetic tone activity (PTA) in response to nociceptive stimulus in conscious non‐sedated horses is unknown. Objectives: Study PTA, heart rate (HR), and horse grimace scale (HGS) at rest and during mechanical nociceptive stimulation. Animals: Ninety healthy young adult horses (females, males): 30 each of Friesians, Quarter Horses, and Warmbloods. Methods: Prospective control study. The study consisted of habituation to equipment (Day 1), baseline recordings (Days 2 and 3), and nociceptive testing applying mild pressure to the metacarpus (Day 4). Parasympathetic tone, HR, and HGS were recorded simultaneously on Days 2 to 4. Each study lasted 30 minutes and was done in triplicate at 3 different time points per day. Results: Baseline PTA was not different among breeds. It decreased in Warmbloods and Quarter Horses during placement of the stimulus device without stimulation (P <.01). A significant decrease in PTA (P <.001) occurred during nociceptive stimulus (marked in Quarter Horses, intermediate in Warmbloods, and mild in Friesians). Heart rate and HGS increased significantly (P <.001) during the stimulus in all breeds but returned to baseline poststimulation. Friesians required higher pressure (P <.05) to elicit an aversive response to the stimulus. Conclusions: Horses' PTA, HR, and HGS change in response to a mild mechanical nociceptive stimulus with Friesians showing less variation. Stress induced a decrease in PTA in Quarter Horses and Warmbloods but not in Friesians. Friesians appeared to be more tolerant to pain based on PTA, HR, and HGS findings compared with other breeds. [ABSTRACT FROM AUTHOR]

Fear and anxiety are rarely confined to specific stimuli or situations. In fear generalisation, there is a spread of fear responses elicited by physically dissimilar generalisation stimuli (GS) along a continuum between danger and safety. The current study investigated fear generalisation with a novel online task using COVID-19-relevant stimuli (i.e., busy or quiet shopping street/mall scenes) during pandemic lockdown restrictions in the United Kingdom. Participants (N = 50) first completed clinically relevant trait measures before commencing a habituation phase, where two conditioned stimuli (CSs; i.e., a busy or quiet high street/mall scene) were presented. Participants then underwent fear conditioning where one conditioned stimulus (CS+) was followed by an aversive unconditioned stimulus (US; a loud female scream accompanied by a facial photograph of a female displaying a fearful emotion) and another (CS-) was not. In a test phase, six generalisation stimuli were presented where the US was withheld, and participants provided threat expectancy and fear ratings for all stimuli. Following successful conditioning, fear generalization was observed for both threat expectancy and fear ratings. Trait worry partially predicted generalised threat expectancy and COVID-19 fear strongly predicted generalised fear. In conclusion, a generalisation gradient was evident using an online remote generalisation task with images of busy/quiet streets during the pandemic. Worry and fear of COVID-19 predicted fear generalisation. [ABSTRACT FROM AUTHOR]

Learning is central to our understanding of how behaviour is shaped by the environment. A key open question is whether learning across contexts evolves as an integrated process, or whether learning in each context is free to evolve separately. Here, we measured learning in two sensory contexts in multiple genotypes and both sexes of two closely related, but ecologically divergent, species of fruit flies, Drosophila simulans and Drosophila sechellia. These species are morphologically very similar but differ dramatically in ecology and population biology. We tested how flies from each genotype, sex and species responded to and learned about different gustatory and visual cues. This approach allowed us to test whether species differences in learning were independent or correlated across contexts. Surprisingly, we found no evidence that D. simulans learned in any of our treatments. In contrast, D. sechellia learned to avoid gustatory stimuli that were paired with an aversive stimulus, as predicted, but unexpectedly learned to approach visual stimuli that were paired with the aversive stimulus. At the genotype level, genotypes, but not species, differed in their naïve responses to stimuli, but genotypes did not differ in learning in either species. Our results demonstrate that D. sechellia indeed differs from D. simulans in both learning contexts, but in a stimulus-dependent way. We suggest that studies of additional species or population pairs that employ this framework will be critical for evaluating the dimensionality of learning and its evolution. • We compared gustatory and visual learning in genotypes of two Drosophila species. • Only D. sechellia (not D. simulans) learned to avoid gustatory + aversive stimuli. • Unexpectedly, D. sechellia also learned to approach visual + aversive stimuli. • Genotypes differed in naïve responses to stimuli but not in learning in either species. • The two species differed in both learning contexts in a stimulus-dependent way. [ABSTRACT FROM AUTHOR]

The Maternity Ring was developed as a free farrowing alternative to crates that preserved space whilst providing the sow with unrestricted movement. This experiment aimed to apply the Five Domains model to assess sow welfare in the Maternity Ring in comparison with the farrowing crate. Eighty-eight sows were housed in a farrowing crate (FC) and 83 in a Maternity Ring (MR), and measures collected focussed on nutrition, environment, health, behaviour, and mental state outcomes. MR sows consumed less feed than FC sows (total feed intake: 93.8  ±  3.06  kg vs. 111.2  ±  3.13  kg; p  <  0.001) but had reduced P2 backfat loss during lactation (0.0  ±  0.11 vs. 1.2  ±  0.11, p  <  0.001). Fewer frustrated and pain-related behaviours during farrowing were observed in MR sows (bar biting: FC 3.3  ±  2.12 vs. MR 0.5  ±  0.29 events, p  =  0.038, and back leg forward: FC 227  ±  50.7 vs. MR 127  ±  26.4 events, p  =  0.019), and a decreased proportion of MR sows had facial injuries after farrowing (10% CI [5, 20] vs. 67% CI [47, 95], p  <  0.001). More FC sows had udder damage at weaning (70% CI [48, 97] vs. 10% CI [6, 24], p  <  0.001), and their piglets were medicated more frequently when compared to those in MR (51% CI [40, 61] vs. 30% [21, 41], p  =  0.008). MR sows tended to have a higher reaction score to piglet processing (MR 2.0  ±  0.38 vs. FC 1.2  ±  0.27, p  =  0.094) and had more contact with piglets once the procedure was complete than FC sows (13.5  ±  2.55 vs. 6.9  ±  1.26 events, respectively, p  =  0.016). Whilst there was no difference in anticipation of a feeding event (p  >  0.05), MR sows displayed a reduced startle response to an aversive noise stimulus at day 18 (FC 2.8  ±  0.35, MR 0.7  ±  0.16, p  <  0.001). Using the Five Domains framework, sows housed in the MR during farrowing and lactation have improved welfare than those in FC and can be thought of as being in a positive affective state. [ABSTRACT FROM AUTHOR]

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• The estrous cycle does not affect the innate startle but influences fear learning. • In high-anxious females, hormonal increase during proestrus reduces learned fear. • In BLA, 5-HT reduces potentiated startle by combining with estrous cycle hormones. • In BLA, 5-HT interacts with female hormones likely through 5-HT1A receptors. • DPAG stimulation of high-anxious females increases the response to stressful stimuli. Despite significant advances in the study of fear and fear memory formation, little is known about fear learning and expression in females. This omission has been proven surprising, as normal and pathological behaviors are highly influenced by ovarian hormones, particularly estradiol and progesterone. In the current study, we investigated the joint influence of serotonin (5-HT) neurotransmission and estrous cycle phases (low or high levels of estradiol and progesterone) on the expression of conditioned fear in a group of female rats that were previously divided according to their response to stressful stimuli into low or high anxiety-like subjects. The baseline amplitude of the unconditioned acoustic startle responses was high in high-anxiety female rats, with no effect on the estrous cycle observed. Data collected during the proestrus-estrus phase revealed that low-anxiety rats had startle amplitudes similar to those of high-anxiety rats. It is supposed that high-anxiety female rats benefit from increased estradiol and progesterone levels to achieve comparable potentiated startle amplitudes. In contrast, female rats experienced a significant decrease in hormone levels during the Diestrus phase. This decrease is believed to play a role in preventing them from displaying a heightened startle response when faced with strongly aversive stimuli. Data collected after 5-HT and 8-OH-DPAT were administered into the basolateral nuclei and dorsal periaqueductal gray suggest that 5-HT neurotransmission works with progesterone and estrogen to reduce startle potentiation, most likely by activating the serotonin-1A receptor subtype. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has increased germ aversion, an aversive affective response to a high likelihood of pathogen transmission. While psychological factors are associated with chronic pain, the relationship between germ aversion and chronic pain remains unexplored. This study aimed to examine the relationship between germ aversion and new-onset and prognosis of chronic pain using longitudinal data collected during the COVID-19 pandemic. We conducted web-based surveys of full-time workers at baseline and after three months. Data were collected on demographic characteristics, psychological factors, and chronic pain. Germ aversion was assessed using a modified Perceived Vulnerability to Disease scale. We analyzed responses from 1265 panelists who completed the survey twice. The prevalence of chronic low back pain (CLBP) and chronic neck and shoulder pain (CNSP) was associated with sex, short sleep duration, psychological distress, loneliness, and germ aversion. Stratified analyses showed that germ aversion was a risk factor for CLBP at three months in both individuals with and without CLBP at baseline, and for CNSP at three months in those with CNSP at baseline, even after adjustment for confounders. In conclusion, this preliminary study suggests that high germ aversion is a risk factor for CLBP and CNSP in young and middle-aged workers. [ABSTRACT FROM AUTHOR]

Research highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusive. Here, LHb neurons are found projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and median raphe nucleus (MnR) exhibit increased bursting following aversive stimuli exposure, correlating with distinct depressive symptoms. Enhanced bursting in DRN‐projecting LHb neurons is pivotal for anhedonia and anxiety, while concurrent bursting in LHb neurons projecting to the DRN, VTA, and MnR is essential for despair. Remarkably, reducing bursting in distinct LHb neuron subpopulations underlies the therapeutic effects of BLT on specific depressive behaviors. These findings provide valuable insights into the mechanisms of depression and the antidepressant action of BLT. [ABSTRACT FROM AUTHOR]

To adapt to threats in the environment, animals must predict them and engage in defensive behavior. While the representation of a prediction error signal for reward has been linked to dopamine, a neuromodulatory prediction error for aversive learning has not been identified. We measured and manipulated norepinephrine release during threat learning using optogenetics and a novel fluorescent norepinephrine sensor. We found that norepinephrine response to conditioned stimuli reflects aversive memory strength. When delays between auditory stimuli and footshock are introduced, norepinephrine acts as a prediction error signal. However, temporal difference prediction errors do not fully explain norepinephrine dynamics. To explain noradrenergic signaling, we used an updated reinforcement learning model with uncertainty about time and found that it explained norepinephrine dynamics across learning and variations in temporal and auditory task structure. Norepinephrine thus combines cognitive and affective information into a predictive signal and links time with the anticipation of danger. [ABSTRACT FROM AUTHOR]

Angiotensin receptor blockade has been linked to aspects of aversive learning and memory formation and to the prevention of posttraumatic stress disorder symptom development. We investigated the influence of the angiotensin receptor blocker losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized, placebo-controlled design, we tested 45 (18 female) healthy volunteers during a baseline session, after application of losartan or placebo (drug session), and during a follow-up session. During each session, participants engaged in a task in which they had to predict the probability of an electrical stimulation on every trial while the true shock contingencies switched repeatedly between phases of high and low shock threat. Computational reinforcement learning models were used to investigate learning dynamics. Acute administration of losartan significantly reduced participants' adjustment during both low-to-high and high-to-low threat changes. This was driven by reduced aversive learning rates in the losartan group during the drug session compared with baseline. The 50-mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out a general reduction in attention and engagement. Decreased adjustment of aversive expectations was maintained at a follow-up session 24 hours later. This study shows that losartan acutely reduces Pavlovian learning in aversive environments, thereby highlighting a potential role of the renin-angiotensin system in anxiety development. [ABSTRACT FROM AUTHOR]

Activity of central amygdala (CeA) PKCδ expressing neurons has been linked to appetite regulation, anxiety-like behaviors, pain sensitivity, and addiction-related behaviors. Studies of the role that CeA PKCδ+ neurons play in these behaviors have largely been carried out in mice, and genetic tools that would allow selective manipulation of PKCδ+ cells in rats have been lacking. Here, we used a CRISPR/Cas9 strategy to generate a transgenic Prkcd-cre knock-in rat and characterized this model using anatomical, electrophysiological, and behavioral approaches in both sexes. In the CeA, Cre was selectively expressed in PKCδ+ cells. Anterograde projections of PKCδ+ neurons to cortical regions, subcortical regions, several hypothalamic nuclei, the amygdala complex, and midbrain dopaminergic regions were largely consistent with published mouse data. In a behavioral screen, we found no differences between Cre+ rats and Cre− wild-type littermates. Optogenetic stimulation of CeA PKCδ+ neurons in a palatable food intake assay resulted in an increased latency to first feeding and decreased total food intake, once again replicating published mouse findings. Lastly, using a real-time place preference task, we found that stimulation of PKCδ+ neurons promoted aversion, without affecting locomotor activity. Collectively, these findings establish the novel Prkcd-Cre rat line as a valuable tool that complements available mouse lines for investigating the functional role of PKCδ+ neurons. [ABSTRACT FROM AUTHOR]

Attentional bias to threat has been almost exclusively examined after participants experienced repeated pairings between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US). This study aimed to determine whether threat-related attentional capture can result from observational learning, when participants acquire knowledge of the aversive qualities of a stimulus without themselves experiencing aversive outcomes. Non-clinical young-adult participants (N = 38) first watched a video of an individual (the demonstrator) performing a Pavlovian conditioning task in which one colour was paired with shock (CS+) and another colour was neutral (CS−). They then carried out visual search for a shape-defined target. Oculomotor measures evidenced an attentional bias toward the CS+ colour, suggesting that threat-related attentional capture can ensue from observational learning. Exploratory analyses also revealed that this effect was positively correlated with empathy for the demonstrator. Our findings extend empirical and theoretical knowledge about threat-driven attention and provide valuable insights to better understand the formation of anxiety disorders. [ABSTRACT FROM AUTHOR]

Previous evidence has suggested that feature-based templates-for-rejection can be maintained in working memory to suppress matching features in the environment. Currently, this effect has only been demonstrated using abstract neutral shapes, meaning that it is unclear whether this generalizes to real-world images, including aversive stimuli. In the current investigation, participants searched amongst an array of real-world objects for a target, after being precued with either a distractor template, target template, or a no template baseline. In Experiment 1, where both distractor and target template cues were presented randomly on a trial-by-trial basis, there was moderate evidence of increased capture by aversive distractors after the distractor template cue. In Experiment 2a, however, when distractor templates were the only available cue and more time was given to encode the cue features, there was moderate evidence of effective distractor inhibition for real-world aversive and neutral stimuli. In Experiment 2b, when the task required a slower more effortful comparison of target features to stereotypical object representations, there was weaker evidence of inhibition, though there was still modest evidence suggesting effective inhibition of aversive distractors. A Bayesian meta-analysis revealed that across Experiment 2, aversive distractors showed strong cumulative evidence of effective inhibition, but inconsistent inhibition for neutral distractors. The results are interpreted from a rational search behaviour framework, which suggests that individuals utilize informative cues when they enable the most beneficial strategy and are accessible, and apply these to distractors when they cause sufficient disruption, either to search speed or emotional state. [ABSTRACT FROM AUTHOR]

Pain can be conceptualized as a precision signal for reinforcement learning in the brain and alterations in these processes are a hallmark of chronic pain conditions. Investigating individual differences in pain-related learning therefore holds important clinical and translational relevance. Here, we developed and externally validated a novel resting-state brain connectivity-based predictive model of pain-related learning. The pre-registered external validation indicates that the proposed model explains 8-12% of the inter-individual variance in pain-related learning. Model predictions are driven by connections of the amygdala, posterior insula, sensorimotor, frontoparietal, and cerebellar regions, outlining a network commonly described in aversive learning and pain. We propose the resulting model as a robust and highly accessible biomarker candidate for clinical and translational pain research, with promising implications for personalized treatment approaches and with a high potential to advance our understanding of the neural mechanisms of pain-related learning. A predictive model based on brain connectivity was developed to explain individual differences in pain learning. Focusing on brain regions linked to aversive learning and pain, this model shows promise as a biomarker in translational pain research. [ABSTRACT FROM AUTHOR]

Three experiments explored whether weakening temporal contiguity between auditory cues and an aversive outcome attenuated cue competition in an avoidance learning task with human participants. Overall, with strong temporal contiguity between auditory cues and the outcome during training (the offset of the predictive auditory signals concurred with the onset of the outcome), the target cue trained as part of a compound yielded less avoidance behaviour than the control cue trained alone, an instance of overshadowing. However, weakening temporal contiguity during training (inserting a 5-s trace) attenuated overshadowing, resulting in similar avoidance behaviour in response to the control and target cues. These results provide evidence that, as predicted by a recent modification of Pearce's configural theory, temporal contiguity is critical for determining cue competition. [ABSTRACT FROM AUTHOR]

In response to a suitably aversive skin stimulus, the marine mollusk Tritonia diomedea launches an escape swim followed by several minutes of high-speed crawling. The two escape behaviors are highly dissimilar: whereas the swim is a muscular behavior involving alternating ventral and dorsal whole body flexions, the crawl is a nonrhythmic gliding behavior mediated by the beating of foot cilia. The serotonergic dorsal swim interneurons (DSIs) are members of the swim central pattern generator (CPG) and also strongly drive crawling. Although the swim network is very well understood, the Tritonia crawling network to date comprises only three neurons: the DSIs and pedal neurons 5 and 21 (Pd5 and Pd21). Since Tritonia's swim network has been suggested to have arisen from a preexisting crawling network, we examined the possible role that another swim CPG neuron, C2, may play in crawling. Because of its complete silence in the postswim crawling period, C2 had not previously been considered to play a role in driving crawling. However, semi-intact preparation experiments demonstrated that a brief C2 spike train surprisingly and strongly drives the foot cilia for ∼30 s, something that cannot be explained by its synaptic connections to Pd5 and Pd21. Voltage-sensitive dye (VSD) imaging in the pedal ganglion identified many candidate crawling motor neurons that fire at an elevated rate after the swim and also revealed several pedal neurons that are strongly excited by C2. It is intriguing that unlike the DSIs, which fire tonically after the swim to drive crawling, C2 does so despite its postswim silence. NEW & NOTEWORTHY:Tritonia swim central pattern generator (CPG) neuron C2 surprisingly and strongly drives the early phase of postswim crawling despite being silent during this period. In decades of research, C2 had not been suspected of driving crawling because of its complete silence after the swim. Voltage-sensitive dye imaging revealed that the Tritonia crawling motor network may be much larger than previously known and also revealed that many candidate crawling neurons are excited by C2. [ABSTRACT FROM AUTHOR]

Society asks individuals, such as front-line medical and emergency personnel or social media moderators, to help others under highly negative emotional circumstances, and those individuals need to regulate their emotions for their own well being. A well-studied form of emotion regulation is reappraisal, the use of cognitive processes used to reinterpret initial emotional responses to negative events. Distancing (pretending that a situation is distant in time or space) is well documented to be an effective form of emotion regulation, but it may not be applicable in social contexts where individuals must engage with distressing events to help others. Here, for the first time, we asked whether a novel reappraisal strategy focused on Social Good–imagining that an aversive event is also an opportunity to prevent harm to others–can be an effective form of reappraisal. In a pre-registered experiment, participants were randomly assigned to Distancing or Social Good conditions as they viewed neutral or highly aversive images and then reported their subjective emotional states with or without reappraisal. Both Distancing and Social Good reappraisals led to significantly less negative affect. Distancing yielded a stronger effect, but importantly, participants reported both Distancing and Social Good as equally easy to employ and both were effective across multiple demographic and personality characteristics, indicating the broad value of both as effective forms of reappraisal. Across both reappraisal conditions, effective reappraisal increased with age and positive affect. These findings indicate that Social Good is an effective reappraisal strategy and raise the possibility that it could be particularly valuable in contexts in which emotionally demanding tasks are completed on behalf of the good for other people. [ABSTRACT FROM AUTHOR]

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior. The neurobiological mechanisms underlying the fast acting and long-lasting effects of these drugs are not fully understood. Here authors show that the psychedelic psilocin increases reactivity in the paraventricular nucleus of the hypothalamus (PVN) in male rats but does not change acute stress response. Male reactivity changes are driven by active threat responding, with clinical implications. [ABSTRACT FROM AUTHOR]

Reward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive punishment, which is defined as addition of an aversive stimulus, and negative punishment, involves the omission of a rewarding outcome. Although the medial prefrontal cortex (mPFC) is important in avoiding punishment, whether it is important for avoiding both positive and negative punishment and how it contributes to such avoidance are not clear. In this study, we trained male mice to perform decision-making tasks under the risks of positive (air-puff stimulus) and negative (reward omission) punishment, and modeled their behavior with reinforcement learning. Following the training, we pharmacologically inhibited the mPFC. We found that pharmacological inactivation of mPFC enhanced the reward-seeking choice under the risk of positive, but not negative, punishment. In reinforcement learning models, this behavioral change was well-explained as an increase in sensitivity to reward, rather than a decrease in the strength of aversion to punishment. Our results suggest that mPFC suppresses reward-seeking behavior by reducing sensitivity to reward under the risk of positive punishment. [ABSTRACT FROM AUTHOR]

The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well-established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within the BLA governs these modulatory effects. However, most current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a low-arousing, hippocampal-dependent task. Our experiments combined a weak object location task (OLT) version with subsequent mild predator odor exposure (POE). To investigate the role of endogenous NA in the BLA in memory modulation, a subset of the animals (Wistar rats) was treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected 90 min after drug infusion or after the OLT test, which was performed 24 h later. We used the obtained samples to estimate the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc)—two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE has the potential to become a valuable behavioral paradigm for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a debilitating psychosomatic condition characterized by impairment of brain fear circuits and persistence of exceptionally strong associative memories resistant to extinction. In this study, we investigated the neural and behavioral consequences of inhibiting protein synthesis, a process known to suppress the formation of conventional aversive memories, in an established PTSD animal model based on contextual fear conditioning in mice. Control animals were subjected to the conventional fear conditioning task. Utilizing c-Fos neural activity mapping, we found that the retrieval of PTSD and normal aversive memories produced activation of an overlapping set of brain structures. However, several specific areas, such as the infralimbic cortex and the paraventricular thalamic nucleus, showed an increase in the PTSD group compared to the normal aversive memory group. Administration of protein synthesis inhibitor before PTSD induction disrupted the formation of traumatic memories, resulting in behavior that matched the behavior of mice with usual aversive memory. Concomitant with this behavioral shift was a normalization of brain c-Fos activation pattern matching the one observed in usual fear memory. Our findings demonstrate that inhibiting protein synthesis during traumatic experiences significantly impairs the development of PTSD in a mouse model. These data provide insights into the neural underpinnings of protein synthesis-dependent traumatic memory formation and open prospects for the development of new therapeutic strategies for PTSD prevention. [ABSTRACT FROM AUTHOR]

Exposure therapy is a first-line, empirically validated treatment for anxiety, obsessivecompulsive, and trauma-related disorders. Extinction learning is the predominant theoretical framework for exposure therapy, whereby repeated disconfirmation of a feared outcome yields fear reduction over time. Although this framework has strong empirical support and substantial translational utility, extinction learning is unlikely to be the sole process underlying the therapeutic effects of exposure therapy. In our clinic, we commonly treat obsessive-compulsive disorder (OCD) patients successfully with exposure therapy even when some or all of their feared outcomes are not amenable to disconfirmation and, by extension, to extinction learning. Herein, we present a generic clinical vignette illustrating a commonly encountered feared outcome in OCD that cannot be disconfirmed through exposure (damnation resulting from blasphemous thoughts). We describe two specific non-extinction-based strategies we commonly employ in such cases, and we associate these strategies with known change mechanisms that might account for their effectiveness: (1) non-associative habituation to aversive stimuli, and (2) fear-memory elicitation and subsequent reconsolidation. We discuss the limitations inherent in the reverse-translational approach taken and its opportunities for expanding the framework of exposure therapy. [ABSTRACT FROM AUTHOR]

The article introduces the "SpiDa" dataset, which contains self-report questionnaires and ratings of spider images from individuals with spider phobia. Spider phobia is a common specific phobia, particularly in females, and can negatively impact quality of life. The dataset offers valuable insights into understanding and treating spider phobia, including subjective levels of fear, disgust, and willingness to approach spiders. The article explains the data collection methods and provides a codebook with descriptive statistics. This resource is useful for researchers investigating fear of spiders and related topics, although it has some limitations. The study was conducted ethically and received funding from various sources. [Extracted from the article]

Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system, yet their exact role in awake behaviors remains unclear. We performed bulk calcium measurements and electrophysiology with optogenetic tagging from the horizontal limb of the diagonal band of Broca (HDB) while male mice were performing an associative learning task. BFPVNs responded with a distinctive, phasic activation to punishment, but showed slower and delayed responses to reward and outcome-predicting stimuli. Optogenetic inhibition during punishment impaired the formation of cue-outcome associations, suggesting a causal role of BFPVNs in associative learning. BFPVNs received strong inputs from the hypothalamus, the septal complex and the median raphe region, while they synapsed on diverse cell types in key limbic structures, where they broadcasted information about aversive stimuli. We propose that the arousing effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions. Whether and how parvalbumin-expressing neural population from Basal forebrain (BFPVNs) nuclei play a role in associative learning are not fully understood. Here authors show that BFPVNs mediate aversive associative learning via playing crucial roles in encoding outcome-related information. [ABSTRACT FROM AUTHOR]

The amygdala (AMY) is widely implicated in fear learning and fear behaviour, but it remains unclear how the many biological components present within AMY interact to achieve these abilities. Building on previous work, we hypothesize that individual AMY nuclei represent different quantities and that fear conditioning arises from error‐driven learning on the synapses between AMY nuclei. We present a computational model of AMY that (a) recreates the divisions and connections between AMY nuclei and their constituent pyramidal and inhibitory neurons; (b) accommodates scalable high‐dimensional representations of external stimuli; (c) learns to associate complex stimuli with the presence (or absence) of an aversive stimulus; (d) preserves feature information when mapping inputs to salience estimates, such that these estimates generalize to similar stimuli; and (e) induces a diverse profile of neural responses within each nucleus. Our model predicts (1) defensive responses and neural activities in several experimental conditions, (2) the consequence of artificially ablating particular nuclei and (3) the tendency to generalize defensive responses to novel stimuli. We test these predictions by comparing model outputs to neural and behavioural data from animals and humans. Despite the relative simplicity of our model, we find significant overlap between simulated and empirical data, which supports our claim that the model captures many of the neural mechanisms that support fear conditioning. We conclude by comparing our model to other computational models and by characterizing the theoretical relationship between pattern separation and fear generalization in healthy versus anxious individuals. [ABSTRACT FROM AUTHOR]

Stimuli-responsive coordination polymers (CPs) are among one of the most prolific research areas in developing the next-generation functional materials. Their capability of being accurately excited by particular external changes with pre-determined and observable/characterizable behaviors correspond, are the so called "stimuli" and "responsive". Abundant types of CP compounds, especially metal-organic frameworks (MOFs), are of rocketing interest owing to their compositional diversity, structural tunability, and in essence their highly engineerable functionality. This present review is aimed to sketch several common types of stimulation and the corresponding responses for CPs, accompanied with the broad logic and mechanisms underneath. And further from the aspect of material revolution, some representative progresses together with the latest advances of CPbased materials in various fields are covered in attempt to display a broader picture towards the possible prospects of this topic. [ABSTRACT FROM AUTHOR]

Rationale: Preclinical studies report attenuated ethanol-induced conditioned taste aversion (CTA) following chronic ethanol exposure, suggesting that tolerance develops to the aversive properties of ethanol. However, these studies are confounded by pre-exposure to the unconditioned stimulus (US; ethanol), which is well known to hinder conditioning. Objectives: This study was designed to determine whether chronic ethanol exposure produces tolerance to the aversive properties of ethanol in the absence of a US pre-exposure confound. Methods: CTA was performed in adult male and female Long-Evans rats by pairing 0.1% ingested saccharin with an intraperitoneal injection of ethanol (1.5 or 2.0 g/kg) or saline. Rats were then rendered ethanol dependent using chronic intermittent ethanol (CIE) vapor exposure. Controls were exposed to room air (AIR). The effect of chronic ethanol on CTA expression and reconditioning were examined following vapor exposure. Results: Prior to vapor exposure, both sexes developed CTA to a comparable degree with 2.0 g/kg producing greater CTA than 1.5 g/kg ethanol. Following vapor exposure, AIR controls exhibited an increase in CTA magnitude compared to pre-vapor levels. This effect was largely absent in CIE-exposed rats. Re-conditioning after vapor exposure facilitated increased CTA magnitude to a similar degree in AIR- and CIE-exposed males. In contrast, CTA magnitude was unchanged by re-conditioning in females. Conclusions: These data suggest that chronic ethanol does not facilitate tolerance to the aversive properties of ethanol but rather attenuates incubation of ethanol-induced CTA. Loss of CTA incubation suggests that CIE exposure disrupts circuits encoding aversion. [ABSTRACT FROM AUTHOR]

Impulse purchases play a vital role in the sales revenue of shopping malls. This study utilized the Stimulus-Organism-Response framework to explore how shopping mall atmosphere stimulates consumer emotions, thereby impacting impulse purchase behavior. Structural equation modeling was employed for data analysis. The findings revealed that both positive and negative emotions can act as mediators in the process of forming impulse purchase behavior, albeit with distinct and sometimes antagonistic effects. This phenomenon is attributed to the differential impact of the service atmosphere on stimulating consumer emotions. Additionally, the study identified that only positive emotions can serve as mediators between spatial atmosphere and impulse purchases. In essence, stimuli in the shopping environment can influence consumer emotional responses, thereby prompting impulse purchase behavior. [ABSTRACT FROM AUTHOR]

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin. [ABSTRACT FROM AUTHOR]