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fear learning and extinction predicts anxiety in daily life: a study of Pavlovian conditioning and ecological momentary assessment

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PSYCHOLOGICAL MEDICINE 2023年第11期53卷 5301-5311页

作者： Modecki, Kathryn L. Ryan, Katherine M. Waters, Allison M. Griffith Univ Menzies Hlth Inst Queensland Mt Gravatt Qld Australia Griffith Univ Ctr Mental Hlth Sch Appl Psychol Mt Gravatt Qld Australia Griffith Univ Mt Gravatt Sch Appl Psychol Mt Gravatt Qld Australia Griffith Univ Mt Gravatt Ctr Mental Hlth Mt Gravatt Qld Australia

Background The association between anxious mood and aberrant fear learning mechanisms has not been fully elucidated. Studying how fear conditioning and extinction constructs relate to anxiety symptoms and reactivity to stressful and benign moments in everyday life provides a powerful addition to experimental paradigms. Method Fifty-one young adults completed laboratory-based differential conditioning and extinction tasks with (CS + ) and without (CS-) an aversive unconditional stimulus (US). Electrodermal skin conductance responses were measured during each phase, followed by ecological momentary assessment (EMA) tapping anxiety and stressors six times daily for seven days (2, 142 moments). Results Conditioned electrodermal reactivity to the CS + and overgeneralisation to the CS- were associated with greater change in anxiety (measured via EMA), across non-stressful situations, remaining the same across stressful situations. Likewise, during extinction when the CS + is now safe, more electrodermal reactivity to the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations. Also, during extinction when threat is absent, more electrodermal reactivity at the late stage of the CS- was associated with less momentary anxiety change in response to stressful situations;more electrodermal activity at the late stage of the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations. Conclusions Sampling 'in vivo' emotion and stress experiences, study findings revealed links between conditioned electrodermal reactivity and overgeneralisation to safe stimuli and heightened anxious reactivity during non-stressful (i.e. safe) moments in daily life, coupled with less change in response to actual stressors.

关键词： Ecological momentary assessment (EMA) Pavlovian conditioning fear learning anxiety

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Scopolamine affects fear learning and social recognition in adult zebrafish

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NEUROSCIENCE 2025年 568卷 219-230页

作者： Fu, Chih-Wei Tong, Sok-Keng Liu, Meng-Xuan Liao, Bo-Kai Chou, Ming-Yi Natl Taiwan Univ Dept Life Sci Taipei Taiwan Natl Taiwan Ocean Univ Dept Aquaculture Keelung Taiwan

Scopolamine is the secondary metabolite of the Datura stramonium and act as a muscarinic receptor antagonist. Previous studies showed that scopolamine caused attention and memory deficit. However, the effects of scopolamine on specific cognitive functions, such as fear learning and social recognition, remain poorly understood. Here, we demonstrate the effects of scopolamine on fear learning, social memory, and neural activity in zebrafish, providing a novel perspective on its impact on cognitive and social behaviors. Here, we used equal number of male and female zebrafish as an animal model and performed a series of behavioral tests after treatment with scopolamine (100 mu M and 200 mu M) for 1 h to evaluate social and cognitive functions. Treatment with scopolamine increased locomotion activity, reduced the level of anxiety in the novel tank diving test, and impaired memory retrieval in the active avoidance test. Scopolamine also increased the preference for newly introduced fish in the social recognition test. In situ hybridization of c-fos mRNA showed that scopolamine decreased the neural activity of the telencephalic regions that are crucial for social, cognitive, and memory functions. Our results demonstrate the effects of scopolamine on fear learning and social recognition in adult zebrafish.

关键词： Scopolamine Social recognition fear learning Zebrafish

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Alterations in fear learning as a mechanism linking childhood exposure to violence with PTSD symptoms: a longitudinal study

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PSYCHOLOGICAL MEDICINE 2024年第12期54卷 3389-3397页

作者： Machlin, Laura Sheridan, Margaret A. Lurie, Lucy A. Kasparek, Steven W. Kim, Stephanie Gyuri Peverill, Matthew France, John McClellan Robertson, Madeline M. Jovanovic, Tanja Lengua, Liliana J. Mclaughlin, Katie A. Harvard Univ Dept Psychol Cambridge MA 02138 USA Univ North Carolina Dept Psychol & Neurosci Chapel Hill NC USA Univ Illinois Dept Human Dev & Family Studies Champaign IL USA Univ Washington Dept Psychol Seattle WA USA Wayne State Univ Dept Psychiat & Behav Neurosci Detroit MI USA

Background fear learning is a core component of conceptual models of how adverse experiences may influence psychopathology. Specifically, existing theories posit that childhood experiences involving childhood trauma are associated with altered fear learning processes, while experiences involving deprivation are not. Several studies have found altered fear acquisition in youth exposed to trauma, but not deprivation, although the specific patterns have varied across studies. The present study utilizes a longitudinal sample of children with variability in adversity experiences to examine associations among childhood trauma, fear learning, and psychopathology in *** The sample includes 170 youths aged 10-13 years (M = 11.56, s.d. = 0.47, 48.24% female). Children completed a fear conditioning task while skin conductance responses (SCR) were obtained, which included both acquisition and extinction. Childhood trauma and deprivation severity were measured using both parent and youth report. Symptoms of anxiety, externalizing problems, and post-traumatic stress disorder (PTSD) were assessed at baseline and again two-years *** Greater trauma-related experiences were associated with greater SCR to the threat cue (CS+) relative to the safety cue (CS-) in early fear acquisition, controlling for deprivation, age, and sex. Deprivation was unrelated to fear learning. Greater SCR to the threat cue during early acquisition was associated with increased PTSD symptoms over time controlling for baseline symptoms and mediated the relationship between trauma and prospective changes in PTSD *** Childhood trauma is associated with altered fear learning in youth, which may be one mechanism linking exposure to violence with the emergence of PTSD symptoms in adolescence.

关键词： adversity fear learning post-traumatic stress disorder skin conductance response trauma

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A Memcapacitor Biomimetic Circuit Realizing Classical Conditioning and fear learning

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IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS I-REGULAR PAPERS 2024年第12期71卷 5694-5706页

作者： Sun, Junwei Chen, Bairen Liu, Peng Wen, Shiping Wang, Yanfeng Zhengzhou Univ Light Ind Sch Elect & Informat Engn Zhengzhou 450002 Peoples R China Univ Technol Sydney Fac Engn & Informat Technol Australian AI Inst Sydney NSW 2007 Australia

Most associative memory neural networks are realized by memristor, but memcapacitor which can simulate the biological behavior of neuron preferably has better characteristics than memristor to realize the pavlov associative memory neural networks. This article introduces a novel neural network paradigm with memcapacitors, encompassing thirteen classical conditional reflection functions. These include pivotal aspects such as learning, forgetting, time interval conditioning, latent inhibition, time delay conditioning, facilitation, blocking, secondary conditioning, and fear learning, meticulously validated through simulation results. The proposed architecture interconnects nine analogous neuron modules through diverse synapses, culminating in a meticulously designed circuit. This memcapacitor biomimetic circuit not only achieves the implementation of thirteen classical conditional reflections but also boasts scalability, offering versatility in its application. Particularly noteworthy is its potential application in marine debris collection robots, showcasing adaptability in working intricate oceanic traffic conditions.

关键词： Circuits Memristors Reflection Neurons Biology Synapses Hysteresis Memcapacitor memristor classical conditioning fear learning biomimetic circuit

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Sex differences in prelimbic cortex calcium dynamics during stress and fear learning

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BIOLOGY OF SEX DIFFERENCES 2024年第1期15卷 79页

作者： Marin-Blasco, Ignacio Vanzo, Giorgia Rusco-Portabella, Joaquin Perez-Molina, Lucas Romero, Leire Florido, Antonio Andero, Raul Univ Autonoma Barcelona Inst Neurociencies Barcelona Spain Univ Autonoma Barcelona Inst Neurociencies Dept Psicobiol & Metodol Ciencies Salut Barcelona 08193 Spain Univ North Carolina Chapel Hill Sch Med Dept Psychiat Chapel Hill NC USA Univ North Carolina Chapel Hill Coll Arts & Sci Dept Appl Phys Sci Chapel Hill NC USA Inst Salud Carlos III Ctr Invest Biomed Red Salud Mental CIBERSAM Madrid 28090 Spain Univ Autonoma Barcelona Unitat Neurociencia Traslac Parc Tauli Hosp Univ Inst Invest & Innovacio Parc Tauli I3PTInst Neuro Bellaterra 08193 Spain ICREA Pg Lluis Co 23 Barcelona Spain

In recent years, research has progressively increased the importance of considering sex differences in stress and fear memory studies. Many studies have traditionally focused on male subjects, potentially overlooking critical differences with females. Emerging evidence suggests that males and females can exhibit distinct behavioral and neurophysiological responses to stress and fear conditioning. These differences may be attributable to variations in hormone levels, brain structure, and neural circuitry, particularly in regions such as the prefrontal cortex (PFC). In the present study, we explored sex differences in prelimbic cortex (PL) calcium activity in animals submitted to immobilization stress (IMO), fear conditioning (FC), and fear extinction (FE). While no significant sex differences were found in behavioral responses, we did observe differences in several PL calcium activity parameters. To determine whether these results were related to behaviors beyond stress and fear memory, we conducted correlation studies between the movement of the animals and PL activity during IMO and freezing behavior during FC and FE. Our findings revealed a clear correlation between PL calcium activity with movement during stress exposure and freezing behavior, with no sex differences observed in these correlations. These results suggest a significant role for the PL in movement and locomotion, in addition to its involvement in fear-related processes. The inclusion of both female and male subjects is crucial for studies like this to fully understand the role of the PFC and other brain areas in stress and fear responses. Recognizing sex differences enhances our comprehension of brain function and can lead to more personalized and effective approaches in the study and treatment of stress and fear-related conditions. In recent years, researchers have started paying more attention to the differences between males and females in how they handle stress and remember fearful events. Tradi

关键词： Sex differences PFC Stress fear learning fear memory Calcium imaging Miniscopes Movement

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The effect of SSRIs on fear learning: a systematic review and meta-analysis

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PSYCHOPHARMACOLOGY 2023年第11期240卷 2335-2359页

作者： Heesbeen, Elise J. Bijlsma, Elisabeth Y. Verdouw, P. Monika van Lissa, Caspar Hooijmans, Carlijn Groenink, Lucianne Univ Utrecht Utrecht Inst Pharmaceut Sci Div Pharmacol Utrecht Netherlands Tilburg Univ Dept Methodol Tilburg Netherlands Radboud Univ Nijmegen Dept Anaesthesiol Pain & Palliat Care Med Ctr Nijmegen Netherlands

RationaleSelective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well *** aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned *** searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal ***-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect *** review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs.

关键词： fear learning Anxiety SSRIs Acquisition Extinction Systematic review Meta-analysis 5-HT re-uptake inhibitor fear conditioning Contextual anxiety

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Exploring the association between early exposure to material hardship and psychopathology through indirect effects of fronto-limbic functional connectivity during fear learning

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CEREBRAL CORTEX 2023年第20期33卷 10702-10710页

作者： Chen, Cheng Wang, Zhengxinyue Cao, Xinyu Zhu, Jianjun Guangzhou Univ Sch Educ Ctr Early Environm & Brain Dev Guangzhou 510006 Peoples R China Guangzhou Univ Dept Psychol Guangzhou 510006 Peoples R China Hangzhou Normal Univ Affiliated Hosp Ctr Cognit & Brain Disorders Hangzhou 311121 Peoples R China

Experiencing family material hardship has been shown to be associated with disruptions in physical and psychological development. However, the association between material hardship and functional connectivity in the fronto-limbic circuit during fear learning is unclear. A total of 161 healthy young adults aged 17-28 were recruited in our brain imaging study, using the fear Conditioning Task to test the associations between material hardship and connectivity in fronto-limbic circuit and psychopathology. The results showed that family material hardship was linked to higher positive connectivity between the left amygdala and bilateral dorsal anterior cingulate cortex, as well as higher negative connectivity between the left hippocampus and right ventromedial prefrontal cortex. A mediation analysis showed that material hardship was associated with depression via amygdala functional connectivity (indirect effect = 0.228, P = 0.016), and also indirectly associated with aggression and anger-hostility symptoms through hippocampal connections (aggression: indirect effect = 0.057, P = 0.001;anger-hostility: indirect effect = 0.169, P = 0.048). That is, family material hardship appears to affect fronto-limbic circuits through changes in specific connectivity, and these specific changes, in turn, could lead to specific psychological symptoms. The findings have implications for designing developmentally sensitive interventions to mitigate the emergence of psychopathological symptoms.

关键词： functional connectivity fear learning material hardship psychopathology indirect effect

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Family Risk Factors in the Acquisition of Anxiety: Behavioral Inhibition and Social fear learning from Parents

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Advances in Psychiatry and Behavioral Health 2024年第1期4卷 225-233页

作者： Aktar, Evin Pérez-Edgar, Koraly Department of Psychology Leiden University Wassenaarseweg 52 Leiden 2333AK Netherlands Department of Psychology The Pennsylvania State University 270 Moore Building University Park 16802 PA United States

Anxiety runs in families, likely reflecting shared genetic risk and shared exposure to signals of threat and fear messaging. Children begin to internalize these signals from the earliest months of life, providing a causal or treatment mechanism that is tractable to intervention. The data suggest that while temperamentally fearful children differentially respond to parental verbal and nonverbal signaling, the impact may be more powerful prior to early childhood.

关键词： Anxiety Behavioral inhibition Children fear learning Intergenerational transmission Parent socialization Temperament

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The association between mnemonic discrimination ability and differential fear learning

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JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY 2022年 75卷 101715-101715页

作者： Davidson, Per Jonsson, Peter Johansson, Mikael Lund Univ Dept Psychol Box 213 S-22100 Lund Sweden Massachusetts Gen Hosp Dept Psychiat CNY 149 13th St Charlestown MA 02129 USA Harvard Med Sch Dept Psychiat CNY 149 13th St Charlestown MA 02129 USA Kristianstad Univ Ctr Psychol Sch Educ & Environm Elmetorpsvagen 15 S-29888 Kristianstad Sweden

Background and objectives: It is important to be able to learn which stimuli in our surroundings predict aversive outcomes. To maintain emotional well-being, it is similarly important to be able to learn which stimuli predict safety. The ability to discriminate between stimuli that predict danger and safety has been suggested to not only have an emotional component, but also a cognitive one. One such candidate mechanism is mnemonic discrimination (MD), the ability to differentiate between two memories that are similar but not identical. In the present study, we wanted to examine if MD performance helps to explain inter-individual differences in the ability to acquire a differentiated fear response during fear conditioning. Methods: Participants performed a task assessing MD ability, and then underwent a fear conditioning procedure. fear responses were measured using skin conductance responses (SCRs). Results: Results revealed no support for MD ability being associated with to which degree a differentiated fear response was acquired, or with the time needed to acquire such a response. Limitations: Our only outcome measurement was SCRs. Future studies need to include fear ratings, expectancy ratings and neural responses. Future studies also need to examine this using a stimulus material where the conditioned stimulus and the safety stimulus are more difficult to distinguish from each other. Conclusions: If MD ability has a role in inhibiting overgeneralization of fear learning, this does not seem to be driven by MD already during the initial learning.

关键词： Mnemonic discrimination Pattern separation fear conditioning fear learning Skin conductance responses

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A posterior insula to lateral amygdala pathway transmits US-offset information with a limited role in fear learning

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CELL REPORTS 2025年第2期44卷 115320页

作者： Palchaudhuri, Shriya Lin, Bei-Xuan Osypenko, Denys Wu, Jinyun Kochubey, Olexiy Schneggenburger, Ralf Ecole Polytech Fed Lausanne EPFL Brain Mind Inst Sch Life Sci Lab Synapt Mech Lausanne Switzerland NYU Grossman Sch Med Neurosci Inst New York NY USA Univ Lausanne Dept Fundamental Neurosci Lausanne Switzerland

During fear learning, associations between a sensory cue (conditioned stimulus, CS) and an aversive stimulus (unconditioned stimulus, US) are formed in specific brain circuits. The lateral amygdala (LA) is involved in CS- US integration;however, US pathways to the LA remain understudied. Here, we investigated whether the posterior insular cortex (pInsCx), a hub for aversive state signaling, transmits US information to the LA during fear learning. We find that the pInsCx makes a robust, glutamatergic projection specifically targeting the anterior LA. In vivo Ca2+ imaging reveals that neurons in the pInsCx and anterior LA display US-onset and US-offset responses;imaging combined with axon silencing shows that the pInsCx selectively transmits US-offset information to the anterior LA. Optogenetic silencing, however, does not show a role for US-driven activity in the anterior LA or its pInsCx afferents in fear memory formation. Thus, we describe a cortical projection that carries US-offset information to the amygdala with a limited role in fear learning.

关键词： fear learning amygdala insular cortex synaptic plasticity excitatory synapse optogenetics behavior neural circuits learning and memory

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