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Fear learning and extinction

How fear is learned, held and unlearned.

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Qurʾān

القرآن6 shown

Verses named for this subject by hand come first. The rest are found by the subject’s own Arabic and English senses and are shown as lexical matches, not as anchors anyone has confirmed.

Qur'ān 21:103Arabic sense: الفزع, فزع

لَا يَحۡزُنُهُمُ ٱلۡفَزَعُ ٱلۡأَكۡبَرُ وَتَتَلَقَّىٰهُمُ ٱلۡمَلَٰٓئِكَةُ هَٰذَا يَوۡمُكُمُ ٱلَّذِي كُنتُمۡ تُوعَدُونَ

They will have no fear of the great Terror: the angels will receive them with the words, ‘This is the Day you were promised!’

Qur'ān 114:4Arabic sense: الوسواس, وسواس

مِن شَرِّ ٱلۡوَسۡوَاسِ ٱلۡخَنَّاسِ

against the harm of the slinking whisperer––

Qur'ān 27:87Arabic sense: فزع

وَيَوۡمَ يُنفَخُ فِي ٱلصُّورِ فَفَزِعَ مَن فِي ٱلسَّمَٰوَٰتِ وَمَن فِي ٱلۡأَرۡضِ إِلَّا مَن شَآءَ ٱللَّهُۚ وَكُلٌّ أَتَوۡهُ دَٰخِرِينَ

On the Day the Trumpet sounds, everyone in heaven and on earth will be terrified- except such as God wills- and all will come to Him in utter humility

Qur'ān 27:89Arabic sense: فزع

مَن جَآءَ بِٱلۡحَسَنَةِ فَلَهُۥ خَيۡرࣱ مِّنۡهَا وَهُم مِّن فَزَعࣲ يَوۡمَئِذٍ ءَامِنُونَ

whoever comes with a good deed will be rewarded with something better, and be secure from the terrors of that Day

Qur'ān 34:23Arabic sense: فزع

وَلَا تَنفَعُ ٱلشَّفَٰعَةُ عِندَهُۥٓ إِلَّا لِمَنۡ أَذِنَ لَهُۥۚ حَتَّىٰٓ إِذَا فُزِّعَ عَن قُلُوبِهِمۡ قَالُواْ مَاذَا قَالَ رَبُّكُمۡۖ قَالُواْ ٱلۡحَقَّۖ وَهُوَ ٱلۡعَلِيُّ ٱلۡكَبِيرُ

Intercession will not work with Him, except by those to whom He gives permission.’ They will be asked, after the terror is lifted from their hearts [on the Day of Judgement], ‘What did your Lord speak?’ and they will answer, ‘The Truth. He is the Most High, the Most Great.’

Qur'ān 34:51Arabic sense: فزع

وَلَوۡ تَرَىٰٓ إِذۡ فَزِعُواْ فَلَا فَوۡتَ وَأُخِذُواْ مِن مَّكَانࣲ قَرِيبࣲ‏

[Prophet], if you could only see their terror! There will be no escape when they are seized from a nearby place

Tafsīr

التفسير6 shown

Commentary on the verses above, at most two editions per verse.

en-asbab-al-nuzul-by-al-wahidi on 21:103en-asbab-al-nuzul-by-al-wahidicommentary on an ayah this subject surfaced

The greatest terror shall not make them sorrow, and the angels will receive them: “This is the day that you were promised.” On the Day of Resurrection in the greatest gathering place and most tremendous courtyard, they will not hear from the angels the call “no good news” [25:22], nor the address, “Stand apart today, O offenders!” [36:59], nor the harsh call, “Slink into it, and do not talk to Me!” [23:108]. They will not hear the call of separation's pain, nor will they despair of mercy. Rather the angels will keep on coming, company after company, and they will give the good news: “This is the day that you were promised,” that is, “This is the day in which you have the promised reward.” Among them are those who will be received by the angels, and among them are those who will be addressed and made known by the King. God will say, “My servants, have you been yearning for Me?” He will sa

en-al-jalalayn on 21:103en-al-jalalayncommentary on an ayah this subject surfaced

The Supreme Terror — which is that a servant be ordered off to the Fire shall not grieve them and the angels shall receive them upon their exiting from their graves saying to them ‘This is your day the one which you were promised’ during the life of the world.

en-al-jalalayn on 114:4en-al-jalalayncommentary on an ayah this subject surfaced

from the evil of the slinking whisperer Satan — he is referred to by the name of the action waswasa on account of his repeated engaging in it — who slinks away and recoils from the heart whenever God is mentioned

en-tafisr-ibn-kathir on 114:4en-tafisr-ibn-kathircommentary on an ayah this subject surfaced

Say: "I seek refuge with the Lord of An-Nas, (1)"The King of An-Nas, (2)"The God of An-Nas, (3)"From the evil of the whisperer who withdraws. (4)"Who whispers in the breasts of An-Nas. (5)"Of Jinn and An-Nas. (6) These are three attributes from the attributes of the Lord, the Mighty and Majestic. They are lordship, sovereignty and divinity. Thus, He is the Lord of everything, the King of everything and the God of everything. All things are created by Him, owned by Him, and subservient to Him. Therefore, He commands whoever is seeking protection to seek refuge with the One Who has these attributes from the evil of the whisperer who withdraws. This (the whisperer) is the devil that is assigned to man. For verily, there is not any of the Children of Adam except that he has a companion that beautifies wicked deeds for him. This devil will go to any lengths to confuse and confound him. The o

en-al-jalalayn on 27:87en-al-jalalayncommentary on an ayah this subject surfaced

And the day when the Trumpet will be blown the Horn will be blown the First Blast by the archangel Isrāfīl and whoever is in the heavens and the earth will be terrified that is a fright that brings about death — as is stated in another verse and whoever is in the heavens and whoever is in the earth will swoon Q. 3968 the past tense fazi‘a is used to express the fact that such events will have occurred; except whom God will namely Gabriel Michael Isrāfīl and the Angel of Death. According to Ibn ‘Abbās however these excepted individuals are the martyrs who are described as living with their Lord provided for by Him’ Q. 3169. And all kullun the nunation compensates for the missing genitive annexation in other words and every one of them after being brought back to life on the Day of Resurrection will come to Him read in the form of the verb atawhu or the active participle ātūhu in utter hum

en-tafisr-ibn-kathir on 27:87en-tafisr-ibn-kathircommentary on an ayah this subject surfaced

And (remember) the Day on which the Trumpet (Şūr) will be blown – and all who are in the heavens and all who are on the earth, will be terrified except him whom Allah wills. And all shall come to Him, humbled (87)And you will see the mountains and think them solid, but they shall pass away as the passing away of the clouds. The work of Allah, Who perfected all things, verily, He is well-acquainted with what you do (88)Whoever brings a good deed, will have better than its worth; and they will be safe from the terror on that Day (89)And whoever brings an evil deed, they will be cast down on their faces in the Fire. (And it will be said to them) "Are you being recompensed anything except what you used to do? (90) The Terrors of the Day of Resurrection, the Rewards for Good Deeds and the Punishments for Evil Deeds Allah tells us about the terrors of the Day when the Şūr will be blown. The

Classical works

كتب التراث6 shown

Arabic originals, reached through the subject’s Arabic senses. Interpretive sources, never proof of a ruling.

ihya §6038ihyaArabic sense: الفزع, فزع

وجملة أدب المريض حسن الصبر وقلة الشكوى والضجر والفزع إلى الدعاء والتوكل بعد الدواء على خالق الدواء

mukhtasar-minhaj §897mukhtasar-minhajArabic sense: الفزع, فزع

وجملة آداب المريض: حسن الصبر، وقلة الشكوى والتضجر، والفزع إلى #

rawdat-muhibbin §149rawdat-muhibbinArabic sense: الفزع, فزع

أي لذلك الماء الذي غمر الأرض ومن عليها فصل وأما الوهل فهو بتحريك الهاء وأصله الفزع والروع يقال وهل يوهل وهو وهل ومستوهل قال القطامي يصف إبلا

rawdat-muhibbin §186rawdat-muhibbinArabic sense: الفزع, فزع

وأما اللوعة فقال في الصحاح لوعة الحب حرقته وقد لاعه الحب يلوعه والتاع فؤاده أي احترق من الشوق ومنه قولهم أتان لاعة الفؤاد إلى جحشها قال الأصمعي أي لائعة الفؤاد وهي التي كأنها ولهى من الفزع فصل

wabil-sayyib §407wabil-sayyibArabic sense: الفزع, فزع

| الفصل الرابع في اذكار الفزع في النوم والفكر

rawdat-muhibbin §2387rawdat-muhibbinArabic sense: الفزع, فزع

وقال أبو هريرة وابن عباس رضي الله عنهم خطب رسول الله صلى الله عليه وسلم قبل وفاته فقال في خطبته ومن قدر على امرأة أو جارية حراما فتركها مخافة من الله أمنه الله يوم الفزع الأكبر وحرمه على النار وأدخله الجنة

Research library

المكتبة البحثية1,226 works held

Peer-reviewed work held with its DOI and abstract, labelled with the study design its publication types report. None of it has been read or assessed, so nothing here may be cited as showing anything. Retracted work is held for the record but never listed; a review that a later version replaced is listed under its replacement and marked.

10.1016/j.biopsycho.2006.01.006Biological psychology (2006)MEDLINE-indexed journal, not yet read by us; matched on Conditioning, Classical, Extinction, Psychological, Fear, Amygdala, fear conditioning

Extending animal models of fear conditioning to humans.: A goal of fear and anxiety research is to understand how to treat the potentially devastating effects of anxiety disorders in humans. Much of this research utilizes classical fear conditioning, a simple paradigm that has been extensively investigated in animals, helping outline a brain circuitry thought to be responsible for the acquisition, expression and extinction of fear. The findings from non-human animal research have more recently been substantiated and extended in humans, using neuropsyc

10.1016/j.biopsycho.2006.01.008Biological psychology (2006)MEDLINE-indexed journal, not yet read by us; matched on Conditioning, Classical, Extinction, Psychological, Fear, Amygdala, fear extinction

Fear extinction in rats: implications for human brain imaging and anxiety disorders.: Fear extinction is the decrease in conditioned fear responses that normally occurs when a conditioned stimulus (CS) is repeatedly presented in the absence of the aversive unconditioned stimulus (US). Extinction does not erase the initial CS-US association, but is thought to form a new memory. After extinction training, extinction memory competes with conditioning memory for control of fear expression. Deficits in fear extinction are thought to contribute to post-traumatic stress disorder (PTSD).

10.1016/j.jpsychires.2008.01.017Journal of psychiatric research (2008)MEDLINE-indexed journal, not yet read by us; matched on Conditioning, Classical, Extinction, Psychological, Fear, fear conditioning, fear extinction

Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study.: Recall of fear extinction, which is thought to aid in recovery from a psychologically traumatic event, is hypothesized to be deficient in post-traumatic stress disorder (PTSD), but this has not yet been demonstrated in the laboratory, nor has its origin been investigated. To address these two issues, 14 pairs of monozygotic twins discordant for combat exposure, in 7 of which the combat-exposed twin had PTSD, underwent a two-day fear conditioning and extinction procedure. On Day 1, subjects viewe

10.1016/j.nlm.2016.05.007Neurobiology of learning and memory (2016)MEDLINE-indexed journal, not yet read by us; matched on Conditioning, Classical, Extinction, Psychological, Fear, fear conditioning, fear extinction

The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans.: A critical component of the treatment for anxiety disorders is the extinction of fear via repeated exposure to the feared stimulus. This process is strongly dependent on successful memory formation and consolidation. Stimulation of the vagus nerve enhances memory formation in both animals and humans. The objective of this study was to assess whether transcutaneous stimulation of the vagus nerve (tVNS) can accelerate extinction memory formation and retention in fear conditioned humans. To assess

10.1017/s0033291719001387Psychological medicine (2020)MEDLINE-indexed journal, not yet read by us; matched on Conditioning, Classical, Extinction, Psychological, Fear, fear conditioning

Neural signatures of conditioning, extinction learning, and extinction recall in posttraumatic stress disorder: a meta-analysis of functional magnetic resonance imaging studies.: Background: Establishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers. Methods: Here, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-based d-mapping, to contrast neural correlates of experimental

10.1523/jneurosci.2713-18.2019The Journal of neuroscience : the official journal of the Society for Neuroscience (2019)MEDLINE-indexed journal, not yet read by us; matched on Conditioning, Classical, Extinction, Psychological, Fear, fear extinction

Role of Human Ventromedial Prefrontal Cortex in Learning and Recall of Enhanced Extinction.: Standard fear extinction relies on the ventromedial prefrontal cortex (vmPFC) to form a new memory given the omission of threat. Using fMRI in humans, we investigated whether replacing threat with novel neutral outcomes (instead of just omitting threat) facilitates extinction by engaging the vmPFC more effectively than standard extinction. Computational modeling of associability (indexing surprise strength and dynamically modulating learning rates) characterized skin conductance responses and vm

Research library, full list

351 to 375 of 1,226
Pavuluri MN, O'Connor MM, Harral E, Sweeney JA (2007)cohort or longitudinalMEDLINE-indexed journal, not yet read by usBiological psychiatry192 citations

Affective neural circuitry during facial emotion processing in pediatric bipolar disorder.

Background: Facial emotions are central to human interaction. Identifying pathophysiology in affect processing circuitry that supports the ability to assess facial emotions might facilitate understanding of affect regulation in pediatric bipolar disorder. Methods: Ten euthymic, unmedicated pediatric bipolar patients and 10 healthy control subjects matched for age, gender, race, socioeconomic status, and IQ were scanned with functional magnetic resonance imaging. Angry, happy, and neutral faces were presented in 30-sec blocks, with a 20-sec rest period between blocks. Subjects were asked to press a button when each face appeared, to ensure that attention was maintained on-task. Results: In bipolar patients, in response to both angry and happy faces relative to neutral faces, we observed reduced activation of right rostral ventrolateral prefrontal cortex together with increased activity in

matched on Amygdala (mesh)

Unoki S, Matsumoto Y, Mizunami M (2006)cohort or longitudinalMEDLINE-indexed journal, not yet read by usThe European journal of neuroscience106 citations

Roles of octopaminergic and dopaminergic neurons in mediating reward and punishment signals in insect visual learning.

Insects, like vertebrates, have considerable ability to associate visual, olfactory or other sensory signals with reward or punishment. Previous studies in crickets, honey bees and fruit-flies have suggested that octopamine (OA, invertebrate counterpart of noradrenaline) and dopamine (DA) mediate various kinds of reward and punishment signals in olfactory learning. However, whether the roles of OA and DA in mediating positive and negative reinforcing signals can be generalized to learning of sensory signals other than odors remained unknown. Here we first established a visual learning paradigm in which to associate a visual pattern with water reward or saline punishment for crickets and found that memory after aversive conditioning decayed much faster than that after appetitive conditioning. Then, we pharmacologically studied the roles of OA and DA in appetitive and aversive forms of vis

matched on Avoidance Learning (mesh)

Urry HL, van Reekum CM, Johnstone T, Kalin NH, Thurow ME, Schaefer HS, Jackson CA, Frye CJ, Greischar LL, Alexander AL, Davidson RJ (2006)cohort or longitudinalMEDLINE-indexed journal, not yet read by usThe Journal of neuroscience : the official journal of the Society for Neuroscience749 citations

Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults.

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing nega

matched on Amygdala (mesh)

Siegle GJ, Carter CS, Thase ME (2006)cohort or longitudinalMEDLINE-indexed journal, not yet read by usThe American journal of psychiatry287 citations

Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy.

Objective: In controlled treatment trials, 40%-60% of unmedicated depressed individuals respond to cognitive behavior therapy (CBT). The authors examined whether pretreatment neural reactivity to emotional stimuli accounted for this variation. Method: Unmedicated depressed individuals (N=14) and never depressed comparison subjects (N=21) underwent fMRI during performance of a task sensitive to sustained emotional information processing. Afterward, depressed participants completed 16 sessions of CBT. Results: Participants whose sustained reactivity to emotional stimuli was low in the subgenual cingulate cortex (Brodmann's area 25) and high in the amygdala displayed the strongest improvement with CBT. Conclusions: The presence of emotion regulation disruptions, which are targeted in CBT, may be the key to recovery with this intervention.

matched on Amygdala (mesh)

Nacewicz BM, Dalton KM, Johnstone T, Long MT, McAuliff EM, Oakes TR, Alexander AL, Davidson RJ (2006)cohort or longitudinalMEDLINE-indexed journal, not yet read by usArchives of general psychiatry191 citations

Amygdala volume and nonverbal social impairment in adolescent and adult males with autism.

Background: Autism is a syndrome of unknown cause, marked by abnormal development of social behavior. Attempts to link pathological features of the amygdala, which plays a key role in emotional processing, to autism have shown little consensus. Objective: To evaluate amygdala volume in individuals with autism spectrum disorders and its relationship to laboratory measures of social behavior to examine whether variations in amygdala structure relate to symptom severity. Design: We conducted 2 cross-sectional studies of amygdala volume, measured blind to diagnosis on high-resolution, anatomical magnetic resonance images. Participants were 54 males aged 8 to 25 years, including 23 with autism and 5 with Asperger syndrome or pervasive developmental disorder not otherwise specified, recruited and evaluated at an academic center for developmental disabilities and 26 age- and sex-matched communi

matched on Amygdala (mesh)

Drabant EM, Hariri AR, Meyer-Lindenberg A, Munoz KE, Mattay VS, Kolachana BS, Egan MF, Weinberger DR (2006)cohort or longitudinalMEDLINE-indexed journal, not yet read by usArchives of general psychiatry270 citations

Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation.

Context: Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val(158)met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation. Objectives: To examine COMT val(158)met effects on corticolimbic circuitry reactivity and functional connectivity during processing of biologically salient stimuli, as well as the relationship to the temperamental trait of novelty seeking. Design: Within-subject functional magnetic resonance imaging study. Setting: National Institute of Mental Health, Genes, Cognition, and Psychosis Program, Bethesda, Md. Patients One hundred one healthy subjects of both sexes. Results: We found that the met allele was associated with a dose-dependent increase in hippocampal formation and ventrolateral prefrontal cortex activat

matched on Amygdala (mesh)

Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, Yurgelun-Todd DA (2005)cohort or longitudinalMEDLINE-indexed journal, not yet read by usBiological psychiatry167 citations

Amygdala and hippocampus volumes in pediatric major depression.

Background: The purpose of this study was to measure amygdala and hippocampus volumes in pediatric major depressive disorder (MDD) and to address the question of neuroanatomical continuity with adult-onset depression. Methods: We studied 20 children and adolescents with MDD (17 female subjects) and 24 healthy comparison subjects (16 female subjects) using 1.5 Tesla magnetic resonance imaging. Group differences in left and right amygdala and hippocampus volumes were examined using repeated measures analyses of covariance, adjusting for age, gender, and whole brain volume. Results: Depressed children had significant reductions of left and right amygdala volumes compared with healthy subjects. Hippocampus volumes did not differ between the groups. No significant correlations were found between amygdala volumes and depressive symptom severity, age at onset, or illness duration. Conclusions:

matched on Amygdala (mesh)

Correll CM, Rosenkranz JA, Grace AA (2005)cohort or longitudinalMEDLINE-indexed journal, not yet read by usBiological psychiatry76 citations

Chronic cold stress alters prefrontal cortical modulation of amygdala neuronal activity in rats.

Background: Recent studies suggest that long-term exposure to stress can sensitize animals to subsequent novel or acute stressors. Stressors affect amygdala activity, and the prefrontal cortex has been implicated in the regulation of responses to stress. Little is known, however, about how the physiology of amygdala neurons is altered by chronic stressors or the role of the prefrontal cortex in these changes. Methods: We used in vivo extracellular recordings from neurons in the rat central and basolateral amygdala nuclei to examine the effects of chronic stress on the basal firing and responses of amygdala neurons to a novel stressor. Additionally, prefrontal cortical afferents were severed to examine its role in the modulation of the response to stressors. Results: Chronic exposure to cold enhanced the sensitivity of central amygdala neurons to footshock. A portion of this may be due to

matched on Amygdala (mesh)

Yamasaki T, Kiyokawa Y, Munetomo A, Takeuchi Y (2024)MEDLINE-indexed journal, not yet read by usThe European journal of neuroscience5 citations

Naloxone increases conditioned fear responses during social buffering in male rats.

Social buffering is the phenomenon in which the presence of an affiliative conspecific mitigates stress responses. We previously demonstrated that social buffering completely ameliorates conditioned fear responses in rats. However, the neuromodulators involved in social buffering are poorly understood. Given that opioids, dopamine, oxytocin and vasopressin play an important role in affiliative behaviour, here, we assessed the effects of the most well-known antagonists, naloxone (opioid receptor antagonist), haloperidol (dopamine D2 receptor antagonist), atosiban (oxytocin receptor antagonist) and SR49059 (vasopressin V1a receptor antagonist), on social buffering. In Experiment 1, fear-conditioned male subjects were intraperitoneally administered one of the four antagonists 25 min prior to exposure to a conditioned stimulus with an unfamiliar non-conditioned rat. Naloxone, but not the oth

matched on Conditioning, Classical (mesh), Fear (mesh), fear conditioning (text)

Cai LX, Pizano K, Gundersen GW, Hayes CL, Fleming WT, Holt S, Cox JM, Witten IB (2020)MEDLINE-indexed journal, not yet read by useLife94 citations

Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times.

Dopamine (DA) neurons are to encode reward prediction error (RPE), in addition to other signals, such as salience. While RPE is known to support learning, the role of salience in learning remains less clear. To address this, we recorded and manipulated VTA DA neurons in mice during fear extinction. We applied deep learning to classify mouse freezing behavior, eliminating the need for human scoring. Our fiber photometry recordings showed DA neurons in medial and lateral VTA have distinct activity profiles during fear extinction: medial VTA activity more closely reflected RPE, while lateral VTA activity more closely reflected a salience-like signal. Optogenetic inhibition of DA neurons in either region slowed fear extinction, with the relevant time period for inhibition differing across regions. Our results indicate salience-like signals can have similar downstream consequences to RPE-like

matched on Extinction, Psychological (mesh), Fear (mesh), fear extinction (text)

The microbiota regulate neuronal function and fear extinction learning.

Multicellular organisms have co-evolved with complex consortia of viruses, bacteria, fungi and parasites, collectively referred to as the microbiota1. In mammals, changes in the composition of the microbiota can influence many physiologic processes (including development, metabolism and immune cell function) and are associated with susceptibility to multiple diseases2. Alterations in the microbiota can also modulate host behaviours-such as social activity, stress, and anxiety-related responses-that are linked to diverse neuropsychiatric disorders3. However, the mechanisms by which the microbiota influence neuronal activity and host behaviour remain poorly defined. Here we show that manipulation of the microbiota in antibiotic-treated or germ-free adult mice results in significant deficits in fear extinction learning. Single-nucleus RNA sequencing of the medial prefrontal cortex of the br

matched on Extinction, Psychological (mesh), Fear (mesh), fear extinction (text)

Negative life experiences contribute to racial differences in the neural response to threat.

Threat-related emotional function is supported by a neural circuit that includes the prefrontal cortex (PFC), hippocampus, and amygdala. The function of this neural circuit is altered by negative life experiences, which can potentially affect threat-related emotional processes. Notably, Black-American individuals disproportionately endure negative life experiences compared to White-American individuals. However, the relationships among negative life experiences, race, and the neural substrates that support threat-related emotional function remains unclear. Therefore, the current study investigated whether the brain function that supports threat-related emotional processes varies with racial differences in negative life experiences. In the present study, adolescent violence exposure, family income, and neighborhood disadvantage were measured prospectively (i.e., at 11-19 years of age) for

matched on Conditioning, Classical (mesh), Fear (mesh), fear conditioning (text)

Luo R, Uematsu A, Weitemier A, Aquili L, Koivumaa J, McHugh TJ, Johansen JP (2018)MEDLINE-indexed journal, not yet read by usNature communications140 citations

A dopaminergic switch for fear to safety transitions.

Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate so that they can be extinguished. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signaling when a better-than-expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signaling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. In contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the

matched on Conditioning, Classical (mesh), Fear (mesh), fear extinction (text)

Yoo SW, Bae M, Tovar-Y-Romo LB, Haughey NJ (2017)MEDLINE-indexed journal, not yet read by usTranslational psychiatry13 citations

Hippocampal encoding of interoceptive context during fear conditioning.

Rodent models of auditory fear conditioning are often used to understand the molecular mechanisms regulating fear- and anxiety-related behaviors. Conditioning and extinction memories are influenced by contextual cues, and the reinstatement of conditioned fear occurs when the conditioning stimulus is presented in a context different from the extinction context. Although it has been proposed that internal state is a feature of context that could influence extinction, contributions of interoception to conditioning have not been experimentally addressed. Here we use ethanol (EtOH) to show that interoceptive cues are encoded through the hippocampus by mechanisms that involve increased phosphorylation of GluR1 on serine 845, and biophysical alterations in neuronal membranes that facilitate stabilization of surface-located calcium-permeable n-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic

matched on Extinction, Psychological (mesh), Fear (mesh), fear conditioning (text)

Ball TM, Knapp SE, Paulus MP, Stein MB (2017)MEDLINE-indexed journal, not yet read by usDepression and anxiety81 citations

Brain activation during fear extinction predicts exposure success.

Background: Exposure therapy, a gold-standard treatment for anxiety disorders, is assumed to work via extinction learning, but this has never been tested. Anxious individuals demonstrate extinction learning deficits, likely related to less ventromedial prefrontal cortex (vmPFC) and more amygdala activation, but the relationship between these deficits and exposure outcome is unknown. We tested whether anxious individuals who demonstrate better extinction learning report greater anxiety reduction following brief exposure. Methods: Twenty-four adults with public speaking anxiety completed (1) functional magnetic resonance imaging during a conditioning paradigm, (2) a speech exposure session, and (3) anxiety questionnaires before and two weeks postexposure. Extinction learning was assessed by comparing ratings to a conditioned stimulus (neutral image) that was previously paired with an avers

matched on Extinction, Psychological (mesh), Fear (mesh), fear extinction (text)

Graham BM, Daher M (2016)MEDLINE-indexed journal, not yet read by usNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology81 citations

Estradiol and Progesterone have Opposing Roles in the Regulation of Fear Extinction in Female Rats.

Fear extinction, the laboratory basis of exposure therapy for anxiety disorders, fluctuates across the female rat estrous cycle, where extinction is enhanced during proestrus (high estradiol and progesterone), and impaired during metestrus (low estradiol and progesterone). During the estrous cycle increasing levels of estradiol precede and then overlap with increased levels of progesterone. We sought to isolate the impact of these hormonal changes on fear extinction by systematically treating ovariectomized female rats with estradiol alone, or in combination with progesterone. We found that estradiol alone facilitated extinction recall, whereas the effects of progesterone on estradiol-treated rats were biphasic and dependent on the time interval between progesterone administration and extinction training. Progesterone potentiated estradiol's facilitation of extinction recall when extinct

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Dunsmoor JE, Murty VP, Davachi L, Phelps EA (2015)MEDLINE-indexed journal, not yet read by usNature202 citations

Emotional learning selectively and retroactively strengthens memories for related events.

Neurobiological models of long-term memory propose a mechanism by which initially weak memories are strengthened through subsequent activation that engages common neural pathways minutes to hours later. This synaptic tag-and-capture model has been hypothesized to explain how inconsequential information is selectively consolidated following salient experiences. Behavioural evidence for tag-and-capture is provided by rodent studies in which weak early memories are strengthened by future behavioural training. Whether a process of behavioural tagging occurs in humans to transform weak episodic memories into stable long-term memories is unknown. Here we show, in humans, that information is selectively consolidated if conceptually related information, putatively represented in a common neural substrate, is made salient through an emotional learning experience. Memory for neutral objects was se

matched on Conditioning, Classical (mesh), Fear (mesh), fear conditioning (text)

Savignac HM, Tramullas M, Kiely B, Dinan TG, Cryan JF (2015)MEDLINE-indexed journal, not yet read by usBehavioural brain research271 citations

Bifidobacteria modulate cognitive processes in an anxious mouse strain.

Increasing evidence suggests that a brain-gut-microbiome axis exists, which has the potential to play a major role in modulating behaviour. However, the role of this axis in cognition remains relatively unexplored. Probiotics, which are commensal bacteria offering potential health benefit, have been shown to decrease anxiety, depression and visceral pain-related behaviours. In this study, we investigate the potential of two Bifidobacteria strains to modulate cognitive processes and visceral pain sensitivity. Adult male BALB/c mice were fed daily for 11 weeks with B. longum 1714, B. breve 1205 or vehicle treatment. Starting at week 4, animals were behaviourally assessed in a battery of tests relevant to different aspects of cognition, as well as locomotor activity and visceral pain. In the object recognition test, B. longum 1714-fed mice discriminated between the two objects faster than a

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Wheelock MD, Sreenivasan KR, Wood KH, Ver Hoef LW, Deshpande G, Knight DC (2014)MEDLINE-indexed journal, not yet read by usNeuroImage66 citations

Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity.

Conditioned changes in the emotional response to threat (e.g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data were reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of

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Lissek S, Kaczkurkin AN, Rabin S, Geraci M, Pine DS, Grillon C (2014)MEDLINE-indexed journal, not yet read by usBiological psychiatry346 citations

Generalized anxiety disorder is associated with overgeneralization of classically conditioned fear.

Background: Meta-analytic results of fear-conditioning studies in the anxiety disorders implicate generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of anxiety pathology. Due to the absence of conditioning studies assessing generalization in generalized anxiety disorder (GAD), results of this meta-analysis do not reveal whether such generalization abnormalities also apply to GAD. The current study fills this gap by behaviorally and psychophysiologically assessing levels of conditioned fear generalization across adults with and without GAD. Methods: Twenty-two patients with a DSM-IV-Text Revision diagnosis of GAD and 26 healthy comparison subjects were recruited and tested. The employed generalization paradigm consisted of quasi-randomly presented rings of gradually increasing size, with extreme sizes serving

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Datta S, O'Malley MW (2013)MEDLINE-indexed journal, not yet read by usThe Journal of neuroscience : the official journal of the Society for Neuroscience85 citations

Fear extinction memory consolidation requires potentiation of pontine-wave activity during REM sleep.

Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. T

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Murray CL, Obiang P, Bannerman D, Cunningham C (2013)MEDLINE-indexed journal, not yet read by usPloS one46 citations

Endogenous IL-1 in cognitive function and anxiety: a study in IL-1RI-/- mice.

Interleukin-1 (IL-1) is a key pro-inflammatory cytokine, produced predominantly by peripheral immune cells but also by glia and some neuronal populations within the brain. Its signalling is mediated via the binding of IL-1α or IL-1β to the interleukin-1 type one receptor (IL-1RI). IL-1 plays a key role in inflammation-induced sickness behaviour, resulting in depressed locomotor activity, decreased exploration, reduced food and water intake and acute cognitive deficits. Conversely, IL-1 has also been suggested to facilitate hippocampal-dependent learning and memory: IL-1RI(-/-) mice have been reported to show deficits on tasks of visuospatial learning and memory. We sought to investigate whether there is a generalised hippocampal deficit in IL-1RI(-/-) animals. Therefore, in the current study we compared wildtype (WT) mice to IL-1RI(-/-) mice using a variety of hippocampal-dependent learn

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Catlow BJ, Song S, Paredes DA, Kirstein CL, Sanchez-Ramos J (2013)MEDLINE-indexed journal, not yet read by usExperimental brain research205 citations

Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.

Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated wi

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Zelinski EL, Hong NS, Tyndall AV, Halsall B, McDonald RJ (2010)MEDLINE-indexed journal, not yet read by usExperimental brain research47 citations

Prefrontal cortical contributions during discriminative fear conditioning, extinction, and spontaneous recovery in rats.

This research examined the roles played by the ventromedial orbital prefrontal cortex (OPFC) and the infralimbic/prelimbic prefrontal cortex (I/P PFC) during discriminative fear conditioning. The first experiment included nine rats with bilateral lesions to the I/P PFC, an additional nine with OPFC lesions, and eight sham lesion controls. Behavioural analysis was conducted using a discriminative fear conditioning to context task 10 days after surgery. Results indicate that lesions to ventromedial orbital prefrontal cortex result in generalized fear and impaired extinction. In contrast, infralimbic/prelimbic cortical lesioned animals exhibit appropriate fear response patterns and extinction, but show a specific impairment in spontaneous recovery. To ascertain why I/P PFC lesion rats did not exhibit spontaneous recovery, a second experiment was conducted. All procedures in the second exper

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Bagot RC, van Hasselt FN, Champagne DL, Meaney MJ, Krugers HJ, Joëls M (2009)MEDLINE-indexed journal, not yet read by usNeurobiology of learning and memory162 citations

Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus.

Maternal care in the rat influences hippocampal development, synaptic plasticity and cognition. Previous studies, however, have examined animals under minimally stressful conditions. Here we tested the hypothesis that maternal care influences hippocampal function differently when this structure is exposed to corticosteroid and noradrenergic hormones, which are elevated during the early phase of a stress response. In the adult male offspring of Long-Evans dams characterised as high or low in maternal care (high LG and low LG) we (1) examined basal dendritic morphology in the dentate gyrus by Golgi staining; (2) investigated rapid modulation of in vitro long term-potentiation (LTP) in the dentate gyrus by glucocorticoid and beta-adrenergic stimulation; (3) examined hippocampal and amygdala-dependent learning under stress using contextual and cued fear conditioning. We found differences in

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