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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

101 to 125 of 1,226
Woodhouse S, Ayers S, Field AP (2015)meta-analysisMEDLINE-indexed journal, not yet read by usJournal of anxiety disorders85 citations

The relationship between adult attachment style and post-traumatic stress symptoms: A meta-analysis.

There is increasing evidence that adult attachment plays a role in the development and perseverance of symptoms of posttraumatic stress disorder (PTSD). This meta-analysis aims to synthesise this evidence and investigate the relationship between adult attachment styles and PTSD symptoms. A random-effects model was used to analyse 46 studies (N=9268) across a wide range of traumas. Results revealed a medium association between secure attachment and lower PTSD symptoms (ρˆ=-.27), and a medium association, in the opposite direction, between insecure attachment and higher PTSD symptoms (ρˆ=.26). Attachment categories comprised of high levels of anxiety most strongly related to PTSD symptoms, with fearful attachment displaying the largest association (ρˆ=.44). Dismissing attachment was not significantly associated with PTSD symptoms. The relationship between insecure attachment and PTSD was m

matched on Fear (mesh)

Exercise for reducing fear of falling in older people living in the community.

Background: Fear of falling is common in older people and associated with serious physical and psychosocial consequences. Exercise (planned, structured, repetitive and purposive physical activity aimed at improving physical fitness) may reduce fear of falling by improving strength, gait, balance and mood, and reducing the occurrence of falls. Objectives: To assess the effects (benefits, harms and costs) of exercise interventions for reducing fear of falling in older people living in the community. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2013), the Central Register of Controlled Trials (CENTRAL 2013, Issue 7), MEDLINE (1946 to July Week 3 2013), EMBASE (1980 to 2013 Week 30), CINAHL (1982 to July 2013), PsycINFO (1967 to August 2013), AMED (1985 to August 2013), the World Health Organization International Clinical Trials Regi

matched on Fear (mesh)

Trickey D, Siddaway AP, Meiser-Stedman R, Serpell L, Field AP (2012)meta-analysisMEDLINE-indexed journal, not yet read by usClinical psychology review454 citations

A meta-analysis of risk factors for post-traumatic stress disorder in children and adolescents.

Post-traumatic stress disorder (PTSD) is a complex and chronic disorder that causes substantial distress and interferes with social and educational functioning. Consequently, identifying the risk factors that make a child more likely to experience traumatic distress is of academic, clinical and social importance. This meta-analysis estimated the population effect sizes of 25 potential risk factors for PTSD in children and adolescents aged 6-18 years across 64 studies (N=32,238). Medium to large effect sizes were shown for many factors relating to subjective experience of the event and post-trauma variables (low social support, peri-trauma fear, perceived life threat, social withdrawal, comorbid psychological problem, poor family functioning, distraction, PTSD at time 1, and thought suppression); whereas pre-trauma variables and more objective measures of the assumed severity of the event

matched on Fear (mesh)

Sabatinelli D, Fortune EE, Li Q, Siddiqui A, Krafft C, Oliver WT, Beck S, Jeffries J (2011)meta-analysisMEDLINE-indexed journal, not yet read by usNeuroImage488 citations

Emotional perception: meta-analyses of face and natural scene processing.

Functional imaging studies of emotional processing typically contain neutral control conditions that serve to remove simple effects of visual perception, thus revealing the additional emotional process. Here we seek to identify similarities and differences across 100 studies of emotional face processing and 57 studies of emotional scene processing, using a coordinate-based meta-analysis technique. The overlay of significant meta-analyses resulted in extensive overlap in clusters, coupled with offset and unique clusters of reliable activity. The area of greatest overlap is the amygdala, followed by regions of medial prefrontal cortex, inferior frontal/orbitofrontal cortex, inferior temporal cortex, and extrastriate occipital cortex. Emotional face-specific clusters were identified in regions known to be involved in face processing, including anterior fusiform gyrus and middle temporal gyr

matched on Fear (mesh)

Burke BL, Martens A, Faucher EH (2010)meta-analysisMEDLINE-indexed journal, not yet read by usPersonality and social psychology review : an official journal of the Society for Personality and Social Psychology, Inc313 citations

Two decades of terror management theory: a meta-analysis of mortality salience research.

A meta-analysis was conducted on empirical trials investigating the mortality salience (MS) hypothesis of terror management theory (TMT). TMT postulates that investment in cultural worldviews and self-esteem serves to buffer the potential for death anxiety; the MS hypothesis states that, as a consequence, accessibility of death-related thought (MS) should instigate increased worldview and self-esteem defense and striving. Overall, 164 articles with 277 experiments were included. MS yielded moderate effects (r = .35) on a range of worldview- and self-esteem-related dependent variables (DVs), with effects increased for experiments using (a) American participants, (b) college students, (c) a longer delay between MS and the DV, and (d) people-related attitudes as the DV. Gender and self-esteem may moderate MS effects differently than previously thought. Results are compared to other reviews

matched on Fear (mesh)

Brewer NT, Salz T, Lillie SE (2007)meta-analysisMEDLINE-indexed journal, not yet read by usAnnals of internal medicine302 citations

Systematic review: the long-term effects of false-positive mammograms.

Background: Although abnormal screening mammograms deleteriously affect the psychological well-being of women during the time immediately surrounding the tests, their long-term effects are poorly understood. Purpose: To characterize the long-term effects of false-positive screening mammograms on the behavior and well-being of women 40 years of age or older. Data sources: English-language studies from the MEDLINE, Web of Science, EMBASE, CINAHL, PsycINFO, and ERIC databases through August 2006. Study selection: Studies were identified that examined the effects of false-positive results of routine screening mammography on women's behavior, well-being, or beliefs. Data extraction: Two investigators independently coded study characteristics, quality, and effect sizes. Data synthesis: 23 eligible studies (n = 313,967) were identified. A random-effects meta-analysis showed that U.S. women who

matched on Fear (mesh)

Lueken U, Straube B, Konrad C, Wittchen HU, Ströhle A, Wittmann A, Pfleiderer B, Uhlmann C, Arolt V, Jansen A, Kircher T (2013)randomised controlled trialMEDLINE-indexed journal, not yet read by usThe American journal of psychiatry83 citations

Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia.

Objective: Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia. Method: Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rati

matched on Amygdala (mesh), fear conditioning (text)

Llera SJ, Newman MG (2017)cohort or longitudinalMEDLINE-indexed journal, not yet read by usJournal of anxiety disorders44 citations

Development and validation of two measures of emotional contrast avoidance: The contrast avoidance questionnaires.

The Contrast Avoidance (CA) model (Newman & Llera, 2011) proposed that individuals with generalized anxiety disorder (GAD) fear sharp emotional shifts (or contrasts), such as the shift from a pleasant or neutral state to one of sudden distress following a negative event. Further, the model suggests that chronic worry is employed by those with GAD to sustain negative emotionality as a means to avoid sudden shifts into negativity. The model has received empirical support; however, no validated measure exists to assess CA tendencies. In this paper we developed and tested two measures of CA: one focusing on worry, and another examining broader mechanisms of CA that could be used test whether CA is applicable to other disorders. In Study 1, Part 1, we used 3 samples of participants (each N=410) to perform item reduction, exploratory factor analysis, and confirmatory factor analysis. In Study

matched on Fear (mesh), Avoidance Learning (mesh)

Prather AA, Bogdan R, Hariri AR (2013)cohort or longitudinalMEDLINE-indexed journal, not yet read by usPsychosomatic medicine93 citations

Impact of sleep quality on amygdala reactivity, negative affect, and perceived stress.

Objective: Research demonstrates a negative impact of sleep disturbance on mood and affect; however, the biological mechanisms mediating these links are poorly understood. Amygdala reactivity to negative stimuli has emerged as one potential pathway. Here, we investigate the influence of self-reported sleep quality on associations between threat-related amygdala reactivity and measures of negative affect and perceived stress. Methods: Analyses on data from 299 participants (125 men, 50.5% white, mean [standard deviation] age = 19.6 [1.3] years) who completed the Duke Neurogenetics Study were conducted. Participants completed several self-report measures of negative affect and perceived stress. Threat-related (i.e., angry and fearful facial expressions) amygdala reactivity was assayed using blood oxygen level-dependent functional magnetic resonance imaging. Global sleep quality was assesse

matched on Fear (mesh), Amygdala (mesh)

Prater KE, Hosanagar A, Klumpp H, Angstadt M, Phan KL (2013)cohort or longitudinalMEDLINE-indexed journal, not yet read by usDepression and anxiety167 citations

Aberrant amygdala-frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder.

Background: Generalized social anxiety disorder (gSAD) is characterized by exaggerated amygdala reactivity to social signals of threat, but if and how the amygdala interacts with functionally and anatomically connected prefrontal cortex (PFC) remains largely unknown. Recent evidence points to aberrant amygdala connectivity to medial PFC in gSAD at rest, but it is difficult to attribute functional relevance without the context of threat processing. Here, we address this by studying amygdala-frontal cortex connectivity during viewing of fearful faces and at rest in gSAD patients. Methods: Twenty patients with gSAD and 17 matched healthy controls (HCs) participated in functional magnetic resonance imaging of an emotional face matching task and a resting state task. Functional connectivity and psychophysiological interaction analysis were used to assess amygdala connectivity. Results: Compar

matched on Fear (mesh), Amygdala (mesh)

Simons LE, Sieberg CB, Carpino E, Logan D, Berde C (2011)cohort or longitudinalMEDLINE-indexed journal, not yet read by usThe journal of pain180 citations

The Fear of Pain Questionnaire (FOPQ): assessment of pain-related fear among children and adolescents with chronic pain.

Unlabelled: An important construct in understanding pain-related disability is pain-related fear. Heightened pain-related fear may result in behavioral avoidance leading to disuse, disability, and depression; whereas confrontation of avoided activities may result in a reduction of fear over time and reengagement with activities of daily living. Although there are several measures to assess pain-related fear among adults with chronic pain, none exist for children and adolescents. The aim of the current study was to develop a new tool to assess avoidance and fear of pain with pediatric chronic pain patients: the Fear of Pain Questionnaire, child report (FOPQ-C), and Fear of Pain Questionnaire, parent proxy report (FOPQ-P). After initial pilot testing, the FOPQ-C and FOPQ-P were administered to 299 youth with chronic pain and their parents at an initial multidisciplinary pain treatment eval

matched on Fear (mesh), Avoidance Learning (mesh)

Olatunji BO, Etzel EN, Tomarken AJ, Ciesielski BG, Deacon B (2011)cohort or longitudinalMEDLINE-indexed journal, not yet read by usBehaviour research and therapy101 citations

The effects of safety behaviors on health anxiety: an experimental investigation.

The present study examined the extent to which safety behaviors exacerbate symptoms of hypochondriasis (severe health anxiety). Participants were randomized into a safety behavior (n=30) or control condition (n=30). After a baseline period, participants in the safety behavior condition spent one week actively engaging in a clinically representative array of health-related safety behaviors on a daily basis, followed by a second week-long baseline period. Participants in the control condition monitored their normal use of safety behaviors. Compared to control participants, those in the safety behavior condition reported significantly greater increases in health anxiety, hypochondriacal beliefs, contamination fear, and avoidant responses to health-related behavioral tasks after the safety behavior manipulation. In contrast, general anxiety symptoms did not significantly differ between the t

matched on Fear (mesh), Avoidance Learning (mesh)

Fales CL, Barch DM, Rundle MM, Mintun MA, Mathews J, Snyder AZ, Sheline YI (2009)cohort or longitudinalMEDLINE-indexed journal, not yet read by usJournal of affective disorders198 citations

Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression.

Background: Major depression (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive amygdala activity and under-recruitment of dorsolateral prefrontal cortex (DLPFC). The purpose of this study was to examine the effects of antidepressant treatment on anomalous neural activity in cognitive-control and emotion-processing circuitry. Methods: Functional magnetic resonance imaging was conducted on depressed patients (n=23) (both before and after antidepressant treatment) compared with matched controls (n=18) while they performed a cognitive task involving attended and unattended fear-related stimuli. Results: After eight weeks of SSRI antidepressant treatment, patients with depression showed significantly increased DLPFC activity to unattended fear-related stimuli and no longer differed fr

matched on Fear (mesh), Amygdala (mesh)

Machado CJ, Bachevalier J (2008)cohort or longitudinalMEDLINE-indexed journal, not yet read by usPsychoneuroendocrinology68 citations

Behavioral and hormonal reactivity to threat: effects of selective amygdala, hippocampal or orbital frontal lesions in monkeys.

We compared the effects of bilateral amygdala, hippocampal or orbital frontal cortex lesions on emotional and hormonal reactivity in rhesus monkeys (Macaca mulatta). Experiment 1 measured behavioral reactivity to an unfamiliar human intruder before and after surgery. Animals with amygdala lesions demonstrated decreases in one passive defensive behavior (freezing), whereas animals with hippocampal lesions showed decreases in a more stimulus-directed defensive behavior (tooth grinding). Orbital frontal cortex lesions also reduced these two defensive behaviors, as well as decreased cage-shaking dominance displays. Animals with amygdala, hippocampal or sham lesions also demonstrated increased tension-related behaviors after surgery, but those with orbital frontal lesions did not. Finally, all three lesions diminished the operated animals' ability to modulate tension-related behaviors dependi

matched on Fear (mesh), Amygdala (mesh)

Monk CS, Klein RG, Telzer EH, Schroth EA, Mannuzza S, Moulton JL, Guardino M, Masten CL, McClure-Tone EB, Fromm S, Blair RJ, Pine DS, Ernst M (2008)cohort or longitudinalMEDLINE-indexed journal, not yet read by usThe American journal of psychiatry258 citations

Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression.

Objective: Offspring of parents with major depressive disorder face a threefold higher risk for major depression than offspring without such family histories. Although major depression is a significant cause of morbidity and mortality, neural correlates of risk for major depression remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for major depression under varying attentional and emotional conditions. Method: Thirty-nine juveniles, 17 offspring of parents with major depression (high-risk group) and 22 offspring of parents without histories of major depression, anxiety, or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials while attention was unconst

matched on Fear (mesh), Amygdala (mesh)

Stein MB, Simmons AN, Feinstein JS, Paulus MP (2007)cohort or longitudinalMEDLINE-indexed journal, not yet read by usThe American journal of psychiatry635 citations

Increased amygdala and insula activation during emotion processing in anxiety-prone subjects.

Objective: Increased amygdala reactivity during processing of certain types of emotional stimuli (e.g., fear, anger) has been observed in patients with anxiety disorders such as social phobia and posttraumatic stress disorder (PTSD). It is uncertain whether this heightened amygdala reactivity is specific to treatment-seeking patients with anxiety disorders or is a general feature of individuals with increased anxiety-related temperamental traits. Method: Thirty-two physically healthy subjects 18-21 years old were recruited from a large pool of college students. Of these, 16 were chosen on the basis of scoring in the upper-15th percentile on a measure of trait anxiety (anxiety-prone group), and 16 were chosen on the basis of scoring in the normative range (40th-60th percentile). Subjects participated in functional magnetic resonance imaging (fMRI) during an emotion face assessment task th

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McClure EB, Monk CS, Nelson EE, Parrish JM, Adler A, Blair RJ, Fromm S, Charney DS, Leibenluft E, Ernst M, Pine DS (2007)cohort or longitudinalMEDLINE-indexed journal, not yet read by usArchives of general psychiatry295 citations

Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.

Context: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. Objective: To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. Design: Case-control study. Setting: Government clinical research institute. Participants: Fifteen adolescents with generalized anxiety disorder and 20 controls. Main outcome measures: Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. Results: While attending to their own subjective fear, patien

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Larson CL, Schaefer HS, Siegle GJ, Jackson CA, Anderle MJ, Davidson RJ (2006)cohort or longitudinalMEDLINE-indexed journal, not yet read by usBiological psychiatry87 citations

Fear is fast in phobic individuals: amygdala activation in response to fear-relevant stimuli.

Background: Two core characteristics of pathologic fear are its rapid onset and resistance to cognitive regulation. We hypothesized that activation of the amygdala early in the presentation of fear-relevant visual stimuli would distinguish phobics from nonphobics. Methods: Chronometry of amygdala activation to phobia-relevant pictures was assessed in 13 spider phobics and 14 nonphobics using functional magnetic resonance imaging (fMRI). Results: Blood oxygen level-dependent (BOLD) responses in the amygdala early in picture processing consistently differentiated between phobic and nonphobic subjects, as well as between phobogenic and nonphobogenic stimuli among phobics. Furthermore, amygdalar BOLD responses associated with timing but not magnitude of activation predicted affective responses to phobogenic stimuli. Computational modeling procedures were used to identify patterns of neural a

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Klein AS, Dolensek N, Weiand C, Gogolla N (2021)MEDLINE-indexed journal, not yet read by usScience (New York, N.Y.)139 citations

Fear balance is maintained by bodily feedback to the insular cortex in mice.

How does the brain maintain fear within an adaptive range? We found that the insular cortex acts as a state-dependent regulator of fear that is necessary to establish an equilibrium between the extinction and maintenance of fear memories in mice. Whereas insular cortex responsiveness to fear-evoking cues increased with their certainty to predict harm, this activity was attenuated through negative bodily feedback that arose from heart rate decelerations during freezing. Perturbation of body-brain communication by vagus nerve stimulation disrupted the balance between fear extinction and maintenance similar to insular cortex inhibition. Our data reveal that the insular cortex integrates predictive sensory and interoceptive signals to provide graded and bidirectional teaching signals that gate fear extinction and illustrate how bodily feedback signals are used to maintain fear within a funct

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

Marin MF, Zsido RG, Song H, Lasko NB, Killgore WDS, Rauch SL, Simon NM, Milad MR (2017)MEDLINE-indexed journal, not yet read by usJAMA psychiatry104 citations

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

Importance: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders. Objectives: To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. Design, setting, and participants: This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study

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

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during

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McLaughlin KA, Sheridan MA, Gold AL, Duys A, Lambert HK, Peverill M, Heleniak C, Shechner T, Wojcieszak Z, Pine DS (2016)MEDLINE-indexed journal, not yet read by usNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology203 citations

Maltreatment Exposure, Brain Structure, and Fear Conditioning in Children and Adolescents.

Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited

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Reznikov R, Diwan M, Nobrega JN, Hamani C (2015)MEDLINE-indexed journal, not yet read by usJournal of psychiatric research27 citations

Towards a better preclinical model of PTSD: characterizing animals with weak extinction, maladaptive stress responses and low plasma corticosterone.

Most of the available preclinical models of PTSD have focused on isolated behavioural aspects and have not considered individual variations in response to stress. We employed behavioural criteria to identify and characterize a subpopulation of rats that present several features analogous to PTSD-like states after exposure to classical fear conditioning. Outbred Sprague-Dawley rats were segregated into weak- and strong-extinction groups on the basis of behavioural scores during extinction of conditioned fear responses. Animals were subsequently tested for anxiety-like behaviour in the open-field test (OFT), novelty suppressed feeding (NSF) and elevated plus maze (EPM). Baseline plasma corticosterone was measured prior to any behavioural manipulation. In a second experiment, rats underwent OFT, NSF and EPM prior to being subjected to fear conditioning to ascertain whether or not pre-stress

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

Graham BM, Milad MR (2013)MEDLINE-indexed journal, not yet read by usBiological psychiatry242 citations

Blockade of estrogen by hormonal contraceptives impairs fear extinction in female rats and women.

Background: Fear extinction is a laboratory model of fear inhibition and is the basis of exposure therapy for anxiety disorders. Emerging evidence from naturally cycling female rodents and women indicates that estrogens are necessary to the consolidation of fear extinction. Hormonal contraceptives (HCs) inhibit estrogen production; yet, their effects on fear extinction are unknown. Methods: We used a cross-species translational approach to investigate the impact of HCs and estradiol supplementation on fear extinction in healthy women (n=76) and female rats (n = 140). Results: Women using HCs exhibited significantly poorer extinction recall compared with naturally cycling women. The extinction impairment was also apparent in HC-treated female rats and was associated with reduced serum estradiol levels. The impairment could be rescued in HC-treated rats either by terminating HC treatment a

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Peña DF, Engineer ND, McIntyre CK (2013)MEDLINE-indexed journal, not yet read by usBiological psychiatry122 citations

Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation.

Background: Fearful experiences can produce long-lasting and debilitating memories. Extinction of conditioned fear requires consolidation of new memories that compete with fearful associations. In human subjects, as well as rats, posttraining stimulation of the vagus nerve enhances memory consolidation. Subjects with posttraumatic stress disorder show impaired extinction of conditioned fear. The objective of this study was to determine whether vagus nerve stimulation (VNS) can enhance the consolidation of extinction of conditioned fear. Methods: Male Sprague-Dawley rats were trained on an auditory fear conditioning task followed by 1 to 10 days of extinction training. Treatment with vagus nerve or sham stimulation was administered concurrently with exposure to the fear conditioned stimulus. Another group was given VNS and extinction training but the VNS was not paired with exposure to co

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