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Fear learning and extinction

How fear is learned, held and unlearned.

Everything below was reached through this subject, not through the words you typed. Every row states how it was reached.

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

426 to 450 of 1,226
Collimore KC, Carleton RN, Hofmann SG, Asmundson GJ (2010)reviewMEDLINE-indexed journal, not yet read by usDepression and anxiety47 citations

Posttraumatic stress and social anxiety: the interaction of traumatic events and interpersonal fears.

Posttraumatic stress disorder (PTSD) and social anxiety disorder (SAD) are frequently comorbid among veteran and community samples. Several studies have demonstrated significant comorbidity between trauma, PTSD, and social anxiety (SA), and a growing number of studies have explored the nature of this association. Although a diagnosis of either PTSD or SAD alone can result in significant impairment in social and occupational functioning, these difficulties are often magnified in persons suffering from both disorders. This review describes the current state-of-the-art regarding the co-occurrence of trauma, PTSD, and SA. First, we provide an overview of empirical data on the prevalence of co-occurring trauma, PTSD, and SAD. Second, we describe possible explanatory models of the co-occurrence, with a specific focus on the shared vulnerability model. Third, we review the available empirical d

matched on Fear (mesh)

Ghitza UE, Zhai H, Wu P, Airavaara M, Shaham Y, Lu L (2010)reviewMEDLINE-indexed journal, not yet read by usNeuroscience and biobehavioral reviews173 citations

Role of BDNF and GDNF in drug reward and relapse: a review.

Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that are critical for the growth, survival, and differentiation of developing neurons. These neurotrophic factors also play important roles in the survival and function of adult neurons, learning and memory, and synaptic plasticity. Since the mid-1990s, investigators have studied the role of BDNF and GDNF in the behavioral effects of abused drugs and in the neuroadaptations induced by repeated exposure to drugs in the mesocorticolimbic dopamine system. Here, we review rodent studies on the role of BDNF and GDNF in drug reward, as assessed in the drug self-administration and the conditioned place preference procedures, and in drug relapse, as assessed in extinction and reinstatement procedures. Our main conclusion is that whether BDNF or GDNF would facilitate or inhibit

matched on Extinction, Psychological (mesh)

Bailey KM, Carleton RN, Vlaeyen JW, Asmundson GJ (2010)reviewMEDLINE-indexed journal, not yet read by usCognitive behaviour therapy109 citations

Treatments addressing pain-related fear and anxiety in patients with chronic musculoskeletal pain: a preliminary review.

This review covers the current cognitive behavioural treatments available to address fear-avoidance beliefs in patients with chronic musculoskeletal pain (CMP). Four types of treatment protocols were identified for inclusion in the review: (a) graded in vivo exposure (GivE); (b) graded activity (GA); (c) acceptance and commitment therapy (ACT); and (d) mixed cognitive behavioural protocols. Most of the research suggests that GivE and ACT result in the best outcomes for treating fear-avoidance beliefs in patients with CMP. There is also a readily apparent paucity of research from North America; indeed, most of the available studies were conducted in the Netherlands and Scandinavia. This relative absence of North American research raises potentially important questions about the role of compensation status and access to care, which differ between countries, on treatment outcome. Implicatio

matched on Fear (mesh)

Shin LM, Liberzon I (2010)reviewMEDLINE-indexed journal, not yet read by usNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology1,338 citations

The neurocircuitry of fear, stress, and anxiety disorders.

Anxiety disorders are a significant problem in the community, and recent neuroimaging research has focused on determining the brain circuits that underlie them. Research on the neurocircuitry of anxiety disorders has its roots in the study of fear circuits in animal models and the study of brain responses to emotional stimuli in healthy humans. We review this research, as well as neuroimaging studies of anxiety disorders. In general, these studies have reported relatively heightened amygdala activation in response to disorder-relevant stimuli in post-traumatic stress disorder, social phobia, and specific phobia. Activation in the insular cortex appears to be heightened in many of the anxiety disorders. Unlike other anxiety disorders, post-traumatic stress disorder is associated with diminished responsivity in the rostral anterior cingulate cortex and adjacent ventral medial prefrontal co

matched on Fear (mesh)

Domes G, Schulze L, Herpertz SC (2009)reviewMEDLINE-indexed journal, not yet read by usJournal of personality disorders189 citations

Emotion recognition in borderline personality disorder-a review of the literature.

Borderline personality disorder (BPD) is characterized by distinct impairments in emotion regulation, resulting in affective instability especially in the social context. It has been suggested that impaired social cognitive functioning such as impaired facial emotion recognition contributes to the social disturbances in BPD. In accordance with this notion, a number of behavioral studies have revealed a pattern of alterations in facial emotion recognition associated with BPD: subtle impairments in basic emotion recognition, a negativity or anger bias, and a heightened sensitivity to the detection of negative emotions. Furthermore, there is increasing evidence for structural and functional changes in the neural networks underlying affective dysregulation and emotional hyperreactivity in BPD. Merging these lines of evidence, we propose that emotional hyperreactivity interferes with the cogn

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Craske MG, Rauch SL, Ursano R, Prenoveau J, Pine DS, Zinbarg RE (2009)reviewMEDLINE-indexed journal, not yet read by usDepression and anxiety318 citations

What is an anxiety disorder?

Initiated as part of the ongoing deliberation about the nosological structure of DSM, this review aims to evaluate whether the anxiety disorders share features of responding that define them and make them distinct from depressive disorders, and/or that differentiate fear disorders from anxious-misery disorders. The review covers symptom self-report as well as on-line indices of behavioral, physiological, cognitive, and neural responding in the presence of aversive stimuli. The data indicate that the anxiety disorders share self-reported symptoms of anxiety and fear; heightened anxiety and fear responding to cues that signal threat, cues that signal no threat, cues that formerly signaled threat, and contexts associated with threat; elevated stress reactivity to aversive stimuli; attentional biases to threat-relevant stimuli and threat-based appraisals of ambiguous stimuli; and elevated am

matched on Fear (mesh)

Bodner E (2009)reviewMEDLINE-indexed journal, not yet read by usInternational psychogeriatrics51 citations

On the origins of ageism among older and younger adults.

Background: Ageism is apparent in many social structures and contexts and in diverse forms over the life cycle. This review discusses the development and consequences of ageism toward elderly people by others of any age, according to the Terror Management Theory (TMT) and the Social Identity Theory (SIT). Method: A systematic search of the literature was carried out on the social and psychological origins of ageism in younger and older adults. Results: Studies on the reasons for ageism among older adults point to attitudes that older adults have toward their own age group, while studies on ageism in young adults explain it as an unconscious defensive strategy which younger adults use against death anxiety. In other words, TMT can serve as a suitable framework for ageism in younger adults, and SIT appears to explain ageism in older adults. Conclusions: A dissociation of the linkage betwee

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Benedetti F (2008)reviewMEDLINE-indexed journal, not yet read by usAnnual review of pharmacology and toxicology248 citations

Mechanisms of placebo and placebo-related effects across diseases and treatments.

The placebo effect has evolved from being thought of as a nuisance in clinical and pharmacological research to a biological phenomenon worthy of scientific investigation in its own right. It is now clear that the term placebo effect is too restrictive and, in fact, many placebo-related effects have recently been investigated. A placebo effect differs from a placebo-like effect in that the former follows the administration of a placebo, whereas in the latter no placebo is administered. However, in both cases, the psychosocial context around the treatment plays a key role. In recent years, placebo and placebo-related effects have been analyzed with sophisticated biological tools that have uncovered specific mechanisms at both the biochemical and cellular level. This recent research has revealed that these psychosocial-induced biochemical changes in a patient's brain and body in turn may af

matched on Conditioning, Classical (mesh)

Bishop SJ (2008)reviewMEDLINE-indexed journal, not yet read by usAnnals of the New York Academy of Sciences237 citations

Neural mechanisms underlying selective attention to threat.

Biased competition models of selective attention suggest that attentional competition is influenced both by bottom-up sensory mechanisms sensitive to stimulus salience and top-down control mechanisms that support the processing of task-relevant stimuli. This provides a framework for investigating the neural mechanisms underlying selective attention to threat. Both subcortical regions implicated in threat detection--specifically the amygdala--and prefrontal cortical regions implicated in top-down attentional control are activated in response to task-irrelevant threat stimuli. A number of questions including the automaticity of the amygdala response to threat distractors, the modulation by anxiety of the amygdala and prefrontal response to these stimuli, and the impact of genetic and environmental factors upon this circuitry are addressed. The empirical literature is considered in the cont

matched on Fear (mesh)

Foster S, Giles-Corti B (2008)reviewMEDLINE-indexed journal, not yet read by usPreventive medicine279 citations

The built environment, neighborhood crime and constrained physical activity: an exploration of inconsistent findings.

Objectives: Personal safety is commonly cited in qualitative research as a barrier to local walking, yet the relationship between safety and constrained physical activity has received mixed support in quantitative studies. This paper reviews the quantitative evidence to date, seeking to explain the inconsistencies, and offers recommendations for future research. Methods: A social-ecological framework was adopted to explore the evidence linking crime-related safety, and factors that influence real and perceived safety, with constrained physical activity. Results: Perceived safety tends to affect the physical activity of groups already known to exhibit greater anxiety about crime; and some elements of the built environment that influence safety appear to constrain physical activity. However the evidence is somewhat inconsistent, and this may be partly attributed to measurement limitations.

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Moreira FA, Lutz B (2008)reviewMEDLINE-indexed journal, not yet read by usAddiction biology154 citations

The endocannabinoid system: emotion, learning and addiction.

The identification of the cannabinoid receptor type 1 (CB1 receptor) was the milestone discovery in the elucidation of the behavioural and emotional responses induced by the Cannabis sativa constituent Delta(9)-tetrahydrocannabinol. The subsequent years have established the existence of the endocannabinoid system. The early view relating this system to emotional responses is reflected by the fact that N-arachidonoyl ethanolamine, the pioneer endocannabinoid, was named anandamide after the Sanskrit word 'ananda', meaning 'bliss'. However, the emotional responses to cannabinoids are not always pleasant and delightful. Rather, anxiety and panic may also occur after activation of CB1 receptors. The present review discusses three properties of the endocannabinoid system as an attempt to understand these diverse effects. First, this system typically functions 'on-demand', depending on environm

matched on Fear (mesh)

Grillon C (2008)reviewMEDLINE-indexed journal, not yet read by usPsychopharmacology306 citations

Models and mechanisms of anxiety: evidence from startle studies.

Rationale: Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by flight or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). Objective: The objectives of the study are to (1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, (2) describe experimental models of anxiety, as opposed to fear, in humans, (3) examine the relevance of these models to clinical anxiety. Results: The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies

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Hofmann SG (2007)reviewMEDLINE-indexed journal, not yet read by usBehaviour research and therapy82 citations

Enhancing exposure-based therapy from a translational research perspective.

Combining an effective psychological treatment with conventional anxiolytic medication is typically not more effective than unimodal therapy for treating anxiety disorders. However, recent advances in the neuroscience of fear reduction have led to novel approaches for combining psychological therapy and pharmacological agents. Exposure-based treatments in humans partly rely on extinction to reduce the fear response in anxiety disorders. Animal studies have shown that D-cycloserine (DCS), a partial agonist at the glycine recognition site of the glutamatergic N-methyl-D-aspartate receptor facilitates extinction learning. Similarly, recent human trials have shown that DCS enhances fear reduction during exposure therapy of some anxiety disorders. This article discusses the biological and psychological mechanisms of extinction learning and the therapeutic value of DCS as an augmentation strat

matched on Extinction, Psychological (mesh)

Benedetti F, Lanotte M, Lopiano L, Colloca L (2007)reviewMEDLINE-indexed journal, not yet read by usNeuroscience336 citations

When words are painful: unraveling the mechanisms of the nocebo effect.

The nocebo effect is a phenomenon that is opposite to the placebo effect, whereby expectation of a negative outcome may lead to the worsening of a symptom. Thus far, its study has been limited by ethical constraints, particularly in patients, as a nocebo procedure is per se stressful and anxiogenic. It basically consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Although some natural nocebo situations do exist, such as the impact of negative diagnoses upon the patient and the patient's distrust in a therapy, the neurobiological mechanisms have been understood in the experimental setting under strictly controlled conditions. As for the placebo counterpart, the study of pain has been fruitful in recent years to understand both the neuroanatomical and the neurochemical bases of the nocebo effect. Recent experimental evidence indica

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Cortese BM, Phan KL (2005)reviewMEDLINE-indexed journal, not yet read by usCNS spectrums149 citations

The role of glutamate in anxiety and related disorders.

Anxiety, stress, and trauma-related disorders are a major public health concern in the United States. Drugs that target the gamma-aminobutyric acid or serotonergic system, such as benzodiazepines and selective serotonin reuptake inhibitors, respectively, are the most widely prescribed treatments for these disorders. However, the role of glutamate in anxiety disorders is becoming more recognized with the belief that drugs that modulate glutamatergic function through either ionotropic or metabotropic glutamate receptors have the potential to improve the current treatment of these severe and disabling illnesses. Animal models of fear and anxiety have provided a method to study the role of glutamate in anxiety. This research has demonstrated that drugs that alter glutamate transmission have potential anxiolytic action for many different paradigms including fear-potentiated startle, punished

matched on Fear (mesh)

Weiss F (2005)reviewMEDLINE-indexed journal, not yet read by usCurrent opinion in pharmacology283 citations

Neurobiology of craving, conditioned reward and relapse.

Chronic vulnerability to relapse is a formidable challenge for the treatment of drug addiction. The neurobiological basis of relapse and its prevention has, therefore, attracted major attention in addiction research. Current conceptualizations of addiction recognize craving as a central driving force for ongoing drug use, as well as for relapse following abstinence. Progress has been made in understanding experiential factors, neurocircuitry components and signaling mechanisms that mediate conditioned drug-seeking behaviour, craving and long-lasting susceptibility to relapse. Importantly, stress contributes to drug craving, and there is evidence for overlap between the neural and neuroendocrine mechanisms implicated in drug desire evoked by drug cues and stress. Recent research has substantially advanced our understanding of the neurobiological factors responsible for drug craving and re

matched on Conditioning, Classical (mesh)

Giustino TF, Maren S (2015)reviewMEDLINE-indexed journal, not yet read by usFrontiers in behavioral neuroscience429 citations

The Role of the Medial Prefrontal Cortex in the Conditioning and Extinction of Fear.

Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD). As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL) and i

matched on Fear (keyword), fear conditioning (text)

Simons LE, Elman I, Borsook D (2014)reviewMEDLINE-indexed journal, not yet read by usNeuroscience and biobehavioral reviews271 citations

Psychological processing in chronic pain: a neural systems approach.

Our understanding of chronic pain involves complex brain circuits that include sensory, emotional, cognitive and interoceptive processing. The feed-forward interactions between physical (e.g., trauma) and emotional pain and the consequences of altered psychological status on the expression of pain have made the evaluation and treatment of chronic pain a challenge in the clinic. By understanding the neural circuits involved in psychological processes, a mechanistic approach to the implementation of psychology-based treatments may be better understood. In this review we evaluate some of the principle processes that may be altered as a consequence of chronic pain in the context of localized and integrated neural networks. These changes are ongoing, vary in their magnitude, and their hierarchical manifestations, and may be temporally and sequentially altered by treatments, and all contribute

matched on Fear (keyword), Amygdala (keyword)

Andero R, Choi DC, Ressler KJ (2014)reviewMEDLINE-indexed journal, not yet read by usProgress in molecular biology and translational science129 citations

BDNF-TrkB receptor regulation of distributed adult neural plasticity, memory formation, and psychiatric disorders.

Brain-derived neurotrophic factor (BDNF) and its single transmembrane receptor, tropomysin-related kinase B (TrkB), are essential for adult synaptic plasticity and the formation of memories. However, there are regional and task-dependent differences underlying differential mechanisms of BDNF-TrkB function in the formation of these memories. Additionally, the BDNF pathway has been implicated in several psychiatric disorders including posttraumatic stress disorder, phobia, and panic disorder. Gaining a better understanding of this pathway and the neurobiology of memory through fundamental research may be helpful to identify effective prevention and treatment approaches both for diseases of memory deficit as well as in cases of enhanced aversive memory, such as in anxiety disorders.

matched on Fear (keyword), Amygdala (keyword)

Craske MG, Treanor M, Zbozinek TD, Vervliet B (2022)MEDLINE-indexed journal, not yet read by usBehaviour research and therapy98 citations

Optimizing exposure therapy with an inhibitory retrieval approach and the OptEx Nexus.

Research from recent decades has highlighted the distinction between excitatory and inhibitory Pavlovian learning mechanisms. Based on this distinction, state-of-the-art exposure therapy for anxiety disorders emphasizes inhibitory learning and retrieval as its primary mechanism for long-term reduction in fear, anxiety, and avoidance. Seven years ago, we (Craske, et al., 2014) summarized exposure therapy from an inhibitory learning approach, focusing on eight exposure optimization strategies. Here, we update this model based on recent work and describe how to conduct exposure therapy from an inhibitory retrieval approach and encourage further empirical investigation of its basic premises. To this end, we guide the reader in the use of the OptEx Nexus: a clinician's tool for conducting exposure therapy from an inhibitory retrieval approach. We categorize exposure strategies as fundamental

matched on Extinction, Psychological (mesh), Fear (mesh)

Zhou F, Zhao W, Qi Z, Geng Y, Yao S, Kendrick KM, Wager TD, Becker B (2021)MEDLINE-indexed journal, not yet read by usNature communications118 citations

A distributed fMRI-based signature for the subjective experience of fear.

The specific neural systems underlying the subjective feeling of fear are debated in affective neuroscience. Here, we combine functional MRI with machine learning to identify and evaluate a sensitive and generalizable neural signature predictive of the momentary self-reported subjective fear experience across discovery (n = 67), validation (n = 20) and generalization (n = 31) cohorts. We systematically demonstrate that accurate fear prediction crucially requires distributed brain systems, with important contributions from cortical (e.g., prefrontal, midcingulate and insular cortices) and subcortical (e.g., thalamus, periaqueductal gray, basal forebrain and amygdala) regions. We further demonstrate that the neural representation of subjective fear is distinguishable from the representation of conditioned threat and general negative affect. Overall, our findings suggest that subjective fea

matched on Conditioning, Classical (mesh), Fear (mesh)

Iino Y, Sawada T, Yamaguchi K, Tajiri M, Ishii S, Kasai H, Yagishita S (2020)MEDLINE-indexed journal, not yet read by usNature167 citations

Dopamine D2 receptors in discrimination learning and spine enlargement.

Dopamine D2 receptors (D2Rs) are densely expressed in the striatum and have been linked to neuropsychiatric disorders such as schizophrenia1,2. High-affinity binding of dopamine suggests that D2Rs detect transient reductions in dopamine concentration (the dopamine dip) during punishment learning3-5. However, the nature and cellular basis of D2R-dependent behaviour are unclear. Here we show that tone reward conditioning induces marked stimulus generalization in a manner that depends on dopamine D1 receptors (D1Rs) in the nucleus accumbens (NAc) of mice, and that discrimination learning refines the conditioning using a dopamine dip. In NAc slices, a narrow dopamine dip (as short as 0.4 s) was detected by D2Rs to disinhibit adenosine A2A receptor (A2AR)-mediated enlargement of dendritic spines in D2R-expressing spiny projection neurons (D2-SPNs). Plasticity-related signalling by Ca2+/calmod

matched on Conditioning, Classical (mesh), Extinction, Psychological (mesh)

Jhang J, Lee H, Kang MS, Lee HS, Park H, Han JH (2018)MEDLINE-indexed journal, not yet read by usNature communications143 citations

Anterior cingulate cortex and its input to the basolateral amygdala control innate fear response.

Prefrontal brain areas are implicated in the control of fear behavior. However, how prefrontal circuits control fear response to innate threat is poorly understood. Here, we show that the anterior cingulate cortex (ACC) and its input to the basolateral nucleus of amygdala (BLA) contribute to innate fear response to a predator odor in mice. Optogenetic inactivation of the ACC enhances freezing response to fox urine without affecting conditioned freezing. Conversely, ACC stimulation robustly inhibits both innate and conditioned freezing. Circuit tracing and slice patch recordings demonstrate a monosynaptic glutamatergic connectivity of ACC-BLA but no or very sparse ACC input to the central amygdala. Finally, our optogenetic manipulations of the ACC-BLA projection suggest its inhibitory control of innate freezing response to predator odors. Together, our results reveal the role of the ACC a

matched on Conditioning, Classical (mesh), Fear (mesh)

Martin-Fardon R, Baptista MA, Dayas CV, Weiss F (2009)MEDLINE-indexed journal, not yet read by usThe Journal of pharmacology and experimental therapeutics84 citations

Dissociation of the effects of MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]piperidine] on conditioned reinstatement and reinforcement: comparison between cocaine and a conventional reinforcer.

To advance understanding of the potential of metabotropic glutamate receptor (mGluR) 5 as treatment targets for cocaine addiction, the effects of MTEP [3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]piperidine] (a selective mGluR5 antagonist) on conditioned reinstatement of cocaine seeking were examined. To test whether modification of conditioned reinstatement by MTEP is selective for drug-directed behavior or reflects general actions on motivated behavior, effects of MTEP on reinstatement induced by a stimulus conditioned to palatable conventional reward, sweetened condensed milk (SCM), were also evaluated. Previous data suggest that mGluR manipulations preferentially interfere with conditioned reinstatement compared with cocaine self-administration. Therefore, the effects of MTEP on cocaine self-administration were compared with MTEP's effects on SCM-reinforced behavior using the same cocaine

matched on Conditioning, Classical (mesh), Extinction, Psychological (mesh)

Zimmermann KS, Richardson R, Baker KD (2019)reviewMEDLINE-indexed journal, not yet read by usBrain sciences78 citations

Maturational Changes in Prefrontal and Amygdala Circuits in Adolescence: Implications for Understanding Fear Inhibition during a Vulnerable Period of Development.

Anxiety disorders that develop in adolescence represent a significant burden and are particularly challenging to treat, due in no small part to the high occurrence of relapse in this age group following exposure therapy. This pattern of persistent fear is preserved across species; relative to those younger and older, adolescents consistently show poorer extinction, a key process underpinning exposure therapy. This suggests that the neural processes underlying fear extinction are temporarily but profoundly compromised during adolescence. The formation, retrieval, and modification of fear- and extinction-associated memories are regulated by a forebrain network consisting of the prefrontal cortex (PFC), the amygdala, and the hippocampus. These regions undergo robust maturational changes in early life, with unique alterations in structure and function occurring throughout adolescence. In thi

matched on fear extinction (text), Amygdala (keyword)