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.
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.
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!’
مِن شَرِّ ٱلۡوَسۡوَاسِ ٱلۡخَنَّاسِ
against the harm of the slinking whisperer––
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
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
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.’
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
Commentary on the verses above, at most two editions per verse.
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
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.
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
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
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
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
Arabic originals, reached through the subject’s Arabic senses. Interpretive sources, never proof of a ruling.
وجملة أدب المريض حسن الصبر وقلة الشكوى والضجر والفزع إلى الدعاء والتوكل بعد الدواء على خالق الدواء
وجملة آداب المريض: حسن الصبر، وقلة الشكوى والتضجر، والفزع إلى #
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
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
| الفصل الرابع في اذكار الفزع في النوم والفكر
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
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.
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
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).
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
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
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
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
Neural responses of OCD patients towards disorder-relevant, generally disgust-inducing and fear-inducing pictures.
This functional magnetic resonance imaging study investigated the disgust- and fear-reactivity of patients suffering from obsessive-compulsive disorder (OCD). Ten OCD patients were scanned while viewing blocks of pictures showing OCD triggers from their personal environment and OCD-irrelevant disgust-inducing, fear-inducing and neutral scenes. Afterwards, the patients rated the intensity of the induced disgust, fear and OCD symptoms. The responses were compared with those of 10 healthy control subjects. The disorder-relevant pictures provoked intense OCD symptoms in the clinical group associated with increased activation in the bilateral prefrontal cortex, the left insula, the right supramarginal gyrus, the left caudate nucleus and the right thalamus. The patients gave higher disgust and fear ratings than the controls for all aversive picture categories. Neural responses towards the diso…
matched on Fear (mesh)
A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis.
Background: Generalized anxiety disorder (GAD) is a prevalent anxiety disorder, but its neurobiological basis has been poorly studied. A few cognitive models have been proposed for understanding GAD development and maintenance. The aim of this study is to review functional Magnetic Resonance Image (fMRI) studies conducted with GAD patients and evaluate if they support and underpin the theoretical cognitive models proposed for this anxiety disorder. Methods: A literature systematic review was undertaken in PubMed and ISI databases with no time limits. Results: From the studies included in this review, 10 explored the "emotional dysregulation model", showing, prefrontal cortex (PFC) and anterior cingulate cortex (ACC) hypofunction and deficient top-down control system during emotion regulation tasks, despite conflicting techniques and results. Only one study explored the "conditioned fear …
matched on Amygdala (mesh)
Dopamine is necessary for cue-dependent fear conditioning.
Dopamine (DA) is implicated in many behaviors, including motor function, cognition, and reward processing; however, the role of DA in fear processing remains equivocal. To examine the role of DA in fear-related learning, dopamine-deficient (DD) mice were tested in a fear-potentiated startle paradigm. DA synthesis can be restored in DD mice through administration of 3, 4-dihydroxy-l-phenylalanine (l-Dopa), thereby permitting the assessment of fear processing in either a DA-depleted or -replete state. Fear-potentiated startle was absent in DD mice but could be restored by l-Dopa administration immediately after fear conditioning. Selective viral-mediated restoration of DA synthesis within the ventral tegmental area fully restored fear learning in DD mice, and restoration of DA synthesis to DA neurons projecting to the basolateral amygdala restored short-term memory but not long-term memory…
matched on Fear (mesh), fear conditioning (text)
Functional Neuroanatomy of Emotion and Its Regulation in PTSD.
Posttraumatic stress disorder (PTSD) is a devastating disorder, linked to profound mental, physical, occupational, and functional impairment. In addition, it is a highly complex disorder, characterized by symptom heterogeneity across multiple domains. Nevertheless, emotion dysregulation arising from the exaggerated response to threat or from the inability to regulate negative emotional states plays a defining role in the pathophysiology of PTSD. In order to improve our understanding of how emotion dysregulation manifests in this illness, functional neuroimaging research over the past 20 years provides great insight into underlying neuroanatomy of each component of emotion dysregulation in the context of PTSD. While prior reviews exist on the topic of neuroimaging findings in PTSD, the present review synthesizes that work through the lens of emotion and its regulation. Studies that employ…
matched on Extinction, Psychological (mesh), Fear (mesh)
Stress, glucocorticoids and memory: implications for treating fear-related disorders.
Glucocorticoid stress hormones are crucially involved in modulating mnemonic processing of emotionally arousing experiences. They enhance the consolidation of new memories, including those that extinguish older memories, but impair the retrieval of information stored in long-term memory. As strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias, the memory-modulating properties of glucocorticoids have recently become of considerable translational interest. Clinical trials have provided the first evidence that glucocorticoid-based pharmacotherapies aimed at attenuating aversive memories might be helpful in the treatment of fear-related disorders. Here, we review important advances in the understanding of how glucocorticoids mediate stress effects on memory processes, and discuss the translational potential of these …
matched on Extinction, Psychological (mesh), Fear (mesh)
Animal models of fear relapse.
Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans.
matched on Extinction, Psychological (mesh), Fear (mesh)
Implications of memory modulation for post-traumatic stress and fear disorders.
Post-traumatic stress disorder, panic disorder and phobia manifest in ways that are consistent with an uncontrollable state of fear. Their development involves heredity, previous sensitizing experiences, association of aversive events with previous neutral stimuli, and inability to inhibit or extinguish fear after it is chronic and disabling. We highlight recent progress in fear learning and memory, differential susceptibility to disorders of fear, and how these findings are being applied to the understanding, treatment and possible prevention of fear disorders. Promising advances are being translated from basic science to the clinic, including approaches to distinguish risk versus resilience before trauma exposure, methods to interfere with fear development during memory consolidation after a trauma, and techniques to inhibit fear reconsolidation and to enhance extinction of chronic fea…
matched on Extinction, Psychological (mesh), Fear (mesh)
Impaired safety signal learning may be a biomarker of PTSD.
A dysregulated fear response is one of the hallmark clinical presentations of patients suffering from posttraumatic stress disorder (PTSD). These patients show over-generalization of fear and in tandem an inability to inhibit fear responses in the presence of safety. Here, we summarize our recent findings using a conditional discrimination paradigm, which assesses safety signal processing (AX+/BX-) in combat and civilian PTSD populations. Overall, PTSD subjects demonstrate a lack of safety signal learning and an inability to modulate the fear responses with safety cues. We then review studies of the neurobiology of fear expression and inhibition in humans and non-humans, in order to provide a background for preliminary studies using reverse translation procedures in which the same AX+/BX- paradigm was used in rhesus macaques. This article is part of a Special Issue entitled 'Post-Traumat…
matched on Extinction, Psychological (mesh), Fear (mesh)
Treatment of addiction and anxiety using extinction approaches: neural mechanisms and their treatment implications.
Clinical interventions which produce cue and contextual extinction learning can reduce craving and relapse in substance abuse and inhibit conditioned fear responses in anxiety disorders. In both types of disorders, classical conditioning links unconditioned drug or fear responses to associated contextual cues and result in enduring pathological responses to multiple stimuli. Extinction therapy countermeasures seek to reduce conditioned responses using a set of techniques in which patients are repeatedly exposed to conditioned appetitive or aversive stimuli using imaginal imagery, in vivo exposure, or written scripts. Such interventions allow patients to rehearse more adaptive responses to conditioned stimuli. The ultimate goal of these interventions, extinction of the original conditioned response, is a new learning process that results in a decrease in frequency or intensity of conditio…
matched on Conditioning, Classical (mesh), Fear (mesh)
Noradrenergic modulation of extinction learning and exposure therapy.
Memory consolidation is enhanced by emotional arousal, an effect mediated by noradrenergic beta-receptor signaling. Norepinephrine strengthens consolidation of both appetitive and aversive learning, and is implicated in extinction of conditioned responses. In this review, we summarize work on the noradrenergic mechanisms of extinction learning and implications for extinction-based exposure therapy. The evidence suggests that norepinephrine release evoked by conditioned stimuli during extinction strengthens extinction memory via beta-receptor signaling. The modulatory effect of norepinephrine during extinction depends on predictable presentation of conditioned stimuli and optimal levels of norepinephrine release. Mechanistically, norepinephrine acts to increase cellular excitability and enhance synaptic plasticity within extinction-related neural circuitry. Currently, drugs that modulate …
matched on Extinction, Psychological (mesh), Fear (mesh)
Encoding of contextual fear memory in hippocampal-amygdala circuit.
In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal-amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1-BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and syna…
matched on Fear (mesh), Amygdala (mesh), Avoidance Learning (mesh), fear conditioning (text)
Personalized fMRI-Guided TMS Targeting the Threat Neurocircuitry in PTSD: A Randomized Clinical Trial.
Objective: Transcranial magnetic stimulation (TMS) has shown promise in reducing posttraumatic stress disorder (PTSD) symptoms, with varied clinical results. A mechanistic understanding is needed to personalize treatment and improve response rates. The threat neurocircuitry, specifically the right amygdala, has consistently been implicated in PTSD pathophysiology. This neuroscience-informed trial aimed to modulate the threat neurocircuitry using functional MRI (fMRI)-guided TMS to treat PTSD. Methods: In a double-blind clinical trial, 50 adults with PTSD symptoms were randomized to 10 twice-daily sessions of either 1-Hz TMS or sham TMS. TMS was delivered to an fMRI-guided target within the right dorsolateral prefrontal cortex with the strongest functional connection to the right amygdala. The primary outcomes were right amygdala threat reactivity, assessed by fMRI, and skin conductance r…
matched on Amygdala (mesh)
A Randomized Controlled Trial of a Parenting Intervention During Infancy Alters Amygdala-Prefrontal Circuitry in Middle Childhood.
Objective: Early adverse parenting predicts various negative outcomes, including psychopathology and altered development. Animal work suggests that adverse parenting might change amygdala-prefrontal cortex (PFC) circuitry, but work in humans remains correlational. The present study leveraged data from a randomized controlled trial examining the efficacy of an early parenting intervention targeting parental nurturance and sensitivity (Attachment and Biobehavioral Catch-up [ABC]) to test whether early parenting quality causally affects amygdala-PFC connectivity later in life. Method: Participants (N = 60, mean age = 10.0 years) included 41 high-risk children whose parents were referred by Child Protective Services and randomly assigned to receive either ABC (n = 21) or a control intervention (n = 20) during the children's infancy and a comparison sample of low-risk children (n = 19). Amygd…
matched on Amygdala (mesh)
Increasing coordination and responsivity of emotion-related brain regions with a heart rate variability biofeedback randomized trial.
Heart rate variability is a robust biomarker of emotional well-being, consistent with the shared brain networks regulating emotion regulation and heart rate. While high heart rate oscillatory activity clearly indicates healthy regulatory brain systems, can increasing this oscillatory activity also enhance brain function? To test this possibility, we randomly assigned 106 young adult participants to one of two 5-week interventions involving daily biofeedback that either increased heart rate oscillations (Osc+ condition) or had little effect on heart rate oscillations (Osc- condition) and examined effects on brain activity during rest and during regulating emotion. While there were no significant changes in the right amygdala-medial prefrontal cortex (MPFC) functional connectivity (our primary outcome), the Osc+ intervention increased left amygdala-MPFC functional connectivity and function…
matched on Amygdala (mesh)
Oxytocinergic Modulation of Threat-Specific Amygdala Sensitization in Humans Is Critically Mediated by Serotonergic Mechanisms.
Background: Overarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking. Methods: To determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/desensitization, we conducted a parallel-group, randomized, placebo-controlled, double-blind experiment during which 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion or the corresponding placebo-control protocol before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity to…
matched on Amygdala (mesh)
Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial.
Background: Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. Methods: This study ('ENGAGE') was a pre-planned element of the randomized controlled trial, 'RAINBOW' (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging u…
matched on Amygdala (mesh)
Exploring neural mechanisms of the health benefits of gratitude in women: A randomized controlled trial.
Background: Gratitude has received growing interest as an emotion that can bring greater happiness and health. However, little is known about the effects of gratitude on objective measures of physical health or the neural mechanisms that underlie these effects. Given strong links between gratitude and giving behavior, and giving and health, it is possible that gratitude may benefit health through the same mechanisms as giving to others. Thus, this study investigated whether gratitude activates a neural 'caregiving system' (e.g., ventral striatum (VS), septal area (SA)), which can downregulate threat responding (e.g., amygdala) and possibly cellular inflammatory responses linked to health. Methods: A parallel group randomized controlled trial examined the effect of a six-week online gratitude (n = 31) vs. control (n = 30) writing intervention on neural activity and inflammatory outcomes. …
matched on Amygdala (mesh)
Neurocognitive processes in d-cycloserine augmented single-session exposure therapy for anxiety: A randomized placebo-controlled trial.
Drugs targeting N-methyl-d-aspartate (NMDA) receptors and the ability to learn new associations have been proposed as adjunct treatments to boost the success of exposure therapy for anxiety disorders. However, the effects of the NMDA partial agonist d-cycloserine on psychological treatment have been mixed. We investigated potential neurocognitive mechanisms underlying the clinical effects of d-cycloserine-augmented exposure, to inform the optimal combination of this and similar agents with psychological treatment. Panic disorder patients were randomised to single-dose d-cycloserine (250 mg; N = 17) or matching placebo (N = 16) 2hrs before one session of exposure therapy. Neurocognitive markers were assessed one day after treatment, including reaction-time based threat bias for fearful faces (primary outcome) and amygdala response to threat (secondary outcome). Clinical symptom severity w…
matched on Amygdala (mesh)
Volitional limbic neuromodulation exerts a beneficial clinical effect on Fibromyalgia.
Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplificating effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation. We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation would improve chronic pain in patients suffering from Fibromyalgia, by r…
matched on Amygdala (mesh)
Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety.
Background: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. Methods: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of re…
matched on Amygdala (mesh)
Impact of short- and long-term mindfulness meditation training on amygdala reactivity to emotional stimuli.
Meditation training can improve mood and emotion regulation, yet the neural mechanisms of these affective changes have yet to be fully elucidated. We evaluated the impact of long- and short-term mindfulness meditation training on the amygdala response to emotional pictures in a healthy, non-clinical population of adults using blood-oxygen level dependent functional magnetic resonance imaging. Long-term meditators (N = 30, 16 female) had 9081 h of lifetime practice on average, primarily in mindfulness meditation. Short-term training consisted of an 8-week Mindfulness- Based Stress Reduction course (N = 32, 22 female), which was compared to an active control condition (N = 35, 19 female) in a randomized controlled trial. Meditation training was associated with less amygdala reactivity to positive pictures relative to controls, but there were no group differences in response to negative pic…
matched on Amygdala (mesh)
Dopaminergic Enhancement of Striatal Response to Reward in Major Depression.
Objective: Major depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals. Method: In a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3 receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in…
matched on Avoidance Learning (mesh)
Complementary Features of Attention Bias Modification Therapy and Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders.
Objective: In the treatment of anxiety disorders, attention bias modification therapy (ABMT) and cognitive-behavioral therapy (CBT) may have complementary effects by targeting different aspects of perturbed threat responses and behaviors. ABMT may target rapid, implicit threat reactions, whereas CBT may target slowly deployed threat responses. The authors used amygdala-based connectivity during a threat-attention task and a randomized controlled trial design to evaluate potential complementary features of these treatments in pediatric anxiety disorders. Method: Prior to treatment, youths (8-17 years old) with anxiety disorders (N=54), as well as healthy comparison youths (N=51), performed a threat-attention task during functional MRI acquisition. Task-related amygdala-based functional connectivity was assessed. Patients with and without imaging data (N=85) were then randomly assigned to …
matched on Amygdala (mesh)
PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation.
Objective: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. Method: Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation pa…
matched on Amygdala (mesh)
Treatment for social anxiety disorder alters functional connectivity in emotion regulation neural circuitry.
Social anxiety disorder (SAD) is characterized at a neurobiological level by disrupted activity in emotion regulation neural circuitry. Previous work has demonstrated amygdala hyperreactivity and disrupted prefrontal responses to social cues in individuals with SAD (Kim et al., 2011). While exposure-based psychological treatments effectively reduce SAD symptoms, not all individuals respond to treatment. Better understanding of the neural mechanisms involved offers the potential to improve treatment efficacy. In this study, we investigated functional connectivity in emotion regulation neural circuitry in a randomized controlled treatment trial for SAD. Participants with SAD underwent fMRI scanning while performing an implicit emotion regulation task prior to treatment (n=62). Following 12 weeks of cognitive behavioral therapy, acceptance and commitment therapy, or wait-list, participants …
matched on Amygdala (mesh)