How fear is learned, held and unlearned.
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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
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission.
Clinical studies have reported that the psychedelic lysergic acid diethylamide (LSD) enhances empathy and social behavior (SB) in humans, but its mechanism of action remains elusive. Using a multidisciplinary approach including in vivo electrophysiology, optogenetics, behavioral paradigms, and molecular biology, the effects of LSD on SB and glutamatergic neurotransmission in the medial prefrontal cortex (mPFC) were studied in male mice. Acute LSD (30 μg/kg) injection failed to increase SB. However, repeated LSD (30 μg/kg, once a day, for 7 days) administration promotes SB, without eliciting antidepressant/anxiolytic-like effects. Optogenetic inhibition of mPFC excitatory neurons dramatically inhibits social interaction and nullifies the prosocial effect of LSD. LSD potentiates the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and 5-HT2A, but not N-methyl-D-aspartate (NMDA) and…
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Distinct neural mechanisms of emotional processing in prolonged grief disorder.
Background: Prolonged grief disorder (PGD) has recently been recognized as a separate psychiatric diagnosis, despite controversy over the extent to which it is distinctive from posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Methods: This study investigated distinctive neural processes underpinning emotion processing in participants with PGD, PTSD, and MDD with functional magnetic resonance study of 117 participants that included PGD (n = 21), PTSD (n = 45), MDD (n = 26), and bereaved controls (BC) (n = 25). Neural responses were measured across the brain while sad, happy, or neutral faces were presented at both supraliminal and subliminal levels. Results: PGD had greater activation in the pregenual anterior cingulate cortex (pgACC), bilateral insula, bilateral dorsolateral prefrontal cortices and right caudate and also greater pgACC-right pallidum connectivity …
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Association of Inflammatory Activity With Larger Neural Responses to Threat and Reward Among Children Living in Poverty.
Objective: Children exposed to severe, chronic stress are vulnerable to mental and physical health problems across the lifespan. To explain how these problems develop, the neuroimmune network hypothesis suggests that early-life stress initiates a positive feedback loop between peripheral inflammatory cells and networked brain regions involved in threat and reward processing. The authors sought to test this hypothesis by studying a sample of urban children from diverse socioeconomic backgrounds. Methods: The authors examined the basic predictions of the neuroimmune network hypothesis in 207 children (mean age=13.9 years, 63% female; 33% Black; 30% Hispanic), focusing on poverty as a stressor. The children had fasting blood drawn to quantify five inflammatory biomarkers-C-reactive protein, tumor necrosis factor-α, and interleukins-6, -8, and -10-which were averaged to form a composite scor…
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Greater decision uncertainty characterizes a transdiagnostic patient sample during approach-avoidance conflict: a computational modelling approach.
Background: Imbalances in approach-avoidance conflict (AAC) decision-making (e.g., sacrificing rewards to avoid negative outcomes) are considered central to multiple psychiatric disorders. We used computational modelling to examine 2 factors that are often not distinguished in descriptive analyses of AAC: decision uncertainty and sensitivity to negative outcomes versus rewards (emotional conflict). Methods: A previously validated AAC task was completed by 478 participants, including healthy controls (n = 59), people with substance use disorders (n = 159) and people with depression and/or anxiety disorders who did not have substance use disorders (n = 260). Using an active inference model, we estimated individual-level values for a model parameter that reflected decision uncertainty and another that reflected emotional conflict. We also repeated analyses in a subsample (59 healthy control…
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Oxytocin in the anterior cingulate cortex is involved in helping behaviour.
Empathy toward the distress of others is thought to motivate helping behaviour, in the form of voluntary action to eliminate that distress. Neuropeptide oxytocin is associated with various social cognitive abilities, including empathy and prosocial behaviour. The anterior cingulate cortex is known to be one of the brain regions underlying empathy, and one in which oxytocin receptors are expressed. However, the relationship between helping behaviour and oxytocin in the anterior cingulate cortex is still unclear. The present study investigated whether oxytocin in the anterior cingulate cortex is involved in rats' helping behaviour. In Experiment 1, we examined the influence of blockading the oxytocin receptors in the anterior cingulate cortex on helping behaviour. Impeding oxytocin in the anterior cingulate cortex delayed learning of the helping behaviour. In Experiment 2, we examined immu…
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Examining the role of cognitive fusion and experiential avoidance in predicting anxiety and depression.
Objectives: Acceptance and Commitment Therapy (ACT) proposes that cognitive fusion and experiential avoidance are inter-related processes underpinning distress. This study investigated whether worry, rumination, and stressful life events on the one hand and anxiety and depression on the other hand were mediated by cognitive fusion and experiential avoidance (bidirectional serial association). Design: A questionnaire design was conducted cross-sectionally in a clinical sample (study 1; N = 57) and cross-sectionally and longitudinally in a non-clinical student sample (study 2; N = 106 and N = 97 respectively). Methods: Participants completed measures of worry, rumination, stressful life events (predictors), cognitive fusion, experiential avoidance (mediators), anxiety, and depression (outcomes) at T1. In study 2, anxiety and depression were measured again 6 weeks later. Results: In the cli…
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Effect of Combat Exposure and Posttraumatic Stress Disorder on Telomere Length and Amygdala Volume.
Background: Traumatic stress can adversely affect physical and mental health through neurobiological stress response systems. We examined the effects of trauma exposure and posttraumatic stress disorder (PTSD) on telomere length, a biomarker of cellular aging, and volume of the amygdala, a key structure of stress regulation, in combat-exposed veterans. In addition, the relationships of psychopathological symptoms and autonomic function with telomere length and amygdala volume were examined. Methods: Male combat veterans were categorized as having PTSD diagnosis (n = 102) or no lifetime PTSD diagnosis (n = 111) based on the Clinician-Administered PTSD Scale. Subjects were assessed for stress-related psychopathology, trauma severity, autonomic function, and amygdala volumes by magnetic resonance imaging. Results: A significant interaction was found between trauma severity and PTSD status f…
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Classifying heterogeneous presentations of PTSD via the default mode, central executive, and salience networks with machine learning.
Intrinsic connectivity networks (ICNs), including the default mode network (DMN), the central executive network (CEN), and the salience network (SN) have been shown to be aberrant in patients with posttraumatic stress disorder (PTSD). The purpose of the current study was to a) compare ICN functional connectivity between PTSD, dissociative subtype PTSD (PTSD+DS) and healthy individuals; and b) to examine the use of multivariate machine learning algorithms in classifying PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our neuroimaging dataset consisted of resting-state fMRI scans from 186 participants [PTSD (n = 81); PTSD + DS (n = 49); and healthy controls (n = 56)]. We performed group-level independent component analyses to evaluate functional connectivity differences within each ICN. Multiclass Gaussian Process Classification algorithms within PRoNTo software …
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Interactions of OXTR rs53576 and emotional trauma on hippocampal volumes and perceived social support in adolescent girls.
Oxytocin (OXT) is a neuropeptide involved in social behaviour and is sensitive to environmental influences to alter individual vulnerability or resilience to stress resulting in both negative and positive outcomes. The effects of the OXT receptor (OXTR) single nucleotide polymorphism (SNP) rs53576 on hippocampal and amygdala structure and functions in adults are differentially associated with susceptibility to adversity and social behaviours, but this evidence is lacking in healthy adolescents. Adolescence is a developmental period characterised by neurobiological and psychosocial changes resulting in higher susceptibility to mood disorders, particularly among girls. As the brain is highly plastic at this stage, to understand psychosocial and emotional development, clarity of the interactions between rs53576 and adversity on hippocampal and amygdala volumes and social behaviours is neede…
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Brain control of humoral immune responses amenable to behavioural modulation.
It has been speculated that brain activities might directly control adaptive immune responses in lymphoid organs, although there is little evidence for this. Here we show that splenic denervation in mice specifically compromises the formation of plasma cells during a T cell-dependent but not T cell-independent immune response. Splenic nerve activity enhances plasma cell production in a manner that requires B-cell responsiveness to acetylcholine mediated by the α9 nicotinic receptor, and T cells that express choline acetyl transferase1,2 probably act as a relay between the noradrenergic nerve and acetylcholine-responding B cells. We show that neurons in the central nucleus of the amygdala (CeA) and the paraventricular nucleus (PVN) that express corticotropin-releasing hormone (CRH) are connected to the splenic nerve; ablation or pharmacogenetic inhibition of these neurons reduces plasma c…
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Dialectical behaviour therapy skills training for the treatment of addictive behaviours among individuals with alcohol use disorder: the effect of emotion regulation and experiential avoidance.
Backgrounds: Dialectical behavior therapy skills training (DBT-ST) is an effective treatment for alcohol use disorder (AUD). AUD frequently co-occurs with other addictive behaviors. Objective: s: These secondary analyses of prior studies on the effectiveness of a 3-month DBT-ST program for AUD investigated pre- post-treatment changes in the severity of concurrent addictive behaviors. The study hypothesized that emotion regulation and experiential avoidance should be the key therapeutic mechanisms involved in the treatment of addictive behaviors. Methods: The research included 186 individuals (110 males; 76 females) with a primary diagnosis of AUD. Mediational models were performed considering shorter PROMIS questionnaire subscales (i.e., gambling, sex, shopping, food binging, and starvation) as dependent variables. The difficulties in emotion regulation scale and acceptance and action qu…
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Cell-type-specific drug-inducible protein synthesis inhibition demonstrates that memory consolidation requires rapid neuronal translation.
New protein synthesis is known to be required for the consolidation of memories, yet existing methods of blocking translation lack spatiotemporal precision and cell-type specificity, preventing investigation of cell-specific contributions of protein synthesis. Here we developed a combined knock-in mouse and chemogenetic approach for cell-type-specific drug-inducible protein synthesis inhibition that enables rapid and reversible phosphorylation of eukaryotic initiation factor 2α, leading to inhibition of general translation by 50% in vivo. We use cell-type-specific drug-inducible protein synthesis inhibition to show that targeted protein synthesis inhibition pan-neuronally and in excitatory neurons in the lateral amygdala (LA) impaired long-term memory. This could be recovered with artificial chemogenetic activation of LA neurons, although at the cost of stimulus generalization. Conversel…
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Nrf2 Suppresses Oxidative Stress and Inflammation in App Knock-In Alzheimer's Disease Model Mice.
Nrf2 (NF-E2-related-factor 2) is a stress-responsive transcription factor that protects cells against oxidative stresses. To clarify whether Nrf2 prevents Alzheimer's disease (AD), AD model AppNL-G-F/NL-G-F knock-in (AppNLGF ) mice were studied in combination with genetic Nrf2 induction model Keap1FA/FA mice. While AppNLGF mice displayed shorter latency to escape than wild-type mice in the passive-avoidance task, the impairment was improved in AppNLGF ::Keap1FA/FA mice. Matrix-assisted laser desorption ionization-mass spectrometry imaging revealed that reduced glutathione levels were elevated by Nrf2 induction in AppNLGF ::Keap1FA/FA mouse brains compared to AppNLGF mouse brains. Genetic Nrf2 induction in AppNLGF mice markedly suppressed the elevation of the oxidative stress marker 8-OHdG and Iba1-positive microglial cell number. We also determined the plasmalogen-phosphatidylethanolamin…
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Higher resting-state BNST-CeA connectivity is associated with greater corrugator supercilii reactivity to negatively valenced images.
The bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA) are hypothesized to be the output nodes of the extended amygdala threat response, integrating multiple signals to coordinate the threat response via outputs to the hypothalamus and brainstem. The BNST and CeA are structurally and functionally connected, suggesting interactions between these regions may regulate how the response to provocation unfolds. However, the relationship between human BNST-CeA connectivity and the behavioral response to affective stimuli is little understood. To investigate whether individual differences in BNST-CeA connectivity are related to the affective response to negatively valenced stimuli, we tested relations between resting-state BNST-CeA connectivity and both facial electromyographic (EMG) activity of the corrugator supercilii muscle and eyeblink startle magnitude dur…
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Choroid Plexus Enlargement and Allostatic Load in Schizophrenia.
Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) …
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Social avoidance in depression: A study using a social decision-making task.
Depression significantly affects interpersonal functioning. Social avoidance may play an important role in depression, limiting opportunities and social skills acquisition, contributing to the maintenance of social difficulties. In the last few years, the need for studying social interactions using interactive tasks has been highlighted. This study investigated social avoidance in unmedicated depressed (n = 26) and matched healthy control (n = 26) participants, using a novel computerized social decision-making task (the TEAM task). In this task, participants choose between a social option (playing in a team with a coplayer) and an individual option (playing alone). Although the social option is more profitable from a material point of view, it can also be challenging because of social comparison and guilt feelings for failing the team. It was found that the higher the rank of the coplaye…
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Neurobiological Markers of Resilience to Depression Following Childhood Maltreatment: The Role of Neural Circuits Supporting the Cognitive Control of Emotion.
Background: Childhood adversity is strongly linked to negative mental health outcomes, including depression and anxiety. Leveraging cognitive neuroscience to identify mechanisms that contribute to resilience in children with a history of maltreatment may provide viable intervention targets for the treatment or prevention of psychopathology. We present a conceptual model of a potential neurobiological mechanism of resilience to depression and anxiety following childhood adversity. Specifically, we argue that neural circuits underlying the cognitive control of emotion may promote resilience, wherein a child's ability to recruit the frontoparietal control network to modulate amygdala reactivity to negative emotional cues-such as during cognitive reappraisal-buffers risk for internalizing symptoms following exposure to adversity. Methods: We provide preliminary support for this model of resi…
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Association of Prepubertal and Postpubertal Exposure to Childhood Maltreatment With Adult Amygdala Function.
Importance: Abnormalities in amygdala response to threatening faces have been observed in anxiety disorders, autism, bipolar disorder, depression, posttraumatic stress disorder, and schizophrenia. Abnormally hyperactive and hypoactive responses have typically been associated with anxiety and inhibition vs risk taking and inappropriate social behaviors. Maltreatment is a major risk factor for most of these disorders and is associated with abnormal amygdala function. Objective: To identify the type and age of exposure to childhood maltreatment that are associated with hyperactive and hypoactive amygdala responses in young adulthood. Design, setting, and participants: Data collection for this retrospective cohort study took place from November 8, 2010, to August 23, 2012. Data analyses were conducted from September 20, 2012, to June 27, 2018. Participants were recruited from the urban and s…
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Gut microbiome and brain functional connectivity in infants-a preliminary study focusing on the amygdala.
Recently, there has been a surge of interest in the possibility that microbial communities inhabiting the human gut could affect cognitive development and increase risk for mental illness via the "microbiome-gut-brain axis." Infancy likely represents a critical period for the establishment of these relationships, as it is the most dynamic stage of postnatal brain development and a key period in the maturation of the microbiome. Indeed, recent reports indicate that characteristics of the infant gut microbiome are associated with both temperament and cognitive performance. The neural circuits underlying these relationships have not yet been delineated. To address this gap, resting-state fMRI scans were acquired from 39 1-year-old human infants who had provided fecal samples for identification and relative quantification of bacterial taxa. Measures of alpha diversity were generated and test…
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Association of Timing of Adverse Childhood Experiences and Caregiver Support With Regionally Specific Brain Development in Adolescents.
Importance: Few data are available to inform the associations and timing of the associations between adversity, caregiver support, and brain outcomes. Consideration of timing has important public health implications to inform more precise prevention strategies. Objective: To evaluate the timing and regional specificity of the association between adverse childhood experiences (ACEs) and caregiver support to structural development of limbic and striatal brain regions in middle childhood and adolescence. Design, setting, and participants: This 15-year developmental, neuroimaging cohort study included 211 children and their caregivers screened from day care centers and preschools in the St Louis, Missouri, metropolitan area during the preschool period, with an additional 4 waves of neuroimaging at school age through adolescence from November 14, 2007, to August 29, 2017. The cohort was overs…
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Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior.
Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 a…
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Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response.
Background: Exposure to threat-related early life stress (ELS) has been related to vulnerability for stress-related disorders in adulthood, putatively via disrupted corticolimbic circuits involved in stress response and regulation. However, previous research on ELS has not examined both the intrinsic strength and flexibility of corticolimbic circuits, which may be particularly important for adaptive stress responding, or associations between these dimensions of corticolimbic dysfunction and acute stress response in adulthood. Methods: Seventy unmedicated women varying in history of threat-related ELS completed a functional magnetic resonance imaging scan to evaluate voxelwise static (overall) and dynamic (variability over a series of sliding windows) resting-state functional connectivity (RSFC) of bilateral amygdala. In a separate session and subset of participants (n = 42), measures of …
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Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli.
Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions1,2; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons3-6, where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). Using an electrochemical approach, we reveal the precise time course of pinch-evoked dopamine release in the mPFC, and show that mPFC dopamine biases behavioural responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behav…
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Late chronotype is associated with enhanced amygdala reactivity and reduced fronto-limbic functional connectivity to fearful versus happy facial expressions.
Increasing evidence suggests late chronotype individuals are at increased risk of developing depression. However, the underlying neural mechanisms that confer risk are not fully understood. Here, fifty healthy, right-handed individuals without a current or previous diagnosis of depression, family history of depression or sleep disorder underwent functional magnetic resonance imaging (FMRI). Participants completed an implicit emotion processing task (gender discrimination) including happy and fearful facial expressions. Linear effects of chronotype on BOLD response in bilateral amygdala were tested for significance using nonparametric permutation tests. Functional connectivity between amygdala and prefrontal cortex was also investigated using psychophysiological interaction (PPI) analysis. A significant negative correlation between BOLD response and chronotype was observed in bilateral am…
matched on Amygdala (mesh)
Dopamine neurons projecting to the posterior striatum reinforce avoidance of threatening stimuli.
Midbrain dopamine neurons are well known for their role in reward-based reinforcement learning. We found that the activity of dopamine axons in the posterior tail of the striatum (TS) scaled with the novelty and intensity of external stimuli, but did not encode reward value. We demonstrated that the ablation of TS-projecting dopamine neurons specifically inhibited avoidance of novel or high-intensity stimuli without affecting animals' initial avoidance responses, suggesting a role in reinforcement rather than simply in avoidance itself. Furthermore, we found that animals avoided optogenetic activation of dopamine axons in TS during a choice task and that this stimulation could partially reinstate avoidance of a familiar object. These results suggest that TS-projecting dopamine neurons reinforce avoidance of threatening stimuli. More generally, our results indicate that there are at least…
matched on Avoidance Learning (mesh)