Anxiety and the Neurobiology of Temporally Uncertain Threat Anticipation

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(41), P. 7949 - 7964

Published: Sept. 21, 2020

When extreme, anxiety—a state of distress and arousal prototypically evoked by uncertain danger—can be debilitating. Uncertain anticipation is a shared feature situations that elicit signs symptoms anxiety across psychiatric disorders, species, assays. Despite the profound significance for human health wellbeing, neurobiology uncertain-threat remains unsettled. Leveraging paradigm adapted from animal research optimized fMRI signal decomposition, we examined neural circuits engaged during temporally certain threat in 99 men women. Results revealed systems recruited are anatomically colocalized frontocortical regions, extended amygdala, periaqueductal gray. Comparison conditions demonstrated this circuitry can fractionated, with regions showing relatively stronger engagement threat, amygdala reverse pattern. Although there widespread agreement bed nucleus stria terminalis dorsal amygdala—the two major subdivisions amygdala—play critical role orchestrating adaptive responses to potential danger, their precise contributions have remained contentious. Follow-up analyses these show statistically indistinguishable anticipation. These observations provide framework conceptualizing fear, understanding functional neuroanatomy humans, accelerating development more effective intervention strategies pathological anxiety. SIGNIFICANCE STATEMENT Anxiety—an emotion associated harm—has public health, yet underlying unclear. novel neuroimaging large sample, identify core circuit responsive both anticipation, fractionated into bias one kind or other. The occupies center stage neuropsychiatric models anxiety, but its architecture has Here demonstrate threat. Collectively, indicate need revise how think about fear.

Language: Английский

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Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

Progress in brain research, Journal Year: 2019, Volume and Issue: unknown, P. 375 - 436

Published: Jan. 1, 2019

Language: Английский

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Anxiety-Related Frontocortical Activity Is Associated With Dampened Stressor Reactivity in the Real World

Psychological Science, Journal Year: 2022, Volume and Issue: 33(6), P. 906 - 924

Published: June 1, 2022

Negative affect is a fundamental dimension of human emotion. When extreme, it contributes to variety adverse outcomes, from physical and mental illness divorce premature death. Mechanistic work in animals neuroimaging research humans monkeys have begun reveal the broad contours neural circuits governing negative affect, but relevance these discoveries everyday distress remains incompletely understood. Here, we used combination approaches—including assays threat anticipation emotional-face perception more than 10,000 momentary assessments emotional experience—to demonstrate that individuals who showed greater activation cingulo-opercular circuit during an anxiety-eliciting laboratory paradigm experienced lower levels stressor-dependent their daily lives ( ns = 202–208 university students). Extended amygdala was not significantly related affect. These observations provide framework for understanding neurobiology real world.

Language: Английский

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Acute and chronic alcohol modulation of extended amygdala calcium dynamics

Alcohol, Journal Year: 2024, Volume and Issue: 116, P. 53 - 64

Published: Feb. 27, 2024

Language: Английский

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Sex and sobriety: Human brain structure and function in AUD abstinence

Alcohol, Journal Year: 2024, Volume and Issue: 121, P. 33 - 44

Published: July 27, 2024

Language: Английский

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Anxiety and the neurobiology of temporally uncertain threat anticipation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Feb. 26, 2020

ABSTRACT When extreme, anxiety—a state of distress and arousal prototypically evoked by uncertain danger—can be debilitating. Uncertain anticipation is a shared feature situations that elicit signs symptoms anxiety across psychiatric disorders, species, assays. Despite the profound significance for human health wellbeing, neurobiology uncertain-threat remains unsettled. Leveraging paradigm adapted from animal research optimized functional MRI signal decomposition, we examined neural circuits engaged during temporally certain threat in 99 men women. Results revealed systems recruited are anatomically co-localized fronto-cortical regions, extended amygdala, periaqueductal gray. Comparison conditions demonstrated this circuitry can fractionated, with regions showing relatively stronger engagement threat, amygdala reverse pattern. Although there widespread agreement bed nucleus stria terminalis dorsal amygdala—the two major subdivisions amygdala—play critical role orchestrating adaptive responses to potential danger, their precise contributions have remained contentious. Follow-up analyses these show statistically indistinguishable anticipation. These observations provide framework conceptualizing fear, understanding neuroanatomy humans, accelerating development more effective intervention strategies pathological anxiety. SIGNIFICANCE STATEMENT Anxiety—an emotion associated harm—has public health, yet underlying unclear. novel neuroimaging large sample, identify core circuit responsive both anticipation, fractionated into bias one kind or other. The extended-amygdala occupies center-stage neuropsychiatric models anxiety, but its architecture has Here demonstrate threat. Collectively, indicate need revise how think about fear. RESOURCE SHARING Raw data available at National Institute Mental Health’s Data Archive. Key statistical maps will publicly NeuroVault.org.

Language: Английский

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Extended‐amygdala intrinsic functional connectivity networks: A population study

Human Brain Mapping, Journal Year: 2020, Volume and Issue: 42(6), P. 1594 - 1616

Published: Dec. 12, 2020

Abstract Pre‐clinical and human neuroimaging research implicates the extended‐amygdala (ExtA) (including bed nucleus of stria terminalis [BST] central amygdala [CeA]) in networks mediating negative emotional states associated with stress substance‐use behaviours. The extent to which individual ExtA structures form a functionally integrated unit is controversial. We utilised large sample ( n > 1,000 healthy young adult humans) compare intrinsic functional connectivity (ICNs) BST CeA using task‐free magnetic resonance imaging (fMRI) data from Human Connectome Project. assessed whether inter‐individual differences within these ICNs were related two principal components representing disposition alcohol use. Building on recent primate evidence, we tested BST‐CeA (iFC) was heritable further examined co‐heritability our components. demonstrate have discrete, but largely overlapping similar previous findings. found no evidence that BST—CeA iFC heritable; however, post hoc analyses significant heritability broader superficial centromedial regions. There correlations or associations either across for specific BST‐Amygdala iFC. Possible phenotype task‐free, task‐based, clinical fMRI are discussed, along suggestions more causal investigative paradigms make use now well‐established ICNs.

Language: Английский

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Unraveling the epigenomic and transcriptomic interplay during alcohol-induced anxiolysis

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(11), P. 4624 - 4632

Published: Sept. 12, 2022

Abstract Positive effects of alcohol drinking such as anxiolysis and euphoria appear to be a crucial factor in the initiation maintenance use disorder (AUD). However, mechanisms that lead from chromatin reorganization transcriptomic changes after acute ethanol exposure remain unknown. Here, we used Assay for Transposase-Accessible Chromatin followed by high throughput sequencing (ATAC-seq) RNA-seq investigate epigenomic underlie anxiolytic using an animal model. Analysis ATAC-seq data revealed overall open or permissive state was associated with amygdala exposure. We identified candidate gene, Hif3a (Hypoxia-inducible 3, alpha subunit), had ‘open’ regions (ATAC-seq peaks), significantly increased active epigenetic histone acetylation marks decreased DNA methylation at these regions. The mRNA levels were exposure, but during withdrawal chronic Knockdown expression central nucleus attenuated ethanol-induced increases blocked rats. These indicate accessibility signatures possibly prime development AUD.

Language: Английский

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An Honest Reckoning With the Amygdala and Mental Illness

American Journal of Psychiatry, Journal Year: 2024, Volume and Issue: 181(12), P. 1059 - 1075

Published: Dec. 1, 2024

Anxiety disorders are a leading source of human misery, morbidity, and premature mortality. Existing treatments far from curative for many, underscoring the need to clarify underlying neural mechanisms. Although many brain regions contribute, amygdala has received most intense scientific attention. Over past several decades, this scrutiny yielded detailed understanding function, but it failed produce new clinical assays, biomarkers, or cures. Rising urgent public health challenge demands an honest reckoning with functional-neuroanatomical complexity shift theories anchored on "the amygdala" models centered specific nuclei cell types. This review begins by examining evidence studies rodents, monkeys, humans "canonical model," idea that plays central role in fear- anxiety-related states, traits, disorders. Next, authors selectively highlight work indicating canonical model, while true, is overly simplistic fails adequately capture actual state evidentiary record, breadth amygdala-associated functions illnesses, amygdala's functional architecture. The describe implications these facts basic neuroimaging research. concludes some general recommendations grappling accelerating efforts understand more effectively treat amygdala-related psychopathology.

Language: Английский

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The emotional brain: Fundamental questions and strategies for future research

Neuroscience Letters, Journal Year: 2018, Volume and Issue: 693, P. 68 - 74

Published: Oct. 20, 2018

Language: Английский

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