Location-dependent threat and associated neural abnormalities in clinical anxiety
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ABSTRACT:
SUBMITTER: Suarez-Jimenez B
PROVIDER: S-EPMC8568971 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In real life, it is not unusual that we face potential threats (i.e., physical stimuli and environments that may cause harm or danger) with other individuals together, yet it remains largely unknown how threat-induced anxious feelings influence prosocial behaviors such as resource sharing. In this study, we investigated this question by combining functional magnetic resonance imaging and a novel paradigm. Together with an anonymous partner, each participant faced the possibility of receiving a 10-s noise administration, which had a low or high probability to be a threat (i.e., the intensity of noise can induce a high level of unpleasantness). Each participant first reported her/his immediate feeling of anxiety about the current situation (being threatened by the unpleasant noise), then decided how to split a number of resources (which could relieve the noise) between her/him and the partner. Behavioral results revealed that the participants showed a selfish bias in the threat conditions than in the safe conditions, and that self-reported anxiety feeling significantly predicted this bias. Functional magnetic resonance imaging results revealed that: (1) the activation level of the anterior insula was correlated with self-reported anxiety and (2) the connectivity between the anterior insula and the temporoparietal junction was sensitive to the modulating effect of anxiety on the selfish bias. These findings indicate the neural correlates of the association between threat-induced anxiety and prosocial tendencies in social interactions.
| S-EPMC10203809 | biostudies-literature
Project description:Anxiety is elicited by excessive apprehension about unpredictable threats. However, the neural circuit governing unpredictable threat induced anxiety remains unclear. Here, we found ventral bed nucleus of the stria terminalis (vBNST) GABAergic neurons displayed selective activation to unpredictable threats by means ofthrough coordinated excitatory input from insular cortex (IC) glutamergic neurons and inhibitory input from lateral nucleus of the amygdala (CeL) somatostatin (SOM) neurons. Using activity-dependent neuronal tagging technology, we found that unpredictable threat responsive cells in vBNST drive freezing and anxiety via projections to ventral lateral periaqueductal grey (vlPAG) and median nucleus of the amygdala (CeM) respectively. Finally, we identified KCNQ3 plays an essential role in hyperactivity of vBNST GABAergic neurons and induced anxiety. These data identified a forward inhibitory circuit that determine the selective activation of vBNST in unpredictable threat and anxiety, and suggest that Kcnq3 KCNQ3 channel acts as a promising target in treatment of anxiety disorder following unpredictable stress.
2024-02-19 | GSE255670 | GEO
Project description:BackgroundAnxiety and irritability frequently co-occur in youth and are mediated by aberrant threat responses. However, empirical evidence on neural mechanisms underlying this co-occurrence is limited. To address this, we apply data-driven latent phenotyping to data from a prior report of a well-validated threat extinction recall fMRI paradigm.MethodsParticipants included 59 youth (28 anxiety disorder, 31 healthy volunteers; Mage=13.15 yrs) drawn from a transdiagnostic sample of 331 youth, in which bifactor analysis was conducted to derive latent factors representing shared vs. unique variance of dimensionally-assessed anxiety and irritability. Participants underwent threat conditioning and extinction. Approximately three weeks later, during extinction recall fMRI, participants made threat-safety discriminations under two task conditions: current threat appraisal and explicit recall of threat contingencies. Linear mixed-effects analyses examined associations of a "negative affectivity" factor reflecting shared anxiety and irritability variance with whole-brain activation and task-dependent amygdala connectivity.ResultsDuring recall of threat-safety contingencies, higher negative affectivity was associated with greater prefrontal (ventrolateral/ventromedial, dorsolateral, orbitofrontal), motor, temporal, parietal, and occipital activation. During threat appraisal, higher negative affectivity was associated with greater amygdala-inferior parietal lobule connectivity to threat/safety ambiguity.LimitationsSample included only healthy youth and youth with anxiety disorders. Results may not generalize to other diagnoses for which anxiety and irritability are also common, and our negative affectivity factor should be interpreted as anxiety disorders with elevated irritability. Reliability of some subfactors was poor.ConclusionsAberrant amygdala-prefrontal-parietal circuitry during extinction recall of threat-safety stimuli may be a mechanism underlying the co-occurrence of pediatric anxiety and irritability.
| S-EPMC8554134 | biostudies-literature
Project description:Contextual threat learning is often associated with two processes: elemental and configural learning. Few studies have examined configural learning where subjects form a representation of the threat-related context as a gestalt whole from the individual features in the environment. The goal of the current study was to compare and contrast neural circuitry recruited by variation in demands placed on configural threat encoding. Subjects (N = 25) completed a configural threat learning task, where we manipulated the amount of configural encoding required to learn the threat association (low demand: changes to a discrete element of the context; and high demand: rearrangement of elements). US expectancy ratings, skin conductance responses (SCR), and functional magnetic resonance imaging (fMRI) were collected. Subjects successfully learned the configural threat association as measured by US expectancy ratings, SCR, and BOLD activity. Hippocampal and amygdala region of interest analyses indicated differential configural threat learning and predicted SCR measures of learning. Furthermore, whole brain analyses identified four circuits that were impacted by the amount of differential configural encoding required, but none correlated with SCR. These results set the stage for a more detailed understanding of how configural threat learning is instantiated in the brain-an important mechanism associated with PTSD and other fear-related disorders.
| S-EPMC7148156 | biostudies-literature
Project description:Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, μg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 μg isoproterenol infusion, the GAD group (n=24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the HC group (n=24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than HC during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 μg isoproterenol infusion. Using analyzable blood oxygenation level dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing according to prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation.
| S-EPMC10312828 | biostudies-literature
Project description:BackgroundSocial reticence in early childhood is characterized by shy and anxiously avoidant behavior, and it confers risk for pediatric anxiety disorders later in development. Aberrant threat processing may play a critical role in this association between early reticent behavior and later psychopathology. The goal of this longitudinal study is to characterize developmental trajectories of neural mechanisms underlying threat processing and relate these trajectories to associations between early-childhood social reticence and adolescent anxiety.MethodsIn this 16-year longitudinal study, social reticence was assessed from 2 to 7 years of age; anxiety symptoms and neural mechanisms during the dot-probe task were assessed at 10, 13, and 16 years of age. The sample included 144 participants: 71 children provided data at age 10 (43 girls, meanage = 10.62), 85 at age 13 (46 girls, meanage = 13.25), and 74 at age 16 (36 girls, meanage = 16.27).ResultsA significant interaction manifested among social reticence, anxiety symptoms, and time, on functional connectivity between the left amygdala and the left dorsolateral prefrontal cortex, voxelwise p < .001, clusterwise familywise error p < .05. Children with high social reticence showed a negative association between amygdala-dorsolateral prefrontal cortex connectivity and anxiety symptoms with age, compared to children with low social reticence, suggesting distinct neurodevelopmental pathways to anxiety.ConclusionsThese findings were present across all conditions, suggesting task-general effects in potential threat processing. Additionally, the timing of these neurodevelopmental pathways differed for children with high versus low social reticence, which could affect the timing of effective preventive interventions.
| S-EPMC10593903 | biostudies-literature
Project description:ContextSocial anxiety disorder is thought to involve emotional hyperreactivity, cognitive distortions, and ineffective emotion regulation. While the neural bases of emotional reactivity to social stimuli have been described, the neural bases of emotional reactivity and cognitive regulation during social and physical threat, and their relationship to social anxiety symptom severity, have yet to be investigated.ObjectiveTo investigate behavioral and neural correlates of emotional reactivity and cognitive regulation in patients and controls during processing of social and physical threat stimuli.DesignParticipants were trained to implement cognitive-linguistic regulation of emotional reactivity induced by social (harsh facial expressions) and physical (violent scenes) threat while undergoing functional magnetic resonance imaging and providing behavioral ratings of negative emotion experience.SettingAcademic psychology department.ParticipantsFifteen adults with social anxiety disorder and 17 demographically matched healthy controls.Main outcome measuresBlood oxygen level-dependent signal and negative emotion ratings.ResultsBehaviorally, patients reported greater negative emotion than controls during social and physical threat but showed equivalent reduction in negative emotion following cognitive regulation. Neurally, viewing social threat resulted in greater emotion-related neural responses in patients than controls, with social anxiety symptom severity related to activity in a network of emotion- and attention-processing regions in patients only. Viewing physical threat produced no between-group differences. Regulation during social threat resulted in greater cognitive and attention regulation-related brain activation in controls compared with patients. Regulation during physical threat produced greater cognitive control-related response (ie, right dorsolateral prefrontal cortex) in patients compared with controls.ConclusionsCompared with controls, patients demonstrated exaggerated negative emotion reactivity and reduced cognitive regulation-related neural activation, specifically for social threat stimuli. These findings help to elucidate potential neural mechanisms of emotion regulation that might serve as biomarkers for interventions for social anxiety disorder.
| S-EPMC4142809 | biostudies-literature
Project description: Not available
| S-EPMC3930442 | biostudies-literature
Project description:Anxiety disorders are common in autism spectrum disorder (ASD) and associated with social-communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala-prefrontal and amygdala-striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala-dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala-striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala-dACC/mPFC pathways, whereas emotion regulation systems involving amygdala-ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.
| S-EPMC8081066 | biostudies-literature
Project description:BackgroundDespite the high prevalence of generalized anxiety disorder (GAD) and its negative impact on society, its neurobiology remains obscure. This study characterizes the neurostructural abnormalities associated with key symptoms of GAD, focusing on indicators of impaired emotion regulation (excessive worry, poor concentration, low mindfulness, and physiological arousal).MethodsThese domains were assessed in 19 (16 women) GAD patients and 19 healthy controls matched for age and gender, using questionnaires and a low demand behavioral task performed before and after an induction of perseverative cognition (i.e. worry and rumination). Continuous pulse oximetry was used to measure autonomic physiology (heart rate variability; HRV). Observed cognitive and physiological changes in response to the induction provided quantifiable data on emotional regulatory capacity. Participants underwent structural magnetic resonance imaging; voxel-based morphometry was used to quantify the relationship between gray matter volume and psychological and physiological measures.ResultsOverall, GAD patients had lower gray matter volume than controls within supramarginal, precentral, and postcentral gyrus bilaterally. Across the GAD group, increased right amygdala volume was associated with prolonged reaction times on the tracking task (indicating increased attentional impairment following the induction) and lower scores on the 'Act with awareness' subscale of the Five Facets Mindfulness Questionnaire. Moreover in GAD, medial frontal cortical gray matter volume correlated positively with the 'Non-react mindfulness' facet. Lastly, smaller volumes of bilateral insula, bilateral opercular cortex, right supramarginal and precentral gyri, anterior cingulate and paracingulate cortex predicted the magnitude of autonomic change following the induction (i.e. a greater decrease in HRV).ConclusionsResults distinguish neural structures associated with impaired capacity for cognitive, attentional and physiological disengagement from worry, suggesting that aberrant competition between these levels of emotional regulation is intrinsic to symptom expression in GAD.
| S-EPMC4683456 | biostudies-literature