Abnormal Attention Modulation of Fear Circuit Function in Pediatric Generalized Anxiety Disorder

1. Context. Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. 2. Objective. To determine whether attention modulates amygdala and cortical responses to facial threat cues differentially in adolescents with generalized anxiety disorder (GAD) and healthy adolescents. 3. Design. Case-control study. 4. Setting. Government clinical research institute. 5. Participants. Adolescent volunteers, 15 with GAD and 20 diagnosis-free. 6. Main Outcome Measure(s). Blood oxygenation level-dependent (BOLD) signal, as measured via functional magnetic resonance imaging (fMRI). During fMRI scans, participants completed a face-emotion rating task that systematically manipulated attention. 7. Results. While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful than to happy faces (small volume corrected p’s \u3c .05) in a distributed network including the amygdala, ventral PFC (vPFC), and anterior cingulate cortex (ACC). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, vPFC, and cingulate. 8. Conclusions. Findings provide the first evidence in juveniles that GAD-associated patterns of pathological fear-circuit activation are particularly evident during certain attention states. Specifically, fear-circuit hyperactivation occurred in an attention state involving focus on subjectively-experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping function of the adolescent human fear circuit

Effect of trait anxiety on prefrontal control mechanisms during emotional conflict

International audienceConverging evidence points to a link between anxiety proneness and altered emotional functioning, including threat-related biases in selective attention and higher susceptibility to emotionally ambiguous stimuli. However, during these complex emotional situations, it remains unclear how trait anxiety affects the engagement of the prefrontal emotional control system and particularly the anterior cingulate cortex (ACC), a core region at the intersection of the limbic and prefrontal systems. Using an emotional conflict task and functional magnetic resonance imaging (fMRI), we investigated in healthy subjects the relations between trait anxiety and both regional activity and functional connectivity (psychophysiological interaction) of the ACC. Higher levels of anxiety were associated with stronger task-related activation in ACC but with reduced functional connectivity between ACC and lateral prefrontal cortex (LPFC). These results support the hypothesis that when one is faced with emotionally incompatible information, anxiety leads to inefficient high-order control, characterized by insufficient ACC-LPFC functional coupling and increases, possibly compensatory, in activation of ACC. Our findings provide a deeper understanding of the pathophysiology of the neural circuitry underlying anxiety and may offer potential treatment markers for anxiety disorders

Relevance to self: A brief review and framework of neural systems underlying appraisal

We argue that many similar findings observed in cognitive, affective, and social neuroimaging research may compose larger processes central to generating self-relevance. In support of this, recent findings from these research domains were reviewed to identify common systemic activation patterns. Superimposition of these patterns revealed evidence for large-scale supramodal processes, which are argued to mediate appraisal of self-relevant content irrespective of specific stimulus types (e.g. words, pictures) and task domains (e.g. induction of reward, fear, pain, etc.). Furthermore, we distinguish between two top-down sub-systems involved in appraisal of self-relevance, one that orients pre-attentive biasing information (e.g. anticipatory or mnemonic) to salient or explicitly self-relevant phenomena, and another that engages introspective processes (e.g. self-reflection, evaluation, recollection) either in conjunction with or independent of the former system. Based on aggregate patterns of activation derived from the reviewed studies, processes in a ventral medial prefrontal cortex (MPFC)-subcortical network appear to track with the former pathway, and processes in a dorsal MPFC-cortical-subcortical network with the latter. As a whole, the purpose of this framework is to re-conceive the functionality of these systems in terms of supramodal processes that more directly reflect the influences of relevance to the self. © 2007 Elsevier Ltd. All rights reserved

Emotional processing of natural visual images in brief exposures and compound stimuli: fMRI and behavioural studies

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Can the brain register the emotional valence of brief exposures of complex natural stimuli under conditions of forward and backward masking, and under conditions of attentional competition between foveal and peripheral stimuli? To address this question, three experiments were conducted. The first, a behavioural experiment, measured subjective valence of response (pleasant vs unpleasant) to test the perception of the valence of natural images in brief, masked exposures in a forward and backward masking paradigm. Images were chosen from the International Affective Picture System (IAPS) series. After correction for response bias, responses to the majority of target stimuli were concordant with the IAPS ratings at better than chance, even when the presence of the target was undetected. Using functional magnetic resonance imaging (fMRI), the effects of IAPS valence and stimulus category were objectively measured on nine regions of interest (ROIs) using the same strict temporal restrictions in a similar masking design. Evidence of affective processing close to or below conscious threshold was apparent in some of the ROIs. To further this line of enquiry, a second fMRI experiment mapping the same ROIs and using the same stimuli were presented in a foveal (‘attended’) peripheral (‘to-be-ignored’) paradigm (small image superimposed in the centre of a large image of the same category, but opposite valence) to investigate spatial parameters and limitations of attention. Results are interpreted as showing both valence and category specific effects of ‘to-be-ignored’ images in the periphery. These results are discussed in light of theories of the limitations of attentional capacity and the speed in which we process natural images, providing new evidence of the breadth of variety in the types of affective visual stimuli we are able to process close to the threshold of conscious perception.Economic and Social Research Council (ESRC

Trait anxiety modulates anterior cingulate activation to threat interference

Background: Individuals vary in the degree to which salient threatening stimuli disrupt or distract from goal-directed cognitive processes. Excessive attention to threat or difficulty resolving the interference created by threat cues could contribute to anxious psychopathology; disruptions in frontal brain regions implicated in attentional control or resolution of emotional interference (e.g. anterior cingulate cortex, “ACC”) might play a role. In this study, we explored the hypothesis that trait anxiety would be associated with ACC activity in an attentional control task with varying levels of threat interference. Methods: During functional magnetic resonance imaging, 20 healthy individuals who varied in trait anxiety levels viewed angry, fearful, and neutral faces superimposed on an indoor or outdoor scene. In a high-threat interference condition, subjects identified the gender of the face (Attend Face). In a low-threat interference condition, they identified the scene type (Attend Scene). Whole-brain analysis was used to compare Attend Face with Attend Scene for angry and fearful (versus neutral) faces. Contrasts were correlated with trait anxiety level. Results: Behavioral data confirmed that Attend Face produced greater threat interference than Attend Scene. Brain imaging results showed that trait anxiety was inversely associated with bilateral rostral ACC activity for Attend Face relative to Attend Scene for angry faces. A similar relationship was not seen for fearful faces. Conclusions: The rostral ACC is implicated in assessing the salience of emotional information and controlling attention to resolve emotional interference. The link between higher trait anxiety and decreased ACC activation for angry faces suggests reduced attentional control for signals of interpersonal threat in healthy anxiety-prone individuals. Depression and Anxiety 28:194–201, 2011. © 2011 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83482/1/20802_ftp.pd

Reappraising the voices of wrath

Cognitive reappraisal recruits prefrontal and parietal cortical areas. Because of the near exclusive usage in past research of visual stimuli to elicit emotions, it is unknown whether the same neural substrates underlie the reappraisal of emotions induced through other sensory modalities. Here, participants reappraised their emotions in order to increase or decrease their emotional response to angry prosody, or maintained their attention to it in a control condition. Neural activity was monitored with fMRI, and connectivity was investigated by using psychophysiological interaction analyses. A right-sided network encompassing the superior temporal gyrus, the superior temporal sulcus and the inferior frontal gyrus was found to underlie the processing of angry prosody. During reappraisal to increase emotional response, the left superior frontal gyrus showed increased activity and became functionally coupled to right auditory cortices. During reappraisal to decrease emotional response, a network that included the medial frontal gyrus and posterior parietal areas showed increased activation and greater functional connectivity with bilateral auditory regions. Activations pertaining to this network were more extended on the right side of the brain. Although directionality cannot be inferred from PPI analyses, the findings suggest a similar frontoparietal network for the reappraisal of visually and auditorily induced negative emotion

Posttraumatic Stress Disorder: A Theoretical Model of the Hyperarousal Subtype

Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framewor

Neural correlates of the behavioral-autonomic interaction response to potentially threatening stimuli

Subjective assessment of emotional valence is typically associated with both brain activity and autonomic arousal. Accurately assessing emotional salience is particularly important when perceiving threat. We sought to characterize the neural correlates of the interaction between behavioral and autonomic responses to potentially threatening visual and auditory stimuli. Twenty-five healthy male subjects underwent fMRI scanning whilst skin conductance responses (SCR) were recorded. One hundred and eighty pictures, sentences, and sounds were assessed as “harmless” or “threatening.” Individuals’ stimulus-locked, phasic SCRs and trial-by-trial behavioral assessments were entered as regressors into a flexible factorial design to establish their separate autonomic and behavioral neural correlates, and convolved to examine psycho-autonomic interaction (PAI) effects. Across all stimuli, “threatening,” compared with “harmless” behavioral assessments were associated with mainly frontal and precuneus activation with specific within-modality activations including bilateral parahippocampal gyri (pictures), bilateral anterior cingulate cortex (ACC) and frontal pole (sentences), and right Heschl’s gyrus and bilateral temporal gyri (sounds). Across stimulus modalities SCRs were associated with activation of parieto-occipito-thalamic regions, an activation pattern which was largely replicated within-modality. In contrast, PAI analyses revealed modality-specific activations including right fusiform/parahippocampal gyrus (pictures), right insula (sentences), and mid-cingulate gyrus (sounds). Phasic SCR activity was positively correlated with an individual’s propensity to assess stimuli as “threatening.” SCRs may modulate cognitive assessments on a “harmless–threatening” dimension, thereby modulating affective tone and hence behavior

Does the amygdala response correlate with the personality trait 'harm avoidance' while evaluating emotional stimuli explicitly?

Background: The affective personality trait 'harm avoidance' (HA) from Cloninger's psychobiological personality model determines how an individual deals with emotional stimuli. Emotional stimuli are processed by a neural network that include the left and right amygdalae as important key nodes. Explicit, implicit and passive processing of affective stimuli are known to activate the amygdalae differently reflecting differences in attention, level of detailed analysis of the stimuli and the cognitive control needed to perform the required task. Previous studies revealed that implicit processing or passive viewing of affective stimuli, induce a left amygdala response that correlates with HA. In this new study we have tried to extend these findings to the situation in which the subjects were required to explicitly process emotional stimuli. Methods: A group of healthy female participants was asked to rate the valence of positive and negative stimuli while undergoing fMRI. Afterwards the neural responses of the participants to the positive and to the negative stimuli were separately correlated to their HA scores and compared between the low and high HA participants. Results: Both analyses revealed increased neural activity in the left laterobasal (LB) amygdala of the high HA participants while they were rating the positive and the negative stimuli. Conclusions: Our results indicate that the left amygdala response to explicit processing of affective stimuli does correlate with HA