•We reviewed relations between endogenous/exogenous cortisol and human brain function.•Studies reported inconsistent findings, due to heterogeneity in methods and analyses.•Associations between ...cortisol and amygdala activity were most consistently found.
To arrive at a coherent understanding of the relation between glucocorticoids and the human brain, we systematically reviewed the literature for studies examining the associations between endogenous or exogenous cortisol and human brain function. Higher levels of endogenous cortisol during psychological stress were related to increased activity in the middle temporal gyrus and perigenual anterior cingulate cortex (ACC), decreased activity in the ventromedial prefrontal cortex, and altered function (i.e., mixed findings, increased or decreased) in the amygdala, hippocampus and inferior frontal gyrus. Moreover, endogenous cortisol response to psychological stress was related to increased activity in the inferior temporal gyrus and altered function in the amygdala during emotional tasks that followed psychological stress. Exogenous cortisol administration was related to increased activity in the postcentral gyrus, superior frontal gyrus and ACC, and altered function in the amygdala and hippocampus during conditioning, emotional and reward-processing tasks after cortisol administration. These findings were in line with those from animal studies on amygdala activity during and after stress.
This report examines the relationship between pediatric anxiety disorders and implicit bias evoked by threats. To do so, the report uses two tasks that assess implicit bias to negative-valence faces, ...the first by eye-gaze and the second by measuring body-movement parameters. The report contrasts task performance in 51 treatment-seeking, medication-free pediatric patients with anxiety disorders and 36 healthy peers. Among these youth, 53 completed an eye-gaze task, 74 completed a body-movement task, and 40 completed both tasks. On the eye-gaze task, patients displayed longer gaze duration on negative relative to non-negative valence faces than healthy peers, F(1, 174) = 8.27, p = .005. In contrast, on the body-movement task, patients displayed a greater tendency to behaviorally avoid negative-valence faces than healthy peers, F(1, 72) = 4.68, p = .033. Finally, implicit bias measures on the two tasks were correlated, r(38) = .31, p = .049. In sum, we found an association between pediatric anxiety disorders and implicit threat bias on two tasks, one measuring eye-gaze and the other measuring whole-body movements. Converging evidence for implicit threat bias encourages future research using multiple tasks in anxiety.
Neuroimaging studies typically focus on either resting state or task-based fMRI data. Prior research has shown that similarity in functional connectivity between rest and cognitive tasks, interpreted ...as reconfiguration efficiency, is related to task performance and IQ. Here, we extend this approach from adults to children, and from cognitive tasks to a threat-based attention task. The goal of the current study was to examine whether similarity in functional connectivity during rest and an attention bias task relates to threat bias, IQ, anxiety symptoms, and social reticence. fMRI was measured during resting state and during the dot-probe task in 41 children (M = 13.44, SD = 0.70). Functional connectivity during rest and dot-probe was positively correlated, suggesting that functional hierarchies in the brain are stable. Similarity in functional connectivity between rest and the dot-probe task only related to threat bias (puncorr < .03). This effect did not survive correction for multiple testing. Overall, children who allocate more attention towards threat also may possess greater reconfiguration efficiency in switching from intrinsic to threat-related attention states. Finally, functional connectivity correlated negatively across the two conditions of the dot-probe task. Opposing patterns of modulation of functional connectivity by threat-congruent and threat-incongruent trials may reflect task-specific network changes during two different attentional processes.
•Similarity in functional connectivity during rest and a dot-probe task was assessed.•Functional connectivity during rest and dot-probe was positively correlated.•Similarity in functional connectivity between rest and task related to threat bias.•This might suggest that reconfiguration efficiency related to bias towards threat.
The field of developmental cognitive neuroscience is advancing rapidly, with large-scale, population-wide, longitudinal studies emerging as a key means of unraveling the complexity of the developing ...brain and cognitive processes in children. While numerous neuroscientific techniques like functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) have proved advantageous in such investigations, this perspective proposes a renewed focus on electroencephalography (EEG), leveraging underexplored possibilities of EEG. In addition to its temporal precision, low costs, and ease of application, EEG distinguishes itself with its ability to capture neural activity linked to social interactions in increasingly ecologically valid settings. Specifically, EEG can be measured during social interactions in the lab, hyperscanning can be used to study brain activity in two (or more) people simultaneously, and mobile EEG can be used to measure brain activity in real-life settings. This perspective paper summarizes research in these three areas, making a persuasive argument for the renewed inclusion of EEG into the toolkit of developmental cognitive and social neuroscientists.
Social anxiety disorder is an invalidating psychiatric disorder characterized by extreme fear and avoidance of one or more social situations in which patients might experience scrutiny by others. The ...goal of this two-generation family study was to delineate behavioral and electrocortical endophenotypes of social anxiety disorder related to social evaluation. Nine families of patients with social anxiety disorder (their spouse and children, and siblings of these patients with spouse and children) performed a social judgment paradigm in which they believed to be evaluated by peers. For each peer, participants indicated their expectation about the evaluative outcome, after which they received social acceptance or rejection feedback. Task behavior, as well as the feedback-related EEG brain potentials (N1, FRN, P3) and theta power were tested as candidate endophenotypes based on two criteria: co-segregation with social anxiety disorder within families and heritability. Results indicated that reaction time for indicating acceptance-expectations might be a candidate behavioral endophenotype of social anxiety disorder, possibly reflecting increased uncertainty or self-focused attention and vigilance during the social judgment paradigm. N1 in response to expected rejection feedback and P3 in response to acceptance feedback might be candidate electrocortical endophenotypes of social anxiety disorder, although the heritability analyses did not remain significant after correcting for multiple tests. Increased N1 possibly reflects hypervigilance to socially threatening stimuli, and increased P3 might reflect that positive feedback is more important for, and/or less expected by, participants with social anxiety disorder. Finally, increased feedback-related negativity and theta power in response to unexpected rejection feedback compared to the other conditions co-segregated with social anxiety disorder, but these EEG measures were not heritable. The candidate endophenotypes might play a new and promising role in future research on genetic mechanisms, early detection and/or prevention of social anxiety disorder.
•This two-generation family study examined candidate endophenotypes of social anxiety.•Reaction time for indicating acceptance-expectations might be an endophenotype.•Increased N1 after expected rejection might be an electrocortical endophenotype.•Increased P3 after acceptance feedback might be an endophenotype of SAD.
Attentional bias to social threat cues has been linked to heightened anxiety and irritability in youth. Yet, inconsistent methodology has limited replication and led to mixed findings. The current ...study aims to 1) replicate and extend two previous pediatric studies demonstrating a relationship between negative affectivity and attentional bias to social threat and 2) examine the test-retest reliability of an eye-tracking paradigm among a subsample of youth. Attention allocation to negative versus non-negative emotional faces was measured using a free-viewing eye-tracking task among youth (N = 185 total, 60 % female, Mage = 13.10 years, SDage = 2.77) with three face-pair conditions: happy-angry, neutral-disgust, sad-happy. Replicating procedures of two previous studies, linear mixed-effects models compared attention bias between children with anxiety disorders and healthy controls. Bifactor analysis was used to parse shared versus unique facets of general negative affectivity (i.e., anxiety, irritability), which were then examined in relation to attention bias. Test-retest reliability of the bias-index was estimated among a subsample of youth (N = 36). No significant differences in attention allocation or bias emerged between anxiety and healthy control groups. While general negative affectivity across the sample was not associated with attention bias, there was a positive relationship for anxiety and irritability on duration of attention allocation toward negative faces. Test-retest reliability for attention bias was moderate (r = 0.50, p < .01). While anxiety-related findings from the two previous studies were not replicated, the relationship between attention bias and facets of negative affect suggests a potential target for treatment. Evidence for test-retest reliability encourages future use of the eye-tracking task for researchers.
Cognitive models posit that the fear of negative evaluation (FNE) is a hallmark feature of social anxiety. As such, individuals with high FNE may show biased information processing when faced with ...social evaluation. The aim of the current study was to examine the neural underpinnings of anticipating and processing social-evaluative feedback, and its correlates with FNE. We used a social judgment paradigm in which female participants (N = 31) were asked to indicate whether they believed to be socially accepted or rejected by their peers. Anticipatory attention was indexed by the stimulus preceding negativity (SPN), while the feedback-related negativity and P3 were used to index the processing of social-evaluative feedback. Results provided evidence of an optimism bias in social peer evaluation, as participants more often predicted to be socially accepted than rejected. Participants with high levels of FNE needed more time to provide their judgments about the social-evaluative outcome. While anticipating social-evaluative feedback, SPN amplitudes were larger for anticipated social acceptance than for social rejection feedback. Interestingly, the SPN during anticipated social acceptance was larger in participants with high levels of FNE. None of the feedback-related brain potentials correlated with the FNE. Together, the results provided evidence of biased information processing in individuals with high levels of FNE when anticipating (rather than processing) social-evaluative feedback. The delayed response times in high FNE individuals were interpreted to reflect augmented vigilance imposed by the upcoming social-evaluative threat. Possibly, the SPN constitutes a neural marker of this vigilance in females with higher FNE levels, particularly when anticipating social acceptance feedback.
Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that ...threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety.
50 pediatric anxiety patients and healthy-comparisons (33 females) completed an instructed threat-anticipation task whereby cues signaled delivery of painful (threat) or non-painful (safety) thermal stimulation. Temporal changes in skin-conductance indexed anxiety effects on anticipatory responding as function of threat imminence. Multivariate network analyses of resting-state functional connectivity data from a subsample were used to identify intrinsic-function correlates of anticipatory-response dynamics, within a specific, distributed network derived from translational research on defensive responding.
By considering threat imminence, analyses revealed specific anxiety effects. Importantly, pathological anxiety was associated with excessive deployment of anticipatory physiological response as threat, but not safety, outcomes became more imminent. Magnitude of increase in threat-anticipatory physiological responses corresponded with magnitude of intrinsic connectivity within a cortical-subcortical circuit. Moreover, more severe anxiety was associated with stronger associations between anticipatory physiological responding and connectivity that ventromedial prefrontal cortex showed with hippocampus and basolateral amygdala, regions implicated in animal models of anxiety.
These findings link basic and clinical research, highlighting variations in intrinsic function in conserved defensive circuitry as a potential pathophysiological mechanism in anxiety.
•We translate animal insight on fear dynamics into human research on anxiety.•Patients and controls completed threat anticipation task and resting-state scan.•We observed aberrant threat-anticipatory physiological response dynamics in anxiety.•Aberrant dynamics in anxiety linked to cortical-subcortical intrinsic function.•Findings link basic, clinical research; highlight potential pathophysiological mechanism.
Highlights • We applied single dose testosterone administration in a placebo-controlled design. • Avoidance of eye contact in SAD is related to the severity of social anxiety. • Testosterone enhanced ...the initial fixations to the eyes of angry faces in SAD. • The findings support and extend social dominance theories of testosterone. • The direct effects on a core characteristic of SAD could have clinical implications.
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