The objective of this study was to determine if a novel game-based digital therapeutic intervention reduced anxiety symptom severity in adults with clinically elevated symptoms of social anxiety disorder (SAD). Participants were randomly allocated (1:1) to receive four weeks of either the active intervention, a game-based form of attention bias modification (Active ABM) for anxiety, or the sham control training (Control). Between June 2022 to June 2023, 104 participants were enrolled with 93 completing the trial per-protocol and 104 included in the final intention-to-treat analysis (54 intervention, 50 control); mean age was 38.08 (10.56) years and 79 were female. The dependent variable was reduction in SAD symptoms, measured via the Liebowitz SAD Scale (LSAS). Participants were classified as having clinically elevated SAD symptoms only, or both SAD and Generalized Anxiety Disorder (GAD) symptoms (comorbid). The Active condition induced significantly greater reductions in SAD symptoms compared to the Control condition between Baseline and Post-Treatment [Active: M = -29.71, SD = 23.68; Control: M = -14.59, SD = 21.52, d = .67, t(102) = -3.40, p < .001] across the four-week study period. While no significant between-groups differences emerged at each timepoint individually, the Active condition induced significantly greater change over time in SAD symptoms compared to the Control condition. Use of this game-based digital ABM intervention showed benefits in the reduction of anxiety symptoms.

Social anxiety-which typically emerges in adolescence-lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused on acute social threat. Much less attention has been devoted to understanding the neural systems recruited during the uncertain anticipation of potential encounters with social threat. Here we used a novel functional magnetic resonance imaging paradigm to probe the neural circuitry engaged during the anticipation and acute presentation of threatening faces and voices in a racially diverse sample of 66 adolescents selectively recruited to encompass a range of social anxiety and enriched for clinically significant levels of distress and impairment. Results demonstrated that adolescents with more severe social anxiety symptoms experience heightened distress when anticipating encounters with social threat, and reduced discrimination of uncertain social threat and safety in the bed nucleus of the stria terminalis, a key division of the central extended amygdala (EAc). Although the EAc-including the bed nucleus of the stria terminalis and central nucleus of the amygdala-was robustly engaged by the acute presentation of threatening faces and voices, the degree of EAc engagement was unrelated to the severity of social anxiety. Together, these observations provide a neurobiologically grounded framework for conceptualizing adolescent social anxiety and set the stage for the kinds of prospective-longitudinal and mechanistic research that will be necessary to determine causation and, ultimately, to develop improved interventions for this often-debilitating illness. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Pediatric anxiety disorders and post-traumatic stress disorder (PTSD) are associated with elevated threat sensitivity and impaired emotion regulation, accompanied by dysfunction in the neural circuits involved in these processes. Despite established treatments like cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors, many children do not achieve remission, underscoring the importance of understanding the neurobiological underpinnings of these disorders. This review synthesizes current research on the neural predictors of treatment response and the neurofunctional changes associated with treatment in pediatric anxiety and PTSD during threat and reward processing. Several key findings emerged. First, enhanced threat/safety discrimination in the amygdala predicted better outcomes of pediatric anxiety and PTSD treatments. Second, differences in pretreatment activation within the lateral prefrontal and dorsal anterior cingulate cortices predicted treatment response, likely reflecting baseline executive control differences. Third, post-CBT decreases in activation in default mode, visuo-attentional, and sensorimotor areas may support treatment-related increases in task engagement. Finally, functional connectivity between the amygdala and other limbic, prefrontal, and default mode network nodes predicts treatment response in anxiety and PTSD, highlighting its potential as a biomarker for therapeutic efficacy. Understanding these neurofunctional markers could lead to more targeted interventions, optimizing treatment planning and potentially leading to the development of "pretreatment" strategies to enhance the efficacy of existing treatments. This review highlights the necessity for future research to establish more direct links between neuroimaging findings and clinical outcomes to facilitate the translation of these findings into clinical practice.

This study focused on the research hotspots and development trends of the neuroimaging of social anxiety (SA) in the past 25 years.

We selected 1,305 studies on SA neuroimaging from the Web of Science and Scopus from January 1998 to December 2023. CiteSpace was used to analyze the number of published articles visually, cited references, cooperation among authors and institutions, co-occurrence of keywords, clustering of keywords, burst of keywords, and time zone of co-occurring keywords.

A total of 1,305 articles were included, and the annual number of articles published over nearly 25 years showed the overall trend is on the rise. The analysis of author and institutional collaboration reveals that most authors collaborate closely. Among them, the team led by Pine, Daniel S published 59 articles, making it the most central team. Harvard University is identified as the most central institution in this network. The research hotspots can be categorized into four areas: research techniques, cognitive processing research areas, core brain regions and brain networks, and the neural predictors of treatment outcomes in SA. The most recent burst keywords are "cognitive behavioral therapy," "systematic review," "machine learning," "major clinical study," "transcranial direct current stimulation," "depression," and "outcome assessment," which provided clues on research frontiers. Based on the burst map and keyword time zone map, it appears that exploring the activity of brain regions involved in cognitive processing, such as face processing and attentional bias, as well as the comorbidity of SA and depression, through brain imaging technology, using brain signals as predictors of treatment outcomes in SA.

This study conducted a comprehensive, objective, and visual analysis of publications, and revealed hot topics and trends concerning the study of the brain mechanism of SA from 1998 to 2023. This work might assist researchers in identifying new insights on potential collaborators and institutions, hot topics, and research directions.

Research has found that the amygdala plays a significant role in underlying pathology of major depressive disorder (MDD). However, few studies have explored machine learning-assisted diagnostic biomarkers based on amygdala functional connectivity (FC).

To investigate the analysis of neuroimaging biomarkers as a streamlined approach for the diagnosis of MDD in adolescents.

Forty-four adolescents diagnosed with MDD and 43 healthy controls were enrolled in the study. Using resting-state functional magnetic resonance imaging, the FC was compared between the adolescents with MDD and the healthy controls, with the bilateral amygdala serving as the seed point, followed by statistical analysis of the results. The support vector machine (SVM) method was then applied to classify functional connections in various brain regions and to evaluate the neurophysiological characteristics associated with MDD.

Compared to the controls and using the bilateral amygdala as the region of interest, patients with MDD showed significantly lower FC values in the left inferior temporal gyrus, bilateral calcarine, right lingual gyrus, and left superior occipital gyrus. However, there was an increase in the FC value in Vermis-10. The SVM analysis revealed that the reduction in the FC value in the right lingual gyrus could effectively differentiate patients with MDD from healthy controls, achieving a diagnostic accuracy of 83.91%, sensitivity of 79.55%, specificity of 88.37%, and an area under the curve of 67.65%.

The results showed that an abnormal FC value in the right lingual gyrus was effective as a neuroimaging biomarker to distinguish patients with MDD from healthy controls.

Major depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs).

Sixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment.

Patients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = -0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases.

The current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined.

Using a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression.

Although static abnormalities of functional brain networks have been observed in patients with social anxiety disorder (SAD), the brain connectome dynamics at the macroscale network level remain obscure. We therefore used a multivariate data-driven method to search for dynamic functional network connectivity (dFNC) alterations in SAD.

We conducted spatial independent component analysis, and used a sliding-window approach with a k-means clustering algorithm, to characterize the recurring states of brain resting-state networks; then state transition metrics and FNC strength in the different states were compared between SAD patients and healthy controls (HC), and the relationship to SAD clinical characteristics was explored.

Four distinct recurring states were identified. Compared with HC, SAD patients demonstrated higher fractional windows and mean dwelling time in the highest-frequency State 3, representing "widely weaker" FNC, but lower in States 2 and 4, representing "locally stronger" and "widely stronger" FNC, respectively. In State 1, representing "widely moderate" FNC, SAD patients showed decreased FNC mainly between the default mode network and the attention and perceptual networks. Some aberrant dFNC signatures correlated with illness duration.

These aberrant patterns of brain functional synchronization dynamics among large-scale resting-state networks may provide new insights into the neuro-functional underpinnings of SAD.

Individuals with social anxiety often exhibit atypical processing of facial expressions. Previous research in social anxiety has primarily emphasized cognitive bias associated with face processing and the corresponding abnormalities in cortico-limbic circuitry, yet whether social anxiety influences early perceptual processing of emotional faces remains largely unknown. We used a psychophysical method to investigate the monocular advantage for face perception (i.e., face stimuli are better recognized when presented to the same eye compared to different eyes), an effect that is indicative of early, subcortical processing of face stimuli. We compared the monocular advantage for different emotional expressions (neutral, angry and sad) in three groups (N = 24 per group): individuals clinically diagnosed with social anxiety disorder (SAD), individuals with high social anxiety in subclinical populations (SSA), and a healthy control (HC) group of individuals matched for age and gender. Compared to SSA and HC groups, we found that individuals with SAD exhibited a greater monocular advantage when processing neutral and sad faces. While the magnitudes of monocular advantages were similar across three groups when processing angry faces, individuals with SAD performed better in this condition when the faces were presented to different eye. The former findings suggest that social anxiety leads to an enhanced role of subcortical structures in processing nonthreatening expressions. The latter findings, on the other hand, likely reflect an enhanced cortical processing of threatening expressions in SAD group. These distinct patterns of monocular advantage indicate that social anxiety altered representation of emotional faces at various stages of information processing, starting at an early stage of the visual system.

Social anxiety-which typically emerges in adolescence-lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused on acute social threat. Much less attention has been devoted to understanding the neural systems recruited during the uncertain anticipation of potential encounters with social threat. Here we used a novel fMRI paradigm to probe the neural circuitry engaged during the anticipation and acute presentation of threatening faces and voices in a racially diverse sample of 66 adolescents selectively recruited to encompass a range of social anxiety and enriched for clinically significant levels of distress and impairment. Results demonstrated that adolescents with more severe social anxiety symptoms experience heightened distress when anticipating encounters with social threat, and reduced discrimination of uncertain social threat and safety in the bed nucleus of the stria terminalis (BST), a key division of the central extended amygdala (EAc). Although the EAc-including the BST and central nucleus of the amygdala-was robustly engaged by the acute presentation of threatening faces and voices, the degree of EAc engagement was unrelated to the severity of social anxiety. Together, these observations provide a neurobiologically grounded framework for conceptualizing adolescent social anxiety and set the stage for the kinds of prospective-longitudinal and mechanistic research that will be necessary to determine causation and, ultimately, to develop improved interventions for this often-debilitating illness.

Social anxiety (SA) is a negative emotional response that can lead to mental health issues, which some have experienced during the coronavirus disease 2019 (COVID-19) pandemic. Little attention has been given to the neurobiological mechanisms underlying inter-individual differences in SA alterations related to COVID-19. This study aims to identify neurofunctional markers of COVID-specific SA development.

110 healthy participants underwent resting-state magnetic resonance imaging and behavioral tests before the pandemic (T1, October 2019 to January 2020) and completed follow-up behavioral measurements during the pandemic (T2, February to May 2020). We constructed individual functional networks and used graph theoretical analysis to estimate their global and nodal topological properties, then used Pearson correlation and partial least squares correlations examine their associations with COVID-specific SA alterations.

In terms of global network parameters, SA alterations (T2-T1) were negatively related to pre-pandemic brain small-worldness and normalized clustering coefficient. In terms of nodal network parameters, SA alterations were positively linked to a pronounced degree centrality pattern, encompassing both the high-level cognitive networks (dorsal attention network, cingulo-opercular task control network, default mode network, memory retrieval network, fronto-parietal task control network, and subcortical network) and low-level perceptual networks (sensory/somatomotor network, auditory network, and visual network). These findings were robust after controlling for pre-pandemic general anxiety, other stressful life events, and family socioeconomic status, as well as by treating SA alterations as categorical variables.

The individual functional network associated with SA alterations showed a disrupted topological organization with a more random state, which may shed light on the neurobiological basis of COVID-related SA changes at the network level.

Although aberrant brain regional responses are reported in social anxiety disorder (SAD), little is known about resting-state functional connectivity at the macroscale network level. This study aims to identify functional network abnormalities using a multivariate data-driven method in a relatively large and homogenous sample of SAD patients, and assess their potential diagnostic value.

Forty-six SAD patients and 52 demographically-matched healthy controls (HC) were recruited to undergo clinical evaluation and resting-state functional MRI scanning. We used group independent component analysis to characterize the functional architecture of brain resting-state networks (RSNs) and investigate between-group differences in intra-/inter-network functional network connectivity (FNC). Furtherly, we explored the associations of FNC abnormalities with clinical characteristics, and assessed their ability to discriminate SAD from HC using support vector machine analyses.

SAD patients showed widespread intra-network FNC abnormalities in the default mode network, the subcortical network and the perceptual system (i.e. sensorimotor, auditory and visual networks), and large-scale inter-network FNC abnormalities among those high-order and primary RSNs. Some aberrant FNC signatures were correlated to disease severity and duration, suggesting pathophysiological relevance. Furthermore, intrinsic FNC anomalies allowed individual classification of SAD v. HC with significant accuracy, indicating potential diagnostic efficacy.

SAD patients show distinct patterns of functional synchronization abnormalities both within and across large-scale RSNs, reflecting or causing a network imbalance of bottom-up response and top-down regulation in cognitive, emotional and sensory domains. Therefore, this could offer insights into the neurofunctional substrates of SAD.

Numerous previous studies have used event-related potentials (ERPs) to examine facial processing deficits in individuals with social anxiety disorder (SAD). However, researchers still need to determine whether the deficits are general or specific and what the dominant factors are behind different cognitive stages. Meta-analysis was performed to quantitatively identify face processing deficits in individuals with SAD. Ninety-seven results in 27 publications involving 1032 subjects were calculated using Hedges' g. The results suggest that the face itself elicits enlarged P1 amplitudes, threat-related facial expressions induce larger P2 amplitudes, and negative facial expressions lead to enhanced P3/LPP amplitudes in SAD individuals compared with controls. That is, there is face perception attentional bias in the early phase (P1), threat attentional bias in the mid-term phase (P2), and negative emotion attentional bias in the late phase (P3/LPP), which can be summarized into a three-phase SAD face processing deficit model. These findings provide an essential theoretical basis for cognitive behavioral therapy and have significant application value for the initial screening, intervention, and treatment of social anxiety.

Exposure-based cognitive behavioral therapy (CBT) is the gold standard for treating social anxiety disorder (SAD), yet response is not universal. CBT is thought to operate via extinction-related learning during exposure, which in turn relies on cognitive processes such as working memory. The present proof-of-concept study investigates the potential for training working memory to improve anxiety related outcomes following exposure. Thirty-three adults with elevated social anxiety were randomized to complete a working memory training or sham training condition. Post-training, participants completed a working memory assessment, speech exposure session, and two fMRI tasks. Participants who received working memory training demonstrated lower distress ratings by the end of the speech exposures and better performance on the fMRI working memory task than those in sham. Working memory training completers had greater neural activation in frontoparietal regions during an in-scanner working memory task and exhibited less neural activation in the fusiform gyrus in response to an emotional face processing task than those in sham. Adding working memory training to exposure procedures could strengthen functioning of frontoparietal regions and alter emotional processing - key mechanisms implicated in extinction learning. Findings provide preliminary evidence that training working memory in conjunction with exposure may enhance exposure success.

The tendency to interpret ambiguous stimuli as threatening has been associated with a range of anxiety disorders. Responses to ambiguity may be particularly relevant to mental health during the transition from adolescence to adulthood ("emerging adulthood"), when individuals encounter unfamiliar challenges and navigate novel social situations. However, it remains unclear whether neural representations of ambiguity relate to risk for anxiety. The present study sought to examine whether multivariate representations of ambiguity - and their similarity to representations of threat - relate to appraisals of ambiguity or anxiety in a sample of emerging adults. Participants (N = 41) viewed threatening (angry), nonthreatening (happy), and ambiguous (surprised) facial stimuli while undergoing fMRI. Outside of the scanner, participants were presented with the same stimuli and categorized the ambiguous faces as positive or negative. Using representational similarity analyses (RSA), we investigated whether the degree of pattern similarity in responses to ambiguous, nonthreatening, and threatening faces within the amygdala related to appraisals of ambiguous stimuli and anxiety symptomatology. We found that individuals who evidenced greater similarity (i.e., less differentiation) in neural representations of ambiguous and nonthreatening faces within the left amygdala reported lower concurrent anxiety. Additionally, trial-level pattern similarity predicted subsequent appraisals of ambiguous stimuli. These findings provide insight into how neural representations of ambiguity relate to risk or resilience for the development of anxiety.

Threat-anticipatory defensive responses have evolved to promote survival in a dynamic world. While inherently adaptive, aberrant expression of defensive responses to potential threat could manifest as pathological anxiety, which is prevalent, impairing, and associated with adverse outcomes. Extensive translational neuroscience research indicates that normative defensive responses are organized by threat imminence, such that distinct response patterns are observed in each phase of threat encounter and orchestrated by partially conserved neural circuitry. Anxiety symptoms, such as excessive and pervasive worry, physiological arousal, and avoidance behavior, may reflect aberrant expression of otherwise normative defensive responses, and therefore follow the same imminence-based organization. Here, empirical evidence linking aberrant expression of specific, imminence-dependent defensive responding to distinct anxiety symptoms is reviewed, and plausible contributing neural circuitry is highlighted. Drawing from translational and clinical research, the proposed framework informs our understanding of pathological anxiety by grounding anxiety symptoms in conserved psychobiological mechanisms. Potential implications for research and treatment are discussed.

Phenotyping approaches grounded in structural network science can offer insights into the neurobiological substrates of psychiatric diseases, but this remains to be clarified at the individual level in social anxiety disorder (SAD). Using a recently developed approach combining probability density estimation and Kullback-Leibler divergence, we constructed single-subject structural covariance networks (SCNs) based on multivariate morphometry (cortical thickness, surface area, curvature, and volume) and quantified their global/nodal network properties using graph-theoretical analysis. We compared network metrics between SAD patients and healthy controls (HC) and analyzed the relationship to clinical characteristics. We also used support vector machine analysis to explore the ability of graph-theoretical metrics to discriminate SAD patients from HC. Globally, SAD patients showed higher global efficiency, shorter characteristic path length, and stronger small-worldness. Locally, SAD patients showed abnormal nodal centrality mainly involving left superior frontal gyrus, right superior parietal lobe, left amygdala, right paracentral gyrus, right lingual, and right pericalcarine cortex. Altered topological metrics were associated with the symptom severity and duration. Graph-based metrics allowed single-subject classification of SAD versus HC with total accuracy of 78.7%. This finding, that the topological organization of SCNs in SAD patients is altered toward more randomized configurations, adds to our understanding of network-level neuropathology in SAD.

Psychiatric disorders are complex, often emerging from multiple atypical processes within specified domains over the course of development. Characterizing the development of the neural circuits supporting these domains may help break down the components of complex disorders and reveal variations in functioning associated with psychiatric risk. This review highlights the current and potential role of infant task-based functional magnetic resonance imaging (fMRI) in elucidating the developmental neurobiology of psychiatric disorders. Task-fMRI measures evoked brain activity in response to specific stimuli through changes in the blood oxygen level-dependent signal. First, we review extant studies using task fMRI from birth through the first few years of life and synthesize current evidence for when, where, and how different neural computations are performed across the infant brain. Neural circuits for sensory perception, the perception of abstract categories, and the detection of statistical regularities have been characterized with task fMRI in infants, providing developmental context for identifying and interpreting variation in the functioning of neural circuits related to psychiatric risk. Next, we discuss studies that specifically examine variation in the functioning of these neural circuits during infancy in relation to risk for psychiatric disorders. These studies reveal when maturation of specific neural circuits diverges, the influence of environmental risk factors, and the potential utility for task fMRI to facilitate early treatment or prevention of later psychiatric problems. Finally, we provide considerations for future infant task-fMRI studies with the potential to advance understanding of both functioning of neural circuits during infancy and subsequent risk for psychiatric disorders.

Perception of social stimuli (faces and bodies) relies on "holistic" (i.e., global) mechanisms, as supported by picture-plane inversion: perceiving inverted faces/bodies is harder than perceiving their upright counterpart. Albeit neuroimaging evidence suggested involvement of face-specific brain areas in holistic processing, their spatiotemporal dynamics and selectivity for social stimuli is still debated. Here, we investigate the spatiotemporal dynamics of holistic processing for faces, bodies and houses (adopted as control non-social category), by applying deep learning to high-density electroencephalographic signals (EEG) at source-level. Convolutional neural networks were trained to classify cortical EEG responses to stimulus orientation (upright/inverted), separately for each stimulus type (faces, bodies, houses), resulting to perform well above chance for faces and bodies, and close to chance for houses. By explaining network decision, the 150-200 ms time interval and few visual ventral-stream regions were identified as mostly relevant for discriminating face and body orientation (lateral occipital cortex, and for face only, precuneus cortex, fusiform and lingual gyri), together with two additional dorsal-stream areas (superior and inferior parietal cortices). Overall, the proposed approach is sensitive in detecting cortical activity underlying perceptual phenomena, and by maximally exploiting discriminant information contained in data, may reveal spatiotemporal features previously undisclosed, stimulating novel investigations.

Social anxiety disorder (SAD) is characterized by social anxiety/fear, self-attention, and interoception. Functional magnetic resonance imaging studies demonstrate increased activity during symptom-sensitive tasks in regions of the default-mode network (DMN), amygdala (AMG), and salience network (SN). What is the source of this task-unspecific symptom-sensitive hyperactivity in DMN? We address this question by probing SAD resting state (rs) changes in DMN including their relation to other regions as possible source of task-unspecific hyperactivity in the same regions. Our findings show the following: (1) rs-hypoconnectivity within-DMN regions; (2) rs-hyperconnectivity between DMN and AMG/SN; (3) task-evoked hyperactivity in the abnormal rs-regions of DMN and AMG/SN during different symptom-sensitive tasks; (4) negative relationship of rest and task changes in especially anterior DMN regions as their rs-hypoconnectivity is accompanied by task-unspecific hyperactivity; (5) abnormal top-down/bottom-up modulation between anterior DMN regions and AMG during rest and task. Findings demonstrate that rs-hypoconnectivity among DMN regions is negatively related to task-unspecific hyperactivity in DMN and AMG/SN. We propose a model of "Topography of the Anxious Self" in SAD (TAS-SAD). Abnormal DMN-AMG/SN topography during rest, as trait feature of an "unstable social self", is abnormally aggravated during SAD-sensitive situations resulting in task-related hyperactivity in the same regions with an "anxious self" as state feature.

Social anxiety disorder (SAD) is a prevalent and impairing mental disorder among children and adolescents. The bed nucleus of the stria terminalis (BNST) plays a critical role in anxiety disorders, including valence surveillance and hypervigilance for potential threats. However, the role of BNST and its related functional network in children and adolescents with SAD has not been fully investigated. This study examined the aberration of BNST's functional connectivity and its age dependence in adolescents with SAD.

Using a sample of 75 SAD patients and 75 healthy controls (HCs) children aged 9-18 years old, we delineated the group-by-age interaction of BNST-seeded functional connectivity (FC) during resting state and movie-watching. The relationships between BNST-seeded FC and clinical scores were also examined.

During movie viewing, the FC between the right BNST and the left amygdala, bilateral posterior cingulate cortex (PCC), bilateral superior temporal cortex, and right pericalcarine cortex showed a diagnostic group-by-age interaction. Compared to HCs, SAD patients showed a significant enhancement of the above FC at younger ages. Meanwhile, they showed an age-dependent decrease in FC between the right BNST and left amygdala. Furthermore, for SAD patients, FC between the right BNST and left amygdala during movie viewing was positively correlated with separation anxiety scores.

The right BNST plays an essential role in the aberrant brain functioning in children and adolescents with SAD. The atypicality of BNST's FC has remarkable age dependence in SAD, suggesting an association of SAD with neurodevelopmental traits.

ADHD has been associated with social cognitive impairments across the lifespan, but no studies have specifically addressed the presence of abnormalities in eye-gaze processing in the adult brain. This study investigated the neural basis of eye-gaze perception in adults with ADHD using event-related potentials (ERP). Twenty-three ADHD and 23 controls performed a delayed face-matching task with neutral faces that had either direct or averted gaze. ERPs were classified using microstate analyses. ADHD and controls displayed similar P100 and N170 microstates. ADHD was associated with cluster abnormalities in the attention-sensitive P200 to direct gaze, and in the N250 related to facial recognition. For direct gaze, source localization revealed reduced activity in ADHD for the P200 in the left/midline cerebellum, as well as in a cingulate-occipital network at the N250. These results suggest brain impairments involving eye-gaze decoding in adults with ADHD, suggestive of neural signatures associated with this disorder in adulthood.

Altered functioning of the brain's threat and reward circuitry has been linked to early life adversity and to symptoms of anxiety and depression. To date, however, these relationships have been studied largely in isolation and in categorical-based approaches. It is unclear to what extent early life adversity and psychopathology have unique effects on brain functioning during threat and reward processing. We examined functional brain activity during a face processing task in threat (amygdala and ventromedial prefrontal cortex) and reward (ventral striatum and orbitofrontal cortex) regions of interest among a sample (N = 103) of young adults (aged 18-19 years) in relation to dimensional measures of early life adversity and symptoms of anxiety and depression. Results demonstrated a significant association between higher scores on the deprivation adversity dimension and greater activation of reward neural circuitry during viewing of happy faces, with the largest effect sizes observed in the orbitofrontal cortex. We found no significant associations between the threat adversity dimension, or symptom dimensions of anxiety and depression, and neural activation in threat or reward circuitries. These results lend partial support to theories of adversity-related alterations in neural activation and highlight the importance of testing dimensional models of adversity and psychopathology in large sample sizes to further our understanding of the biological processes implicated.

Shame and guilt are distinct negative moral emotions, although they are usually regarded as overlapping affective experiences. Of these two emotions, shame is more closely related to concerns about other people's judgment, whereas guilt is more related to concerns about one's own judgment. Although some studies have tried to identify the psychological process underlying shame as opposed to guilt, there is no clear evidence of brain regions that are specifically relevant to the experience of shame rather than guilt and, more generally, self-blame. We therefore investigated associations between individual differences in shame- and guilt-proneness and the gray and white matter structures of the brain using magnetic resonance imaging and voxel-based morphometry while controlling for associations with guilt- or shame-proneness. To accomplish this goal, we enrolled 590 healthy, right-handed individuals (338 men and 252 women; age, 20.6 ± 1.8 years). We administered a questionnaire to assess shame proneness and guilt proneness. Based on our hypothesis, we found that high shame proneness was associated with decreased regional white matter density only in the right inferior temporal pole, whereas no significant region was associated with guilt. The function of this area may be important for the underlying processes differentiating shame from guilt.

Although functional and structural abnormalities in brain regions involved in the neurobiology of fear and anxiety have been observed in patients with social anxiety disorder (SAD), the findings have been heterogeneous due to small sample sizes, demographic confounders, and methodological differences. Besides, multimodal neuroimaging studies on structural-functional deficits and couplings are rather scarce. Herein, we aimed to explore functional network anomalies in brain regions with structural deficits and the effects of structure-function couplings on the SAD diagnosis. High-resolution structural magnetic resonance imaging (MRI) and resting-state functional MRI images were obtained from 49 non-comorbid patients with SAD and 53 demography-matched healthy controls. Whole-brain voxel-based morphometry analysis was conducted to investigate structural alterations, which were subsequently used as seeds for the resting-state functional connectivity analysis. In addition, correlation and mediation analyses were performed to probe the potential roles of structural-functional deficits in SAD diagnosis. SAD patients had significant gray matter volume reductions in the bilateral putamen, right thalamus, and left parahippocampus. Besides, patients with SAD demonstrated widespread resting-state dysconnectivity in cortico-striato-thalamo-cerebellar circuitry. Moreover, dysconnectivity of the putamen with the cerebellum and the right thalamus with the middle temporal gyrus/supplementary motor area partially mediated the effects of putamen/thalamus atrophy on the SAD diagnosis. Our findings provide preliminary evidence for the involvement of structural and functional deficits in cortico-striato-thalamo-cerebellar circuitry in SAD, and may contribute to clarifying the underlying mechanisms of structure-function couplings for SAD. Therefore, they could offer insights into the neurobiological substrates of SAD.

Patients suffering from social anxiety disorder (SAD) fear social interaction and evaluation, which severely undermines their everyday life. There is evidence of increased prosocial behavior after acute social stress exposure in healthy individuals, which may be interpreted as stress-regulating "tend-and-befriend" behavior. In a randomized controlled trial, we measured empathic abilities in a first diagnostic session. In the following experimental session, we investigated how patients with SAD (n = 60) and healthy control participants (HC) (n = 52) respond to an acute social stressor (Trier Social Stress Test for groups) or a non-stressful control condition, and whether empathic abilities and acute social stress interact to modulate anxious appearance and social behavior in a social conversation test. Salivary cortisol, heart rate, and subjective stress response were repeatedly measured. The anxious appearance and social behavior of participants were rated by the conversation partner. SAD patients demonstrated stronger subjective stress responses while the biological responses did not differ from HC. Moreover, patients performed worse overall in the conversation task, which stress additionally undermined. Finally, we found that both emotional and cognitive empathy buffered the negative effects of acute stress on social behavior in SAD, but not in HC. Our data highlight the importance of empathic abilities for SAD during stressful situations and call for multimodal clinical diagnostics. This may help to differentiate clinical subtypes and offer better-tailored treatment for patients. General Scientific Summary: This study shows that high levels of cognitive and emotional empathy can buffer the negative effects of acute stress on social behavior in social anxiety disorder (SAD). Empathic abilities may be included as an additional diagnostic resource marker for SAD.

Recent resting-state functional magnetic resonance imaging studies have provided strong evidence of abnormal regional spontaneous brain activities among anxiety-disordered patients. However, the evidence has been divergent and inconclusive. Therefore, it is necessary to perform a meta-analysis identifying a common pattern of altered regional spontaneous brain activity for anxiety disorders.

Corresponding research of anxiety disorders, namely, whole-brain rs-fMRI studies that measured differences in regional homogeneity, amplitude of low-frequency fluctuations, or fractional amplitude of low-frequency fluctuations, were analyzed in this study. Overall, seven studies with 235 anxiety-disordered patients and 241 healthy controls were ultimately included in the meta-analysis. The meta-analysis was processed by seed-based d mapping.

Compared with healthy controls, patients with anxiety disorders showed significantly decreased regional spontaneous brain activities in the right putamen, the right orbital inferior frontal gyrus, and the right temporal pole. No increases in regional spontaneous brain activities were detected in patients relative to the controls.

Limited number of available studies, only Asian samples, and insufficient information of sample characteristics.

The present study suggests that anxiety disorders are associated with aberrant regional brain activity in areas connected with emotion processing, which extends our understanding of anxiety disorders' pathophysiology.

Background In recent years, a growing body of eye-tracking research has investigated gaze behavior in individuals with social anxiety during the visual perception of emotional stimuli. The aim of this article was to review and synthesize studies examining attention orientation in patients with clinical social anxiety by means of eye-tracking methodology. Methods Through a systematic search, 30 articles were identified, including 11 studies in which single emotional faces were used as stimuli and seven eligible studies in which threatening faces were paired with neutral stimuli. Meta-analyses were conducted to compare prolonged eye-contact behavior and early attentional biases to threats in individuals with social anxiety disorder (SAD) and healthy controls. Results Moderate group differences were revealed for single face viewing studies, with SAD patients showing significantly reduced eye contact with negative (Hedges' g = -0.67) and positive emotional faces (g = -0.49) compared to that of healthy participants. Type of task and duration of stimulus presentation were (marginally) significant moderators of between-study variance in effect size. Small but significant group differences were found for early attentional biases toward angry faces versus neutral stimuli (g = 0.21) but not toward happy faces versus neutral stimuli (g = 0.05). Preliminary evidence for a hyperscanning strategy in SAD patients relative to healthy controls emerged (g = 0.42). Limitations The number of included studies with face pairings was low, and two studies were excluded due to unavailable data. Conclusions Our results suggest that eye contact avoidance with emotional faces is a prominent feature in SAD patients. Patients might benefit from guidance to learn to make adequate eye contact during therapeutic interventions, such as exposure therapy. SAD patients demonstrated slightly heightened attention allocation toward angry faces relative to that of healthy participants during early processing stages. Threat biases can be potential targets for attention modification training as an adjuvant to other treatments. Future research on early attentional processes may benefit from improved arrangements of paired stimuli to increase the psychometric properties of initial attention indices.

Altered amygdala activation in response to the emotional matching faces (EMF) task, a task thought to reflect implicit emotion detection and reactivity, has been found in some patients with internalizing disorders; mixed findings from the EMF suggest individual differences (within and/or across diagnoses) that may be important to consider. Attention Bias Modification (ABM), a mechanistic attention-targeting intervention, has demonstrated efficacy in treatment of internalizing disorders. Individual differences in neural activation to a relatively attention-independent task, such as the EMF, could reveal novel neural substrates relevant in ABM's transdiagnostic effects, such as the brain's generalized threat reactivity capacity.

In a sample of clinically anxious patients randomized to ABM (n = 43) or sham training (n = 18), we measured fMRI activation patterns during the EMF and related them to measures of transdiagnostic internalizing symptoms (i.e., anxious arousal, general distress, anhedonic depression, and general depressive symptoms).

Lower baseline right amygdala activation to negative (fearful/angry) faces, relative to shapes, predicted greater pre-to-post reduction in general depression symptoms in ABM-randomized patients. Greater increases in bilateral amygdalae activation from pre-to-post ABM were associated with greater reductions in general distress, anhedonic depression, and general depression symptoms.

ABM may lead to greater improvement in depressive symptoms in individuals exhibiting blunted baseline amygdalar responses to the EMF task, potentially by enhancing neural-level discrimination between negative and unambiguously neutral stimuli. Convergently, longitudinal increases in amygdala reactivity from pre-to-post-ABM may be associated with greater improvement in depression, possibly secondary to improved neural discrimination of threat and/or decreased neurophysiological threat avoidance in these specific patients.

Though a plethora of functional magnetic resonance imaging (fMRI) studies explored the neurobiological underpinnings of borderline personality disorder (BPD), findings across different tasks were divergent. We conducted a systematic review and activation likelihood estimation (ALE) meta-analysis on the fMRI studies conducted in BPD patients compared to healthy controls (HC). We systematically searched PubMed and PsychINFO from inception until July 9th 2020 using combinations of database-specific terms like 'fMRI', 'Neuroimaging', 'borderline'. Eligible studies employed task-based fMRI of the brain in participants of any age diagnosed with BPD compared to HC, during any behavioral task and providing a direct contrast between the groups. From 762 entries, we inspected 92 reports full-texts and included 52 studies (describing 54 experiments). Across all experiments, the HC > BPD and BPD > HC meta-analyses did not yield any cluster of significant convergence of differences. Analyses restricted to studies of emotion processing revealed two significant clusters of activation in the bilateral hippocampal/amygdala complex and anterior cingulate for the BPD > HC meta-analysis. Fail-safe N and single study sensitivity analysis suggested significant findings were not robust. For the subgroup of emotional processing experiments, on a restricted number of experiments providing results for each group separately, another meta-analysis method (difference of convergence) showed a significant cluster in the insula/inferior frontal gyrus for the HC > BPD contrast. No consistent pattern of alteration in brain activity for BPD was evidenced suggesting substantial heterogeneity of processes and populations studied. A pattern of amygdala dysfunction emerged across emotion processing tasks, indicating a potential pathophysiological mechanism that could be transdiagnostic.

Background: Social anxiety disorder (SAD) has its typical onset in childhood and adolescence. Maladaptive processing of social information may contribute to the etiology and maintenance of SAD. During face perception, individuals execute a succession of visual fixations known as a scanpath which facilitates information processing. Atypically long scanpaths have been reported in adults with SAD, but no data exists from pediatric samples. SAD has also been linked to atypical arousal during face perception. Both metrics were examined in one of the largest eye-tracking studies of pediatric SAD to date. Methods: Participants were children and adolescents with SAD (n = 61) and healthy controls (n = 39) with a mean age of 14 years (range 10-17) who completed an emotion recognition task. The visual scanpath and pupil dilation (an indirect index of arousal) were examined using eye tracking. Results: Scanpaths of youth with SAD were shorter, less distributed, and consisted of a smaller number of fixations than those of healthy controls. These findings were supported by both frequentist and Bayesian statistics. Higher pupil dilation was also observed in the SAD group, but despite a statistically significant group difference, this result was not supported by the Bayesian analysis. Conclusions: The results were contrary to findings from adult studies, but similar to what has been reported in neurodevelopmental conditions associated with social interaction impairments. Restricted scanpaths may disrupt holistic representation of faces known to favor adaptive social understanding.

Previous fMRI research has applied a variety of tasks to examine brain activity underlying emotion processing. While task characteristics are known to have a substantial influence on the elicited activations, direct comparisons of tasks that could guide study planning are scarce. We aimed to provide a comparison of four common emotion processing tasks based on the same analysis pipeline to suggest tasks best suited for the study of certain target brain regions. We studied an n-back task using emotional words (EMOBACK) as well as passive viewing tasks of emotional faces (FACES) and emotional scenes (OASIS and IAPS). We compared the activation patterns elicited by these tasks in four regions of interest (the amygdala, anterior insula, dorsolateral prefrontal cortex (dlPFC) and pregenual anterior cingulate cortex (pgACC)) in three samples of healthy adults (N = 45). The EMOBACK task elicited activation in the right dlPFC and bilateral anterior insula and deactivation in the pgACC while the FACES task recruited the bilateral amygdala. The IAPS and OASIS tasks showed similar activation patterns recruiting the bilateral amygdala and anterior insula. We conclude that these tasks can be used to study different regions involved in emotion processing and that the information provided is valuable for future research and the development of fMRI biomarkers.

Social anxiety disorder (SAD) and major depressive disorder (MDD) are highly comorbid and share impairments in self-referential and social processing. Many naturalistic judgements activate these processes concurrently, which can be referred to as "self-other referential processing". We sought to examine its neural correlates in young people with SAD and MDD using a novel experimental task.

Fifty six young people aged 16 to 25 with diagnoses of SAD and/or MDD (15 with SAD [M = 20.3 years, 60% female], 17 with MDD [M = 19.8 years, 53% female], 24 with comorbid SAD and MDD [M = 19.8 years, 67% female]) and 76 age and gender-matched healthy controls (HCs; M = 20.7 years, 66% female) completed a novel self-other referential processing fMRI task that involved rating how much one related to emotional faces in active conditions and judging how far apart each person's eyes were in control conditions.

Participants with SAD had more and those with MDD had less activity in social cognitive areas than HCs when processing social information across all conditions and emotion types. Participants with comorbid SAD-MDD exhibited a distinct pattern of neural activity to patients with single diagnoses. Across the whole sample, the activation of reward system areas (the medial orbitofrontal cortex and caudate) in response to increasing relatedness correlated positively with a dimensional measure of social anxiety.

Young people with SAD, MDD and comorbid SAD-MDD showed deficits in social processing, but they were not specifically related to self-other referential processing. Dimensional social anxiety symptoms were correlated with reward system activation, suggesting that such symptoms are associated with an overestimation of the hedonic value of social stimuli. These novel findings have implications for our understanding of the neural correlates of SAD and MDD, suggesting that alterations in social processing and reward functioning underlie the impairments in self and social processing that characterize both disorders.

Generalized anxiety disorder (GAD) can significantly impair quality of life and is associated with a relatively poor long-term prognosis. Anxiety disorders are often associated with hyper-responsiveness to threat, perhaps coupled with impaired executive functioning. However, GAD, particularly adolescent GAD, has been the focus of little functional neuroimaging work compared to other anxiety disorders. Here, we examine the neural association of adolescent GAD with responsiveness to threat and response control.

The study involved 35 adolescents with GAD and 34 healthy comparison individuals (N = 69) matched on age, gender, and IQ. Participants were scanned during an affective number Stroop task.

We found significant Group-by-Task Condition interactions in regions involved in response control/motor responding (bilateral precentral gyri and cerebellum) and/or cognitive control/attention (dorsomedial and lateral frontal cortex, posterior cingulate cortex, cuneus, and precuneus). In line with predictions, the youth with GAD showed significantly less recruitment during task trials than the healthy comparison individuals. However, no indications of specific heightened responses to threat were seen.

GAD involves reduced capacity for engaging regions involved in response control/motor responding and/or cognitive control/attention. This might reflect either a secondary consequence of the patient's worry or an early risk factor for the development of worry.

Social anxiety disorder (SAD) is linked to atypical attention to other's eyes. Empirical literature about this phenomenon in childhood and adolescence is scarce. Previous studies in adults have suggested that SAD may be characterized by either rapid avoidance of eye contact, or by impaired shifting of attention away from eyes once eye contact has been established. SAD has also been linked to quick orienting towards eyes, indicating vigilant monitoring of perceived threat.

In the largest eye-tracking study of youth with SAD to date, 10 to 17 year-olds with SAD (n = 88) and healthy controls (n = 62) were primed to look at either the eyes or the mouth of human faces. The latency and likelihood of a first gaze shift from, or to the eyes, was measured.

Individuals with SAD were slower to shift their gaze away from the eye region of faces than controls, but did not differ in orienting toward eyes.

Participants were assessed once after the onset of SAD symptoms, meaning that the longitudinal predictive value of delayed gaze shifts from others' eyes could not be examined.

Youth with SAD may be impaired in shifting attention from other's eyes. This could contribute to the experience of eye contact as aversive, and may be a maintaining factor of childhood SAD.

Introduction: Individuals tend to explore the left side of a face first and for a longer time in comparison to the right side. This left visual field (LVF) bias is suggested to reflect right hemispheric dominance for face processing. Social anxiety disorder (SAD) is associated with maladaptive interpretations of facial expressions, but it is not known whether this is linked to an atypical LVF bias. Previous studies have reported a reduced LVF bias in autism, a condition overlapping with SAD. This pre-registered study examined the LVF bias in adolescents with SAD. Methods: Eye-tracking was used to investigate the ratio of first fixations to the left on upright and inverted face stimuli in 26 adolescents (13-17 years) with SAD and 23 healthy controls primed to look either between the eyes or at the mouth. Results: The SAD group showed a smaller LVF bias and an atypical face inversion effect when primed to look at the eyes. Autistic traits predicted a smaller LVF bias, independently of social anxiety level. Conclusions: Results suggest that SAD is associated with impaired processing of faces at an early stage of visual scanning. The findings contribute to a better understanding of SAD and its overlap with autism.

Prospection (mentally simulating future events) generates emotionally-charged mental images that guide social decision-making. Positive and negative social expectancies-imagining new social interactions to be rewarding versus threatening-are core components of social approach and avoidance motivation, respectively. Interindividual differences in such positive and negative future-related cognitions may be underpinned by distinct neuroanatomical substrates. Here, we asked 100 healthy adults to vividly imagine themselves in a novel self-relevant event that was ambiguous with regards to possible social acceptance or rejection. During this task we measured participants' expectancies for social reward (anticipated feelings of social connection) or threat (anticipated feelings of rejection). On a separate day they underwent structural MRI; voxel-based morphometry was used to explore the relation between social reward and threat expectancies and regional grey matter volumes (rGMV). Increased rGMV in key default-network regions involved in prospection, socio-emotional cognition, and subjective valuation, including ventromedial prefrontal cortex, correlated with both higher social reward and lower social threat expectancies. In contrast, social threat expectancies uniquely correlated with rGMV of regions involved in social attention (posterior superior temporal sulcus, pSTS) and interoception (somatosensory cortex). These findings provide novel insight into the neurobiology of future-oriented cognitive-affective processes critical to adaptive social functioning.

Humans and animals live in social relationships shaped by actions of approach and avoidance. Both are crucial for normal physical and mental development, survival, and well-being. Active withdrawal from social interaction is often induced by the perception of threat or unpleasant social experience and relies on adaptive mechanisms within neuronal networks associated with social behavior. In case of confrontation with overly strong or persistent stressors and/or dispositions of the affected individual, maladaptive processes in the neuronal circuitries and its associated transmitters and modulators lead to pathological social avoidance. This review focuses on active, fear-driven social avoidance, affected circuits within the mesocorticolimbic system and associated regions and a selection of molecular modulators that promise translational potential. A comprehensive review of human research in this field is followed by a reflection on animal studies that offer a broader and often more detailed range of analytical methodologies. Finally, we take a critical look at challenges that could be addressed in future translational research on fear-driven social avoidance.

A critical cognitive symptom that is commonly involved in social anxiety and depression is attentional deficit. However, the functional relationship between attentional deficit and these two disorders remains poorly understood. Here, we behaviorally disentangled the three key attentional components (alerting, orienting, and executive control) using the established attentional network task (ANT) to investigate how social anxiety and depression are related to deficits in these attention components. We identified a double dissociation between the symptoms of social anxiety and depression and the attentional component deficits when processing non-emotional stimuli. While individuals vulnerable to social anxiety exhibited deficits in the orienting component, individuals vulnerable to depression were impaired in the executive control component. Our findings showed that social anxiety and depression were associated with deficits in different attentional components, which are not specific to emotional information.

Social anxiety disorder (SAD) runs in families, but the neurobiological pathways underlying the genetic susceptibility towards SAD are largely unknown. Here, we employed an endophenotype approach, and tested the hypothesis that amygdala hyperreactivity to faces conditioned with a social-evaluative meaning is a candidate SAD endophenotype. We used data from the multiplex, multigenerational Leiden Family Lab study on Social Anxiety Disorder (eight families, n = 105) and investigated amygdala activation during a social-evaluative conditioning paradigm with high ecological validity in the context of SAD. Three neutral faces were repeatedly presented in combination with socially negative, positive or neutral sentences. We focused on two endophenotype criteria: co-segregation of the candidate endophenotype with the disorder within families, and heritability. Analyses of the fMRI data were restricted to the amygdala as a region of interest, and association analyses revealed that bilateral amygdala hyperreactivity in response to the conditioned faces co-segregated with social anxiety (SA; continuous measure) within the families; we found, however, no relationship between SA and brain activation in response to more specific fMRI contrasts. Furthermore, brain activation in a small subset of voxels within these amygdala clusters was at least moderately heritable. Taken together, these findings show that amygdala engagement in response to conditioned faces with a social-evaluative meaning qualifies as a neurobiological candidate endophenotype of social anxiety. Thereby, these data shed light on the genetic vulnerability to develop SAD.

Faces and voices are very important sources of threat in social anxiety disorder (SAD), a common psychiatric disorder where core elements are fears of social exclusion and negative evaluation. Previous research in social anxiety evidenced increased cerebral responses to negative facial or vocal expressions and also generally increased hemodynamic responses to voices and faces. But it is unclear if also the cerebral process of face-voice-integration is altered in SAD. Applying functional magnetic resonance imaging, we investigated the correlates of the audiovisual integration of dynamic faces and voices in SAD as compared to healthy individuals. In the bilateral midsections of the superior temporal sulcus (STS) increased integration effects in SAD were observed driven by greater activation increases during audiovisual stimulation as compared to auditory stimulation. This effect was accompanied by increased functional connectivity with the visual association cortex and a more anterior position of the individual integration maxima along the STS in SAD. These findings demonstrate that the audiovisual integration of facial and vocal cues in SAD is not only systematically altered with regard to intensity and connectivity but also the individual location of the integration areas within the STS. These combined findings offer a novel perspective on the neuronal representation of social signal processing in individuals suffering from SAD.

What people think about, the intentional aspect of cognition, is distinguished from its operational aspect, or how proficiently they think. Many psychiatric disorders as well as social problems like racism, are defined largely by specified thought contents, whereas neurological disorders including dementia are defined by low proficiency. Intentionality contrasts with operational cognition in resisting objectification and in being expressed primarily in verbal narratives and subjective self-disclosure. This yields insecure data that have slowed progress in fields where intentional cognition plays a key role. The question is how to produce more secure knowledge and open the intentional domain itself to objective investigation. The use of operational methods to infer intentionality has provided only partial answers. However, the science of reconstructing mental events with neural data is providing a new horizon for the study of intentional cognition. Reconstruction science must address major challenges related to fidelity and validity. Nevertheless, this approach is showing the first steps on the road to accessing and revealing objectively the contents of thought.

Early-life adversity (ELA) is a risk factor for internalizing psychopathology (IP). ELA is also linked to alterations in neural phenotypes of emotion processing and maladaptive emotion regulatory strategies, such as ruminative brooding, in adulthood. We therefore expected that ELA would predict cortical brain activation to emotional faces in transdiagnostic IP and in turn, mediate the extent of rumination amongst patients with IPs and ELA (IP + ELA).

One hundred and thirty-two individuals, including 102 treatment-seeking adults with heterogeneous IPs and 30 healthy controls (HCs) performed an Emotional Face-Matching Task during functional magnetic resonance imaging. Whole-brain analyses compared HC (n = 30), IP (n = 52), and IP + ELA (n = 50) neural responses to emotional (angry, fearful, happy, and sad) faces v. shapes, controlling for depression and anxiety symptoms. Parameter estimates of activation were extracted for significant between-group differences and tested as a mediator of ruminative brooding in IP + ELA.

IP + ELA demonstrated increased activation in the superior frontal gyrus and anterior cingulate cortex (fear), superior parietal lobule, precuneus, posterior cingulate, and inferior temporal gyrus (fear only), and cuneus (fear and angry). These regions were preferentially correlated with ruminative brooding in IP + ELA, many of which mediated the link between IP + ELA and ruminative brooding.

Results provide evidence that ELA history amongst IP patients augments engagement of brain regions involved in emotion processing, above and beyond what is accounted for by current symptoms. Though longitudinal designs are needed, alterations in the neural correlates of maladaptive processing of socio-emotional information may be a common pathway by which ELA poses risk for psychopathology.

Enhanced odor sensitivity, particularly toward threat-related cues, may be adaptive during periods of danger. Research also suggests that chronic psychological distress may lead to functional changes in the olfactory system that cause heightened sensitivity to odors. Yet, the association between self-reported odor sensitivity, objective odor detection, and affective psychopathology is currently unclear, and research suggests that persons with affective problems may only be sensitive to specific, threat-related odors.

The current study compared adults with self-reported odor sensitivity that was described as functionally impairing (OSI; n = 32) to those who reported odor sensitivity that was non-impairing (OS; n = 17) on affective variables as well as quantitative odor detection.

Increased anxiety sensitivity, trait anxiety, depression, and life stress, even while controlling for comorbid anxiety and depressive disorders, was found for OSI compared to OS. While OSI, compared to OS, demonstrated only a trend increase in objective odor detection of a smoke-like, but not rose-like, odor, further analysis revealed that increased detection of that smoke-like odor was positively correlated with anxiety sensitivity.

These findings suggest that persons with various forms of psychological distress may find themselves significantly impaired by an intolerance of odors, but that self-reported odor sensitivity does not necessarily relate to enhanced odor detection ability. However, increased sensitivity to a smoke-like odor appears to be associated with sensitivity to aversive anxiogenic stimuli. Implications for the pathophysiology of fear- and anxiety-related disorders are discussed.