Aberrant amygdala-frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder.
ABSTRACT: Generalized social anxiety disorder (gSAD) is characterized by exaggerated amygdala reactivity to social signals of threat, but if and how the amygdala interacts with functionally and anatomically connected prefrontal cortex (PFC) remains largely unknown. Recent evidence points to aberrant amygdala connectivity to medial PFC in gSAD at rest, but it is difficult to attribute functional relevance without the context of threat processing. Here, we address this by studying amygdala-frontal cortex connectivity during viewing of fearful faces and at rest in gSAD patients.Twenty patients with gSAD and 17 matched healthy controls (HCs) participated in functional magnetic resonance imaging of an emotional face matching task and a resting state task. Functional connectivity and psychophysiological interaction analysis were used to assess amygdala connectivity.Compared to HCs, gSAD patients exhibited less connectivity between amygdala and the rostral anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) while viewing fearful faces. gSAD patients also showed less connectivity between amygdala and rostral ACC at rest in the absence of fearful faces. DLPFC connectivity was negatively correlated with LSASFear (where LSAS is Liebowitz Social Anxiety Scale).Task and rest paradigms provide unique and important information about discrete and overlapping functional networks. In particular, amygdala coupling to DLPFC may be a phasic abnormality, emerging only in the presence of a social predictor of threat, whereas amygdala coupling to the rostral ACC may reflect both phasic and tonic abnormalities. These findings prompt further studies to better delineate intrinsic and externally evoked brain connectivity in anxiety and depression in relation to amygdala dysfunction.
Project description:The neuropeptide oxytocin (OXT) is thought to attenuate anxiety by dampening amygdala reactivity to threat in individuals with generalized social anxiety disorder (GSAD). Because the brain is organized into networks of interconnected areas, it is likely that OXT impacts functional coupling between the amygdala and other socio-emotional areas of the brain. Therefore, the aim of the current study was to examine the effects of OXT on amygdala functional connectivity during the processing of fearful faces in GSAD subjects and healthy controls (HCs). In a randomized, double-blind, placebo (PBO)-controlled, within-subjects design, 18 HCs and 17 GSAD subjects performed a functional magnetic resonance imaging task designed to probe amygdala response to fearful faces following acute intranasal administration of PBO or OXT. Functional connectivity between the amygdala and the rest of the brain was compared between OXT and PBO sessions using generalized psychophysiological interaction analyses. Results indicated that within individuals with GSAD, but not HCs, OXT enhanced functional connectivity between the amygdala and the bilateral insula and middle cingulate/dorsal anterior cingulate gyrus during the processing of fearful faces. These findings suggest that OXT may have broad pro-social implications such as enhancing the integration and modulation of social responses.
Project description:Generalized social anxiety disorder (gSAD) is associated with impoverished anterior cingulate cortex (ACC) engagement during attentional control. Attentional Control Theory proposes such deficiencies may be offset when demands on resources are increased to execute goals. To test the hypothesis attentional demands affect ACC response 23 patients with gSAD and 24 matched controls performed an fMRI task involving a target letter in a string of identical targets (low load) or a target letter in a mixed letter string (high load) superimposed on fearful, angry, and neutral face distractors. Regardless of load condition, groups were similar in accuracy and reaction time. Under low load gSAD patients showed deficient rostral ACC recruitment to fearful (vs. neutral) distractors. For high load, increased activation to fearful (vs. neutral) distractors was observed in gSAD suggesting a compensatory function. Results remained after controlling for group differences in depression level. Findings indicate perceptual demand modulates ACC in gSAD.
Project description:OBJECTIVE:The functioning of neural systems supporting emotion processing and regulation in youth with bipolar disorder not otherwise specified (BP-NOS) remains poorly understood. We sought to examine patterns of activity and connectivity in youth with BP-NOS relative to youth with bipolar disorder type I (BP-I) and healthy controls (HC). METHOD:Participants (18 BP-I youth, 16 BP-NOS youth, and 18 HC) underwent functional magnetic resonance imaging while performing two emotional-face gender labeling tasks (happy/neutral, fearful/neutral). Analyses focused on a priori neural regions supporting emotion processing (amygdala) and emotion regulation (ventromedial prefrontal cortex (VMPFC), dorsolateral prefrontal cortex (DLPFC). Connectivity analyses used VMPFC as a seed region. RESULTS:During the happy-face task, BP-I youth had greater amygdala, VMPFC, and DLPFC activity to happy faces whereas BP-NOS youth had reduced VMPFC and DLPFC activity to neutral faces relative to HC, and reduced amygdala, VMPFC, and DLPFC activity to neutral faces versus BP-I. During the fearful-face task, BP-I youth had reduced DLPFC activity to fearful faces whereas BP-NOS youth had reduced DLPFC activity to neutral faces relative to HC. BP-NOS youth showed greater VMPFC-DLPFC connectivity to happy faces relative to HC and BP-I youth. BP-I youth showed reduced VMPFC-amygdala connectivity to fearful faces relative to HC and BP-NOS youth. CONCLUSIONS:This is the first study to document differential patterns of abnormal neural activity in, and connectivity between, neural regions supporting emotion processing and regulation in BP-NOS versus BP-I youth. Findings suggest that despite similarities in symptom presentation, there are differential patterns of abnormal neural functioning in BP-NOS and BP-I relative to HC, which might reflect an "intermediate state" in the course of BP-I illness. Future longitudinal studies are needed to relate these findings with future conversion to BP-I/II.
Project description:Aberrant subcortical-prefrontal connectivity may contribute to insula hyper-reactivity to threat in generalized social anxiety disorder (gSAD). A novel PsychoPhysiological Interaction (PPI) analysis was used to examine functional 'coupling' between the insula and prefrontal cortex in gSAD patients and healthy controls (HCs). During fMRI, 29 gSAD and 26 HC volunteers performed an Emotional Face Matching Task, involving the processing of fear, angry, and happy expressions. As expected, compared with HCs, gSAD patients exhibited greater bilateral anterior insula (aINS) reactivity for fear vs. happy faces; this group difference was less robust for angry vs. happy faces. PPI of insula connectivity when processing fearful faces revealed the gSAD group had less right aINS-dorsal anterior cingulate coupling compared to HCs. Findings indicate that aINS hyper-reactivity for fear faces in gSAD, compared to controls, involves reduced connectivity with a prefrontal region implicated in cognitive control and emotion regulation.
Project description:BACKGROUND:Development of cortico-amygdala circuitry underlies the maturation of emotion processing and regulation, and age-related changes in amygdala connectivity with anterior cingulate cortex (ACC) have been shown to mediate normative developmental decreases in anxiety. It remains unclear whether developmental changes in this circuitry relate to pathological anxiety in youth. The current functional magnetic resonance imaging (fMRI) study addresses this question by examining amygdala functional connectivity in anxious and healthy individuals spanning the developmental period from childhood through adulthood. METHODS:Youth and young adults (age 7-25) with current anxiety disorders (n=57) and healthy comparisons (n=61) completed an fMRI emotional face processing task known to elicit amygdala activation in youth and adults. We examined interaction effects of anxiety group and age on amygdala connectivity with frontolimbic regions during processing of happy, angry, and fearful faces. RESULTS:Anxiety interacted with age to predict amygdala-ACC connectivity across emotional faces. Among healthy comparisons, age was negatively related to connectivity. In contrast, age was positively associated with amygdala-ACC connectivity in the anxious group. Group effects were also observed on amygdala connectivity with midcingulate and middle frontal gyri. Effects of anxiety and age on amygdala activation were not significant. CONCLUSIONS:Results indicate that anxiety is characterized by altered patterns of age-related changes in amygdala connectivity during emotional face processing. Positive associations between age and amygdala-ACC connectivity among anxious youth and young adults may indicate failure to establish early bottom-up connections in childhood and/or less top-down regulation of the amygdala into adulthood.
Project description:The amygdala plays a critical role in emotion. Its functional coupling with the hippocampus and ventromedial prefrontal cortex extending to a portion of the anterior cingulate cortex (ACC) is implicated in anxiogenesis and hypothalamic-pituitary-adrenal (HPA) system regulation. However, it remains unclear how amygdala-centred functional connectivity (FC) affects anxiety and cortisol concentrations in everyday life. Here, we investigate the relationship between daily cortisol concentrations (dCOR) and amygdala-centred FC during emotional processing in forty-one healthy humans. FC analyses revealed that higher dCOR predicted strengthened amygdala-centred FC with the hippocampus and cerebellum, but inhibited FC with the supramarginal gyrus and a perigenual part of the ACC (pgACC) when processing fearful faces (vs. neutral faces). Notably, the strength of amygdala-hippocampus FC mediated the positive relationship between cortisol and anxiety, specifically when the effect of amygdala-pgACC FC, a presumptive neural indicator of emotional control, was taken into account. Individuals with diminished connectivity between the amygdala and pgACC during fear-related processing might be more vulnerable to anxiogenesis as it pertains to greater circulating cortisol levels in everyday life. Individual functional patterns of amygdala-hippocampal-pgACC connectivity might provide a key to understand the complicate link between cortisol and anxiety-related behaviors.
Project description:Relational bullying and victimization are common social experiences during adolescence, but relatively little functional magnetic resonance imaging (fMRI) research has examined the neural correlates of bullying and victimization in adolescents. The aim of the present study was to address this gap by examining the association between amygdala activity to angry and fearful faces and peer relational bullying and victimization in a community-based sample of adolescents. Participants included 49 adolescents, 12-15 years old, who underwent fMRI scanning while completing an emotional face matching task. Results indicated that interactions between amygdala activity to angry and fearful faces predicted self-reported relational bullying and victimization. Specifically, a combination of higher amygdala activity to angry faces and lower amygdala activity to fearful faces predicted more bullying behavior, whereas a combination of lower amygdala activity to angry faces and lower amygdala activity to fearful faces predicted less relational victimization. Exploratory whole-brain analyses also suggested that increased rostral anterior cingulate cortex activity to fearful faces was associated with less bullying. These results suggest that relational bullying and victimization are related to different patterns of neural activity to angry and fearful faces, which may help in understanding how patterns of social information processing predict these experiences.
Project description:Intimate-partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) among women. PTSD neuroimaging studies have identified functional differences in the amygdala and anterior cingulate cortex (ACC)/medial prefrontal cortex during emotion processing. Recent investigations of the limbic sensory system and its associated neural substrate, the insular cortex, have demonstrated its importance for emotional awareness. This study examined the hypothesis that women with IPV-PTSD show a dysregulation of this limbic sensory system while processing threat-related emotional faces.12 women with IPV-PTSD and 12 nontraumatized comparison women underwent blood oxygenation level-dependent functional magnetic resonance imaging while completing an emotional face-matching task.IPV-PTSD subjects relative to comparison subjects displayed increased activation of the anterior insula and amygdala and decreased connectivity among the anterior insula, amygdala, and ACC while matching to fearful versus happy target faces. A similar pattern of activation differences was also observed for angry versus happy target faces. IPV-PTSD subjects relative to comparison subjects also displayed increased dorsal ACC/medial prefrontal cortex activation and decreased ventral ACC activation when matching to a male versus a female target, and the extent of increased dorsal ACC activation correlated positively with hyperarousal symptoms.Women with IPV-PTSD display hyperactivity and disconnection among affective and limbic sensory systems while processing threat-related emotion. Furthermore, hyperactivity of cognitive-appraisal networks in IPV-PTSD may promote hypervigilant states of awareness through an exaggerated sensitivity to contextual cues, i.e., male gender, which relate to past trauma.
Project description:Recent studies have revealed structural and functional abnormalities in amygdala due to Internet addiction (IA) associated with emotional disturbance. However, the role of amygdala connectivity that is responsible for emotion-cognition interactions is largely unknown in IA. This study aims to explore the amygdala connectivity abnormalities in IA. The functional and structural connectivity of bilateral amygdala were examined using seed-based connectivity analysis, and the structural integrity on white mater tracts passing through amygdala was also examined. Additionally, a correlation analysis was performed to investigate the relationship between brain connectivity and duration of IA. We found that IA subjects had decreased negative functional connectivity (FC) between amygdala and dorsolateral prefrontal cortex (DLPFC), and had increased negative FC between amygdala and precuneus and superior occipital gyrus (SOG). While IA subjects had decreased positive FC between amygdala and anterior cingulate cortex (ACC), and had increased positive FC between amygdala and thalamus. The FC between left amygdala and right DLPFC had significant correlation with duration of IA. The structural connectivity and integrity between amygdala and ACC were also decreased in IA subjects. These findings indicate that the amygdala connectivity is altered in IA subjects. The altered FC of amygdala-DLPFC is associated with duration of IA.