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Altered Development of Amygdala-Anterior Cingulate Cortex Connectivity in Anxious Youth and Young Adults.

ABSTRACT: 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.

SUBMITTER: Kujawa A

PROVIDER: S-EPMC4979579 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Altered Development of Amygdala-Anterior Cingulate Cortex Connectivity in Anxious Youth and Young Adults.

Kujawa Autumn A Wu Minjie M Klumpp Heide H Pine Daniel S DS Swain James E JE Fitzgerald Kate D KD Monk Christopher S CS Phan K Luan KL

Biological psychiatry. Cognitive neuroscience and neuroimaging 20160701 4

<h4>Background</h4>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 ...[more]

PMID: 27525316

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Project description:ObjectivesAltered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, was previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first-episode manic participants who remitted after 8 weeks of treatment compared to those who did not.MethodsForty-two participants with bipolar disorder (60% female) during their first manic episode were recruited and received 8 weeks of treatment. Twenty-one remitted following treatment. Participants completed fMRI scans, at baseline and following 8 weeks of treatment, while performing a continuous performance task with emotional and neutral distractors. A healthy comparison group (n = 41) received fMRI evaluations at the same intervals. Differences in functional connectivity of the amygdala and caudate with the rostral anterior cingulate and ventrolateral prefrontal cortices at baseline (and changes in functional connectivity following treatment) were modeled between groups.ResultsAt baseline, non-remitters showed an increase in positive connectivity between right anterior cingulate and caudate and a loss of negative connectivity between right anterior cingulate and amygdala, compared to healthy participants. Individuals who remitted following treatment showed an increase in negative connectivity between amygdala and left anterior cingulate 8 weeks following treatment.ConclusionsResults provide evidence of alterations in anterior cingulate amygdala and caudate functional connectivity in bipolar disorder non-remitters during a first manic episode and changes in anterior cingulate functional connectivity associated with remission suggesting targets to predict treatment response. Registered at ClinicalTrials.Gov; Functional and Neurochemical Brain Changes in First-episode Bipolar Mania. NCT00609193. URL: https://clinicaltrials.gov/ct2/show/NCT00609193?term=strakowskirank=1.

Project description:IntroductionResting state functional connectivity (FC) is widely used to assess functional brain alterations in patients with chronic pain. However, reports of FC accompanying tonic pain in pain-free persons are rare. A network we term the Descending Pain Modulatory Network (DPMN) is implicated in healthy and pathologic pain modulation. Here, we evaluate the effect of tonic pain on FC of specific nodes of this network: anterior cingulate cortex (ACC), amygdala (AMYG), periaqueductal gray (PAG), and parabrachial nuclei (PBN).MethodsIn 50 pain-free participants (30F), we induced tonic pain using a capsaicin-heat pain model. functional MRI measured resting BOLD signal during pain-free rest with a 32 °C thermode and then tonic pain where participants experienced a previously warm temperature combined with capsaicin. We evaluated FC from ACC, AMYG, PAG, and PBN with correlation of self-report pain intensity during both states. We hypothesized tonic pain would diminish FC dyads within the DPMN.ResultsOf all hypothesized FC dyads, only PAG and subgenual ACC was weakly altered during pain (F = 3.34; p = 0.074; pain-free>pain d = 0.25). After pain induction sACC-PAG FC became positively correlated with pain intensity (R = 0.38; t = 2.81; p = 0.007). Right PBN-PAG FC during pain-free rest positively correlated with subsequently experienced pain (R = 0.44; t = 3.43; p = 0.001). During pain, this connection's FC was diminished (paired t=-3.17; p = 0.0026). In whole-brain analyses, during pain-free rest, FC between left AMYG and right superior parietal lobule and caudate nucleus were positively correlated with subsequent pain. During pain, FC between left AMYG and right inferior temporal gyrus negatively correlated with pain. Subsequent pain positively correlated with right AMYG FC with right claustrum; right primary visual cortex and right temporo-occipitoparietal junction CONCLUSION: We demonstrate sACC-PAG tonic pain FC positively correlates with experienced pain and resting right PBN-PAG FC correlates with subsequent pain and is diminished during tonic pain. Finally, we reveal PAG- and right AMYG-anchored networks which correlate with subsequently experienced pain intensity. Our findings suggest specific connectivity patterns within the DPMN at rest are associated with subsequently experienced pain and modulated by tonic pain. These nodes and their functional modulation may reveal new therapeutic targets for neuromodulation or biomarkers to guide interventions.

Dataset Information

Altered Development of Amygdala-Anterior Cingulate Cortex Connectivity in Anxious Youth and Young Adults.

Publications

Altered Development of Amygdala-Anterior Cingulate Cortex Connectivity in Anxious Youth and Young Adults.

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