Disrupted Amygdalar Subregion Functional Connectivity and Evidence of a Compensatory Network in Generalized Anxiety Disorder

By Amit Etkin, Katherine E. Prater, A. Schatzberg, Vinod Menon, Michael D. Greicius. Archives of General Psychiatry, 2009

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Context: Little is known about the neural abnormalities underlying generalized anxiety disorder (GAD). Studies in other anxiety disorders have implicated the amygdala, but work in GAD has yielded conflicting results. The amygdala is composed of distinct subregions that interact with dissociable brain networks, which have been studied only in experimental animals. A functional connectivity approach at the subregional level may therefore yield novel insights into GAD. Objectives: To determine whether distinct connectivity patterns can be reliably identified for the basolateral (BLA) and centromedial (CMA) subregions of the human amygdala, and to examine subregional connectivity patterns and potential compensatory amygdalar connectivity in GAD. Design: Cross-sectional study. Setting: Academic medical center. Participants: Two cohorts of healthy control subjects (consisting of 17 and 31 subjects) and 16 patients withGAD. Main Outcome Measures: Functional connectivity with cytoarchitectonically determined BLA and CMA regions of interest, measured during functional magnetic resonance imaging performed while subjects were resting quietly in the scanner. Amygdalar gray matter volume was also investigated with voxel-based morphometry. Results: Reproducible subregional differences in large-scale connectivity were identified in both cohorts of healthy controls. The BLA was differentially connected with primary and higher-order sensory and medial prefrontal cortices. The CMA was connected with the midbrain, thalamus, and cerebellum. In GAD patients, BLA and CMA connectivity patterns were significantly less distinct, and increased gray matter volume was noted primarily in the CMA. Across the subregions, GAD patients had increased connectivity with a previously characterized frontoparietal executive control network and decreased connectivity with an insula- and cingulate-based salience network. Conclusions: Our findings provide new insights into the functional neuroanatomy of the human amygdala and converge with connectivity studies in experimental animals. In GAD, we find evidence of an intra-amygdalar abnormality and engagement of a compensatory frontoparietal executive control network, consistent with cognitive theories of GAD.

Subfields: Cognitive Neuroscience, Experimental and Cognitive Psychology

View Paper: https://www.semanticscholar.org/paper/6fa2fa52c02a7364ed7d3dea499112ffff6364b4

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Citations in the corpus

Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress (2012, background): “Accordingly, BL shows greater resting connectivity with vmPFC than with dACC, and Ce shows greater connectivity with dACC than with vmPFC (Etkin et al 2009, Roy et al 2009) Consistent with a role in reducing fear, the hippocampus shows greater connectivity with the BL than with Ce (Roy et al 2009).”
Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder (2011, background): “Functional connectivity analysis furthermore revealed a discoordination of taskrelated networks in patients with generalized anxiety disorder (Etkin et al., 2009; Monk et al., 2008), social anxiety disorder in adolescents (Guyer et al.”
Selective aberrant functional connectivity of resting state networks in social anxiety disorder (2010, background): “According to our results, the AN did not demonstrate different functional connectivity between SAD and HC, which was consistent with a previous fMRI study (Etkin et al., 2009).”
Neuroimaging of the Periaqueductal Gray: State of the Field (2011, background): “, 2011), field mapping (Dhond et al., 2008; Etkin et al., 2009; Gray et al., 2009; Mobbs et al., 2010; Ploner et al., 2010; Salomons et al., 2007), and midbrain/brainstem dedicated normalization procedures (Beissner et al.”