Functional connectivity profiles of amygdala subregions in posttraumatic stress disorder

Abstract The amygdala is crucial to understanding posttraumatic stress disorder (PTSD), yet knowledge of the connectivity of its substructures and their contribution to the functional heterogeneity characteristic of the disorder remains limited. This study sought to delineate the functional profiles...

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Main Authors: Elizabeth M. Haris, Richard A. Bryant, Kim L. Felmingham, Leanne M. Williams, Mayuresh S. Korgaonkar
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03508-y
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author Elizabeth M. Haris
Richard A. Bryant
Kim L. Felmingham
Leanne M. Williams
Mayuresh S. Korgaonkar
author_facet Elizabeth M. Haris
Richard A. Bryant
Kim L. Felmingham
Leanne M. Williams
Mayuresh S. Korgaonkar
author_sort Elizabeth M. Haris
collection DOAJ
description Abstract The amygdala is crucial to understanding posttraumatic stress disorder (PTSD), yet knowledge of the connectivity of its substructures and their contribution to the functional heterogeneity characteristic of the disorder remains limited. This study sought to delineate the functional profiles of amygdala substructures to advance a more nuanced understanding of their contribution to the neural circuitry underlying PTSD in a large sample. Task-derived intrinsic functional magnetic resonance imaging (rs-fMRI) data for 64 non-trauma-exposed controls (NEC) and 65 individuals with PTSD were analyzed. Amygdala subnuclei were segmented using FreeSurfer and combined into three major substructures for each hemisphere: the basolateral (BLA), centromedial (CMA), and superficial (SFA) nuclei. Seed-to-voxel functional connectivity analyses for the whole brain were performed to investigate group differences in subnuclei connectivity profiles. A significant group by subnuclei interaction was found for four clusters, driven by group differences in connectivity related to the BLA. There was lower connectivity in the PTSD group for the left BLA and precuneus, posterior cingulate, right superior parietal lobe, right postcentral gyrus, and bilateral precentral gyri. Higher connectivity was found in the PTSD group for the left BLA and brainstem, and for the right BLA and cerebellum, and brainstem and right pallidum. No group differences were found for the CMA or SFA. These results illustrate the importance of the BLA in driving task-derived intrinsic functional connectivity between NEC and PTSD groups. Findings suggest that group differences lie in lower connectivity with cortical areas involved in self-referential and sensorimotor processing, but higher connectivity with subcortical areas involved in arousal, salience, sensory, and reward processing.
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spelling doaj-art-0cb5ba65cd9a4b8dbb9584d54aad1a3d2025-08-20T04:02:42ZengNature Publishing GroupTranslational Psychiatry2158-31882025-08-0115111010.1038/s41398-025-03508-yFunctional connectivity profiles of amygdala subregions in posttraumatic stress disorderElizabeth M. Haris0Richard A. Bryant1Kim L. Felmingham2Leanne M. Williams3Mayuresh S. Korgaonkar4Brain Dynamics Centre, Westmead Institute for Medical Research, The University of SydneyBrain Dynamics Centre, Westmead Institute for Medical Research, The University of SydneySchool of Psychological Sciences, Department of Medicine, Dentistry and Health Sciences, The University of MelbourneDepartment of Psychiatry and Behavioral Sciences, Stanford University School of MedicineBrain Dynamics Centre, Westmead Institute for Medical Research, The University of SydneyAbstract The amygdala is crucial to understanding posttraumatic stress disorder (PTSD), yet knowledge of the connectivity of its substructures and their contribution to the functional heterogeneity characteristic of the disorder remains limited. This study sought to delineate the functional profiles of amygdala substructures to advance a more nuanced understanding of their contribution to the neural circuitry underlying PTSD in a large sample. Task-derived intrinsic functional magnetic resonance imaging (rs-fMRI) data for 64 non-trauma-exposed controls (NEC) and 65 individuals with PTSD were analyzed. Amygdala subnuclei were segmented using FreeSurfer and combined into three major substructures for each hemisphere: the basolateral (BLA), centromedial (CMA), and superficial (SFA) nuclei. Seed-to-voxel functional connectivity analyses for the whole brain were performed to investigate group differences in subnuclei connectivity profiles. A significant group by subnuclei interaction was found for four clusters, driven by group differences in connectivity related to the BLA. There was lower connectivity in the PTSD group for the left BLA and precuneus, posterior cingulate, right superior parietal lobe, right postcentral gyrus, and bilateral precentral gyri. Higher connectivity was found in the PTSD group for the left BLA and brainstem, and for the right BLA and cerebellum, and brainstem and right pallidum. No group differences were found for the CMA or SFA. These results illustrate the importance of the BLA in driving task-derived intrinsic functional connectivity between NEC and PTSD groups. Findings suggest that group differences lie in lower connectivity with cortical areas involved in self-referential and sensorimotor processing, but higher connectivity with subcortical areas involved in arousal, salience, sensory, and reward processing.https://doi.org/10.1038/s41398-025-03508-y
spellingShingle Elizabeth M. Haris
Richard A. Bryant
Kim L. Felmingham
Leanne M. Williams
Mayuresh S. Korgaonkar
Functional connectivity profiles of amygdala subregions in posttraumatic stress disorder
Translational Psychiatry
title Functional connectivity profiles of amygdala subregions in posttraumatic stress disorder
title_full Functional connectivity profiles of amygdala subregions in posttraumatic stress disorder
title_fullStr Functional connectivity profiles of amygdala subregions in posttraumatic stress disorder
title_full_unstemmed Functional connectivity profiles of amygdala subregions in posttraumatic stress disorder
title_short Functional connectivity profiles of amygdala subregions in posttraumatic stress disorder
title_sort functional connectivity profiles of amygdala subregions in posttraumatic stress disorder
url https://doi.org/10.1038/s41398-025-03508-y
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