PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting‐state functional connectivity and its predictive validity using machine learning

Harricharan, Sherain; Nicholson, Andrew A.; Thome, Janine; Densmore, Maria; McKinnon, Margaret C.; Théberge, Jean; Frewen, Paul A.; Neufeld, Richard W. J.; Lanius, Ruth A.

doi:10.1111/psyp.13472

Cited by 94Posttraumatic Stress Disorder ResearchFunctional Brain Connectivity StudiesPsychosomatic Disorders and Their Treatments

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting‐state functional connectivity and its predictive validity using machine learning

Harricharan, Sherain, Nicholson, Andrew A., Thome, Janine, Densmore, Maria, McKinnon, Margaret C., Théberge, Jean, Frewen, Paul A., Neufeld, Richard W. J. +1 more·2020·Psychophysiology

DOI 10.1111/psyp.13472

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Abstract

Individuals with post‐traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting‐state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed‐based resting‐state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD ( n = 84), PTSD+DS ( n = 49), and age‐matched healthy controls ( n = 51). As compared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, as compared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy ( p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting‐state connectivity patterns to discriminate between participant groups with high predictive accuracy.

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Disrupted functional connectivity patterns of the insula subregions in drug-free major depressive disorder
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Initial Evidence of a Failure to Activate Right Anterior Insula During Affective Set Shifting in Posttraumatic Stress Disorder
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Memory, Amnesia, and Dissociative Identity Disorder
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Complex PTSD and borderline personality disorder
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Alterations in large-scale functional networks in adult posttraumatic stress disorder: A systematic review and meta-analysis of resting-state functional connectivity studies
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A randomized, controlled trial of alpha-rhythm EEG neurofeedback in posttraumatic stress disorder: A preliminary investigation showing evidence of decreased PTSD symptoms and restored default mode and salience network connectivity using fMRI
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A systematic review of the neural correlates of sexual minority stress: towards an intersectional minority mosaic framework with implications for a future research agenda
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The neurobiology of misophonia and implications for novel, neuroscience-driven interventions
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Evaluation of Risk of Bias in Neuroimaging-Based Artificial Intelligence Models for Psychiatric Diagnosis: A Systematic Review
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The posterior insular cortex is necessary for the consolidation of tone fear conditioning
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Sampling inequalities affect generalization of neuroimaging-based diagnostic classifiers in psychiatry
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How the body remembers: Examining the default mode and sensorimotor networks during moral injury autobiographical memory retrieval in PTSD
Kearney, B. E., Terpou, B. A., Densmore, M., Shaw, S. B., Théberge, J., Jetly, R., McKinnon, M. C., & Lanius, R. A. (2023) · NeuroImage: Clinical · doi:10.1016/j.nicl.2023.103426 · Cited by 33 · see citing works
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Why reliving is not remembering and the unique neurobiological representation of traumatic memory
Kearney, B. E., & Lanius, R. A. (2024) · Nature Mental Health · doi:10.1038/s44220-024-00324-z · Cited by 32 · see citing works
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Increased top-down control of emotions during symptom provocation working memory tasks following a RCT of alpha-down neurofeedback in PTSD
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Systematic review of machine learning in PTSD studies for automated diagnosis evaluation
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Altered Resting-State functional connectivity in the anterior and posterior hippocampus in Post-traumatic stress disorder: The central role of the anterior hippocampus
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Intrusive experiences in posttraumatic stress disorder: Treatment response induces changes in the directed functional connectivity of the anterior insula
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Out of touch? How trauma shapes the experience of social touch – Neural and endocrine pathways
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The Posterior Insular Cortex is Necessary for the Consolidation of Tone Fear ConditioningPreprint
de Paiva, J. P. Q., Bueno, A. P. A., Corrêa, M. D. S., Oliveira, M. G. M., Ferreira, T. L., & Fornari, R. V. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.12.248294 · Cited by 23 · see citing works
Heartbeat evoked potentials in patients with post-traumatic stress disorder: an unaltered neurobiological regulation system?
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Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach
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Acute Posttrauma Resting-State Functional Connectivity of Periaqueductal Gray Prospectively Predicts Posttraumatic Stress Disorder Symptoms
Webb, E. K., Huggins, A. A., Belleau, E. L., Taubitz, L. E., Hanson, J. L., deRoon‐Cassini, T. A., & Larson, C. L. (2020) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2020.03.004 · Cited by 18 · see citing works
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Top-down control of vestibular inputs by the dorsolateral prefrontal cortex
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Alterations in regional homogeneity and functional connectivity associated with cognitive impairment in patients with hypertension: a resting-state functional magnetic resonance imaging study
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Fibromyalgia and the painful self: A meta-analysis of resting-state fMRI data
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PTSD subtypes and their underlying neural biomarkers: a systematic review
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Families With Violence Exposure and the Intergenerational Transmission of Somatization
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Impact of Post-Traumatic Stress Disorder Duration on Volumetric and Microstructural Parameters of the Hippo-Campus, Amygdala, and Prefrontal Cortex: A Multiparametric Magnetic Resonance Imaging Study with Correlation Analysis
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Dissociative Symptoms and Interoceptive Integration
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Brain Connectivity and Symptom Changes After Transcranial Magnetic Stimulation in Patients With Borderline Personality Disorder
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Application of machine learning techniques in the diagnostic approach of PTSD using MRI neuroimaging data: A systematic review
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Changes in neural responses during affective and non-affective tasks and improvement of posttraumatic stress disorder symptoms following trauma-focused psychotherapy
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The Induction of Dissociative States: A Meta-Analysis
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Stress‐Related Brain Alterations in Chronic Pain
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Neural evidence of implicit emotion regulation deficits: An explorative study of comparing PTSD with and without alcohol dependence
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Post-traumatic stress disorder
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Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype.
Nicholson, A. A., Sapru, I., Densmore, M., Frewen, P. A., Neufeld, R. W. J., Théberge, J., McKinnon, M. C., & Lanius, R. A. (2016) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2016.02.002 · Cited by 128 · see citing works
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The Dissociative Subtype of Posttraumatic Stress Disorder: Unique Anterior, Mid, and Posterior Insula Resting-State Functional Connectivity with the Basolateral Amygdala Complex
Lanius, R. A. (2016)
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The Role of the Insula in Classical and Dissociative PTSD: A Double Case Study
Blades, R. B., Becerra, S. A., Jordan, S., Eusebio, B., Heatwole, M., Iovine, J., Mahdavi, K. D., Mamoun, M. S., Nicodemus, N., Packham, H., et al. (2022) · Neurocase · doi:10.1080/13554794.2021.1978502 · Cited by 2 · see citing works

Authors: Harricharan, S., Nicholson, A. A., Thome, J., Densmore, M., McKinnon, M. C., Théberge, J., Frewen, P. A., Neufeld, R. W. J., & Lanius, R. A.
Affiliations: Western University (CA)
University of Vienna (AT)
Homewood Research Institute (CA)
Corresponding author: Lanius, Ruth A.
ORCID: Harricharan, Sherain
Nicholson, Andrew A.
Thome, Janine
McKinnon, Margaret C.
Théberge, Jean
Frewen, Paul A.
Neufeld, Richard W. J.
Lanius, Ruth A.
Venue: Psychophysiology
Publisher: Wiley
Published: 2019-09-10
Volume: 57
Issue: 1
Pages: e13472-e13472
ISSN: 0048-5772 (ISSN-L)
1469-8986
DOI: 10.1111/psyp.13472
OpenAlex: W2972984907
Cited by: 94
References: 109
Citations by year: 2026: 13 · 2025: 14 · 2024: 19 · 2023: 19 · 2022: 11 · 2021: 9 · 2020: 8 · 2019: 1
FWCI: 8.46
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Psychophysiology (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research (137150, 97914)
Topics: Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
Keywords: post-traumatic stress disorder, dissociative subtype of PTSD, insula, resting-state functional connectivity, anterior insula, posterior insula, periaqueductal gray, precuneus, lingual gyrus, seed-based functional connectivity, machine learning classification, predictive validity, depersonalization, derealization, frontal lobe connectivity, subcortical connectivity
MeSH terms: Machine Learning, Adult, Cerebral Cortex, Depersonalization, Dissociative Disorders, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Stress Disorders, Post-Traumatic, Reproducibility of Results, Connectome

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PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting‐state functional connectivity and its predictive validity using machine learning

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