Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptoms

IntroductionExposure to trauma produces abnormal intrinsic brain activity, but its association to stress-related symptom severity is often elusive, and the relationships with co-occurring psychiatric and cognitive changes are poorly understood.MethodsThis study investigated the neurobehavioral mecha...

Full description

Saved in:
Bibliographic Details
Main Authors: Deborah L. Harrington, Qian Shen, Annemarie Angeles-Quinto, Sharon Nichols, Tao Song, Hayden Hansen, Kate A. Yurgil, Roland R. Lee, Dewleen G. Baker, Ming-Xiong Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Psychiatry
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1591938/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849706190446002176
author Deborah L. Harrington
Deborah L. Harrington
Qian Shen
Qian Shen
Annemarie Angeles-Quinto
Annemarie Angeles-Quinto
Sharon Nichols
Tao Song
Hayden Hansen
Kate A. Yurgil
Kate A. Yurgil
Roland R. Lee
Roland R. Lee
Dewleen G. Baker
Dewleen G. Baker
Dewleen G. Baker
Ming-Xiong Huang
Ming-Xiong Huang
author_facet Deborah L. Harrington
Deborah L. Harrington
Qian Shen
Qian Shen
Annemarie Angeles-Quinto
Annemarie Angeles-Quinto
Sharon Nichols
Tao Song
Hayden Hansen
Kate A. Yurgil
Kate A. Yurgil
Roland R. Lee
Roland R. Lee
Dewleen G. Baker
Dewleen G. Baker
Dewleen G. Baker
Ming-Xiong Huang
Ming-Xiong Huang
author_sort Deborah L. Harrington
collection DOAJ
description IntroductionExposure to trauma produces abnormal intrinsic brain activity, but its association to stress-related symptom severity is often elusive, and the relationships with co-occurring psychiatric and cognitive changes are poorly understood.MethodsThis study investigated the neurobehavioral mechanisms of persistent disability in male combat-exposed military personnel and veterans with symptoms of post-traumatic stress disorder (CE-PTSD) (n=19) and trauma-exposed healthy controls with similar combat experiences (n=24). Disturbances in intrinsic activity during resting-state fMRI were identified using a whole-brain analytic approach that quantified regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF). To determine if functional abnormalities were related to changes in brain macrostructure, cortical thickness and gray/white-matter volume were measured. Regional abnormalities in CE-PTSD were identified by comparing measures of brain function and structure between the two groups. The behavioral relevance of regional abnormalities in the CE-PTSD group was then assessed by their correlations with stress and psychiatric symptom severity and cognitive functioning.ResultsDespite the absence of changes in brain structure in CE-PTSD, fALFF was abnormally increased in the right anterior insula/temporal pole (aIn/TP), left aIn, and bilateral parahippocampus (PH), whereas ReHo was reduced in the right inferior temporal gyrus. Greater increases in right aIn/TP fALFF correlated with more severe hyperarousal and impulsivity in CE-PTSD, suggesting ruminative thoughts or negative feelings hamper emotion regulation. Conversely, greater right PH fALFF correlated with lower hyperarousal and depression, signifying an adaptive response to stress that promotes better affective processing. Importantly, regional abnormalities were detrimental for more complex executive functions, consistent with observations that stress impedes cognitive flexibility and inhibitory control due to a persistent reliance on hypervigilant behaviors.DiscussionAn unbiased, efficient and computationally reliable imaging approach identified intrinsic dysfunction in brain regions that may be core features of CE-PTSD. Though larger samples are needed for verification, the preliminary results provide new insights into the associations between regional abnormalities and different facets of emotion regulation and cognition, which in turn may impact an individual’s functional abilities in daily life and responsiveness to psychotherapy.
format Article
id doaj-art-e6f3dc3a9a51478784fdfec244af117c
institution DOAJ
issn 1664-0640
language English
publishDate 2025-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Psychiatry
spelling doaj-art-e6f3dc3a9a51478784fdfec244af117c2025-08-20T03:16:15ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-07-011610.3389/fpsyt.2025.15919381591938Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptomsDeborah L. Harrington0Deborah L. Harrington1Qian Shen2Qian Shen3Annemarie Angeles-Quinto4Annemarie Angeles-Quinto5Sharon Nichols6Tao Song7Hayden Hansen8Kate A. Yurgil9Kate A. Yurgil10Roland R. Lee11Roland R. Lee12Dewleen G. Baker13Dewleen G. Baker14Dewleen G. Baker15Ming-Xiong Huang16Ming-Xiong Huang17Department of Radiology, University of California, San Diego, San Diego, CA, United StatesResearch Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, San Diego, CA, United StatesResearch Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, San Diego, CA, United StatesResearch Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesDepartment of Neuroscience, University of California, San Diego, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, San Diego, CA, United StatesResearch Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesPsychiatry Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesDepartment of Psychological Sciences, Loyola University, New Orleans, LA, United StatesDepartment of Radiology, University of California, San Diego, San Diego, CA, United StatesRadiology Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesPsychiatry Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesVeterans Affairs (VA) Center of Excellence for Stress and Mental Health, San Diego, CA, United StatesDepartment of Psychiatry, University of California, San Diego, San Diego, CA, United StatesDepartment of Radiology, University of California, San Diego, San Diego, CA, United StatesRadiology Service, Veterans Affairs (VA) San Diego Healthcare System, San Diego, CA, United StatesIntroductionExposure to trauma produces abnormal intrinsic brain activity, but its association to stress-related symptom severity is often elusive, and the relationships with co-occurring psychiatric and cognitive changes are poorly understood.MethodsThis study investigated the neurobehavioral mechanisms of persistent disability in male combat-exposed military personnel and veterans with symptoms of post-traumatic stress disorder (CE-PTSD) (n=19) and trauma-exposed healthy controls with similar combat experiences (n=24). Disturbances in intrinsic activity during resting-state fMRI were identified using a whole-brain analytic approach that quantified regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF). To determine if functional abnormalities were related to changes in brain macrostructure, cortical thickness and gray/white-matter volume were measured. Regional abnormalities in CE-PTSD were identified by comparing measures of brain function and structure between the two groups. The behavioral relevance of regional abnormalities in the CE-PTSD group was then assessed by their correlations with stress and psychiatric symptom severity and cognitive functioning.ResultsDespite the absence of changes in brain structure in CE-PTSD, fALFF was abnormally increased in the right anterior insula/temporal pole (aIn/TP), left aIn, and bilateral parahippocampus (PH), whereas ReHo was reduced in the right inferior temporal gyrus. Greater increases in right aIn/TP fALFF correlated with more severe hyperarousal and impulsivity in CE-PTSD, suggesting ruminative thoughts or negative feelings hamper emotion regulation. Conversely, greater right PH fALFF correlated with lower hyperarousal and depression, signifying an adaptive response to stress that promotes better affective processing. Importantly, regional abnormalities were detrimental for more complex executive functions, consistent with observations that stress impedes cognitive flexibility and inhibitory control due to a persistent reliance on hypervigilant behaviors.DiscussionAn unbiased, efficient and computationally reliable imaging approach identified intrinsic dysfunction in brain regions that may be core features of CE-PTSD. Though larger samples are needed for verification, the preliminary results provide new insights into the associations between regional abnormalities and different facets of emotion regulation and cognition, which in turn may impact an individual’s functional abilities in daily life and responsiveness to psychotherapy.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1591938/fullpost-traumatic stress disorderresting-state functional MRIReHofALFFstress symptomspsychiatric symptoms
spellingShingle Deborah L. Harrington
Deborah L. Harrington
Qian Shen
Qian Shen
Annemarie Angeles-Quinto
Annemarie Angeles-Quinto
Sharon Nichols
Tao Song
Hayden Hansen
Kate A. Yurgil
Kate A. Yurgil
Roland R. Lee
Roland R. Lee
Dewleen G. Baker
Dewleen G. Baker
Dewleen G. Baker
Ming-Xiong Huang
Ming-Xiong Huang
Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptoms
Frontiers in Psychiatry
post-traumatic stress disorder
resting-state functional MRI
ReHo
fALFF
stress symptoms
psychiatric symptoms
title Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptoms
title_full Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptoms
title_fullStr Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptoms
title_full_unstemmed Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptoms
title_short Linking intrinsic brain dysfunction to behavioral outcomes in combat-exposed males with PTSD symptoms
title_sort linking intrinsic brain dysfunction to behavioral outcomes in combat exposed males with ptsd symptoms
topic post-traumatic stress disorder
resting-state functional MRI
ReHo
fALFF
stress symptoms
psychiatric symptoms
url https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1591938/full
work_keys_str_mv AT deborahlharrington linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT deborahlharrington linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT qianshen linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT qianshen linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT annemarieangelesquinto linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT annemarieangelesquinto linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT sharonnichols linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT taosong linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT haydenhansen linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT kateayurgil linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT kateayurgil linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT rolandrlee linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT rolandrlee linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT dewleengbaker linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT dewleengbaker linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT dewleengbaker linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT mingxionghuang linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms
AT mingxionghuang linkingintrinsicbraindysfunctiontobehavioraloutcomesincombatexposedmaleswithptsdsymptoms