Dynamic and Static Resting-State Functional Connectivity of Canonical Networks in Military and Civilian Populations with Posttraumatic Stress Disorder and/or Mild Traumatic Brain Injury.

IF 4.8
Alexandra K Dwulit, Delin Sun, Courtney C Haswell, Ahmed Hussain, Emily L Dennis, Elisabeth A Wilde, Mary R Newsome, David F Tate, William C Walker, Chadi G Abdallah, Christopher L Averill, Jennifer Urbano Blackford, Bunmi O Olatunji, Anthony King, Israel Liberzon, Michael Angstadt, Ivan Rektor, Pavel Říha, Markéta Nečasová, Monika Fňašková, Judith K Daniels, Henrik Walter, Antje Manthey, Anika Sierk, Miranda Olff, Mirjam van Zuiden, Saskia B J Koch, Dick Veltman, Jessie Frijiling, Laura Nawijn, Neda Jahanshad, Paul M Thompson, Rajendra A Morey
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Abstract

Background: Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are associated with alterations in the functional connectome, specifically in canonical resting state networks including the default mode (DMN), central executive (CEN), and salience networks (SN). Comorbid PTSD+mTBI is linked to worse functional outcomes, but little is known about effects on the functional connectome.

Methods: We investigated brain phenotypes from resting-state fMRI associated with PTSD (n=326), mTBI (n=448), and comorbid PTSD+mTBI (n=289) in military veterans and civilians (n=1526) from ENIGMA-TBI and -PTSD. We examined static functional connectivity (SFC) and dynamic functional connectivity (DFC), quantified both as variability in FC (VFC) over time and as dwell time in recurring FC states identified through clustering. ANCOVA was followed by post-hoc linear regression to test main and interaction effects of diagnosis on FC metrics.

Results: We found a significant (pFDR<0.05) interaction of diagnosis by age on VFC. Older comorbid subjects had greater VFC within SN, between SN-to-CEN and SN-to-DMN than older controls. Comorbid relative to control subjects had significantly greater dwell time in an externally focused state. Comorbid and mTBI groups, relative to control subjects, had greater dwell time in a moderate connectivity transition state.

Conclusions: DFC related to the SN revealed distinct brain network patterns across diagnostic groups, with comorbid PTSD+mTBI showing age- and anxiety-related effects. Older comorbid subjects had heightened hypervigilance and reduced network segregation. PTSD and anxiety may synergistically worsen network instability, while mTBI reflects more rigid, disconnected states, highlighting DFC as a sensitive marker of neuropsychiatric comorbidity.

军事和平民创伤后应激障碍和/或轻度创伤性脑损伤患者规范网络的动态和静态静息状态功能连通性。
背景:创伤后应激障碍(PTSD)和轻度创伤性脑损伤(mTBI)与功能连接体的改变有关,特别是在典型静息状态网络中,包括默认模式(DMN)、中央执行(CEN)和突出网络(SN)。PTSD+mTBI共病与较差的功能结果有关,但对功能连接体的影响知之甚少。方法:我们通过静息状态fMRI研究了来自ENIGMA-TBI和-PTSD的退伍军人和平民(n=1526)与PTSD (n=326)、mTBI (n=448)和合并PTSD+mTBI (n=289)相关的脑表型。我们研究了静态功能连接(SFC)和动态功能连接(DFC),将两者量化为FC随时间的变化(VFC)和通过聚类确定的重复FC状态的停留时间。ANCOVA之后采用事后线性回归来检验诊断对FC指标的主要影响和交互影响。结论:与SN相关的DFC在诊断组中显示出不同的脑网络模式,PTSD+mTBI共病表现出与年龄和焦虑相关的影响。老年共病受试者高度警惕,网络隔离减少。创伤后应激障碍和焦虑可能协同恶化网络不稳定性,而mTBI反映的是更僵化、断开的状态,这突出了DFC作为神经精神共病的敏感标志物。
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