Altered White Matter Diffusivity of the Cingulum Angular Bundle in Posttraumatic Stress Disorder

Abstract

Purpose of the Study: Prior studies showed posttraumatic stress disorder (PTSD)-related alterations in white matter integrity, but most of these studies have used region-based approaches. We address this limitation by investigating the relationship between PTSD severity and fractional anisotropy (FA) using a tract-based approach. Procedures: Structural and diffusion magnetic resonance imaging were acquired from 67 combat-exposed US Veterans and processed using FSL/FreeSurfer TRActs Constrained by UnderLying Anatomy. Partial correlations were conducted between PTSD severity and FA of the cingulum and uncinate fasciculi covarying for age, sex, and head motion. Results: Only FA of the left cingulum angular bundle (CAB) was positively correlated with PTSD symptom severity (r = 0.433, p = 0.001, df = 57) and remained significant after Bonferroni correction. Conclusions: This finding may imply greater organization of the CAB with increasing PTSD severity. The CAB connects directly to the cingulate cortex and the hippocampal subiculum, critical nodes of the default mode network, as well as being implicated in neurodegeneration pathology, decision-making, and executive functions, which may help explain previously shown alterations in this network in PTSD. Message of the Paper: Further study of white matter tract integrity in PTSD is warranted, particularly to investigate whether the CAB connections with both higher-order cognitive functioning and emotion processing regions contribute to the pathophysiology and comorbidity of PTSD.

Altered White Matter Microstructural Organization in Post-Traumatic Stress Disorder across 3,049 Adults: Results from the PGC-ENIGMA PTSD Consortium

“…Here we report microstructural evidence that structural connectivity between the left and right hippocampus may also be disrupted in PTSD. While many studies have reported that PTSD is associated with alterations in the cingulum bundle [9][10][11][12][13]16,18,21,[23][24][25][26][27][28][29]31,32,36 , which has a hippocampal component, the tapetum has not yet emerged for several possible reasons. Many prior studies took an ROI approach, which limited analyses to pre-determined regions that frequently omitted the tapetum, a small region often grouped with other tracts such as the splenium or posterior thalamic radiation.…”

“…Most prior dMRI studies in civilians report lower FA in PTSD 9,10,[12][13][14]16,17,[21][22][23][24][25][30][31][32]67 . Studies of military cohorts have been mixed, reporting higher FA [26][27][28][29]36 , lower FA 8,15,[18][19][20] , and null results [33][34][35] . This discrepancy may be due to differences in age, chronicity, and type of trauma exposure, although military personnel often also experience civilian trauma.…”

“…Studies of white matter microstructure in PTSD have reported inconsistent results. The majority report that PTSD is associated with lower FA [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] , but some report higher FA [25][26][27][28][29][30][31] , higher and lower FA in different regions 32 , or null results [33][34][35] .…”

“…Alterations in the cingulum bundle are frequently reported [9][10][11][12][13]16,18,21,[23][24][25][26][27][28][29]31,32,36 , with differences also observed in the uncinate, corpus callosum, and corona radiata 14,16,18,19,24,26,29 . Inconsistent findings may be partially due to the use of hypothesis-driven rather than whole brain approaches, choice of analytic pipeline, selection of diffusion metrics, gender-specific studies, homogeneity of single cohort samples such as trauma-exposed vs. unexposed controls, and focus on military vs. civilian samples.…”

Salience Network Disruption in US Army Soldiers with PTSD

“…Therefore, we speculate that the difference in study population may have led to the differing results. In particular, the target population and study criteria of the previous report may have led to enrolling patients with ABP, as evidenced by widespread structural and connectivity deficits in the previous cohort (28,(52)(53)(54)(55).…”