Disruption of white matter structural integrity and connectivity in posttraumatic stress disorder: A TBSS and tractography study

Abstract

Most studies of brain white matter (WM) in posttraumatic stress disorder (PTSD) have focused on combat trauma, and often were confounded by neurological and substance dependence comorbidity. This study used tract-based spatial statistics (TBSS) and probabilistic tractography to characterize WM microstructure in a mixed-sex community sample of PTSD patients exposed to diverse and multiple traumas, and in trauma-exposed normal comparison (TENC) subjects. TBSS compared diffusion measures between 20 adults with DSM-IV PTSD and 17 TENC, using a whole-brain voxel-wise approach. Probabilistic tractography using Freesurfer's TRACULA was employed to measure diffusion tensor imaging (DTI) metrics within anatomically defined pathways. DTI metrics were compared between groups and correlated with PTSD symptom severity and trauma load. Controlling for age, sex, and motion, PTSD subjects had significantly reduced fractional anisotropy (FA) in a left frontal lobe cluster compared with TENC, at p < .05, family-wise error corrected. Tractography identified significant group differences in the inferior longitudinal fasciculus (ILF), including lower FA and higher radial diffusivity in PTSD compared with TENC. Within the PTSD group, FA values were not correlated with symptom severity or trauma load. Results remained significant after removing participants using psychotropic medication or those with comorbid major depression. PTSD patients had reduced WM integrity in left hemisphere frontal WM and temporal-occipital WM tracts, compared to trauma-exposed controls. Reduced frontal FA is consistent with compromised top-down attentional control and emotion regulation in PTSD, while reduced ILF FA may be related to sensory processing and gating abnormalities in this disorder.