Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach

Abstract

The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.

Figure 1

Functional dysconnectivity in posttraumatic stress disorder (PTSD). Voxel-wise whole-brain correlations between PTSD severity, as measured by the Clinician Administered PTSD Scale (CAPS) and functional global brain connectivity with global signal regression. The color bar depicts the z-values of the negative (blue) and positive (yellow–red) correlations.

Figure 2

Dimension-specific prefrontal dysconnectivity. Voxel-wise correlations between functional global brain connectivity with global signal regression within the prefrontal cortex and the severity of the four posttraumatic stress disorder dimensions ((a) numbing; (b) avoidance; (c) arousal; (d) re-experiencing). The prefrontal cortex region is labeled with a black line. The color bar depicts the z-values of the negative (blue) and positive (yellow–red) correlations.

Figure 3

Anatomical dysconnectivity in posttraumatic stress disorder (PTSD). (a) Scatter plot depicting the correlation between PTSD severity, as measured by the Clinician Administered PTSD Scale (CAPS) and anterior hippocampal (aHPC) diffusion global brain connectivity (d-GBC). The gray area is the 95% confidence band of the best-fit line. (b) Voxel-wise whole-brain correlations between PTSD severity and aHPC tractography seed-based connectivity. (c, d) Voxel-wise correlations between aHPC tractography seed-based connectivity within the prefrontal cortex and the severity of the PTSD dimensions ((c) arousal; (d) numbing; avoidance and re-experiencing had no significant correlations). The prefrontal cortex region is labeled with a black line. The color bar depicts the z-values of the negative (blue) and positive (yellow–red) correlations.