Spontaneous brain activity, graph metrics, and head motion related to prospective post-traumatic stress disorder trauma-focused therapy response

Abstract

Introduction: Trauma-focused psychotherapy for post-traumatic stress disorder (PTSD) is effective in about half of all patients. Investigating biological systems related to prospective treatment response is important to gain insight in mechanisms predisposing patients for successful intervention. We studied if spontaneous brain activity, brain network characteristics and head motion during the resting state are associated with future treatment success.

Methods: Functional magnetic resonance imaging scans were acquired from 46 veterans with PTSD around the start of treatment. Psychotherapy consisted of trauma-focused cognitive behavioral therapy (tf-CBT), eye movement desensitization and reprocessing (EMDR), or a combination thereof. After intervention, 24 patients were classified as treatment responders and 22 as treatment resistant. Differences between groups in spontaneous brain activity were evaluated using amplitude of low-frequency fluctuations (ALFF), while global and regional brain network characteristics were assessed using a minimum spanning tree (MST) approach. In addition, in-scanner head motion was assessed.

Results: No differences in spontaneous brain activity and global network characteristics were observed between the responder and non-responder group. The right inferior parietal lobule, right putamen and left superior parietal lobule had a more central position in the network in the responder group compared to the non-responder group, while the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal gyrus and left inferior temporal gyrus had a less central position. In addition, responders showed less head motion.

Discussion: These results show that areas involved in executive functioning, attentional and action processes, learning, and visual-object processing, are related to prospective PTSD treatment response in veterans. In addition, these findings suggest that involuntary micromovements may be related to future treatment success.

Keywords: DLPFC; PTSD; graph analysis; head motion; minimum spanning tree; post-traumatic stress disorder; psychotherapy.

FIGURE 1

Graph analysis pipeline. In the first step, the Brainnetome atlas was applied to the functional data (A). The second step consisted of extracting the time-courses for each region of interest (ROI) of the atlas (B). After this, functional connectedness was calculated between all possible pairs of ROIs i and j in each subject (C). Hereafter, the minimum spanning tree (MST) was constructed from the functional connectivity matrix by including the strongest connections while avoiding loops. All edges in the MST were set to 1 while edges outside the MST were set to 0 (D). Image (E) provides a theoretical example of an MST superimposed on a template brain. As a final step, the MST network was characterized using global and regional (node specific) graph metrics (F). ROI, region of interest. The reader is referred to the web version of this paper for the color representation of this figure.

FIGURE 2

Examples of three minimum spanning trees (MSTs) consisting of nine nodes. MST structures can be found on a continuum between a path-like tree to a star-like tree, with the figure showing a path-like (I), hierarchical (II), and star-like tree (III). Path-like trees have the drawback that information does not flow easily from node to node. Star-like trees have the advantage that information can flow easily across the network and the downside that the central node might suffer from information overload. As such, a hierarchical tree is the hypothesized optimal topology. Figure adapted from van Lutterveld et al. (2017). The reader is referred to the web version of this paper for the color representation of this figure.