Neural Mechanisms Underlying Attention Deficits in Posttraumatic Stress Disorder

Abstract

OBJECTIVE: Post-traumatic stress disorder (PTSD) is associated with altered attentional performance and functional connectivity in intrinsic connectivity networks (ICNs) related to attention. There is conflicting research regarding the specific type of attention impairments present in PTSD as the commonly used tests of attention do not isolate the mechanisms behind attention abnormalities. Additionally, because ICNs are typically measured at rest, it is unclear how altered connectivity may contribute to task performance. Understanding which aspects of attention are affected in PTSD could improve our understanding of the mechanisms by which these deficits influence symptoms, in turn, improving treatment by targeting these processes. AIM 1: We sought to characterize the type of behavioral attentional impairment present in PTSD according to Posner and Peterson’s tripartite model of attention using the Attention Network Task (ANT). We then examined the association between attention performance and resting-state functional connectivity (rsFC). Male veterans with PTSD were impaired at disengaging spatial attention relative to male community controls and exhibited greater cross-network rsFC of the salience network. Moreover, attention performance was related to rsFC in the control, but not in the PTSD group. However, it remained unclear whether patterns of rsFC are also related to changes in neural function during attention performance as the ANT was completed outside of scanner. We investigated this question in aim 2. AIM 2: We examined whether patterns of rsFC were predictive of attention task performance, activity and connectivity across a sample of non-trauma exposed controls, trauma-exposed controls and individuals with PTSD. Across all subjects, we found that ICNs present at rest were predictive of attention task neural activation, connectivity and behavioral performance. However, the relationships we found were very different depending on the task condition, network node and task measure (i.e. activation vs connectivity). This suggests that resting-state could be an alternative to active tasks to study brain function in psychiatric populations in the future, such that alterations in ICNs at rest in PTSD may be reflective of impairments on an attention task. However, the mechanisms by which ICNs contribute to attention abnormalities in PTSD remained unclear. Additionally, it remained unclear whether alterations of ICNs are specific to PTSD or are partially related to trauma-exposure. We investigated these questions in aim 3. AIM 3: We investigated the neural mechanisms underlying attention impairments in PTSD by using the same measures as aim 2. We found that the PTSD group showed deficits in the utilization of spatial information. During cue processing, the PTSD group exhibited salience network intrusions, but during target processing, they showed both a failure to suppress the default-mode network and a greater engagement of attentional control regions. Lastly, trauma-exposed controls showed some behavioral and neural alterations in attention measures. CONCLUSION: In this dissertation, we demonstrated that 1) resting-state ICNs are predictive of attention-task measures and 2) spatial attention is disrupted in PTSD. Our results suggest a possible mechanism of attention disruptions in PTSD, by which the salience network interferes with goal-directed attention, resulting in a reduced ability to encode contextual information. This in turn may influence one’s propensity for attentional lapses, thus requiring greater engagement of attentional control regions to execute correct responses. Treatments which target these neural networks or cognitive deficits could be a new avenue for PTSD research.