Sustained attention heterogeneity in post-9/11 Veterans: Functional connectivity profiles across large-scale cortical networks and subcortical regions during task-based fMRI

Abstract

Background: Post-9/11 Veterans with co-occurring mild traumatic brain injury (mTBI) and psychopathology frequently exhibit persistent and heterogeneous deficits in sustained attention. These attention impairments are associated with reduced quality of life and occupational functioning. However, available treatments remain inconsistently effective across individuals. A major gap in the research is understanding why these attention problems differ from person to person. In particular, little is known about how diverse attention symptoms relate to underlying brain mechanisms. Clarifying these neural differences may help explain the nature of attentional variability in this population and guide the development of more effective interventions. Objective: This study explores functional connectivity (statistical correlations between brain regions) variations that characterize sustained attention in post-9/11 Veterans. We hypothesized that different and distinct functional connectivity patterns, measured during a sustained attention task, would correspond to distinct attentional heterogeneity. Methods: We conducted a secondary data-driven analysis of task-based (gradCPT) fMRI data. The data were from 134 Veterans enrolled in the TRACTS study and used in Fortenbaugh et al. (2018) and Evans et al. (2022) studies. We applied principal component analysis (PCA) to functional connectivity edges of large scale-networks and subcortical regions. The analyses were followed by unsupervised k-means clustering technique to identify any distinct functional connectivity profiles. The clusters distinctions were statistically verified with attention score variations using ANOVA. Findings: Four statistically distinct functional connectivity profiles were identified (see Frontispiece). These profiles represented different configurations in functional connectivity, including the degree of integration, the level of anticorrelation, and the connection strengths among networks and subcortical regions. Notably, similar mean attention scores were observed across groups, which suggested that "attention" may not be a singular state, nor is "inattention" a single type of failure. Significance: These findings may suggest that preserved sustained attention can be supported by multiple large-scale functional connectivity architectures, rather than a single canonical organization. Likewise, sustained attention deficits may emerge from diverse patterns of neural disorganization instead of a uniform disruption. Accounting for such individual differences in neural connectivity may be critical for developing and delivering consistently effective treatments in clinically heterogeneous Veteran populations. Keywords: Sustained attention, TRACTS, gradCPT, Veterans, mTBI