title: Disrupted insula-based neural circuit organization and conflict interference in trauma-exposed youth.
abstract: Childhood trauma exposure is a potent risk factor for psychopathology. Emerging research suggests that aberrant saliency processing underlies the link between early trauma exposure and later cognitive and socioemotional deficits that are hallmark of several psychiatric disorders. Here, we examine brain and behavioral responses during a face categorization conflict task, and relate these to intrinsic connectivity of the salience network (SN). The results demonstrate a unique pattern of SN dysfunction in youth exposed to trauma (n = 14) relative to comparison youth (n = 19) matched on age, sex, IQ, and sociodemographic risk. We find that trauma-exposed youth are more susceptible to conflict interference and this correlates with higher fronto-insular responses during conflict. Resting-state functional connectivity data collected in the same participants reveal increased connectivity of the insula to SN seed regions that is associated with diminished reward sensitivity, a critical risk/resilience trait following stress. In addition to altered intrinsic connectivity of the SN, we observed altered connectivity between the SN and default mode network (DMN) in trauma-exposed youth. These data uncover network-level disruptions in brain organization following one of the strongest predictors of illness, early life trauma, and demonstrate the relevance of observed neural effects for behavior and specific symptom dimensions. SN dysfunction may serve as a diathesis that contributes to illness and negative outcomes following childhood trauma.
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA ; Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit, MI, USA.
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Marusak
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA ; Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Etkin
authors.affiliation: Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit, MI, USA ; Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Moriah E
authors.initials: ME
authors.lastname: Thomason
mesh_terms: D000293:Adolescent; D002540:Cerebral Cortex / Q000503:physiopathology*; D002648:Child; D003220:Conflict, Psychological; D063132:Connectome / Q000379:methods*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D000067073:Psychological Trauma / Q000503:physiopathology*
keywords: Adolescent; Child; Conflict; DMN, default mode network; RS, reward sensitivity; Resting-state; SN, salience network; Salience network; dACC, dorsal anterior cingulate cortex; rFIC, right fronto-insular cortex