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.

Sex Differences in Trauma-Related Psychopathology: a Critical Review of Neuroimaging Literature (2014–2017)

“…Studies examining the neural mechanisms of development and maintenance of trauma-related psychopathology have focused mainly on circuits implicated in fear processing [17–19], emotional regulation [20, 21], and stress response [22, 23], including cortical, limbic, and salience regions. Most commonly, these regions have included the amygdala, limbic and salience hub linked to emotional processing and response [24, 25], hippocampus, associated with learning and memory [26], insula, a major salience hub implicated in self-referential processing [20], and prefrontal cortex (PFC).…”

“…Most commonly, these regions have included the amygdala, limbic and salience hub linked to emotional processing and response [24, 25], hippocampus, associated with learning and memory [26], insula, a major salience hub implicated in self-referential processing [20], and prefrontal cortex (PFC). The PFC is involved in executive functions [27] and includes sub-regions such as the orbitofrontal (OFC; implicated in emotional processing [28]) and anterior cingulate (ACC; associated with monitoring [29]) cortices.…”

Toward understanding the impact of trauma on the early developing human brain

“…Philip and colleagues found reduced connectivity between nodes of the DMN (2013) and weaker down regulation of DMN activity during a cognitively demanding working memory task (Philip et al, 2012) in adults with history of early life stress. Results obtained by our group demonstrate that connectivity within the SN is enhanced and that connectivity between the SN and DMN is diminished in trauma-exposed children (Marusak et al, 2015a). These findings provide a valuable heuristic understanding of neural outcomes following exposure to stress and trauma in early life and may help us to generate new hypotheses about what disposes some individuals to more deleterious trauma-related outcomes.…”

“…In addition, cognitive control, selective attention, and reward processing pathways have been identified as conduits of trauma and stress related change (Mueller et al, 2010, Pechtel and Pizzagalli, 2011, McLaughlin et al, 2014b, Lim et al, 2015, Marusak et al, 2015a). While these are often conceptualized as unique pathways, systems of the brain are highly integrated.…”

“…For instance, in secondary analyses it is possible to isolate main effects that relate to participant characteristics or to confirm whether main effects replicate in subsamples deliberately matched on these characteristics. These strategies have been employed in prior fMRI studies of youth with histories of trauma (Marusak et al, 2015a, Marusak et al, 2015b, Thomason et al, 2015). …”