(PS5-62) Aberrant Functional Connectivity Between the Salience Network and Emotion-reward-related Brain Regions in Youth Experiencing Early Life Stress

Aberrant Functional Connectivity Between the Salience Network and Emotion-Reward-Related Brain Regions in Youth Experiencing Early Life Stress.

Background: Early life stress (ELS) is associated with differences in the brain’s reward and salience networks that are implicated in psychiatric disorders. However, the mechanisms of these relationships are not well understood. Altered resting state connectivity between the salience network and reward- and emotion-related regions can have significant implications for both cognitive and emotional processing, as the salience network plays an important role in the detection and filtering of salient stimuli. To explore the associations between ELS and salience network coupled with reward and emotion pathways, we analyzed resting-state functional connectivity (rsFC) between the salience network (SN) and emotion and reward regions of interest (ROIs) in relation to stressful life experiences, including negative life events, familial conflicts, and objective and subjective ratings of neighborhood crime exposure. 

Methods: Youth (9 to 10 years old) were drawn from the Adolescent Brain Cognitive Development study (N=11,876). The frequency of negative life events in the child’s life was measured using the Negative Life Events Scale. Neighborhood crime rates were determined using the Area Deprivation Index and the self-report Neighborhood Safety Protocol scale. Familial conflicts were assessed using the Parent Family Environment Scale. Two years later, the participants completed a resting-state fMRI scan. Multiple regressions were conducted, and we implemented a Benjamin-Hochberg correction with a false discovery rate of 5% (q = 0.05). Adjusted p-values are reported below.

Results: Regressions showed that negative life events were positively associated with rsFC between SN-right hippocampus (B= 0.035, SE= 0.012, t= 2.966, p= 0.024) and SN-left caudate (B= 0.037, SE= 0.012, t= 3.017, p= 0.024)and negatively associated with connectivity between SN-right nucleus accumbens (NAc) (B= -0.070, SE= 0.012, t= -5.940 p< 0.001) and SN-left thalamus (B= -0.042, SE= 0.012, t= -3.537 p= 0.006). Moreover, neighborhood crime was negatively associated with connectivity between SN-right NAc (B= -0.051, SE= 0.017, t= -2.899 p= 0.026), SN-left thalamus (B= -0.056, SE= 0.018, t= -3.11 p= 0.022), SN-right thalamus (B= -0.074, SE= 0.018, t= -4.099 p= 0.001), and SN-caudate (B=-0.07960, SE= 0.018, t= -4.433 p< 0.001). There were no significant associations between any SN-ROIs and subjective rating of neighborhood crime and familial conflict.

Discussion: Our results offer more insight into the differences in resting-state neural function among individuals facing more negative life events and those living in high-crime neighborhoods compared to those with fewer of these adversities. Given that these neural regions and networks have been linked to diminished approach motivation and cognitive and emotional control, these findings may have implications for how individuals confer risk for related psychiatric issues following exposure to negative life events and neighborhood crime. Future directions should examine the links between the observed distinct brain function and mental health outcomes.