Altered Functional Connectivity of Fronto-Cingulo-Striatal Circuits during Error Monitoring in Adolescents with a History of Childhood Abuse

Abstract

Childhood maltreatment is associated with error hypersensitivity. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA) interaction on functional brain connectivity during error processing in medication/drug-free adolescents. Functional connectivity was compared, using generalized psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 22 age- and gender-matched medication-naïve and substance abuse-free adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed an individually adjusted tracking stop-signal task, designed to elicit 50% inhibition failures. During inhibition failures, abused participants relative to healthy controls exhibited reduced connectivity between right and left putamen, bilateral caudate and anterior cingulate cortex (ACC), and between right supplementary motor area (SMA) and right inferior and dorsolateral prefrontal cortex. Abuse-related connectivity abnormalities were associated with longer abuse duration. No group differences in connectivity were observed for successful inhibition. The findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-cingulo-striatal networks during error processing. Furthermore that the severity of connectivity abnormalities increases with abuse duration. Reduced connectivity of error detection networks in maltreated individuals may be linked to constant monitoring of errors in order to avoid mistakes which, in abusive contexts, are often associated with harsh punishment.

Keywords: MAOA genotype; child abuse; childhood maltreatment; error processing; fronto-cingulo-striatal; functional connectivity.

Figure 1

Schematic presentation of the tracking Stop Task. Subjects have to respond to go arrows that point either right or left with a right/left button response. In 20% of trials, the go signals are followed (about 250 ms later) by stop signals and subjects had to inhibit their motor responses. *A tracking algorithm changes the time interval between go signals and stop signals according to each subject’s performance on previous trials (average percentage of inhibition over previous stop trials, recalculated after each stop trial), resulting in 50% successful and 50% unsuccessful inhibition trials.

Figure 2

Within group functional connectivity for the 10 seed regions for (A) Response Inhibition and (B) Error Processing. The threshold is P < 0.05 FWE corrected. The right of the image corresponds to the right side of the brain. L, left; R, right; ACC, anterior cingulate cortex; IFC, inferior frontal cortex; SMA, supplementary motor area.

Figure 3

Between group differences in functional connectivity for Maltreated < healthy controls for (A) the right putamen seed region and (B) the right supplementary motor area (SMA) seed region for the unsuccessful stop vs. go contrast. The threshold is P < 0.05 FWE corrected at the cluster level. Z-coordinates represent distance from the anterior–posterior commissure in mm. The right side of the image corresponds to the right side of the brain.

Figure 4

Significant gene-by-environment (GxE) interaction effect between group (childhood abuse vs. healthy controls) and monoamine oxidase type A (MAOA) genotype (MAOA-Low vs. MAOA-High) on functional connectivity between right Putamen and right Caudate/ACC, p < 0.05. Error bars represent 95% confidence interval.