Abstract
We aimed to uncover differences in brain circuits of adolescents with parental positive or negative histories of substance use disorders (SUD), when performing a task that elicits emotional conflict, testing whether the brain circuits could serve as endophenotype markers to distinguish these adolescents. We acquired functional magnetic resonance imaging data from 11 adolescents with a positive familial history of SUD (FH+ group) and seven adolescents with a negative familial history of SUD (FH− group) when performing an emotional stroop task. We extracted brain features from the conflict-related contrast images in group level analyses and granger causality indices (GCIs) that measure the causal interactions among regions. Support vector machine (SVM) was applied to classify the FH+ and FH− adolescents. Adolescents with FH+ showed greater activity and weaker connectivity related to emotional conflict, decision making and reward system including anterior cingulate cortex (ACC), prefrontal cortex (PFC), and ventral tegmental area (VTA). High classification accuracies were achieved with leave-one-out cross validation (89.75% for the maximum conflict, 96.71% when combining maximum conflict and general conflict contrast, 97.28% when combining activity of the two contrasts and GCIs). Individual contributions of the brain features to the classification were further investigated, indicating that activation in PFC, ACC, VTA and effective connectivity from PFC to ACC play the most important roles. We concluded that fundamental differences of neural substrates underlying cognitive behaviors of adolescents with parental positive or negative histories of SUD provide new insight into potential neurobiological mechanisms contributing to the elevated risk of FH+ individuals for developing SUD.
Highlights
Substance Use Disorder (SUD) refers to pathological use and/or dependence on a drug or other chemicals leading to detrimental effects to the individual’s physical or mental health and the welfare of others (Pitkanen et al, 2008)
Significant differences were found in the second-level analysis on the contrast images cI vs. cC in the regions related to conflict, decision making and reward system [p = 0.01, corrected by cluster extent thresholding with k = 30, which was determined by Monte Carlo Simulation (Slotnick et al, 2003)], including anterior cingulate cortex (ACC), insula, prefrontal cortex (PFC), middle cingulate cortex (MCC), ventral tegmental area (VTA), superior temporal gyrus (STG), putamen, precentral gyrus, thalamus, amygdala, and hippocampus (Figure 3A, Table 3)
This study examined the neural activity and connectivity in response to the performance of an emotional stroop task in adolescents with a family history of substance use disorders (SUD) (FH+ group) compared to age-matched controls without such a history (FH− group)
Summary
Substance Use Disorder (SUD) refers to pathological use and/or dependence on a drug or other chemicals leading to detrimental effects to the individual’s physical or mental health and the welfare of others (Pitkanen et al, 2008). As the high risk of mental disorders of SUD family, several brain areas associated with emotional and reward dysfunction are affected in FH+ individuals including prefrontal gyrus, insula, putamen (Heitzeg et al, 2008), amygdala (Glahn et al, 2007), and nucleus accumbens (NAcc) (Andrews et al, 2011) compared to negative family history (FH−) individuals during various tasks, such as a monetary incentive delay (MID) task (Andrews et al, 2011), a task of viewing words with positive, negative, or neutral valence (Heitzeg et al, 2008) and a recognition task using faces expressing fear vs geometric objects (Glahn et al, 2007). Another study examined intrinsic functional connectivity with fMRI and showed differences involving the NAcc in the reward circuit between FH+ adolescents and FH− adolescents (Cservenka et al, 2014a)
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