Left middle frontal gyrus response to inhibitory errors in children prospectively predicts early problem substance use

Abstract

Background A core vulnerability trait for substance use disorder (SUD) is behavioral disinhibition. Error processing is a central aspect of inhibitory control that determines adaptive adjustment of performance; yet it is a largely overlooked aspect of disinhibition as it relates to risk for SUD. We investigated whether differences in brain activation during both successful and failed inhibition predicts early problem substance use. Method Forty-five 9–12 year olds underwent a functional MRI scan during a go/no-go task. They were then followed over approximately 4 years, completing assessments of substance use. Externalizing behavior was measured at ages 3–8, 9–12 and 11–13. Participants with drug use or problem alcohol use by ages 13–16 (n=13; problem-user group) were individually matched by gender, age, and family history of alcoholism with non-substance-using children (n=13; non-user group). The remaining 19 participants provided an independent sample from which to generate unbiased regions-of-interest for hypothesis testing in the problem-user and non-user groups. Results No differences were observed between groups in activation during correct inhibition compared with baseline. A significant difference arose in left middle frontal gyrus (LMFG) activation during failed inhibition compared with correct inhibition, with the problem-user group demonstrating blunted activation. The problem-user group also had more externalizing problems at ages 11–13. Logistic regression found that activation of LMFG significantly predicted group membership over and above externalizing problems. Conclusions Blunted LMFG activation during performance errors may underlie problems adapting behavior appropriately, leading to undercontrolled behavior, early problem substance use and increased risk for SUD.

Alcohol and Drug Use and the Developing Brain

“…Early maturation of neural features could be considered a vulnerability for youth, increasing the likelihood of engaging in sensation-seeking behaviors at an earlier age. Together, these studies suggest that neurodevelopmentally precocious youth may have a greater tendency to initiate and escalate risk-taking behaviors like substance use relative to peers [33, 76–78]. In a separate study, adolescent recent (past 90 day) binge drinkers were found to have reduced posterior cerebellar activity during reward processing above and beyond their baseline substance-naive neural functioning; more drinks per drinking day was related to less cerebellar activation.…”

“…fMRI studies on healthy, non-substance using youth have shown that neural circuitry underlying inhibitory control undergoes significant neurodevelopment during adolescence [29, 30]. Longitudinal fMRI studies of youth have shown that even in the presence of comparable performance, abnormal brain activation during inhibition tasks predicts alcohol use by mid-to-late adolescence [31–33], future substance use and dependence symptoms [33, 34], and significant alcohol-related consequences like blackouts (i.e., when a person is awake while drunk but does not remember pieces or large sections of time) [35]. Furthermore, less frontal and parietal brain activation on tasks of visual working memory in substance-naive youth have been found to be predictive of greater substance involvement by late adolescence [36].…”

Neuroimaging Risk Markers for Substance Abuse: Recent Findings on Inhibitory Control and Reward System Functioning

“…Much of the work using the go/no-go task to investigate familial risk either focuses on successful trials only [19, 22] or does not differentiate between successful and failed no-go trials [18, 23•, 24, 27•]. Recent work by Heitzeg et al [29] extends this literature by differentiating between successful and failed inhibitory (no-go) trials. Participants underwent a baseline scan at age 9–12 years, and those who demonstrated problem substance use by age 13–16 were matched on age, gender, and parental AUD to substance-naive controls.…”

“…Gender differences were investigated directly in only one study [29], as an exploratory analysis with a small sample of females. No suggestion of a gender difference in the relationship between brain mechanisms involved in inhibitory control and early risk for problem substance use was found in this 9–12-year-old sample; however, evidence in adults indicates that increased thalamic activation during inhibitory errors uniquely marks parental risk in males but not females [36].…”

Functional near infrared spectroscopy as a potential biological assessment of addiction recovery: preliminary findings

“…It is also predictive of later substance use disorders (51). This region is also particularly susceptible to atrophy associated with chronic alcohol use (52).…”