title: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Addiction Research Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mheitzeg@umich.edu.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Heitzeg
authors.affiliation: Departments of Psychiatry and Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Nigg
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Addiction Research Center, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Hardee
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Addiction Research Center, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Soules
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Addiction Research Center, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Davia
authors.initials: D
authors.lastname: Steinberg
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Addiction Research Center, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zucker
mesh_terms: D000293:Adolescent; D002648:Child; D016241:Child of Impaired Parents; D002675:Child, Preschool; D042241:Early Diagnosis; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006801:Humans; D007266:Inhibition, Psychological; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011597:Psychomotor Performance / Q000502:physiology; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000175:diagnosis* / Q000503:physiopathology
keywords: Development; Error monitoring; Inhibitory control; Substance abuse; Vulnerability