Some 200,000 adolescent admissions annually occur in American substance-treatment programs 
. Adolescent substance use disorders (SUD) are so strongly comorbid with antisocial conduct disorder (CD) 
that the combination may be termed “antisocial substance disorder” (ASD). Both antecedent genetic influences 
and toxic effects of drugs 
may contribute to these behavioral problems, which often persist for decades 
. ASD's great costs, both to those with the disorder and to society, make it important to understand this condition's etiology.
“Risky behaviors” are behaviors that may result unpredictably in rewarding and/or adverse outcomes. Adolescents generally tend to take more risks than adults, but in laboratories and in real life ASD youths, even when abstinent, take more risks than other adolescents 
. Indeed, ASD's symptoms of SUD and CD (e.g.
, fire-setting, break-ins, and continued substance use despite problems 
) epitomize extreme risky behaviors. Of note, ASD's risky behaviors are not necessarily “impulsive”, i.e.
, done quickly without considering possible consequences. Indeed, they often require sustained preparation, such as “casing” a building before breaking in, or obtaining false identification to buy alcohol.
The excessive risky behaviors of ASD youths might result, first, from aberrant neural processing of behavior-motivating rewards; e.g.
, among normal adolescents a risk-taking propensity does correlate with more reward-related activation of nucleus accumbens (NAc) 
(also see 
). Second, aberrant processing of behavior-inhibiting punishments could result in risky behaviors; e.g.
, after punished responses in reversal learning, children with psychopathic traits show abnormally increased neural activation in ventromedial prefrontal cortex (vmPFC) and caudate 
(also see 
). Third, apart from initial processing of rewards or punishments, impaired integration of reward-punishment information in regions that decide on future behaviors could cause excessive risky behavior; e.g.
, under risky conditions substance-dependent adults under-recruit specialized conflict-monitoring circuitry in posterior mesofrontal cortex 
; also see 
. To address these three possibilities, we asked whether ASD youths under conditions of risk process decisions, rewards, or punishments differently from community-comparison youths.
Only a few studies have compared brain activation in ASD youths and controls. ASD youths did show greater activation in amygdala and regions of the default network while performing the Stroop task 
. In a go/no-go task marijuana-using youths (without CD) had more activation frontally (and elsewhere) than controls 
. Conversely, youths with familial risk for ASD had less frontal activation than controls during a motor inhibition task 
, perhaps like substance-involved adults who, when considering risky decisions, showed hypoactivity in brain regions processing potential losses and response conflicts 
Structural alterations of brain have been associated with the risk-taking of ASD youngsters, even among those merely vulnerable to ASD through family history. Youngsters with CD reportedly have reduced volume in insula and amygdala 
, and in temporal lobes, hippocampus, and vmPFC 
. Compared with controls, alcohol-naïve sons of alcoholic men reportedly have widespread gray-matter volume reductions, the severity of which correlates with the severity of inattention, impulsivity, hyperactivity, and conduct problems 
. Aggression and defiance negatively correlate with right ACC gray-matter volume among community boys not selected for ASD 
, while impulsivity negatively correlates with vmPFC volume 
Because ASD youths combine antisocial conduct problems with SUD, recent publications suggest partially conflicting possibilities for the neural underpinnings of their problems. First, like adults with antisocial or psychopathic traits (but substance-free) 
, ASD youths' repeated risk-taking might occur because they experience increased dopaminergic response
to reward anticipation. Among antisocial adults impaired amygdala and vmPFC function also are thought 
to reduce responses to punishment or loss. Increased response to reward and decreased response to punishment could cause excessive pursuit of exciting rewards with failure to inhibit behaviors that may be punished.
Alternatively, reviewing human and animal studies, Koob and Volkow 
suggest that repeated intoxication-withdrawal cycles from addictive drugs are associated with decreased dopaminergic response
to reward, due to increased stimulation thresholds in compromised reward circuits (see also 
). These processes would produce “reward insensitivity”, reducing motivation for non-drug stimuli. Koob and Volkow 
also indicate that chronic drug use disrupts frontal activity in ACC, OFC, and DLPFC, a disruption continuing well into protracted abstinence. Because those areas contribute to decision-making and behavioral inhibition, such disruption would facilitate recurring risk-taking and relapses. These authors further propose that repeated intoxication-withdrawal cycles activate a brain stress system mediated by corticotropin releasing factor (CRF) and other neurotransmitters 
. They suggest that in human addicts hypodopaminergic reward insensitivity and stress activation present as subjective dysphoria, a “negative emotional state” that continues long into protracted abstinence (). Relapses at least briefly would relieve that dysphoria, negatively reinforcing further drug use ( and 
Schematic illustration of dysphoria induced by repeated intoxication-withdrawal cycles.
With such conflicting suggestions in the literature, we could not make a directional hypothesis for this study. Thus, we simply hypothesized that, as adolescent boys repeatedly decide between doing a risky or a cautious behavior, and as they experience wins or losses from their risky choices, functional magnetic resonance imaging (fMRI) will show that youths with ASD have different brain activation patterns than community-control boys. Unlike some previous adolescent studies, our z-shim procedure 
allowed good visualization of orbitofrontal regions that are important in processing reward and punishment 
. Our results strongly supported our hypothesis.