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1.  Default mode network activity in male adolescents with conduct and substance use disorder* 
Drug and alcohol dependence  2013;134:242-250.
Adolescents with conduct disorder (CD) and substance use disorders (SUD) experience difficulty evaluating and regulating their behavior in anticipation of future consequences. Given the role of the brain's default mode network (DMN) in self-reflection and future thought, this study investigates whether DMN is altered in adolescents with CD and SUD, relative to controls.
Twenty adolescent males with CD and SUD and 20 male controls of similar ages underwent functional magnetic resonance imaging as they completed a risk-taking decision task. We used independent component analysis as a data-driven approach to identify the DMN spatial component in individual subjects. DMN activity was then compared between groups.
Compared to controls, patients showed reduced activity in superior, medial and middle frontal gyrus (Brodmann area (BA) 10), retrosplenial cortex (BA 30) and lingual gyrus (BA 18), and bilateral middle temporal gryus (BA 21/22) - DMN regions thought to support self-referential evaluation, memory, foresight, and perspective taking. Furthermore, this pattern of reduced activity in patients remained robust after adjusting for the effects of depression and attention-deficit hyperactivity disorder (ADHD). Conversely, when not adjusting for effects of depression and ADHD, patients demonstrated greater DMN activity than controls solely in the cuneus (BA 19).
Collectively, these results suggest that comorbid CD and SUD in adolescents is characterized by atypical activity in brain regions thought to play an important role in introspective processing. These functional imbalances in brain networks may provide further insight into the neural underpinnings of conduct and substance use disorders.
PMCID: PMC3895766  PMID: 24210423
Default Mode Network; Conduct Disorder; Substance Use Disorder; Independent Component Analysis; Functional MRI
2.  Risky Decisions and Their Consequences: Neural Processing by Boys with Antisocial Substance Disorder 
PLoS ONE  2010;5(9):e12835.
Adolescents with conduct and substance problems (“Antisocial Substance Disorder” (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys.
Methodology/Principal Findings
We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere.
Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders.
PMCID: PMC2943904  PMID: 20877644
3.  Substance Use Disorder Genetic Research: Investigators and Participants Grapple with the Ethical Issues 
Psychiatric genetics  2009;19(2):83-90.
This qualitative research examined the ethical concerns regarding the psychosocial issues, research design and implementation, and application of psychiatric genetic research on substance use disorders (SUD) from multiple perspectives.
A literature review of the bioethics literature related to psychiatric genetics and focus groups explored the ethical implications of SUD genetic research. Twenty-six National Institute on Drug Abuse (NIDA) funded principal investigators in the field of psychiatric genetic research, 9 adolescent patients in residential SUD treatment, and 10 relatives of patients participated in focus groups (held separately). The focus groups were recorded, transcribed, and the content was analyzed. The themes that emerged from the literature and the focus group transcripts were organized using NVIVO7, a software package designed to manage, analyze and compare narrative data.
Investigators and the literature expressed similar concerns regarding the ethical concerns associated with psychiatric genetic research including violation of privacy, misunderstanding about psychiatric genetics, stigmatization, commercialization, discrimination, eugenics, consequences of research on illegal behavior, unforeseen consequences, altered notion of individual responsibility, and others. Patients and their relatives demonstrated little familiarity with the ethical issues as identified by professionals and little concern regarding most of the potential risks. The exception was apprehension associated with potential criminal justice uses of stored genetic information and enforced therapy, which elicited some concern from all perspectives.
The challenge for further research is to identify risks and benefits of SUD research that are germane in a behaviorally disinhibited population and devise effective tools to communicate information to participants through an improved informed consent process.
PMCID: PMC2796541  PMID: 19668113
Substance use disorders; psychiatric genetic research; privacy; prevention and treatment; criminal justice; responsibility
4.  Brain activation during the Stroop task in adolescents with severe substance and conduct problems: A pilot study 
Drug and alcohol dependence  2007;90(2-3):175-182.
Although many neuroimaging studies have examined changes in brain function in adults with substance use disorders, far fewer have examined adolescents. This study investigated patterns of brain activation in adolescents with severe substance and conduct problems (SCP) compared to controls.
Functional magnetic resonance imaging (fMRI) at 1.5 Tesla assessed brain activation in 12 adolescent males with SCP, ranging in age from 14 to 18, and 12 controls similar in age, gender, and neighborhood while performing the attentionally-demanding Stroop task.
Even though the adolescents with SCP performed as well as the controls, they activated a more extensive set of brain structures for incongruent (e.g., “red” in blue ink) versus congruent (e.g. “red” in red ink) trials. These regions included parahippocampal regions bilaterally, posterior regions involved in language-related processing, right-sided medial prefrontal areas, and subcortical regions including the the thalamus and caudate.
These preliminary results suggest that the neural mechanisms of attentional control in youth with SCP differ from youth without such problems. This difficulty may prevent SCP youth from ignoring salient but distracting information in the environment, such as drug-related information.
PMCID: PMC2828145  PMID: 17499456

Results 1-5 (5)