Manish S Dalwani1, Jason R Tregellas2, Jessica R Andrews-Hanna3, Susan K Mikulich-Gilbertson4, Kristen M Raymond5, Marie T Banich6, Thomas J Crowley7, Joseph T Sakai8. 1. Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States. Electronic address: manish.dalwani@ucdenver.edu. 2. Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States. Electronic address: Jason.Tregellas@ucdenver.edu. 3. Institute of Cognitive Science and Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, United States. Electronic address: Jessica.andrews-hanna@colorado.edu. 4. Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States. Electronic address: Susan.Mikulich@ucdenver.edu. 5. Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States. Electronic address: Kristen.Raymond@ucdenver.edu. 6. Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States; Institute of Cognitive Science and Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, United States. Electronic address: Marie.Banich@colorado.edu. 7. Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States. Electronic address: Thomas.Crowley@ucdenver.edu. 8. Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States. Electronic address: Joseph.Sakai@ucdenver.edu.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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