Despite the well-documented variable but often persisting course of Attention-Deficit/Hyperactivity Disorder (ADHD) into adulthood, little is known about underlying neural correlates of adulthood outcome. Neuroimaging studies of ADHD adults typically include small subsets of ADHD children who, as adults, self-report symptoms to clinicians. Thus, adults with limited insight into their ADHD (a well-known characteristic), or adults who fail to seek treatment (the majority with childhood ADHD), are excluded from these studies. A study of brain function in adults with well-characterized childhood ADHD, with collateral reports and repeated assessment of symp- toms from childhood into adulthood, may contribute needed information about the pathophysiology of ADHD. Existing studies of adult ADHD have typically focused on the functioning of dorsal and lateral prefrontal sys- tems underlying """"""""cool"""""""" executive functions (EF). However, recent evidence suggests that fronto-striatal-limbic systems supporting processing at the interface of cognition and motivational/emotional processes - also known as """"""""hot"""""""" EF and implicated in self-regulation of behavior and emotion - may also be impaired in ADHD. This application proposes to examine the functioning of neural systems supporting both """"""""cool"""""""" and """"""""hot"""""""" EF in relation to powerful latent variable growth curves of ADHD symptoms estimated from the uniquely frequent long-term assessments reaching beyond age 25 of the Pittsburgh ADHD Longitudinal Study (PALS). Partici- pants will be 200 young adults (150 with, and 50 without, childhood ADHD) from the PALS -- an ongoing study (R37AA11873) of the course and outcomes of childhood ADHD. Using fMRI paradigms, we will assess neural activity in, and functional connectivity between, neural regions implicated in a) reward modulation of inhibitory control during a rewarded antisaccade task and b) interference control of emotionally salient information during an emotional working memory task. Importantly, given recent evidence that emotional dysregulation (specifical- ly, anger-irritability) may have distinct neurobiological substrates in ADHD, we will test the extent to which vari- ation in the above neuroimaging indices is associated with anger-irritability also measured longitudinally. Neu- roimaging indices will be tested as moderators of the relations between symptom course and performance on tasks assessing affective decision making, risk taking, and affective response inhibition. Finally, we will explore associations between these neuroimaging indices of rewarded inhibitory control and emotional working memory and a) white matter integrity, b) stimulant treatment history, and c) self-reported variables such as re- ward sensitivity and positive/negative urgency. The proposed study will be unique in the adult ADHD neuroim- aging literature due to its emphasis on the dual """"""""cool"""""""" and """"""""hot"""""""" EF systems in adults with well-characterized childhood histories prospectively tracked into adulthood with uniquely frequent repeated assessments tapping underlying traits over time. The integrated brain-behavior findings may stimulate research on new targets for therapeutic interventions and advance understanding of ADHD pathophysiology.

Public Health Relevance

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most widely diagnosed mental health disorders of childhood. The majority of children with ADHD will continue to exhibit symptoms into adulthood and these are associated with significant and costly impairments such as lowered occupational attainment, relationship volatility, and legal consequences. Understanding the neurobiological underpinnings of ADHD outcomes in adulthood may help explain why certain children with ADHD continue to experience problems as adults. To this end, the current project uses MRI technology to investigate the functioning of the brain in relation to ADHD children's outcomes as adults. The findings will inform our understanding of ADHD biology and provide new knowledge that may ultimately improve treatments for the disorder.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Friedman-Hill, Stacia
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University of Pittsburgh
Schools of Medicine
United States
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Feldstein Ewing, Sarah W; Tapert, Susan F; Molina, Brooke S G (2016) Uniting adolescent neuroimaging and treatment research: Recommendations in pursuit of improved integration. Neurosci Biobehav Rev 62:109-14