Studies utilizing modern neuroimaging techniques have provided clear evidence that the adolescent brain is actively developing. This neurodevelopment, particularly in the frontal lobes, coincides with improvements in several areas of higher order cognitive functioning, including working memory abilities. It has been documented that working memory skills are crucial to the intact performance in several other cognitive domains. Deficits in working memory have been demonstrated among a number of neurological and psychiatric conditions that manifest during adolescence. However, the neurobiological substrates of working memory in even normally developing adolescents remain unclear. The current cross-sectional study proposes to integrate neuropsychological, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques to more clearly explore frontal lobe white matter development as it relates to both verbal and spatial working memory functioning in 90 typically developing adolescents (ages 12 to 17). It is hypothesized that 1) working memory abilities will be positively associated with age, 2) adolescents will show a hemispheric dissociation between the verbal and spatial working memory tasks that will become more pronounced with increasing age, 3) prefrontal white matter integrity will show a significant positive correlation with age and will mediate the positive relationship between age and working memory performance, and 4) prefrontal white matter integrity will be positively associated with nearby cortical fMRI response during the working memory tasks. The applicant is requesting a five-year mentored Career Development Award (K08) in order to develop the skills and expertise necessary for answering these research questions. Career development activities will include training in DTI data collection and analysis, development of expertise in fMRI, training in developmentally-focused longitudinal study design and analytical techniques and continued training in the ethical conduct of scientific research with children and adolescents. The proposed training plan will include structured coursework, seminars, and mentoring by experts in the fields of development and neuroimaging. Together, the implementation of this training and research plan will provide the beginnings of a much-needed framework for understanding the neurobiological substrates of working memory during adolescence and will allow the applicant to transition into an independent investigator specializing in longitudinal examination of adolescent cognition and neurodevelopment.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Clinical Investigator Award (CIA) (K08)
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NST-2 Subcommittee (NST)
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Babcock, Debra J
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Oregon Health and Science University
Schools of Medicine
United States
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Alarcón, Gabriela; Ray, Siddharth; Nagel, Bonnie J (2016) Lower Working Memory Performance in Overweight and Obese Adolescents Is Mediated by White Matter Microstructure. J Int Neuropsychol Soc 22:281-92
Herting, Megan M; Keenan, Madison F; Nagel, Bonnie J (2016) Aerobic Fitness Linked to Cortical Brain Development in Adolescent Males: Preliminary Findings Suggest a Possible Role of BDNF Genotype. Front Hum Neurosci 10:327
Peraza, Jennifer; Cservenka, Anita; Herting, Megan M et al. (2015) Atypical parietal lobe activity to subliminal faces in youth with a family history of alcoholism. Am J Drug Alcohol Abuse 41:139-45
Herting, Megan M; Colby, John B; Sowell, Elizabeth R et al. (2014) White matter connectivity and aerobic fitness in male adolescents. Dev Cogn Neurosci 7:65-75
Alarcón, Gabriela; Cservenka, Anita; Fair, Damien A et al. (2014) Sex differences in the neural substrates of spatial working memory during adolescence are not mediated by endogenous testosterone. Brain Res 1593:40-54
Seghete, Kristen L Mackiewicz; Herting, Megan M; Nagel, Bonnie J (2013) White matter microstructure correlates of inhibition and task-switching in adolescents. Brain Res 1527:15-28
Herting, Megan M; Nagel, Bonnie J (2013) Differences in brain activity during a verbal associative memory encoding task in high- and low-fit adolescents. J Cogn Neurosci 25:595-612
Nagel, Bonnie J; Herting, Megan M; Maxwell, Emily C et al. (2013) Hemispheric lateralization of verbal and spatial working memory during adolescence. Brain Cogn 82:58-68
Herting, Megan M; Maxwell, Emily C; Irvine, Christy et al. (2012) The impact of sex, puberty, and hormones on white matter microstructure in adolescents. Cereb Cortex 22:1979-92
Cservenka, Anita; Nagel, Bonnie J (2012) Risky decision-making: an FMRI study of youth at high risk for alcoholism. Alcohol Clin Exp Res 36:604-15

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