Adolescence is a developmental period during which substantial changes in neural and social development occur and coincides with the onset of internalizing disorders and alcohol abuse disorders (AUD) that manifest in a sexually dimorphic manner. Understanding the social and neurobiological changes that occur during adolescence and exploring which factors relate to the onset of psychopathology will be crucial for elucidating the biological mechanisms of internalizing disorders and AUDs. Cognitive control function is often compromised in states of psychopathology, and is an important process to study during adolescence because the fronto-parietal network, a primary substrate of cognitive control, has a protracted rate of development with distinct developmental trajectories for boys and girls. As such, adolescents often show inconsistent performance on cognitively demanding tasks, especially during emotionally heightened contexts such as those involving peers groups. Peers play an important role in the development of self, which is determined through self-referential processing (SRP), during adolescence. Sex differences in SRP have not been explicitly measured;however, data suggest that girls exhibit more prosocial behavior, which may lead to a heightened social orientation that, in turn, impacts SRP. SRP engages the default mode network (DMN) and is a healthy and necessary process that informs motivated behavior;however, excessive SRP mirrors ruminative processes found in internalizing disorders and internalizing pathways leading to alcohol abuse. In fact, the DMN has been shown to be chronically active and more robustly functionally connected in depressed patients, compared to healthy controls. Furthermore, cognitive control deficits observed in depressed patients may be due to overactive SRP or ruminative processes. To examine how SRP interacts with cognitive control, state and trait functional connectivity between the networks supporting these processes will be assessed during a mixed block/event-related task intermixing SRP and cognitive control (Flanker task) trials and during resting state, respectively. The state-dependent functional connectivity of networks activated by the task, the DMN (medial prefrontal cortex and posterior cingulate cortex) and fronto-parietal network [dorsolateral prefrontal cortex and superior parietal cortex), will be examined. Trait-dependent functional connectivity within and between these networks will be examined at rest, using resting state functional connectivity and graph theoretical techniques. Differences in state and trait functional connectivity during task and at rest, respectively, will be correlated with measures of social behavior and rumination, and performance on the Flanker task. Due to the prominence of sex differences in prosocial behavior and onset of internalizing disorders and AUDs during adolescence, sex differences in functional connectivity during task and rest conditions will be examined as well.

Public Health Relevance

Self-referential processing is a normal part of healthy adolescent social neurodevelopment that may evolve into unhealthy rumination, a feature of internalizing psychopathology. Given the stark sex differences in the prevalence of internalizing disorders and their interactions with alcohol abuse, the proposed research aims to understand how self-referential processing interferes with cognitive control function, and how these relationships vary by sex. Uncovering how self-referential processing interacts with cognitive control can provide insight about the shift from healthy self-reflection to unhealthy rumination, and may illuminate a mechanism that explains the different rates of internalizing psychopathology, including alcohol abuse disorders via internalizing pathways, in male and female adolescents.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Predoctoral Individual National Research Service Award (F31)
Project #
Application #
Study Section
Biomedical Research Review Subcommittee (AA)
Program Officer
Urbanas, Diana
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Other Basic Sciences
Schools of Medicine
United States
Zip Code
Scheuer, Hannah; Alarcón, Gabriela; Demeter, Damion V et al. (2017) Reduced fronto-amygdalar connectivity in adolescence is associated with increased depression symptoms over time. Psychiatry Res Neuroimaging 266:35-41
Alarcón, Gabriela; Cservenka, Anita; Nagel, Bonnie J (2017) Adolescent neural response to reward is related to participant sex and task motivation. Brain Cogn 111:51-62
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