Hannah R. Snyder - US grants

DESCRIPTION (provided by applicant): The proposed research investigates the ability to respond flexibly and appropriately when a situation affords multiple possible responses. This aspect of executive function is compromised in many disorders affecting prefrontal cortex (PFC), contributing to problems in communication, planning, and decision-making. The research aims, first, to identify neural substrates supporting this flexibility, and second, to explore potential neural mechanisms. Progress in adjudicating between competing theories of the role of PFC regions in flexible responding has been limited by flawed measures and failure to manipulate demands within the same task. Two fMRI studies remedy these problems, in order to cleanly differentiate regions supporting controlled retrieval of responses, selection between competing task-relevant responses (underdetermined competition), and selection of a task-relevant response in the face of prepotent task-irrelevant competitors. There is debate as to the role of ventrolateral PFC (VLPFC) in selection versus controlled retrieval. The first study uses new unconfounded measures to identify VLPFC regions supporting these processes. Selection in the face of prepotent competition has been found to tap regions of dorsolateral PFC (DLPFC) as well as VLPFC, but has not been contrasted with selection when there is underdetermined competition. A second study will contrast these two forms of competition. The second aim is to bridge levels of analysis, probing the mechanisms supporting controlled retrieval and selection using a neural network model. The model will allow investigation of the effects of NMDA receptor, GABA, and dopamine function which may contribute to cognitive control deficits in conditions such as schizophrenia, anxiety disorders and ADHD. A better understanding of the neural substrates and mechanisms supporting executive function is critical for developing better behavioral and pharmacological interventions to treat such cognitive control deficits. Relevance: We are constantly faced with the task of choosing one option from among many, such as when we select words to express a thought. This ability is impaired in many disorders, including ADHD, anxiety, and schizophrenia. These studies explore how the brain is able to choose between multiple options, and how these disorders may affect this ability, with the goal of aiding development of new treatments.

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) is one of the most common mental illnesses, affecting approximately one out of every six Americans during their life, with many individuals experiencing their first depressive episode during adolescence. There is strong evidence that adults with MDD experience deficits in executive function (EF), the cognitive ability that allows us to respond flexibly to the environment and is thus essential for successfully navigating nearly all of our daily activities. However, it is unknown whether EF deficits (a) precede, and are a risk factor for, developing depression, (b) are a consequence of depression, or (c) both, setting up a positive- feedback loop leading to recurrent depression and increasing functional impairments. The vast majority of research on EF in depression has used cross-sectional designs and tested adults who have already experience one, or often multiple, episodes of depression; therefore the previous literature cannot address whether EF impairments are a risk factor for, or effect of, depression. In addition, a focus on adults misses key age period for both depression vulnerability and EF development: adolescence. The proposed research aims to make an innovative contribution by testing the temporal relations between EF and depression in adolescents. The proposed study uses a longitudinal design to investigate the direction of links between depression and EF in adolescents, and explore how those links may interact with stress and emotional trait risk factors and with biased attention to emotion. Participants will be adolescents from whom the sponsor has already collected multiple assessments of depression and depression risk factors. EF was not assessed in these previous sessions. Thus, for the proposed study, these adolescents will complete two additional sessions, 12 months apart, assessing EF and current depression. This design has a strong advantage over previous research because it enables directional hypotheses to be tested, by determining whether EF deficits proceed or follow the onset of depression. Understanding which of these models (e.g. EF as risk factor or effect of MDD) best accounts for EF deficits associated with depression will be critical for developing strategies for prevention and remediation. For example, if EF deficits are a risk factor for depression, adolescents who are vulnerable to depression (e.g. due to parental history of MDD) might benefit from early intervention to train EF or teach compensatory strategies to mitigate the effects of EF impairments. The proposed research thus has implications for future research on prevention approaches for adolescents at risk for depression.