The long-range goal of the proposed study is to characterize the neural mechanisms that mediate between internal goal-directed behavior and externally guided behavior. Failing to suppress environmental information when it conflicts with current goals may lead to inappropriate behaviors. For example, failing to suppress drug-related cues leads to drug seeking behavior, and is associated with relapse following treatment. Further, such failures are observed in many psychiatric and neurological disorders. However, most studies that have examined the underlying neural mechanisms of flexible, goal-directed behavior have relied on paradigms where subjects switch between tasks according to explicit cue stimuli. Therefore, these paradigms may not be able to fully capture the neural mechanisms associated with internally generated goal or task selection. As preliminary studies have suggested that control processes are recruited differentially when the task selection is explicitly instructed versus under participant control, it is important to identify the differences in the pattern of brain activation for these different modes of task selection. In two main experiments, we aim to 1) investigate the neural mechanisms underlying internally generated and externally biased task selection, and 2) examine the role of the posterior medial prefrontal cortex (pMFC), a region whose functional organization has been a topic of intense debate, in task selection. A parallel magnetic resonance imaging (MRI) and event- related brain potential (ERP) study will first be conducted that manipulates whether task selection is under experimenter or subject control (external vs. internal control) and manipulates the presence of irrelevant cues that may bias task selection (i.e., external bias on task selection). We will examine the differences in the spatial organization (MRI, DTI) and timecourse (ERP) of brain regions when task choice is externally or internally generated and under external bias or not. Finally, a functional MRI meta-analysis will be conducted to examine whether distinct subregions of the pMFC underlie separable processes of task selection, response selection, and response evaluation. By combining across multiple studies, the meta-analysis will yield sufficient statistical power to detect subtle differences in the pattern of activation for these processes. Knowledge of the neural mechanisms that govern executive control of internally vs. externally driven task selection will provide additional insight into the causes of successful and unsuccessful behavior in young adults, will help explain the mechanisms that underlie cued drug-seeking behavior in addiction (as well as disrupted cognitive flexibility observed across multiple clinical populations, and will facilitate the development of cognitive training and rehabilitation paradigms applicable to these populations.

Public Health Relevance

The proposed research will examine the neural systems that help people decide what goal to pursue or task to perform, especially in the face of potent environmental information that could bias such a choice. This information is very important for expanding our knowledge regarding why individuals continue to take substances of abuse despite their subsequent negative consequences. Drugs of abuse are known to alter brain systems, and one difficulty that occurs in individuals with substance use face is an inability to ignore drug-related cues when deciding on whether or not to take drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DA034412-01A1
Application #
8522594
Study Section
Special Emphasis Panel (ZRG1-F02B-M (20))
Program Officer
Bjork, James M
Project Start
2013-09-15
Project End
Budget Start
2013-09-15
Budget End
Support Year
1
Fiscal Year
2013
Total Cost
$49,214
Indirect Cost
Name
University of Colorado at Boulder
Department
Psychology
Type
Other Domestic Higher Education
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Orr, Joseph M; Paschall, Courtnie J; Banich, Marie T (2016) Recreational marijuana use impacts white matter integrity and subcortical (but not cortical) morphometry. Neuroimage Clin 12:47-56
Bernard, Jessica A; Orr, Joseph M; Mittal, Vijay A (2016) Differential motor and prefrontal cerebello-cortical network development: Evidence from multimodal neuroimaging. Neuroimage 124:591-601
Dean, Derek J; Orr, Joseph M; Bernard, Jessica A et al. (2016) Hippocampal Shape Abnormalities Predict Symptom Progression in Neuroleptic-Free Youth at Ultrahigh Risk for Psychosis. Schizophr Bull 42:161-9
Depue, B E; Orr, J M; Smolker, H R et al. (2016) The Organization of Right Prefrontal Networks Reveals Common Mechanisms of Inhibitory Regulation Across Cognitive, Emotional, and Motor Processes. Cereb Cortex 26:1634-46
Dean, Derek J; Orr, Joseph M; Newberry, Raeana E et al. (2016) Motor behavior reflects reduced hemispheric asymmetry in the psychosis risk period. Schizophr Res 170:137-42
Shott, M E; Cornier, M-A; Mittal, V A et al. (2015) Orbitofrontal cortex volume and brain reward response in obesity. Int J Obes (Lond) 39:214-21
Bernard, Jessica A; Orr, Joseph M; Mittal, Vijay A (2015) Abnormal hippocampal-thalamic white matter tract development and positive symptom course in individuals at ultra-high risk for psychosis. NPJ Schizophr 1:
Dean, Derek J; Kent, Jerillyn S; Bernard, Jessica A et al. (2015) Increased postural sway predicts negative symptom progression in youth at ultrahigh risk for psychosis. Schizophr Res 162:86-9
Smolker, H R; Depue, B E; Reineberg, A E et al. (2015) Individual differences in regional prefrontal gray matter morphometry and fractional anisotropy are associated with different constructs of executive function. Brain Struct Funct 220:1291-306
Orr, Joseph M; Smolker, Harry R; Banich, Marie T (2015) Organization of the Human Frontal Pole Revealed by Large-Scale DTI-Based Connectivity: Implications for Control of Behavior. PLoS One 10:e0124797

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