It is highly plausible that heritable individual differences in executive functions (EFs), mediated by variation in identifiable neural circuits, contribute to a generalized genetic vulnerability to psychopathology and psychiatric disorder. Determining the extent to which functional variation in neural circuits supporting EF is itself heritable, or influenced by environmental factors, will provide information critical to understanding the role of neural circuits in mediating the genetic and environmental vulnerability to mental illness. In this competitive renewal, we propose to extend our twin study of individual differences in EFs by conducting the following: (1) the first large-scale functional magnetic resonance imaging (fMRI) study of individual differences in the multiple EFs;(2) the first fMRI study of EFs to incorporate latent variables measured outside of the scanner;and (3) the first behavior genetic study of functional neural indices of these multiple EFs in adulthood. By collecting fMRI data on a carefully selected set of EF tasks and analyzing it in conjunction with additional EF tasks measured outside the scanner, as well as new assessments of psychopathology linked to EFs, we will be able to determine neural circuits related to individual differences in EFs and associated psychopathology. Because the data come from twins, we will also assess the genetic and environmental etiologies of individual differences in these neural indices, and examine their genetic and environmental correlations with the behavioral EF measures. Finally, by integrating the neural data with assessments of symptoms related to psychopathology (e.g., attention problems, depression), we will test whether the brain areas related to EFs mediate the relations between EFs and these symptoms identified in this sample. To achieve these aims we conduct an fMRI study on twins who have participated in the Colorado Longitudinal Twin Study (LTS) since infancy and have previous EF assessments. Based on recruitment rates for prior waves and a pilot study, we estimate 640 participants from 320 twin pairs (167 monozygotic and 153 dizygotic). In the scanner they will perform 3 tasks tapping 3 separable but correlated EFs: inhibiting prepotent responses, updating working memory, and shifting between tasks or mental sets. They will complete 3 additional EF tasks outside the scanner so we can construct latent variables for each component. They will also complete phone inverviews and online questionnaire assessments of symptoms related to mental illness before the imaging session. We will analyze the imaging data using independent components analysis to identify separable neural circuits that correlate with individual differences in performance. We will then examine whether these neural measures mediate the relations between EFs and symptoms of psychopathology.

Public Health Relevance

This is an fMRI twin study of adult individual differences in executive functions. These abilities have been linked to mental health problems such as schizophrenia, depression, obsessive compulsive disorder, and attention deficit hyperactivity disorder. Determining the extent to which functional variation in neural circuits supporting EFs is itself heritable, or influenced by environmental factors, will provide a critical piece of informaton for understanding the role of neural circuits in mediating the genetic and environmental vulnerability to mental illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH063207-10A1
Application #
8631457
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Rossi, Andrew
Project Start
2001-06-01
Project End
2019-01-31
Budget Start
2014-02-15
Budget End
2015-01-31
Support Year
10
Fiscal Year
2014
Total Cost
$755,723
Indirect Cost
$260,167
Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Drake, Christopher L; Vargas, Ivan; Roth, Thomas et al. (2015) Quantitative measures of nocturnal insomnia symptoms predict greater deficits across multiple daytime impairment domains. Behav Sleep Med 13:73-87
Johnson, Daniel P; Whisman, Mark A; Corley, Robin P et al. (2014) Genetic and environmental influences on rumination and its covariation with depression. Cogn Emot 28:1270-86
Smith Watts, Ashley K; Patel, Deepika; Corley, Robin P et al. (2014) Testing alternative hypotheses regarding the association between behavioral inhibition and language development in toddlerhood. Child Dev 85:1569-85
Herd, Seth A; O'Reilly, Randall C; Hazy, Tom E et al. (2014) A neural network model of individual differences in task switching abilities. Neuropsychologia 62:375-89
Gustavson, Daniel E; Miyake, Akira; Hewitt, John K et al. (2014) Genetic relations among procrastination, impulsivity, and goal-management ability: implications for the evolutionary origin of procrastination. Psychol Sci 25:1178-88
Palmer, Rohan H C; Knopik, Valerie S; Rhee, Soo Hyun et al. (2013) Prospective effects of adolescent indicators of behavioral disinhibition on DSM-IV alcohol, tobacco, and illicit drug dependence in young adulthood. Addict Behav 38:2415-21
Palmer, R H C; Young, S E; Corley, R P et al. (2013) Stability and change of genetic and environmental effects on the common liability to alcohol, tobacco, and cannabis DSM-IV dependence symptoms. Behav Genet 43:374-85
Chatham, Christopher H; Herd, Seth A; Brant, Angela M et al. (2011) From an executive network to executive control: a computational model of the n-back task. J Cogn Neurosci 23:3598-619
Friedman, Naomi P; Miyake, Akira; Robinson, JoAnn L et al. (2011) Developmental trajectories in toddlers' self-restraint predict individual differences in executive functions 14 years later: a behavioral genetic analysis. Dev Psychol 47:1410-30
Willcutt, Erik G; Betjemann, Rebecca S; McGrath, Lauren M et al. (2010) Etiology and neuropsychology of comorbidity between RD and ADHD: the case for multiple-deficit models. Cortex 46:1345-61

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