In concert with Projects 1-3. this revised Project 4 probes the effects of fragmented eariy life experience on neuronal network structure and function using magnetic resonance brain imaging (MRI) of rats (with Project 1) and humans (with Projects 2-3). The results will be integrated with parameters generated by the other projects to accomplish the Center's goal of generating predictive models and markers of adolescent mental vulnerabilities. We will start by examining whether fragmented eariy-life experience influences the structure of brain regions and networks that are salient to cognitive and emotional functions. We then define a trajectory of these structural and functional alterations with development, and their correlation with cognitive and emotional behavior, resulting in potential biomarkers of vulnerability to overt cognitive and emotional pathology. The goal of this project is to employ MRI-derived measures to establish predictors of regional brain connectivity (as well as structural changes) that best correlate with developmental and cognitive vulnerabilities as a function of early life exposure to fragmented maternal signals. This novel analysis will identify a series of pathological changes that occur at varying intervals in the pre-symptomatic period that might guide the timing of future interventions """"""""and provide insights into intrinsic compensatory mechanisms. Its significance derives from the crucial importance of the clinical hypothesis: that fragmented patterns of sensory input modulate the function and connectivity of brain networks. The Project innovation stems from (a) The concept of developmentally evolving neuronal networks as the target of fragmented/unpredictable maternal input, (b) from the use of novel methodologies (e.g.. Structural Equation Modeling);(c) from the use of analysis of distributed hippocampal connectivity using multiple modalities across species, and (d) from inclusion of MRI parameters in multivariate models orchestrated by the Computational Core, to generate potentially predictive models for adolescent vulnerabilities.

Public Health Relevance

Mental disorders pose a profoundly important health problem. These disorders are generally believed to arise from an interaction of genetic and environmental influences during sensitive developmental periods. The projects of the Center explore the hypothesis that fragmented experiences early in life promote vulnerabilities to such disorders. Project 4 uses imaging across species to understand the neurobiological foundations of vulnerability to disorders such as anxiety, depression and learning problems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
1P50MH096889-01A1
Application #
8654010
Study Section
Special Emphasis Panel (ZMH1-ERB-L (02))
Project Start
Project End
Budget Start
2013-06-17
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$197,186
Indirect Cost
$32,864
Name
University of California Irvine
Department
Type
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Molet, J; Heins, K; Zhuo, X et al. (2016) Fragmentation and high entropy of neonatal experience predict adolescent emotional outcome. Transl Psychiatry 6:e702
Chen, Yuncai; Baram, Tallie Z (2016) Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks. Neuropsychopharmacology 41:197-206
Schoemaker, Dorothee; Buss, Claudia; Head, Kevin et al. (2016) Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation. Neuroimage 129:1-14
Chen, Yuncai; Molet, Jenny; Lauterborn, Julie C et al. (2016) Converging, Synergistic Actions of Multiple Stress Hormones Mediate Enduring Memory Impairments after Acute Simultaneous Stresses. J Neurosci 36:11295-11307
Stern, Hal S (2016) A Test by Any Other Name: P Values, Bayes Factors, and Statistical Inference. Multivariate Behav Res 51:23-9
Kim, Dae-Jin; Davis, Elysia Poggi; Sandman, Curt A et al. (2016) Children's intellectual ability is associated with structural network integrity. Neuroimage 124:550-6
Howland, Mariann A; Sandman, Curt A; Glynn, Laura M et al. (2016) Fetal exposure to placental corticotropin-releasing hormone is associated with child self-reported internalizing symptoms. Psychoneuroendocrinology 67:10-7
Maumet, Camille; Auer, Tibor; Bowring, Alexander et al. (2016) Sharing brain mapping statistical results with the neuroimaging data model. Sci Data 3:160102
Fox, Molly; Sandman, Curt A; Davis, Elysia Poggi et al. (2015) Intra-Individual Consistency in Endocrine Profiles Across Successive Pregnancies. J Clin Endocrinol Metab 100:4637-47
Chen, Yuncai; Molet, Jenny; Gunn, Benjamin G et al. (2015) Diversity of Reporter Expression Patterns in Transgenic Mouse Lines Targeting Corticotropin-Releasing Hormone-Expressing Neurons. Endocrinology 156:4769-80

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