This application requests 5 years of funding through the K25 Mentored Quantitative Research Scientist Development Award mechanism. With a Ph.D. degree in engineering, the candidate received additional training in experimental psychology, focusing specifically on human emotional speech processing and voice pattern recognition. As a postdoctoral associate and, more recently, a research faculty at Yale University, he conducted numerous fMRI studies on healthy individuals and patients with substance use disorders. The candidate's career goals are to build on an extensive background in engineering and computation and continue to develop advanced, novel computational methods to investigate altered cerebral function and connectivity as a circuit level biomarker of substance misuse. The support of this K25 award will provide time and resources for him to solidify his knowledge of brain structure and function and facilitate an independent career in addiction neuroscience research. His training plan will cover: 1) systems, cognitive, and addiction neuroscience through formal course work and research collaboration with his mentors; 2) neuroimaging, with a specific focus on state-of-the-art imaging techniques, experimental psychology, and design of fMRI studies; 3) biology, treatment, and clinical trials research of substance abuse; 4) scientific writing; and 5) grant preparation. To implement this training plan, the candidate has assembled an outstanding team of mentors and proposed to use a novel computational approach to understand how thalamic cortical functions are compromised and how these deficits are related to relapse in chronic cocaine users. Specifically, he proposed to employ resting state and task-modulated connectivity analysis to functionally parcellate the thalamus during resting, cognitive control, reward processing and cue-induced craving, and to investigate how thalamic cortical circuit functions are altered in individuals with cocaine dependence. With the concurrent support of an ongoing R01 study, the candidate will study more than 250 cocaine dependent patients in a longitudinal setting to identify thalamic cortical predictors of relapse. The study will thus advance our understanding of the etiological processes of cocaine addiction in multiple dimensions. The study may also facilitate research of other neuropsychiatric disorders through its new conceptual and methodological platform. By completing the proposed training and research projects, the candidate will benefit extensively from the support of this K25 award in achieving his career goal to become an independent investigator in systems and addiction neuroscience research.

Public Health Relevance

Understanding the neural processes leading to uncontrollable use of cocaine is of urgent and critical importance to public health. The aim of this project is to combine brain imaging and a novel computational approach to understand the neural deficits and how these deficits predict relapse in cocaine addicts. The proposed work will further our understanding of the etiology of cocaine addiction and prepare the candidate for future research in the proposed directions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
1K25DA040032-01
Application #
8949921
Study Section
Special Emphasis Panel (ZRG1-BDCN-C (02))
Program Officer
Grant, Steven J
Project Start
2015-08-15
Project End
2020-07-31
Budget Start
2015-08-15
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$166,512
Indirect Cost
$11,919
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06510
Ide, Jaime S; Zhornitsky, Simon; Chao, Herta H et al. (2018) Thalamic Cortical Error-Related Responses in Adult Social Drinkers: Sex Differences and Problem Alcohol Use. Biol Psychiatry Cogn Neurosci Neuroimaging 3:868-877
Yoo, Kwangsun; Rosenberg, Monica D; Hsu, Wei-Ting et al. (2018) Connectome-based predictive modeling of attention: Comparing different functional connectivity features and prediction methods across datasets. Neuroimage 167:11-22
Zhang, Sheng; Li, Chiang-Shan R (2018) Ventral striatal dysfunction in cocaine dependence - difference mapping for subregional resting state functional connectivity. Transl Psychiatry 8:119
Wang, Wuyi; Hu, Sien; Ide, Jaime S et al. (2018) Motor Preparation Disrupts Proactive Control in the Stop Signal Task. Front Hum Neurosci 12:151
Hu, Sien; Ide, Jaime S; Chao, Herta H et al. (2018) Resting state functional connectivity of the amygdala and problem drinking in non-dependent alcohol drinkers. Drug Alcohol Depend 185:173-180
Zhang, Sheng; Wang, Wuyi; Zhornitsky, Simon et al. (2018) Resting State Functional Connectivity of the Lateral and Medial Hypothalamus in Cocaine Dependence: An Exploratory Study. Front Psychiatry 9:344
Zhang, Sheng; Zhornitsky, Simon; Angarita, Gustavo A et al. (2018) Hypothalamic response to cocaine cues and cocaine addiction severity. Addict Biol :
Wang, Wuyi; Worhunsky, Patrick D; Zhang, Sheng et al. (2018) Response inhibition and fronto-striatal-thalamic circuit dysfunction in cocaine addiction. Drug Alcohol Depend 192:137-145
Zhang, Yihe; Zhang, Sheng; Ide, Jaime S et al. (2018) Dynamic network dysfunction in cocaine dependence: Graph theoretical metrics and stop signal reaction time. Neuroimage Clin 18:793-801
Xiao, Ting; Zhang, Sheng; Lee, Lue-En et al. (2018) Exploring Age-Related Changes in Resting State Functional Connectivity of the Amygdala: From Young to Middle Adulthood. Front Aging Neurosci 10:209

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