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A neurocognitive and computational study of inhibitory control in substance use

物质使用抑制控制的神经认知和计算研究

基本信息

批准号：
8190352
负责人：
Angela Yu
金额：
$ 11.59万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8190352
关键词：
20 year old Affect Age Alcohol or Other Drugs use Attention deficit hyperactivity disorder Behavior Behavior Therapy Behavioral Brain Brain region Cognitive Cognitive deficits Collaborations Data Data Analyses Dependence Diagnostic Drug Addiction Drug usage Drug user Functional Magnetic Resonance Imaging Funding Generations Goals Grant Illicit Drugs Individual Learning Light Measures Modeling National Institute of Drug Abuse Nature Neurocognitive Perception Pharmacological Treatment Population Population Control Procedures Process Psychiatry Psychostimulant dependence Reporting Rewards Risk Signal Transduction Staging Surveys United States United States National Institutes of Health addiction base behavior measurement computer studies disinhibitory psychopathology follow-up neurophysiology novel relating to nervous system remediation research study sensory discrimination stimulant abuse tool young adult

项目摘要

DESCRIPTION (provided by applicant): Stimulant abuse and dependence are significant problems facing young adults in the United States. Around 20% of young adults report the use of illicit drugs between the ages of 18-20 years, and approximately one in seven subjects initiating stimulant use progress eventually to dependence. There is strong evidence that drug use and dependence are associated with deficits in inhibitory control. However, the basic cognitive and neural processes underlying such disinhibitory psychopathology are poorly understood. The long-term goal of this project is to delineate the neural provenance and behavioral consequence of inhibitory dysregulation in casual stimulant users, which would be valuable for developing novel tools for the identification of at-risk individuals, for preventative intervention, and for behavioral and pharmacological remediation. The specific aims are (1) to investigate the cognitive differences between stimulant users and normal controls, specifically evaluating the hypotheses that altered error processing and/or temporal perception in stimulant users contribute to impaired inhibitory control, (2) to identify the differential contributions of various brain regions in stopping behavior, as well as neurophysiological differences between stimulant users and matched controls, and (3) to uncover early behavioral and neurophysiological markers that predict whether a casual stimulant user will eventually develop dependent use or not. To achieve Aim 1, a novel, quantitative model for inhibitory control, differentiating the contributions of various cognitive processes such as sensory discrimination, temporal perception, reward/error processing, learning and adaptation, will be used to analyze stimulant users and matched controls performing the stop signal paradigm. To achieve Aim 2, subject- and trial-specific parametric regressors, corresponding to distinct cognitive processes of the quantitative model of Aim 1, will be used to identify the neural substrate (using fMRI data) of the various cognitive processes, and to characterize any neurophysiological differences between stimulant users and matches controls. To achieve Aim 3, three-year follow-up surveys, indicating which casual users eventually develop dependence, will be correlated with behavioral and neurophysiological measures collected in the original fMRI/behavioral experiments, to identify early behavioral and neurophysiological markers that predict transition from casual use to dependence. The behavioral and fMRI data have already been collected under a different grant; the follow-up survey, funded by another grant, will soon be completed. PUBLIC HEALTH RELEVANCE: Stimulant abuse and dependence are significant problems among young adults, making it imperative to identify the causative factors for stimulant use, as well as the nature of cognitive deficits in problem use, in order to develop more powerful diagnostic, preventative, and remedial procedures. In this project, a sophisticated, novel, quantitative model of inhibitory control will be developed, yielding a rich set of cognitive and behavioral measures that can characterizes subtle differences between stimulant users and control populations at different stages of drug use and addiction. The model will be applied to a large set of behavioral and functional MRI data of casual stimulant users and matched control subjects, with the goal of identifying behavioral and neural features that best predict whether an individual eventually develops addiction or not.

描述（由申请人提供）：兴奋剂滥用和依赖是美国年轻人面临的重大问题。大约 20% 的年轻人报告在 18 至 20 岁之间使用过非法药物，大约七分之一的受试者开始使用兴奋剂，最终发展成依赖。有强有力的证据表明药物使用和依赖性与抑制控制缺陷有关。然而，人们对这种去抑制性精神病理学背后的基本认知和神经过程知之甚少。该项目的长期目标是描绘休闲兴奋剂使用者抑制性失调的神经起源和行为后果，这对于开发用于识别高危个体、预防性干预以及行为和药物补救的新工具非常有价值。具体目标是（1）研究兴奋剂使用者和正常对照之间的认知差异，特别评估兴奋剂使用者错误处理和/或时间感知的改变导致抑制控制受损的假设，（2）确定不同大脑区域在停止行为中的不同贡献，以及兴奋剂使用者和匹配对照之间的神经生理学差异，以及（3）揭示早期行为以及预测临时兴奋剂使用者最终是否会产生依赖性的神经生理学标记。为了实现目标 1，一种新颖的抑制控制定量模型，区分各种认知过程（如感觉辨别、时间感知、奖励/错误处理、学习和适应）的贡献，将用于分析兴奋剂使用者和执行停止信号范例的匹配控制。为了实现目标 2，特定于受试者和试验的参数回归量（对应于目标 1 定量模型的不同认知过程）将用于识别各种认知过程的神经基质（使用 fMRI 数据），并表征兴奋剂使用者和匹配对照之间的任何神经生理学差异。为了实现目标 3，为期三年的跟踪调查将表明哪些临时使用者最终会产生依赖，并将与原始功能磁共振成像/行为实验中收集的行为和神经生理学测量值相关联，以识别预测从临时使用到依赖的早期行为和神经生理学标记。行为和功能磁共振成像数据已经在另一项资助下收集；由另一笔赠款资助的后续调查很快就会完成。公共健康相关性：兴奋剂滥用和依赖是年轻人中的一个重大问题，因此必须确定兴奋剂使用的致病因素以及问题使用中认知缺陷的性质，以便制定更强大的诊断、预防和补救程序。在这个项目中，将开发一种复杂的、新颖的、定量的抑制控制模型，产生一套丰富的认知和行为测量方法，可以表征兴奋剂使用者和对照人群在药物使用和成瘾的不同阶段之间的微妙差异。该模型将应用于休闲兴奋剂使用者和匹配对照受试者的大量行为和功能 MRI 数据，目的是识别最能预测个体最终是否上瘾的行为和神经特征。