Brain Function and Structure in Cocaine Dependence Treatment

可卡因依赖治疗中的大脑功能和结构

• 批准号: 8004214
• 负责人: FREDERICK Gerard MOELLER
• 金额: $ 30.53万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8004214
• 关键词: Anisotropy; Anterior; Behavioral; Behavioral inhibition; Brain; Brain region; Chronic; Citalopram; Clinical; Cocaine; Cocaine Dependence; Cocaine Users; Corpus Callosum; Corpus striatum structure; Data; Decision Making; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dopamine; Drug usage; FDA approved; Feedback; Frontal gyrus; Functional Magnetic Resonance Imaging; Funding; Human; Imaging Techniques; Impairment; Impulsivity; Lead; Levodopa; Magnetic Resonance Imaging; Measures; Medial; Neurobiology; Neurotransmitters; Outcome; Parietal; Pharmaceutical Preparations; Pharmacotherapy; Prefrontal Cortex; Public Health; Radial; Relative (related person); Reversal Learning; Role; Serotonin; Short-Term Memory; Signal Transduction; Structure; Thalamic structure; Treatment outcome; base; blood oxygen level dependent; cocaine use; follow-up; frontal lobe; non-drug; response; treatment response; white matter

Over the last 4 years since the funding of this project, the UT Houston SAR-MDC has shown that cocaine dependence is associated with behavioral deficits including decision-making, behavioral inhibition, and the broader clinical construct of impulsivity. Likewise, we found differences between cocaine dependent subjects and non-drug using controls on Magnetic Resonance Imaging (MRI) measures of brain structure and function. In addition, we have acquired data showing that within cocaine users there is an association between these behavioral deficits and alterations in brain structure, brain function, and poor treatment response. For the renewal of this project, the focus will advance to determining the specific role of these brain MRI findings in treatment outcome by means of a carefully chosen battery of functional and structural MRI techniques in order to predict treatment response to specific classes of medication based on mechanism of action. Our previous blood oxygen level dependent (BOLD) fMRI data showed that cocaine dependent subjects (relative to controls) have (1) less dorsolateral prefrontal cortical, striatal, and thalamic activation during a working memory task, possibly reflecting impaired dopamine function; (2) greater activation in medial orbitofrontal cortex during impulsive responding on a Go-Nogo task, possibly reflecting impaired serotonin function; and (3) greater activation in medial orbitofrontal cortex and medial frontal cortex after negative feedback on a reversal learning task, also possibly reflecting impairment of serotonin function. In order to follow-up the treatment implications of this data, this project will examine (a) pretreatment brain activation on these tasks as predictors of neurotransmitter-specific treatment response, and (b) eariy changes (after three weeks of pharmacotherapy) in task-related fMRI activation as predictors of subsequent longer-term neurotransmitter-specific treatment response. In addition, the relationship between treatment response and measures of white-matter structural integrity as measured by diffusion tensor MRI (DTI) and magnetization transfer ratio MRI (MTR) will be examined.

自该项目资助以来的过去4年，UT休斯顿SAR-MDC表明可卡因 依赖性与行为缺陷有关，包括决策，行为抑制和 冲动性的更广泛的临床结构。同样，我们发现可卡因依赖受试者之间的差异 和非药物使用对照进行磁共振成像（MRI）脑结构和 功能。此外，我们获得了数据，显示可卡因用户有一个关联 在这些行为缺陷和大脑结构，大脑功能和治疗不佳之间的改变之间 回复。 为了续签该项目，重点将促进确定这些大脑MRI的具体作用 通过精心选择的功能和结构MRI的电池进行治疗结果的结果 技术以预测基于机制的特定类药物治疗反应 行动。我们以前的血氧水平依赖性（BOLD）fMRI数据表明可卡因依赖性 受试者（相对于对照组）具有（1）较少的背外侧前额叶皮质，纹状体和丘脑激活 在工作记忆任务中，可能反映了多巴胺功能受损； （2）更大的激活 冲动性响应GO-NOGO任务期间的内侧轨道额皮质，可能反映了受损 5-羟色胺功能； （3）在内侧轨道额皮层和内侧额叶皮质中更大的激活 逆转学习任务的负面反馈，也可能反映了5-羟色胺功能的损害。在 为了跟踪该数据的治疗含义，该项目将检查（a）预处理大脑 将这些任务激活为神经递质特异性治疗反应的预测因素，并且（b）eariy 任务相关的fMRI激活的变化（在药物治疗三周后）作为随后的预测指标 长期神经递质特异性治疗反应。另外，治疗之间的关系 通过扩散张量MRI（DTI）和 将检查磁化转移率MRI（MTR）。