Brain Function and Structure in Cocaine Dependence Treatment

可卡因依赖治疗中的大脑功能和结构

基本信息

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
项目类别：
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

项目摘要

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 年里，UT 休斯敦 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存在差异以及对大脑结构和磁共振成像 (MRI) 测量的非药物使用控制功能。此外，我们获得的数据显示，可卡因使用者之间存在关联这些行为缺陷与大脑结构、大脑功能的改变和不良治疗之间的关系回复。对于该项目的更新，重点将进一步确定这些脑部 MRI 的具体作用通过精心挑选的一系列功能性和结构性 MRI 来了解治疗结果技术，以根据机制预测对特定类别药物的治疗反应行动。我们之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）（1）背外侧前额皮质、纹状体和丘脑激活较少在工作记忆任务期间，可能反映多巴胺功能受损； (2) 更大的激活 Go-Nogo 任务的冲动反应期间内侧眶额皮层，可能反映受损血清素功能； (3) 内侧眶额皮质和内侧额叶皮质在对逆转学习任务的负面反馈，也可能反映了血清素功能的损害。在为了跟踪该数据对治疗的影响，该项目将检查（a）预处理大脑这些任务的激活作为神经递质特异性治疗反应的预测因素，以及（b）早期任务相关功能磁共振成像激活的变化（药物治疗三周后）作为后续的预测因素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) 测量的白质结构完整性的反应和测量将检查磁化传输比 MRI (MTR)。