Functional and Structural Connectivity in Cocaine Addiction

可卡因成瘾的功能和结构连接

• 批准号: 7451439
• 负责人: Anne Marie Clare Kelly
• 金额: $ 26.32万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7451439
• 关键词: Adaptive Behaviors; Adult; Age; Allegra; Amygdaloid structure; Anisotropy; Anterior; Area; Basal Ganglia; Behavioral; Brain; Brain region; Chronic; Classification; Clinical; Cocaine; Cocaine Dependence; Cognitive; Comorbidity; Condition; Corpus striatum structure; Data; Diffusion Magnetic Resonance Imaging; Disease regression; Dorsal; Drug Addiction; Emotional; Exhibits; Functional Magnetic Resonance Imaging; Future; Handedness; Hippocampus (Brain); Individual; Investigation; Maps; Matched Group; Measures; Medial; Memory; Meta-Analysis; Metabolism; Methods; Modality; Moods; Motivation; Neuronal Dysfunction; Neurons; Obsessive compulsive behavior; Pattern; Population; Prefrontal Cortex; Process; Public Health; Purpose; Relapse; Relative (related person); Rest; Sampling; Scanning; Substance abuse problem; System; Techniques; Testing; Time; Ventral Striatum; Week; addiction; base; blood oxygen level dependent; cingulate cortex; classical conditioning; cognitive control; cognitive rehabilitation; drug craving; gray matter; healthy volunteer; hemodynamics; improved; indexing; neural circuit; neuroimaging; neuropathology; neurophysiology; novel; relating to nervous system; sex; white matter

DESCRIPTION (provided by applicant): Cocaine dependence involves profound alterations in functional networks that subserve motivation, associative learning, memory and cognitive control. Neuroimaging modalities have improved our understanding of the neuropathology associated with chronic cocaine use. The spatial correlations of spontaneous hemodynamic brain activity (obtained through blood oxygenation level dependent functional magnetic resonance imaging, BOLD fMRI) define statistical maps that are strikingly convergent with known or hypothesized functionally connected circuits. We have developed methods to systematically apply this approach of functional connectivity in two brain areas centrally implicated in drug addiction, anterior cingulate cortex (ACC) and basal ganglia (BG) of healthy volunteers. Functional connectivity statistical maps are stable across individuals and across time, and have been shown to be useful in delineating novel loci of neuronal dysfunction in other psychopathologic conditions. We propose to apply this approach in 30 cocaine-dependent individuals who will be compared to a matched subset of non-dependent healthy comparisons that we have already scanned on the same 3.0 Tesla Siemens Allegra. We hypothesize that cocaine-dependent individuals will exhibit decreased functional connectivity, particularly between ventral striatum and rostral (limbic) ACC. Accordingly we will examine functional connectivity of ACC and BG in cocaine addicted individuals (abstinent for 2-8 weeks) in comparison with already scanned healthy non-dependent subjects who will be matched for age, sex, and handedness. We hypothesize that the strength of functional connectivity between ventral striatum and BA25 will be positively related to fractional anisotropy within the same circuit. For this purpose, we propose to obtain 29-direction diffusion tensor imaging (DTI) scans in the cocaine-dependent subjects. In addition to testing hypotheses concerning the impact of cocaine addiction on the FC of neural circuits associated with the ACC and BG, the proposed study will determine the extent to which these two parameters, which are hypothesized to index a common neurophysiological basis, are related in this clinical population. This project will lay the groundwork for future studies that will examine the clinical implications of decreased connectivity with respect to prediction of relapse, mood comorbidity, and cognitive rehabilitation. Cocaine dependence remains a serious public health problem. We have developed techniques for defining brain circuitry by observing patterns of correlated brain activity that we believe can also be related to methods useful for tracing the white matter connections between neurons. We propose an initial one-year study to validate our methods in a newly collected sample of cocaine dependent adults, to compare to already collected data from healthy comparison subjects. This project will provide the basis for future studies.

描述(由申请者提供)：可卡因依赖涉及有助于动机、联想学习、记忆和认知控制的功能网络的深刻变化。神经成像方法提高了我们对与慢性可卡因使用相关的神经病理的理解。自发血流动力学脑活动的空间相关性(通过血氧水平依赖的功能磁共振成像，BOLD fMRI获得)定义了与已知或假想的功能连接电路惊人地收敛的统计图谱。我们已经开发出方法，将这种功能连接的方法系统地应用于两个与药物成瘾有关的大脑区域，健康志愿者的前扣带回皮质(ACC)和基底节(BG)。功能连通性统计图在不同个体和不同时间都是稳定的，并已被证明在描述其他精神病理条件下神经元功能障碍的新部位是有用的。我们建议将这种方法应用于30名可卡因依赖者，他们将与我们已经在相同的3.0特斯拉西门子Allegra上扫描的非依赖健康比较的匹配子集进行比较。我们假设可卡因依赖者将表现出功能连接降低，特别是腹侧纹状体和吻部(边缘)ACC之间的连接。因此，我们将检查可卡因成瘾者(戒毒2-8周)的ACC和BG的功能连接性，并与已经扫描的健康非依赖者进行比较，后者将在年龄、性别和利手方面匹配。我们假设腹侧纹状体和BA25之间的功能连接强度将与同一回路内的各向异性分数呈正相关。为此，我们建议对可卡因依赖者进行29向扩散张量成像(DTI)扫描。除了测试有关可卡因成瘾对与ACC和BG相关的神经回路FC的假设外，拟议的研究还将确定这两个参数在临床人群中的关联程度，这两个参数被假设为索引一个共同的神经生理学基础。该项目将为未来的研究奠定基础，这些研究将检验连接性降低在预测复发、情绪共病和认知康复方面的临床意义。可卡因依赖仍然是一个严重的公共卫生问题。我们已经开发出通过观察相关大脑活动模式来定义大脑电路的技术，我们相信这些技术也可以与追踪神经元之间白质连接的方法有关。我们建议进行一项为期一年的初步研究，以验证我们的方法在新收集的可卡因依赖成年人样本中的有效性，并与已经从健康对照对象中收集的数据进行比较。该项目将为今后的研究提供基础。

项目成果

L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study.

• DOI: 10.1523/jneurosci.0810-09.2009
• 发表时间: 2009-06-03
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Kelly C;de Zubicaray G;Di Martino A;Copland DA;Reiss PT;Klein DF;Castellanos FX;Milham MP;McMahon K
• 通讯作者: McMahon K