Functional and Structural Connectivity in Cocaine Addiction

描述（由申请人提供）：可卡因依赖涉及服务于动机、联想学习、记忆和认知控制的功能网络的深刻改变。神经影像学模式提高了我们对慢性可卡因使用相关神经病理学的理解。自发血流动力学脑活动的空间相关性（通过依赖于血氧水平的功能性磁共振成像（BOLD fMRI）获得）定义的统计图与已知或假设的功能连接回路惊人地趋同。我们开发了一种方法，系统地应用这种方法在健康志愿者的两个与药物成瘾有关的大脑区域，前扣带皮层（ACC）和基底神经节（BG）中进行功能连接。功能连接统计图在个体和时间上都是稳定的，并且在描述其他精神病理条件下神经元功能障碍的新位点方面被证明是有用的。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对照者的匹配子集进行比较。我们假设可卡因依赖的个体会表现出功能连通性下降，特别是在腹侧纹状体和吻侧（边缘）ACC之间。因此，我们将检查可卡因成瘾个体（戒断2-8周）ACC和BG的功能连通性，并与已经扫描的年龄、性别和利手性相匹配的健康非依赖性受试者进行比较。我们假设腹侧纹状体和BA25之间的功能连接强度与同一回路内的分数各向异性呈正相关。为此，我们建议在可卡因依赖受试者中获得29向扩散张量成像（DTI）扫描。除了测试关于可卡因成瘾对与ACC和BG相关的神经回路FC的影响的假设外，拟议的研究将确定这两个参数在该临床人群中的关联程度，这两个参数被假设为一种共同的神经生理基础。该项目将为未来的研究奠定基础，这些研究将检查连接减少在预测复发、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。我们已经开发了通过观察相关大脑活动模式来定义大脑回路的技术，我们相信这些技术也与追踪神经元之间白质连接的有用方法有关。我们建议进行为期一年的初步研究，在新收集的可卡因依赖成人样本中验证我们的方法，并与健康对照受试者已经收集的数据进行比较。本课题将为今后的研究奠定基础。

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.