Changes in Addictive Behaviors after Brain Lesions

描述（由申请人提供）：CEBRA的R21：功能性神经影像学研究的蓬勃发展表明，神经结构网络支持药物成瘾的认知和行为过程，包括尼古丁。该神经网络包括眶额皮质、前扣带皮层、岛状皮质、杏仁核和纹状体（背侧和腹侧（伏隔核）纹状体）。然而，到目前为止，还没有研究表明这种神经网络的不同组成部分的损伤是如何影响人类对药物的渴望、主观感觉和主动寻找药物的。也没有任何研究问过，如果有的话，这些成分中哪一个对维持药物成瘾是至关重要的。该提案将利用我们独特的爱荷华大学神经病学患者登记处的优势，开始解决吸烟成瘾患者的一些重要问题。我们的目标是了解被假设为成瘾关键神经基质的大脑区域的局灶性病变如何影响吸烟行为、线索诱导的渴望和吸烟冲动，以及吸烟的急性主观效应。我们在此提出的研究旨在解决三个具体目标：(1)确定脑损伤发生后吸烟行为、吸烟渴望和吸烟满意度的现实变化；(2)在实验室实验中确定局灶性脑损伤对(a)对吸烟线索的情绪反应，(b)对吸烟的渴望和冲动的主观感觉，以及(c)吸烟的主观感觉的影响；(3)建立发病前已知滥用其他物质（包括酒精、兴奋剂和阿片类药物）的神经系统患者登记册，以便他们参与未来对药物成瘾的研究。这一建议是有希望的，因为(1)它为观察成瘾的神经生物学基础提供了一个新的视角，这是对功能性神经成像技术正在进行的工作的补充和验证；(2)它可以帮助我们识别特定的大脑区域，哪些受损（或功能障碍）可以有效地打破成瘾的循环。拟议的研究是可行的，因为(1)我们获得了进行这类研究所需的患者群体和资源；2)通过已建立的理论框架，体细胞标记假说和来自功能神经影像学研究的丰富背景证据来指导我们的研究。因此，拟议的研究是一种新方法的开始，有可能开发出更有效的治疗方法来打破成瘾的恶性循环。

DESCRIPTION (provided by applicant): An R21 for CEBRA: The blossoming field of functional neuroimaging studies has pointed to a network of neural structures that subserve the cognitive and behavioral processes of drug addiction, including nicotine. This neural network includes the orbitofrontal cortex, anterior cingulate, insular cortices, the amygdala, and the striatum (dorsal and ventral (nucleus accumbens) striatum). However, no work to date has addressed how damage to different components of this neural network in humans may impact the craving, subjective feeling of drug administration, and active seeking of drugs. Nor any study has asked which, if any, of these components is critically necessary for maintaining the addiction to drugs. This proposal will take advantage of our unique University of Iowa Department of Neurology Patient Registry to begin addressing some of these important issues in patients addicted to cigarette smoking. Our goal is to understand how focal lesions in brain areas hypothesized to be critical neural substrates for addiction affect cigarette smoking behavior, cue-induced craving and smoking urge, as well as the acute subjective effects of smoking. The studies we propose here seek to address 3 specific aims: (1) determining the real-life changes in smoking behavior, cigarette craving, and smoking satisfaction after the onset of brain damage; (2) determining in laboratory experiments the effects of focal brain lesions on (a) the emotional reactivity to smoking cues, (b) the subjective feeling of craving and urge to smoke, and (c) the subjective feeling of smoking a cigarette; and (3) establishing a Registry of neurological patients pre-morbidly known to abuse other substances, including alcohol, stimulants, and opiates, so that they will participate in future research on addiction to drugs. The proposal is promising because (1) it provides a novel perspective for looking at the neurobiological basis of addiction, which compliments and validates the ongoing work with functional neuroimaging techniques; (2) it may help us identify specific brain regions, which damage (or dysfunction) can effectively break the cycle of addiction. The proposed studies are feasible because of (1) our access to the patient population and resources necessary for the conduction of this type research; 2) the guidance of our investigations by an established theoretical framework, the somatic marker hypothesis, and by abundance of background evidence from functional neuroimaging studies. Thus, the proposed research is a beginning of a novel approach with potential for developing more effective therapies for breaking the vicious cycle of addiction.