Changes in Addictive Behaviors After Brain Lesions

描述（由申请人提供）：对药物成瘾（包括尼古丁）的认知和行为过程至关重要的神经结构网络，包括眶额皮质、前扣带、岛状皮质、杏仁核和纹状体。然而，目前还没有研究表明，对人类神经网络的不同组成部分的损害可能会影响药物成瘾的维持。在通过CEBRA（尖端基础研究奖）授予的R21任期内，我们开始在吸烟成瘾和中风患者中解决这一重要问题，包括这些领域中的任何一个。研究发现，虽然在实验室中，腹内侧前额叶皮层（VMPFC）的损伤与提示诱导的冲动的显著损伤有关，但它们与戒烟可能性的增加无关。事实上，岛叶皮层的损伤与戒烟容易、迅速、不复发、不持久的欲望有关。虽然是初步的，但这些结果表明，虽然VMPFC损伤可能会破坏提示引起的冲动，但它们不会破坏吸烟成瘾。然而，在冲动中也起关键作用的脑岛，似乎对维持吸烟成瘾和驱动吸烟行为最为关键。研究结果还表明，脑岛在心理过程中的功能可能会导致戒烟困难。受到这些有趣但初步的结果的鼓舞，我们的主要目标是：(1)在更大的样本中扩展和证实这些发现，使用更精确的解剖分析来表征病变的大小和位置；(2)检查病变后戒烟难易程度是否存在性别差异；(3)对中风吸烟者进行前瞻性研究，监测其发病后数年的吸烟行为。这项提议的研究是一种新方法的开始，有可能开发出更有效的疗法来打破成瘾的恶性循环。具体来说，这项研究提出的一种治疗方法是直接调节脑岛的功能。公共健康相关性：大脑深处一个被称为脑岛的小李子大小的区域与吸烟成瘾密切相关，对该结构的破坏可以完全消除身体吸烟的冲动。显然，脑损伤不是治疗尼古丁成瘾的一种选择，但如果得到证实，这些结果可能会为帮助吸烟者戒烟的疗法提供线索，或者在使用现有疗法的同时监测吸烟者的进展。

DESCRIPTION (provided by applicant): A network of neural structures crucial for the cognitive and behavioral processes of drug addiction, including nicotine, includes the orbitofrontal cortex, anterior cingulate, insular cortices, the amygdala, and the striatum. However, no work has addressed how damage to different components of this neural network in humans may impact the maintenance of addiction to drugs. Under the tenure of an R21 awarded through CEBRA (Cutting- Edge Basic Research Awards), we began addressing this important issue in patients addicted to cigarette smoking and who had suffered a stroke that included any of these areas. It was found that although lesions of the ventromedial prefrontal cortex (VMPFC) were associated with a marked impairment of cue-induced urge in the laboratory, they were not associated with an increased likelihood of quitting smoking. In fact, lesions of the insular cortex were associated with an ability to quit smoking easily, immediately, without relapses and without a lasting urge to smoke. Although preliminary, these results suggest that, while VMPFC lesions may disrupt cue-induced urges, they do not disrupt smoking addiction. However, the insula, which also plays a key role in urges, seems most critical for maintaining smoking addiction and driving smoking behavior. The results also suggest that the insula functions in psychological processes that may contribute to the difficulty of quitting smoking. Encouraged by these intriguing, but preliminary, results, our primary aims are to (1) expand and confirm these findings in a larger sample, using more precise anatomical analyses to characterize the size and placement of lesions; (2) examine whether there are gender differences in terms of the ease to quit smoking after a lesion; and (3) conduct prospective studies on smokers who suffer strokes and monitor their smoking behavior for several years after the lesion onset. The proposed research is a beginning of a novel approach with potential for developing more effective therapies for breaking the vicious cycle of addiction. Specifically, one therapeutic approach called up by the proposed research would be to directly modulate the function of the insula. PUBLIC HEALTH RELEVANCE: A prune-sized region deep in the brain called the insula is intimately involved in smoking addiction, and damage to this structure can completely erase the body's urge to smoke. Obviously brain damage is not a treatment option for nicotine addiction, but if confirmed, these results may offer leads for therapies to help smokers kick the habit, or for monitoring smokers' progress while using existing therapies.