Changes in Addictive Behaviors After Brain Lesions

项目总结/摘要 一种神经结构网络，对药物成瘾的认知和行为过程至关重要，包括 尼古丁包括眶额皮质、前扣带回、岛皮质、杏仁核和纹状体。 然而，还没有研究表明，人类神经网络的不同组成部分的损害如何可能 影响对药物成瘾的维持。根据通过CEBRA授予的R21的任期（切割- 边缘基础研究奖），我们开始解决这个重要的问题，在患者上瘾的香烟 吸烟和中风的患者，包括任何这些领域。研究发现，虽然 腹内侧前额叶皮层（VMPFC）与线索诱导的冲动的显著损害有关， 在实验室中，它们与戒烟的可能性增加无关。事实上， 岛叶皮质与戒烟容易，立即，没有复发， 持久的吸烟欲望尽管是初步的，这些结果表明，虽然VMPFC病变可能会破坏 暗示诱导的冲动，他们不破坏吸烟成瘾。然而，在这方面也发挥关键作用的 冲动，似乎是维持吸烟成瘾和驾驶吸烟行为的最关键因素。结果还 这表明，在心理过程中，可能会导致戒烟困难， smoking.在这些有趣但初步的结果的鼓舞下，我们的主要目标是（1）扩大和 在更大的样本中证实这些发现，使用更精确的解剖分析来表征尺寸， 病灶的位置;（2）检查是否存在戒烟难易程度方面的性别差异 （3）对中风患者进行前瞻性研究，并监测他们的吸烟情况 在病变发生后的几年内，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。具体地说， 拟议的研究提出的一种治疗方法是直接调节 - 是的项目叙述 大脑深处一个被称为“吸烟区”的李子大小的区域与吸烟成瘾密切相关， 对这个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 尼古丁成瘾的治疗选择，但如果得到证实，这些结果可能会为治疗提供线索，以帮助 吸烟者戒烟，或在使用现有疗法的同时监测吸烟者的进展。

Project Summary/ Abstract 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. Project Narrative 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.