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、前扣带回、岛叶皮质、杏仁核和纹状体。然而，还没有研究表明，对人类神经网络不同组成部分的损害可能会影响对药物成瘾的维持。在CEBRA（尖端基础研究奖）授予的R21的任期内，我们开始解决吸烟成瘾患者和中风患者的这一重要问题，包括任何这些领域。研究发现，虽然腹内侧前额叶皮层（VMPFC）的病变与实验室中线索诱导冲动的明显受损有关，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的能力有关，戒烟容易，立即，没有复发，没有持久的吸烟冲动。虽然是初步的，但这些结果表明，虽然VMPFC病变可能会破坏线索诱导的冲动，但它们不会破坏吸烟成瘾。然而，在冲动中起关键作用的大脑皮层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，吸烟者的心理过程可能会导致戒烟的困难。受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）检查是否存在性别差异，在病变后戒烟的容易程度;（3）对中风患者进行前瞻性研究，并在病变发生后数年内监测他们的吸烟行为。这项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。具体来说，拟议的研究提出的一种治疗方法是直接调节大脑皮层的功能。公共卫生相关性：大脑深处有一个被称为“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的吸烟冲动。显然，脑损伤不是尼古丁成瘾的治疗选择，但如果得到证实，这些结果可能会为帮助吸烟者戒烟的治疗提供线索，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.