Neuroscience-based Interventions for Cancer Risk Behavior Change

 描述（由申请人提供）：烟草使用和肥胖占可预防癌症死亡的45%以上。然而，这些癌症风险行为对长期变化具有抵抗力，尽管对风险有广泛的了解。即使有最好的治疗方法，大多数人还是会恢复到以前的吸烟或饮食习惯。虽然行为改变干预措施可以解决这些行为的习惯性，但它们不能解决破坏可持续行为改变的破坏性大脑过程。烟草使用和肥胖与认知障碍和大脑功能改变有关，这可能会干扰目标导向行为的维持。更具体地说，我实验室的工作指出，背外侧前额叶皮层（DLPFC）中与工作记忆相关的激活的改变起着核心作用。DLPFC是大脑认知控制网络的核心，它支持计划，决策和认知（自我）控制。重要的是，我们的试点数据表明，DLPFC功能可以安全地恢复使用一种新的和低成本的神经科学为基础的干预。因此，这项应用的大胆前提是，它可以增强大脑的能力，以克服导致肥胖和吸烟的行为习惯，并最终导致癌症。总体计划：扩展我们的试点工作，拟议的7年研究计划从机制实验证明开始，以验证DLPFC靶向经颅直流脑刺激（tDCS）与认知训练的效果。进展到原理证明阶段，实验将确定补充tDCS的最佳认知训练类型和最佳治疗次数，重点是中间终点（例如，认知功能、风险决策、自我报告的行为）。在研究计划的最后阶段，II期随机对照临床试验将评估优化的基于神经科学的干预措施对寻求戒烟（研究1）和减肥（研究2）治疗的个人的疗效。这些成果是有效的神经科学干预措施，将在III期临床试验中得到验证，并转化为行为癌症预防的实践。资格：作为玛丽W。卡尔金斯精神病学教授和宾夕法尼亚大学艾布拉姆森癌症中心副主任，我有几十年的经验进行创新的行为科学研究，桥梁神经科学，药理学和遗传学领域。自1989年以来，我一直受到NCI的资助，总费用约为6700万美元（包括NCI挑衅性问题奖）。有超过345篇同行评议的出版物，我的谷歌学术H-Index是90。我的服务包括NCI科学顾问委员会、国家人类基因组研究咨询理事会和国家药物滥用研究所咨询理事会的成员。我是尼古丁和烟草研究协会的前任主席，也是美国国家科学院医学研究所的当选成员。

 DESCRIPTION (provided by applicant): Tobacco use and obesity account for over 45% of preventable cancer deaths. Yet, these cancer risk behaviors are resistant to long-term change, despite widespread knowledge of the risks. Even with the best treatments available, most people revert to their former practices of cigarette smoking or eating. While behavior change interventions may address the habitual nature of these behaviors, they do not tackle the disruptive brain processes that undermine sustainable behavior change. Tobacco use and obesity are associated with cognitive impairments and altered brain functions that can interfere with the maintenance of goal-directed behaviors. More specifically, work in my laboratory points to the central role of alterations in working memory-related activation in the dorsolateral prefrontal cortices (DLPFC). DLPFC is at the core of the brain's cognitive control network, which supports planning, decision- making, and cognitive (self) control. Importantly, our pilot data show that DLPFC function can be safely restored using a novel and low-cost neuroscience-based intervention. Thus, the bold premise of this application is that it is possible to enhance th brain's capacity to over-ride behavioral habits that contribute to obesity and cigarette smoking, and ultimately to cancer. Broad Plan: Extending our pilot work, the proposed 7-year research plan begins with a Proof of Mechanism experiment to validate the effects of DLPFC-targeted transcranial direct current brain stimulation (tDCS) with cognitive training. Progressing to the Proof of Principle stage, experiments will identify the optimal type of cognitive training to complement tDCS and the optimal number of treatment sessions, with a focus on intermediate endpoints (e.g., cognitive function, risky decision-making, self-reported behaviors). In the final stage of the research plan, Phase II randomized controlled clinical trials will evaluate the efficacy of the optimized neuroscience-based interventions for individuals seeking treatment for smoking cessation (Study 1) and weight loss (Study 2). The deliverables are efficacious neuroscience-based interventions to be validated in Phase III clinical trials and translated to practice for behavioral cancer prevention. Qualifications: As the Mary W. Calkins Professor of Psychiatry and Deputy Director of the Abramson Cancer Center at UPenn, I have decades of experience conducting innovative behavioral science research that bridges the fields of neuroscience, pharmacology, and genetics. I have been continuously funded by NCI since 1989, with grants totaling ~$67 million in total costs (including an NCI Provocative Question Award). With >345 peer-reviewed publications, my Google Scholar H-INDEX is 90. My service includes membership on the NCI Board of Scientific Advisors, National Human Genome Research Advisory Council, and the National Institutes on Drug Abuse Advisory Council. I am a past President of the Society for Research on Nicotine and Tobacco, and an Elected Member of the Institute of Medicine of the National Academies.