Functional Spectroscopy with Real-Time Feedback for Altering Preferences in Addic

描述（由申请人提供）：该项目将开发一种实时神经成像和行为方法，通过该方法，成瘾者可以使用基于大脑和按键的反馈来调节他们对药物线索的反应，并改变成瘾的大脑和行为特征。吸毒成瘾的特点是奖励系统重组为短期快速奖励、减少对长期后果的评估、冲动和行为范围的缩小（即限制一个人表现出偏好的一组事物）。为了应对这些成瘾症状，一种治疗方法是通过行为疗法的调整来开发冲动最小化技术。这些治疗技术传统上侧重于成瘾的心理社会测量，而这些测量很难客观地量化或改变。成瘾神经科学的最新进展揭示了奖赏/厌恶回路的强烈改变以及成瘾中的实验心理学变量，这些变量可能适合与行为技术一起使用。具体来说，前额皮质的结构和功能 MRI 测量表明，成瘾者的局部差异可能与基于按键的相对偏好表型有关，该表型量化了他们受限的行为库。技术和计算的进步表明这些神经科学措施可以用于行为治疗。为此，该项目制定了一系列里程碑作为 R21 提案，以开发 (a) 基于单体素和双体素光谱的高 SNR、定量 BOLD 激活测量的技术工作流程； (b) 实时信号分析和显示软件，用于根据行为和 BOLD 信号向个人反馈； (c) 将成像、实验心理学和反馈平台与扫描仪中的受试者集成。在成功实现这些里程碑之后，进一步的一系列里程碑被组织为 R33 提案，以证明：（d）这些技术可用于监测受试者的大脑信号调制和相对偏好表型，（e）在实际测试条件下整合大脑信号调制和按键反应，以及（f）将这些技术应用于可卡因依赖受试者。我们预计这些概念验证里程碑将成为未来在治疗试验中使用这种方法的先决条件。 公共卫生相关性：该项目将为成瘾者开发一种方法，以自我调节其大脑反应和药物偏好的行为表型。具体来说，来自涉及药物使用改变判断和决策的大脑区域的实时反馈将与偏好行为中类似规律模式的定量测量相结合，因此个人可以客观地应用行为治疗技术来改变成瘾的神经特征。

DESCRIPTION (provided by applicant): This project will develop a real-time neuroimaging and behavioral method by which individuals with addiction may use brain- and key press-based feedback to modulate their responses to drug cues, and alter brain and behavior signatures of addiction. Drug addiction can be characterized by a restructuring of the reward system to short-term rapid rewards, decreased assessment of long-term consequences, impulsivity, and a narrowing of the behavioral repertoire (i.e., restriction in the set of things toward which one shows preference). To deal with these symptoms of addiction, one therapeutic approach has been to develop urge minimization techniques through adaptations of behavioral therapy. These therapy techniques have traditionally focused on psychosocial measures of addiction that can be difficult to quantify or alter objectively. Recent advances in addiction neuroscience have revealed robust alterations of reward/aversion circuitry along with experimental psychology variables in addiction that may be amenable to use with behavioral techniques. Specifically, structural and functional MRI measures of prefrontal cortex, point to localized differences in addicts that can be connected with a key press-based phenotype of relative preference that quantifies their restricted behavioral repertoire. Technical and computational advances suggest that these neuroscience measures might be harnessed for behavioral therapy. Toward this end, this project lays out a set of milestones as an R21 proposal to develop (a) a technical work-flow for high SNR, quantitative BOLD activation measurement based on single and double voxel spectroscopy; (b) real-time signal analysis and display software for feedback to individuals based on behavior and BOLD signal; (c) integration of platforms for imaging, experimental psychology, and feedback with subjects in the scanner. Following successful attainment of these milestones, a further set of milestones are organized as an R33 proposal to demonstrate: (d) that these technologies can be applied to monitor modulation of brain signal and relative preference phenotype by subjects, (e) integration of modulation of brain signal and key press responses during realistic testing conditions, and (f) the application of these techniques to cocaine dependent subjects. We foresee these proof-of-concept milestones to be prerequisites for the future use of such a method in therapeutic trials. PUBLIC HEALTH RELEVANCE: This project will develop a method for individuals with addiction to self-modulate their brain responses and behavioral phenotype of drug preference. Specifically, real-time feedback from brain regions involved with altered judgment and decision-making around drug use, will be merged with quantitative measures of law-like patterns in preference behavior, so individuals can objectively apply behavioral therapy techniques to alter neural signatures of addiction.