Multivariate Machine Learning to Characterize Opioid-induced Alterations in the Brain in Chronic Pain

多变量机器学习表征阿片类药物引起的慢性疼痛大脑变化

• 批准号: 10203904
• 负责人: Behnaz Jarrahi
• 金额: $ 17.59万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203904
• 关键词: Address; Affect; American; Amygdaloid structure; Anterior; Award; Behavior; Behavioral; Brain; Caring; Chronic; Chronic low back pain; Clinical; Clinical Trials; Cognitive; Consult; Corpus striatum structure; Data; Data Analyses; Decision Making; Development; Diagnostic; Dopamine; Dopamine D1 Receptor; Dopamine D2 Receptor; Drug usage; Epidemic; Epidemiologist; Epidemiology; Executive Dysfunction; Faculty; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Health; Hyperalgesia; Iatrogenesis; Imaging Techniques; Infrastructure; Insula of Reil; Intercept; Investigation; Link; Long-Term Effects; MRI Scans; Machine Learning; Magnetic Resonance Imaging; Measures; Mediating; Medical; Mentors; Molecular; Morphology; Multimodal Imaging; National Institute of Drug Abuse; Neuropsychological Tests; Neuropsychology; Nucleus Accumbens; Opiate Addiction; Opioid; Opioid Analgesics; Pain; Pain Research; Pain management; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Play; Positron-Emission Tomography; Prefrontal Cortex; Prevalence; Principal Investigator; Psyche structure; Psychophysics; Questionnaires; Raclopride; Recovery; Research; Research Personnel; Research Project Grants; Research Training; Resolution; Rest; Rewards; Role; Sensory; Short-Term Memory; Societies; Specialist; Strategic Planning; Structure; Substance Use Disorder; Substance abuse problem; Symptoms; System; Techniques; Testing; Thick; Time; Training; addiction; base; brain circuitry; brain morphology; chronic pain; chronic pain patient; chronic painful condition; classification algorithm; clinical application; cognitive control; cognitive function; cognitive performance; cognitive process; cohort; data modeling; dopamine system; executive function; experience; flexibility; gray matter; imaging scientist; innovation; learning classifier; multimodality; neuroimaging; neurotransmission; opioid tapering; opioid therapy; opioid use; pain behavior; pain patient; pain processing; patient oriented; prescription opioid; receptor binding; recruit; relating to nervous system; response; responsible research conduct; risk mitigation; skills; substance use; tool

PROJECT SUMMARY/ABSTRACT Prescription opioids are a potent class of drugs for treating pain. However, growing body of research has described iatrogenic consequences of long-term (> 90 days) opioid use in patients with chronic pain including hyperalgesia and impaired executive function. Dopamine is a critical modulator of executive function. While changes in pain and behavior have been noted, little is known about the brain’s morphology, neural and dopaminergic activity that change over time with long-term prescription opioid use. Consistent with the NIDA Strategic Plan objective 1.3, this K25 proposal seeks to “establish the effects of drug use, addiction, and recovery on brain circuits, behavior, and health” using neuroimaging-informed tools. Specifically, the present study combines multiple levels of investigation, including structural and functional Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Quantitative Sensory Testing (QST) and neuropsychological assessments of executive function, and employ machine learning techniques for analysis to identify the effects of long-term prescription opioid use on the brain in chronic pain patients. The applicant will use her advanced quantitative skills in neuroimaging data analysis and modeling to training in QST, and experience in cognitive neuropsychology, epidemiology of chronic pain and addiction to develop an independent research plan in translational pain and successfully compete for future R01 funding. To achieve the training needed to facilitate this investigation, the applicant has consulted with an expert in chronic pain research and opioid therapy, a substance abuse specialist, a neuropsychologist, an epidemiologist, an imaging scientist, and a machine learning leader in neuroimaging field to develop an innovative study and training plan. 40 patients with a diagnostically homogeneous chronic pain condition (i.e., chronic low back pain; CLBP) on long-term opioid therapy, as compared to 40 opioid-naïve CLBP patients, will be studied to achieve the following Aims: 1) Measure pain, cognitive performance, neural and dopaminergic activity during concurrent pain and executive function task fMRI-PET to characterize the effects of opioids on pain processing and executive function in CLBP; 2) measure intrinsic brain activity during resting state fMRI-PET to identify intrinsic brain alterations associated with long-term opioid use in CLBP; and 3) apply high-resolution structural MRI to measure opioid-induced morphological changes in CLBP. This research is innovative in its use of combined QST and neuro- psychological measures with multimodal imaging and sophisticated statistical approaches. It is significant because of its comprehensive approach towards addressing the NIDA Strategic Plan objective. Findings stand to inform medical decision-making regarding pain care and opioid prescription, as well as risk mitigation strategies. The research, training and results obtained will provide a platform for applicant’s long-term scientific research goal of becoming an independent R01-funded, faculty-level principal investigator performing translational pain research aimed at developing neuroimaging tools to have clinical application.

项目摘要/摘要 处方阿片类药物是治疗疼痛的潜在药物。但是，越来越多的研究已经 描述了长期（> 90天）阿片类药物在慢性疼痛患者中的长期（> 90天）使用的医源性后果 Hypergesia和执行功能受损。多巴胺是执行功能的关键调节剂。尽管 已经注意到疼痛和行为的变化，对大脑的形态，神经和 多巴胺能活性随着时间的流逝而随着长期处方使用而改变。与NIDA一致 战略计划目标1.3，该K25提案旨在“建立吸毒，成瘾和恢复的影响 使用神经影像学的工具上的脑电路，行为和健康”。具体而言，本研究 结合了多个级别的投资，包括结构和功能磁共振成像（MRI）， 正电子发射断层扫描（PET），定量感觉测试（QST）和神经心理学 评估执行功能和员工机器学习技术以识别效果 慢性疼痛患者大脑上长期处方的使用。申请人将使用她的高级 神经成像数据分析和QST培训的建模方面的定量技能，并经验 认知神经心理学，慢性疼痛的流行病学以及制定独立研究计划的补充 在翻译疼痛中并成功竞争未来的R01资金。实现促进所需的培训 这项投资是适用的，已咨询了慢性疼痛研究和阿片类药物疗法专家 药物滥用专家，神经心理学家，流行病学家，成像科学家和机器 神经影像领域的学习领导者制定创新的研究和培训计划。 40例患者 长期阿片类药物的诊断性均质慢性疼痛状况（即慢性下背部疼痛； CLBP） 与40名未经阿片类药物的CLBP患者相比，治疗将是实现以下目的的研究：1） 在并发疼痛和执行期间测量疼痛，认知表现，神经和多巴胺能活性 功能任务fMRI-PET表征阿片类药物对CLBP疼痛处理和执行功能的影响； 2）在静止状态fMRI-PET期间测量内在的大脑活动，以鉴定与固有的大脑改变相关 在CLBP中使用长期阿片类药物； 3）应用高分辨率结构MRI测量阿片类药物诱导的 CLBP的形态变化。这项研究在使用QST和Neuro-的联合使用方面具有创新性 具有多模式成像和复杂统计方法的心理措施。这很重要 由于其全面解决NIDA战略计划目标的方法。发现立场 告知有关疼痛护理和阿片类药物处方的医疗决策，以及降低风险 策略。所获得的研究，培训和结果将为申请人的长期科学提供平台 成为独立的R01资助的教师级首席研究员的研究目标 翻译疼痛研究旨在开发神经影像学工具以进行临床应用。