Chemotherapy effect on brain structure, neurophysiology and psychomotor behavior

化疗对大脑结构、神经生理学和精神运动行为的影响

• 批准号: 8322288
• 负责人: GUANG H YUE
• 金额: $ 16.64万
• 依托单位: KESSLER FOUNDATION, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322288
• 关键词: Adjuvant Chemotherapy; Adverse effects; Affect; Aftercare; Animals; Anisotropy; Behavior; Brain; Brain imaging; Brain region; Cancer Patient; Cancer Survivor; Cognitive; Communication; Corpus Callosum; Corticospinal Tracts; Coupling; Cross-Sectional Studies; Data; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Electroencephalography; Female; Fiber; Fingers; Gender; Goals; Human; Imaging Techniques; Impaired cognition; Impairment; Link; Longitudinal Studies; Magnetic Resonance; Measures; Metric; Motor; Nerve Fibers; Nervous system structure; Neuraxis; Outcome Measure; Participant; Patient Self-Report; Patients; Performance; Peripheral Nervous System; Pharmaceutical Preparations; Pharmacologic Substance; Physiological; Postoperative Period; Psychomotor Performance; Quality of life; Reaction Time; Relapse; Reporting; Research; Risk; Signal Transduction; Spinal Cord; Structure; Symptoms; System; Toxic effect; Transcranial magnetic stimulation; Variant; Water; Woman; behavior change; cancer therapy; cancer type; chemotherapy; cognitive function; design; experience; functional disability; imaging modality; malignant breast neoplasm; neurophysiology; neurotoxic; relating to nervous system; research study; white matter; white matter damage

DESCRIPTION (provided by applicant): Adjuvant chemotherapy (CTh) is an established postoperative treatment often prescribed to cancer patients to reduce risk of relapse. However, a great proportion of patients report experiencing cognitive, psychomotor, and other functional impairments associated with CTh. Some symptoms may persist for years after treatment and can have dramatic consequences on cancer survivors' quality of life. Despite numerous studies reporting various symptoms during/after CTh treatment, mechanisms underlying these symptoms are not well understood. Recent animal and human brain imaging studies suggest that CTh may have direct neurotoxic effects on the brain, in particular on brain white matter (WM). However, to date, no longitudinal studies have been done to examine the effects of CTh on cortical/subcortical WM integrity in human patients. Furthermore, no effort has yet been made to correlate a given WM structure with its corresponding neurophysiological function (NPF) and behavior. This study proposes longitudinal experiments in women diagnosed with breast cancer to examine the effects of CTh on the corpus callosum (CC) and corticospinal tract (CST) (Aim 1), on NPF that directly depends on the quality of CC/CST structure, and on psychomotor behavior critically relying on CC/CST function (conductivity) (Aim 2). The relationship between CC/CST structural integrity and their corresponding NPF and psychomotor behavior will also be examined (Aim 3). The general underlying hypotheses of the study are that (1) CTh has a direct neurotoxic effect on the CC and CST, resulting in microstructural degeneration and (2) structural damage to the CC and CST impairs relevant neurophysiological function and behavior. This research is expected to yield significant information regarding neural structural and physiological causes of CTh-related side effects; known this information would help more effectively manage the symptoms. By demonstrating direct evidence of detrimental consequences of CTh on the central nervous system, it is hoped that the evidence would encourage pharmaceutical companies to develop safer cancer treatment drugs. PUBLIC HEALTH RELEVANCE: A majority of cancer survivors suffer chemotherapy side effects, including cognitive and psychomotor function impairment that diminishes their quality of life. The goal of this research is to investigate how currently widely used chemotherapy drugs affect structure and function of brain nerve fibers and relevant psychomotor behavior. The findings are expected to help uncover the cause of cancer treatment side effects and better manage them and facilitate development of safer cancer treatment drugs by showing harmful effects of chemotherapy on the nervous system.

描述(由申请人提供)：辅助化疗(CTH)是一种公认的术后治疗方法，通常用于癌症患者，以降低复发风险。然而，很大比例的患者报告经历了认知、精神运动和其他与CTH相关的功能障碍。一些症状可能会在治疗后持续数年，并可能对癌症幸存者的生活质量产生戏剧性的后果。尽管许多研究报告了在CTH治疗期间/之后的各种症状，但这些症状背后的机制尚不清楚。最近的动物和人脑成像研究表明，CTH可能对大脑有直接的神经毒性作用，特别是对脑白质(WM)。然而，到目前为止，还没有进行纵向研究来检验CTH对人类患者皮质/皮质下WM完整性的影响。此外，还没有人试图将特定的WM结构与其相应的神经生理功能(NPF)和行为联系起来。这项研究建议在被诊断为乳腺癌的妇女中进行纵向实验，以考察CTH对穹隆(CC)和皮质脊髓束(CST)的影响(目标1)，对直接取决于CC/CST结构质量的NPF的影响，以及对严重依赖CC/CST功能的精神运动行为的影响(目标2)。还将审查CC/CST结构完整性及其相应的NPF和精神运动行为之间的关系(目标3)。本研究的基本假设是：(1)CTH对CC和CST有直接的神经毒性作用，导致微结构变性；(2)CC和CST的结构损伤损害了相关的神经生理功能和行为。这项研究有望获得有关CTH相关副作用的神经结构和生理原因的重要信息；已知这些信息将有助于更有效地管理症状。通过展示Cth对中枢神经系统有害影响的直接证据，人们希望这些证据将鼓励制药公司开发更安全的癌症治疗药物。 公共卫生相关性：大多数癌症幸存者遭受化疗副作用，包括认知和精神运动功能障碍，降低他们的生活质量。本研究的目的是研究目前广泛使用的化疗药物如何影响脑神经纤维的结构和功能以及相关的精神运动行为。这些发现有望通过显示化疗对神经系统的有害影响，帮助揭示癌症治疗副作用的原因，更好地管理它们，并促进更安全的癌症治疗药物的开发。