Spectral Features of Raphe fMRI Time Series Data in Depression

抑郁症 Raphe fMRI 时间序列数据的频谱特征

• 批准号: 8105307
• 负责人: RONALD MURRAY SALOMON
• 金额: $ 22.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-05 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8105307
• 关键词: Acute; Affect; Aftercare; Anterior; Antidepressive Agents; Autoreceptors; Brain; Brain Stem; Brain imaging; Brain region; Cell Nucleus; Cerebrospinal Fluid; Characteristics; Communication; Data; Depressed mood; Diagnosis; Diet; Double-Blind Method; Drops; Etiology; Exclusion; Feedback; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; High Frequency Oscillation; Image; Informal Social Control; Interneurons; Measurable; Measures; Mental Depression; Metabolic; Methods; Metric; Modeling; Moods; Music; Neurons; Pathway interactions; Patients; Plasma; Pontine structure; Probability; Proxy; Publishing; Regulation; Relapse; Reporting; Resistance; Scanning; Screening procedure; Selective Serotonin Reuptake Inhibitor; Series; Serotonin; Sertraline; Signal Transduction; Source; Testing; Thalamic structure; Therapeutic Effect; Time; Time Series Analysis; Tryptophan; base; blood oxygen level dependent; experience; improved; inhibitor/antagonist; public health relevance; response; suicidal risk; uptake

DESCRIPTION (provided by applicant): Depression remains devastating, lethal, and financially burdensome. Antidepressants target serotonin (5HT) neurons in raph¿ nuclei, but 5HT pathway causation and involvment in the pathophysiology of depression remains unclear. Evidence suggests that the raph¿ is metabolically hyper-active in depression, but, paradoxically, levels of the 5HT metabolite are low in spinal fluid. Antidepressants improve serotonin function, but cause further decrease levels of the serotonin metabolite. Reasons for this are not fully understood. Regional activity may be viewed as a time series, revealing dynamic features of metabolic activity relevant to inter-regional communication. Regional activities and signaling appear to fluctuate within multiple narrow ranges of the frequency spectrum. Each unit may be a source of several signals at once. Spectral analysis of time series data separates signals into groups by their frequencies (similar to pitch, in music). To study this, a pilot group of antidepressant-treated patients (n=11) was scanned with functional MRI twice, one week apart. Prior to each scan, a diet (or sham) was given to rapidly deplete the precursor of 5HT, called acute tryptophan depletion (ATD). Time series features of raphi BOLD signals were compared between the two tests. Spectral power describes the intensity of fluctuations at specific frequencies within a signal over time. Rapid fluctuations (.25 to .12 Hz) in the raphi became more intense with ATD (p=.004). Functional connectivity was measured as the correlation between slow fluctuations (.03 to .06 Hz) from raph¿ and anterior thalamus signals. It declined markedly with ATD. These two findings fit together in a model of raph¿ dysfunction. Low 5HT availability during ATD may be associated with a loss of 5HT inhibitory activity at local interneurons and axonal collateral autoreceptors. Interneurons, more active without 5HT inhibitory effects, would appear activated in blood oxygenation level dependent (BOLD) signals. Neuronal activity would also increase in metabolic efforts to respond to lost autoreceptor feedback. This increased activity appeared at the higher frequencies, which would not improve the functional connectivity that was present at low frequencies. Functional connectivity at low frequencies was diminished in the absence of the 5HT precursor. Replication and extension of these findings is needed. Goals for this extension include examinations of these metrics in untreated depression, comparisons of untreated with remitted depression, and associations of pretreatment metrics with antidepressant response. A response-predictive test may become a long-range goal. raph¿ testing would specifically reflect response probability for available treatment mechanisms. Twenty unipolar depressed patients will complete two scan tests before treatment and two scans after 12 weeks of sertraline treatment. ATD and sham diets will be given in a double-blind, random sequence. The study will improve our understanding of dynamical features of raphi dysfunction in depression. PUBLIC HEALTH RELEVANCE: Brain imaging will be used to measure fluctuations in activity in a region affected by antidepressants. When we decreased serotonin availability, a new analysis method showed increased rapid fluctuations in the region but decreased sharing of slow fluctuations with other regions. These methods may help us understand serotonin contributions to brain network function.

描述（由申请人提供）：抑郁症仍然具有破坏性、致命性和经济负担，抗抑郁药针对的是 raph 中的血清素 (5HT) 神经元。核，但 5HT 通路在抑郁症病理生理学中的因果关系和参与仍不清楚。抑郁症患者代谢过度活跃，但矛盾的是，抗抑郁药改善血清素功能，但导致血清素代谢物水平进一步降低。其原因尚不完全清楚。被视为一个时间序列，揭示了与区域间通信相关的代谢活动的动态特征。区域活动和信号传导似乎在多个狭窄的频谱范围内波动。时间序列数据的频谱分析按频率将信号分为几组（类似于音乐中的音高），为了研究这一点，使用功能性 MRI 扫描了一组接受抗抑郁药治疗的患者（n = 11）。 ，在每次扫描之前，进行饮食（或假手术）以快速消耗 5HT 前体，称为急性色氨酸消耗（ATD），比较 raphi BOLD 信号的时间序列特征。频谱功率描述了信号内特定频率的波动强度（0.25 至 0.12 Hz）随着 ATD 的测量而变得更加强烈（p=0.004）。来自 raph 的缓慢波动（0.03 至 0.06 Hz）之间的相关性和前丘脑信号随着 ATD 显着下降，这两个发现在 raph 模型中吻合。 ATD 期间 5HT 可用性低可能与局部中间神经元和轴突侧支自身受体的 5HT 抑制活性丧失有关，如果没有 5HT 抑制作用，中间神经元会在血氧水平依赖性 (BOLD) 信号中出现激活。响应丢失的自身受体反馈的代谢努力也会增加，这种增加的活动出现在较高频率下，这不会改善低频下存在的功能连接。需要复制和扩展这些发现，包括检查未经治疗的抑郁症的这些指标，比较未经治疗的抑郁症和缓解的抑郁症，以及治疗前指标与抗抑郁反应的关联。预测测试可能成为一个长期目标。测试将具体反映现有治疗机制的反应概率。20 名单相抑郁患者将在治疗前完成两次扫描测试，并在接受舍曲林治疗 12 周后进行两次扫描，并以双盲、随机顺序进行。将提高我们对抑郁症中缝针功能障碍动力学特征的理解。 公共健康相关性：大脑成像将用于测量受抗抑郁药影响的区域的活动波动，当我们降低血清素的可用性时，一种新的分析方法显示该区域的快速波动增加，但与其他区域的缓慢波动共享减少。可能有助于我们了解血清素对大脑网络功能的贡献。