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（由应用程序提供）：抑郁症仍然具有毁灭性，致命性和财务状况。抗抑郁药靶向raph核中的5-羟色胺（5HT）神经元，但是5HT途径的原因和参与抑郁症的病理生理学仍不清楚。有证据表明，raph知识在抑郁症中具有代谢性过高，但自相矛盾的是，5HT代谢产物的水平较低。抗抑郁药改善5-羟色胺功能，但会导致5-羟色胺代谢产物的水平进一步降低。原因尚未完全理解。区域活动可能被视为时间序列，揭示了与区域间交流相关的代谢活动的动态特征。区域活动和信号传导似乎在频谱的多个狭窄范围内波动。每个单元可以一次是几个信号的来源。时间序列数据的光谱分析通过其频率将信号分为组（类似于音调，在音乐中）。为了研究这一点，将一组抗抑郁药治疗的患者（n = 11）进行了两次功能性MRI扫描，相距一周。在每次扫描之前，给予饮食（或假）快速复制5HT的前体，称为急性色氨酸部署（ATD）。在两个测试之间比较了Raphi Bold信号的时间序列特征。光谱功率描述了信号内特定频率的波动强度，随着时间的流逝。随着ATD的速度，Raphi中的快速波动（.25至.12 Hz）变得更加强烈（p = .004）。功能连通性的测量是从raph¿和丘脑前信号的缓慢波动（.03至.06 Hz）之间的相关性。它随着ATD的明显下降。这两个发现将说唱歌手功能障碍的模型融合在一起。 ATD期间低5HT的可用性可能与局部神经元和轴突侧支自身受体受体的5HT抑制活性丧失有关。中间神经元在没有5HT抑制作用的情况下更活跃，在血液氧合水平依赖性（BOLD）信号中似乎被激活。神经元活动还将增加代谢努力，以应对损失的自身受体反馈。这种增加的活性出现在较高的频率下，这将无法改善低频下存在的功能连通性。在没有5HT前体的情况下，低频处的功能连通性降低。需要复制和扩展这些发现。该扩展的目标包括对未处理抑郁症的这些指标的检查，未经治疗的抑郁症的比较以及预处理指标与抗抑郁反应的关联。响应预测的测试可能成为一个远程目标。强奸测试将特别反映可用治疗机制的响应概率。二十名单极抑郁症患者将在治疗前完成两次扫描测试，并在连续治疗12周后进行两次扫描。 ATD和假饮食将以双盲的随机序列给出。这项研究将提高我们对抑郁症Raphi功能障碍动态特征的理解。 公共卫生相关性：将使用大脑成像来测量受抗抑郁药影响的区域的活动波动。当我们降低5-羟色胺的可用性时，一种新的分析方法显示，该地区的快速波动增加，但与其他区域的慢速波动的共享减少。这些方法可能有助于我们了解5-羟色胺对大脑网络功能的贡献。