Identification of distributed neural sources of the auditory steady-state response in psychosis Biotypes

精神病生物型中听觉稳态反应的分布式神经源的识别

• 批准号: 10373165
• 负责人: BRETT A CLEMENTZ
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373165
• 关键词: Acoustic Stimulation; Affect; Anatomy; Architecture; Attenuated; Auditory; Auditory area; Biological Markers; Bipolar Disorder; Clinical; Clinical Pharmacology; Clozapine; Cognition; Cognitive deficits; Communication; Control Groups; Diagnosis; Electroencephalography; Equilibrium; Etiology; Event; First Degree Relative; Frequencies; Future; Health; Impairment; Individual; Intervention; Investigation; Knowledge; Link; Literature; Magnetic Resonance Imaging; Magnetoencephalography; Measures; Neurobiology; Neurons; Outcome; Paper; Patients; Pattern; Persons; Pharmaceutical Preparations; Plant Roots; Psychoses; Pyramidal Cells; Radial; Reporting; Sampling; Schizoaffective Disorders; Schizophrenia; Sensory; Signal Transduction; Source; Stimulus; Subgroup; Symptoms; Syndrome; Treatment Efficacy; auditory stimulus; cognitive control; high risk; indexing; multimodal neuroimaging; neural circuit; neuronal circuitry; neurophysiology; neurotransmission; proband; relating to nervous system; response; sensory system; source localization; temporal measurement; treatment trial

The auditory steady-state response (aSSR) is a promising translational biomarker for psychosis. Entrainment to different frequencies of stimulation engage unique neural generators and cortical circuitry. Auditory 40-Hz gamma responses have been preferentially proposed as a schizophrenia biomarker. In a sample of over 500 total observations, with subjects across the psychosis spectrum (schizophrenia, schizoaffective disorder, bipolar disorder with psychosis) we did not find any aSSR measure that was unique to any DSM psychosis syndrome. Alternatively, neurobiologically defined psychosis subgroups (psychosis Biotypes) have unique and differentiating aSSR features. The type and extent of these differences were associated with level of cognition, independent of psychosis. In this proposal, we will use multimodal neuroimaging with electroencephalography (EEG), magnetoencephalography (MEG), and structural magnetic resonance imaging (sMRI) to investigate neural source distribution of the aSSR at multiple frequencies (20-, 40-, and 80-Hz) in psychosis cases with either deficient (psychosis Biotype-1; n=35) or exuberant (psychosis Biotype-2; n=35) neural responses to the aSSR. Both of these subgroups have poor cognition. Rather than comparing them to a mixed health group, healthy individuals will be subdivided by cognitive control (high or low, n=35 of each subgroup). The low cognitive control group will be similar to the psychosis cases on cognition but without psychosis symptoms. EEG and MEG recordings will be used to detect radial and tangential neural sources of initial auditory registration and the aSSR with high temporal resolution. EEG, with its sensitivity to both radial and tangential neural sources, will provide a link to the majority of the previous literature on this topic, while MEG, with its excellent ability to measure auditory neural signals, will yield complimentary information about the mostly tangential neural sources of the aSSR. These measures will be used to examine the distributed neural activity of the aSSR from beta to high gamma frequencies, and how they differ as a function of psychosis subtype and cognitive control abilities. Hypotheses: (1a) Biotype-2 cases will have exuberant neural activity as measured by single trial power (STP) in primary auditory cortex; (1b) Biotype-2 cases will show exuberance of their STP response in distributed cortical regions that will be more extensive in gamma frequency ranges; (1c) Biotype-1 cases will have reduced amplitude responses in primary auditory cortex and no evidence of a more distributed cortical response pattern on STP; (2a) High cognitive control healthy persons will differ from all other groups on ITC and the magnitude of its local (auditory cortical) and distributed neural sources, especially as stimulation frequency increases into the high gamma range; (2b) Low cognitive control healthy persons will not differ from the psychosis groups on ITC in auditory cortex, but will differ on magnitude of ITC sources outside of auditory cortex. This project will clarify psychosis-specific from general cognition-related features of aSSR and support a path to better etiological studies that are not currently possible using conventional diagnoses.

听觉稳态反应（aSSR）是一种有前途的精神病转化生物标志物。夹带至 不同频率的刺激涉及独特的神经发生器和皮质电路。听觉 40Hz 伽玛反应已被优先提议作为精神分裂症的生物标志物。在超过 500 个样本中 总体观察结果，受试者涵盖精神病谱系（精神分裂症、分裂情感性障碍、双相情感障碍） 精神病）我们没有发现任何 DSM 精神病综合征特有的 aSSR 测量方法。 或者，神经生物学定义的精神病亚组（精神病生物型）具有独特且 区分 aSSR 功能。这些差异的类型和程度与认知水平相关， 独立于精神病。在本提案中，我们将使用多模式神经影像与脑电图 (EEG)、脑磁图 (MEG) 和结构磁共振成像 (sMRI) 进行研究 精神病病例中 aSSR 在多个频率（20、40 和 80 Hz）下的神经源分布 对神经反应的缺乏（精神病 Biotype-1；n=35）或旺盛（精神病 Biotype-2；n=35） 一个SSR。这两个亚组的认知能力都很差。与其将他们与混合健康组进行比较， 健康个体将按认知控制进行细分（高或低，每个亚组 n=35）。认知能力低下 对照组在认知上与精神病病例相似，但没有精神病症状。脑电图和脑磁图 录音将用于检测初始听觉注册和 aSSR 的径向和切向神经源 具有高时间分辨率。脑电图以其对径向和切向神经源的敏感性，将提供 与该主题相关的大多数先前文献的链接，而 MEG 具有出色的测量能力 听觉神经信号，将产生有关大部分切向神经源的补充信息 一个SSR。这些措施将用于检查 aSSR 从 beta 到 high 的分布式神经活动 伽玛频率，以及它们作为精神病亚型和认知控制能力的函数有何不同。 假设：(1a) Biotype-2 病例将具有旺盛的神经活动，如通过单次试验功效 (STP) 测量的 初级听觉皮层； (1b) Biotype-2 病例将在分布式皮质中表现出旺盛的 STP 反应 伽马频率范围更广泛的区域； (1c) Biotype-1 病例将会减少 初级听觉皮层的振幅反应，没有证据表明皮层反应模式分布更均匀 在STP上； (2a) 高认知控制的健康人与 ITC 上的所有其他群体不同，并且认知控制的程度也不同。 它的局部（听觉皮层）和分布式神经源，特别是当刺激频率增加到 高伽玛范围； (2b) 低认知控制健康人与 ITC 上的精神病组没有差异 在听觉皮层中，但在听觉皮层之外的 ITC 源的大小上会有所不同。该项目将澄清 从 aSSR 的一般认知相关特征中找出精神病特异性，并支持更好的病因学途径 目前使用传统诊断无法进行的研究。