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）是精神病的有前途的转化生物标志物。夹带 刺激的不同频率参与独特的神经发生器和皮质回路。听觉40-Hz 伽马反应已被优先提出为精神分裂症生物标志物。在500多个样本中 总观察结果，跨精神病谱系受试者（精神分裂症，精神分裂症，双极性 精神病的疾病）我们没有发现任何DSM精神病综合征独有的ASSR措施。 另外，神经生物学定义的精神病亚组（精神病生物型）具有独特的和 区分ASSR功能。这些差异的类型和程度与认知水平有关， 独立于精神病。在此提案中，我们将使用脑电图的多模式神经影像学 （脑电图），磁性摄影（MEG）和结构磁共振成像（SMRI） 在精神病病例中，ASSR的神经源分布在多个频率（20-、40和80-Hz） 缺乏（精神病生物型1; n = 35）或旺盛（精神病生物型2; n = 35）对神经的神经反应 Assr。这两个亚组的认知差。而不是将它们与混合健康小组进行比较，而是 健康个体将通过认知对照（高或低，每个亚组的n = 35）来细分。低认知 对照组将类似于认知的精神病病例，但没有精神病症状。脑电图和梅格 记录将用于检测初始听觉登记和ASSR的径向和切向神经源 具有高时间分辨率。脑电图对径向和切向神经来源的敏感性将提供 与以前有关该主题的大多数文献的链接，而MEG具有出色的衡量能力 听觉神经信号将产生有关大多数切向神经来源的免费信息 Assr。这些措施将用于检查ASSR从beta到高的分布式神经活动 伽马频率以及它们与精神病亚型和认知控制能力的函数的差异。 假设：（1A）生物型-2病例将具有通过单个试验能力（STP）在 主要听觉皮层； （1B）生物型2病例将显示其在分布式皮质中的STP响应的旺盛 在伽马频率范围内将更广泛的区域； （1C）生物型1病例将减少 主要听觉皮层中的振幅反应，没有证据表明皮质反应模式更分布 在STP上； （2a）高认知控制健康的人将与ITC上所有其他组和大小不同 它的局部（听觉皮质）和分布神经来源，尤其是随着刺激频率增加 高伽玛范围； （2b）低认知控制健康人员与ITC上的精神病组无异 在听觉皮层中，但在听觉皮层以外的ITC源的幅度会有所不同。这个项目将澄清 来自ASSR的一般认知相关特征的精神病特异性，并支持更好的病因的道路 使用常规诊断目前无法进行的研究。