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

听觉稳态反应(ASSR)是一种很有前途的精神病翻译生物标志物。夹带到 不同的刺激频率会产生独特的神经生成器和大脑皮层回路。听觉40赫兹 伽玛反应被优先认为是精神分裂症的生物标记物。在超过500个样本中 对不同精神病谱的受试者(精神分裂症、分裂情感障碍、躁郁症)进行全面观察 精神障碍)我们没有发现任何DSM精神病综合征独有的ASSR测量。 或者，神经生物学定义的精神病亚组(精神病生物型)具有独特的 区分ASSR功能。这些差异的类型和程度与认知水平有关， 独立于精神错乱。在这项提议中，我们将使用多模式神经成像和脑电 脑电(EEG)、脑磁图(MEG)和结构磁共振成像(SMRI)检查 精神病患者ASSR在多个频率(20、40和80赫兹)的神经源分布 缺乏(1型精神病；n=35)或旺盛(2型精神病；n=35)神经反应 ASSR。这两个亚组的认知能力都很差。而不是将他们与混合健康组进行比较， 健康的个体将根据认知控制(高或低，每个亚组n=35)进行细分。低认知度 对照组在认知功能上与精神病患者相似，但无精神病症状。脑电和脑磁图 录音将用于检测初始听觉配准和ASSR的径向和切向神经源 具有很高的时间分辨率。EEG对放射状和切向神经源都很敏感，它将提供 关于这一主题的大多数先前文献的链接，而MEG凭借其出色的测量能力 听觉神经信号，将产生关于大多数切线神经源的补充信息 ASSR。这些措施将被用来检查ASSR的分布神经活动从Beta到High 伽马频率，以及它们作为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患者将具有旺盛的神经活动，如在 初级听觉皮质；(1b)生物型-2患者将在分布的皮质表现出旺盛的STP反应。 伽马频率范围将更加广泛的区域；(1c)生物型1病例将减少 初级听觉皮质的幅度反应，没有证据表明皮质反应模式更分散 在STP上；(2a)高认知控制力健康人在ITC上与所有其他组不同，并且 它的局部(听觉皮质)和分布的神经源，特别是当刺激频率增加到 高伽马范围；(2b)认知控制力低下的健康人与精神病患者在ITC上没有差别 在听觉皮质，但在听觉皮质以外的ITC来源的大小将有所不同。这个项目将澄清 从ASSR的一般认知相关特征中得出精神病的特异性，并支持一条更好的病因学道路 目前无法使用常规诊断方法进行的研究。

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.