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。夹带以 不同频率的刺激使用独特的神经发生器和皮层电路。听觉40 Hz γ反应已被优先提出作为精神分裂症生物标志物。在超过500个样本中 所有观察结果，包括精神病谱（精神分裂症、情感障碍、双相情感障碍）受试者 我们没有发现任何DSM精神病综合征特有的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特征。这些差异的类型和程度与认知水平有关， 与精神病无关。在这个建议中，我们将使用多模式神经成像与脑电图 (EEG)、脑磁图（MEG）和结构磁共振成像（sMRI）来研究 精神病患者aSSR在多个频率（20、40和80 Hz）下的神经源分布 缺乏（精神病生物型-1; n=35）或旺盛（精神病生物型-2; n=35）的神经反应， 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， 健康个体将通过认知控制（高或低，每个亚组n=35）进行细分。低认知 对照组在认知方面与精神病患者相似，但无精神病症状。EEG和MEG 记录将用于检测初始听觉配准和aSSR的径向和切向神经源 具有高时间分辨率。EEG对径向和切向神经源都很敏感， 一个链接到大多数以前的文献对这一主题，而MEG，其出色的能力，以衡量 听觉神经信号，将产生有关的主要切向神经源的互补信息， aSSR。这些测量将用于检查aSSR从β到高的分布神经活动。 伽马频率，以及它们如何作为精神病亚型和认知控制能力的函数而不同。 假设：（1a）生物型-2病例将具有旺盛的神经活动，如通过单次试验功率（STP）测量的， （1b）生物型2例在分布的皮层中显示其STP反应的旺盛 伽马频率范围将更广泛的区域;（1c）生物型-1病例将减少 初级听觉皮层的振幅反应，没有证据表明皮层反应模式更分散 （2a）高认知控制健康人在ITC上与所有其他组不同， 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 高伽马范围;（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 aSSR的一般认知相关特征中的精神病特异性，并支持更好的病因学 这些研究目前无法使用常规诊断。

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.