Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.

临床高危人群与健康人群睡眠纺锤体纵向差异的研究 项目摘要：精神分裂症及相关疾病是全球残疾的主要原因之一，因此 使及早识别可能作为治疗靶点的神经生物学脆弱性成为关键 研究优先。在最近的工作中，我们发现慢性精神分裂症患者在 睡眠纺锤波。阶段2非快速眼动(N_2)睡眠的标志，纺锤波短(S 0.5-2)， 在12-16赫兹范围内的增减振荡。纺锤体异常也出现在早期病程和 早发性精神分裂症和纺锤相关的测量，包括幅度、持续时间和密度，是 与健康个体的认知能力、社会功能和神奇思维倾向有关， 包括青少年和年轻人。通过调查各个主轴的参数，我们确定了 纺锤体密度和幅度的降低与症状的严重程度和认知障碍有关 分别在慢性精神分裂症患者中。我们还发现，集成心轴活动(ISA)，这是 将各个主轴参数组合在一个值中，是最具区分性的衡量标准，收益率约为90% 精神分裂症和对照组之间的分离。临床高危青年(CHR)是一个独特的人群 富含主要精神疾病的前驱症状，如精神分裂症，他们也经历了紧急情况 认知障碍、社交功能障碍和亚综合征临床症状。我们不知道的是 纺锤体损伤的发生，以及它们可能如何影响这一人群中精神病理学的发展。 因此，这个项目的第一个广泛目标是表征睡眠纺锤体参数在调节 认知、社会和临床功能轨迹，包括向精神病的转变，在CHR的年轻人中。 睡眠纺锤体是由丘脑网状核(TRN)和背侧丘脑相互作用而启动的。 然后，丘脑的活动被传递到大脑皮层，在那里，纺锤波被同步。的特定功能 纺锤波的密度、幅度和时长反映了丘脑、皮质和丘脑皮质的神经功能。 分别是连接。此外，GABA神经传递和丘脑-大脑皮层的连接性起着关键作用。 在产生和维持主轴振荡方面的作用。在最近的工作中，我们发现纺锤体缺陷是最多的 突出在额叶和前额叶头皮区，丘脑内侧背侧(MD)体积减少 精神分裂症患者来源局限性前额叶皮质(PFC)睡眠纺锤波减少。建房 根据这些发现，我们将整合多个层次的分析数据，从电生理学到神经学，再到 分子，来描述这种与纺锤相关的丘脑-皮质回路。具体地说，第二个广泛目标是 这个项目是利用高睡眠来确定睡眠纺锤体缺陷的神经元和分子基础。 密度(HD)-脑电、7T静息(RS)-fMRI和磁共振波谱成像(MRSI)。 为了达到这些总体目标，我们建议对45名慢性阻塞性肺病患者和45名健康患者进行纵向研究。 对照组(HC)，在两年内进行三次临床和认知功能评估、HD-EEG、fMRI和MRSI。

Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally Project summary: Schizophrenia and related disorders are one of leading causes of disability worldwide, thus making the early identification of neurobiological vulnerabilities, which may serve as treatment targets, a critical research priority. In recent work, we found that individuals with chronic schizophrenia had a striking deficit in sleep spindles. A hallmark of Stage 2 Non-Rapid Eye Movement (N2) Sleep, spindles are short (0.5-2 s), waxing/waning oscillations within the 12-16 Hz range. Spindle abnormalities are also present in early course and early onset schizophrenia, and spindle-related measures, including amplitude, duration, and density, are associated with cognitive ability, social functioning, and tendency for magical thinking in healthy individuals, including adolescents and young adults. By investigating individual spindle parameters, we established that reduced spindle density and amplitude are associated with severity of symptoms and cognitive impairments respectively, in chronic schizophrenia patients. We also found that Integrated Spindle Activity (ISA), which combines individual spindle parameters in a single value, was the most discriminating measure, yielding ~90% separation between schizophrenia and control groups. Youth at Clinical High Risk (CHR) are a unique population enriched for precursors of major psychiatric disorders, such as schizophrenia, who also experience emergent cognitive impairments, social dysfunction, and sub-syndromal clinical symptoms. What we do not know is when spindle impairments occur, and how they may affect the development of psychopathology in this population. Thus, the first broad aim of this project is to characterize the role of sleep spindle parameters in moderating cognitive, social, and clinical functioning trajectories, including transition to psychosis, among youth at CHR. Sleep spindles are initiated by the interplay of the Thalamic Reticular Nucleus (TRN) with the dorsal thalamus. Thalamic activity is then relayed to the cortex, where spindle oscillations are synchronized. Specific features of spindles—density, amplitude and duration—reflect neural function in the thalamus, cortex, and thalamo-cortical connections, respectively. Moreover, GABA neurotransmission and thalamo-cortical connectivity play a critical role in generating and sustaining spindle oscillations. In recent work, we found that spindle deficits were most prominent in frontal and prefrontal scalp regions, and that reduced medio-dorsal (MD) thalamic volumes were associated with decreased sleep spindles in source localized prefrontal cortex (PFC) in schizophrenia. Building on these findings, we will integrate data across multiple levels of analysis, from electrophysiology to neural to molecules, to characterize this spindle-related thalamo-cortical circuitry. Specifically, the second broad aim of this project is to identify the neuronal and molecular underpinnings of sleep spindle defects using sleep high density (hd)-EEG, 7T resting state (rs)-fMRI, and Magnetic Resonance Spectroscopy Imaging (MRSI). In order to address these general aims, we propose to conduct longitudinal studies in 45 CHR and 45 healthy controls (HC), with three assessments of clinical and cognitive function, hd-EEG, fMRI, and MRSI over two years.