Neural substrates of deficits in naturalistic social cognition in schizophrenia

项目摘要：精神分裂症等精神障碍通常以社会认知能力差为标志，但 人们对这些缺陷背后的神经机制知之甚少。视觉扫描社交场景，以 相关的社会线索是社会认知的一个重要领域，是发现和使用社会线索来 在社交场景中理解他人的想法和感受(心理化)。瞄准那些眼睛- 动作通常是由面部表情驱动的，这种表情很突出，或者从其他视觉上脱颖而出 特征，并且在行为上相关，或已知包含有助于理解社会 情况。我的实验室最近的研究发现，自然主义社交场景的视觉扫描出现了异常 (上演社交场景的电影)在精神分裂症中，导致面部表情检测减少 并影响了对这些场景的理解。我还发现了颞顶叶的严重功能缺陷 交界处/后颞叶上沟(TPJ-PSTS)，大脑中包含相关脑区的区域 到面部表情的感知、眼球运动的引导和心灵化。这笔赠款 应用程序旨在通过调查涉及的皮质区域的功能完整性来建立这些发现 在将视觉信息转化为眼球跳动计划的过程中 精神分裂症与人口统计相匹配的健康对照组。 我提议表演一种自由观看的自然主义和严格控制的组合 用心理物理实验来研究这些区域。我们将使用我的实验室采用的技术。 David Leopold等人分别评估了TPJ-PSTS在视觉处理中的完整性， 与其他区域的交流，以及在免费观看电影期间产生扫视。我们还将 检查控制眼球运动的背部注意区域的组织和功能。这些 额顶区是视网膜定位图，这意味着它们包含1：1的视野图 以视网膜中心凹为中心。与克莱顿·柯蒂斯博士一起，我将绘制每个个体的这些区域，然后 检查这些地图中的活动是否反映了 参与者观看的电影。最后，我们将检查SZP中视觉扫描的失败是否 与TPJ-PSTS、背侧注意区域或两者的功能缺陷有关。 拟议的实验解决了NIMH战略目标中概述的几个未得到满足的需求。 拟议的实验结果将提供(据我们所知)第一个完整的电路级地图 与精神疾病有直接关系的复杂行为。这一结果也将阐明可能的微电路 可能导致视网膜地形图异常的缺陷。有了这些信息，我就能够设计出低成本的- 易于在临床环境中部署的社会功能负荷测试，并开始调查康复 或神经调节治疗，以修复或补偿精神分裂症的这些社会认知缺陷。

Project Summary: Psychiatric disorders such as schizophrenia are often marked by poor social cognition, but little is known about the neural mechanisms underlying these deficits. Visual scanning of social scenes for relevant social cues is a key domain of social cognition, and is necessary to detect and use social cues to understand the thoughts and feelings of others in the social scene (mentalization). The targeting of those eye- movements are often driven by facial expressions of emotion, which are salient, or stand out from other visual features, and are behaviorally relevant, or known to contain information useful for understanding the social situation. Recent work from my lab has found abnormalities in the visual scanning of naturalistic social scenes (movies of staged social scenes) in schizophrenia, which resulted in decreased detection of facial expressions and affected understanding of those scenes. I have also found gross functional deficits in the temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS), a region of the brain that contains brain areas related to the perception of facial expressions of emotion, guiding of eye-movements, and mentalization. This grant application aims to build on these findings by investigating the functional integrity of the cortical areas involved in the transformation of the visual information into plans for saccadic eye-movements in individuals with schizophrenia versus demographically matched healthy controls. I am proposing to perform a combination of free-viewing naturalistic and rigorously controlled psychophysical experiments to study these areas. We will use techniques that my lab has adapted from Dr. David Leopold and others to separately assess the integrity of the TPJ-pSTS in the visual processing, communications with other areas, and generation of saccades during free-viewing of movies. We will also examine the organization and functioning of the dorsal attention areas that control eye-movements. These frontoparietal areas are retinotopically mapped, meaning that they contain a 1:1 map of the visual field centered on the fovea of the retina. With Dr. Clayton Curtis, I will map these areas in each individual, and then examine whether the activity within these maps mirrors the salient and behaviorally relevant visual features in the movies viewed by the participants. Lastly, we will examine whether failures in visual scanning in SzP are related to deficits in the functioning of the TPJ-pSTS, dorsal attention areas, or both. The proposed experiments address several unmet needs outlined in the NIMH Strategic Objectives. The results of the proposed experiments will provide (as far as we know) the first full circuit-level map of a complex behavior that has direct psychiatric relevance. The results will also shed light on possible microcircuit deficits that may lead to retinotopic map abnormalities. With this information, I will then be able to design low- burden tests of social functioning easily deployed in clinical settings, and also start investigating rehabilitation or neuromodulation treatments to repair or compensate for these social cognition deficits in schizophrenia.