Disrupted eye gaze perception as a biobehavioral marker of social dysfunction: An RDoC investigation

项目摘要/摘要 在各种精神疾病中，社交功能障碍是一个棘手的问题，损害了患者的 就业、独立生活和维持有意义的关系的能力。确定共同之处 跨障碍的社会损害的标记物和了解其机制是 开发可在诊断和疾病中有效应用的有针对性的神经生物学治疗 改善功能结局的阶段。这个项目的重点是眼睛凝视感知，准确的能力 并有效地辨别他人的凝视方向，作为社交功能的潜在生物标记物 精神病学诊断。这一前提建立在猴子和人类表现出凝视知觉的文献之上。 作为支持更高级别的社会沟通和社会发展的基本构件，以及 伴显著社会功能障碍的多种精神疾病患者的异常凝视知觉 (例如，精神病谱系障碍、自闭症谱系障碍、社交恐惧症)。大样本(n=225) 青少年和青壮年(14-30岁)精神病患者(不论诊断如何)，有不同程度的 这项研究将招募75名人口学上匹配的健康对照。 参与者的精神表型、认知、社会认知和社区功能 具有维度特征的。眼睛凝视知觉将通过一项心理物理任务和两项 分别利用视觉上的凝视感知干扰的指标(精确度、自我参照偏差) 感知和解释水平，与一般缺陷无关，将使用贝叶斯建模得出。 参与者的一部分(150名精神病患者，75名健康对照)还将接受多模式治疗 功能磁共振成像以确定凝视知觉改变的功能和结构的脑网络特征。具体的 本研究的目的有三个方面：目的1)确定儿童凝视知觉障碍的普遍性 有明显社会功能障碍的精神病患者；2)凝视知觉的MAP行为指数 精神疾病表型和核心功能区维度的障碍；以及3)识别神经 精神病人凝视知觉改变与社交功能障碍的相关性。已成功完成 这些特定的目标将确定特定的基本缺陷、临床特征和潜在的神经回路 与社会功能障碍相关，可用于指导有针对性的个性化治疗，从而促进 NIMH的战略目标1(描述与精神疾病相关的神经回路并绘制 精神疾病的联系)和目标3(根据在 神经科学和行为科学)。

Project Summary/Abstract Social dysfunction is an intractable problem in a wide spectrum of psychiatric illnesses, undermining patients’ capacities for employment, independent living, and maintaining meaningful relationships. Identifying common markers of social impairment across disorders and understanding their mechanisms are prerequisites to developing targeted neurobiological treatments that can be applied productively across diagnoses and illness stages to improve functional outcome. This project focuses on eye gaze perception, the ability to accurately and efficiently discriminate others’ gaze direction, as a potential biomarker of social functioning that cuts across psychiatric diagnoses. This premise builds on both the monkey and human literatures showing gaze perception as a basic building block supporting higher-level social communication and social development, and reports of abnormal gaze perception in multiple psychiatric conditions accompanied by prominent social dysfunction (e.g., psychosis-spectrum disorders, autism-spectrum disorders, social phobia). A large sample (n= 225) of adolescent and young adult (age 14-30) psychiatric patients (regardless of diagnosis) with various degrees of impaired social functioning, and 75 demographically matched healthy controls will be recruited for this study. Participant’s psychiatric phenotypes, cognition, social cognition, and community functioning will be dimensionally characterized. Eye gaze perception will be assessed using a psychophysical task, and two metrics (precision, self-referential bias) that respectively tap into gaze perception disturbances at the visual perceptual and interpretation levels, independent of general deficits, will be derived using Bayesian modeling. A subset of the participants (150 psychiatric patients, 75 healthy controls) will additionally undergo multimodal fMRI to determine the functional and structural brain network features of altered gaze perception. The specific aims of this project are three fold: Aim 1) Determine the generality of gaze perception disturbances in psychiatric patients with prominent social dysfunction; 2) Map behavioral indices of gaze perception disturbances to dimensions of psychiatric phenotypes and core functional domains; and 3) Identify the neural correlates of altered gaze perception in psychiatric patients with social dysfunction. Successfully completing these specific aims will identify the specific basic deficits, clinical profile, and underlying neural circuits associated with social dysfunction that can be used to guide targeted, personalized treatments, thus advancing NIMH’s Strategic Objective 1 (describe neural circuits associated with mental illnesses and map the connectomes for mental illnesses) and Objective 3 (develop new treatments based on discoveries in neuroscience and behavioral science).