Mapping and Modulating the Spatiotemporal dynamics of socio-affective processing.

摘要 解读人类面部表情是人类社会的核心能力，在不同的环境中受到负面影响。 神经精神疾病人类社会认知的失败导致了情绪中的疾病负担 障碍，以及自闭症谱系和焦虑症，加强和加剧了社会孤立， 和绝望的患者。拟议的研究审查了RDoC “面部交流”的子结构和“负配价系统”的域使用行为 认知任务对解读情绪面部表情的能力有很高的要求。之前 努力开发用于神经精神疾病的难治性病例的神经调节范例 以社会情感功能障碍为特征的研究已经不足，部分原因是缺乏明确的神经功能障碍。 功能失调的信号这个R 01提案的总体目标是绘制 社会情感处理，并检查这些动态的选择性调制人类经历 难治性癫痫和抑郁症的侵入性颅内监测。追踪这个信号 具有侵入性颅内记录电极的新型平台提供了急需的空间和 时间分辨率来表征社会情感处理的神经动力学。我们将利用 首次在人类颅内神经记录的机会，创造了一种新的治疗平台，称为 “立体定向脑电图知情脑深部电刺激”（立体脑电图知情DBS;父母 研究UH 3-NS 103549），以及颅内立体定向记录和刺激的强大平台， 在贝勒医学院接受癫痫手术评估的患者。sEEG知情DBS试验 为颅内记录患者的影响相关网络区域提供了独特的机会， 难治性抑郁症（TRD）。记录在癫痫患者的相同区域， 经常表现出轻度-中度抑郁症状的人， 症状谱为了提供关于社会情感加工的时空动态的关键数据， 将利用这两个人类颅内记录和刺激队列来研究精确的结构 (Aim 1），功能（目标2）和因果（目标3）的情感显着性网络的属性。更大 对由情感显著性网络介导的社会处理电路的理解可以用于 推动治疗创新，开创一种新的范式，改善广泛的社会情感功能， 各种神经精神疾病。这项提案的结果有可能改善 社会情感处理功能障碍的患者，对广泛的神经精神疾病有影响。 疾病

ABSTRACT Interpreting human facial expressions is a core human social capacity negatively impacted in diverse neuropsychiatric conditions. Failures of human social cognition contribute to disease burden in mood disorders, as well as autism spectrum and anxiety disorders, reinforcing and exacerbating the social isolation and hopelessness of patients across diagnostic categories. The proposed study examines the RDoC subconstruct of “Facial Communication” and the domain of “Negative Valence Systems” using behavioral cognitive tasks that place heavy demands on the capacity to interpret emotional facial expressions. Prior efforts to develop neuromodulation paradigms for treatment-resistant cases of neuropsychiatric diseases characterized by socio-affective dysfunction have fallen short, in part due to an absence of defined neural dysfunctional-state signals. The overall goal of this R01 proposal is to map the spatiotemporal dynamics of social affective processing and to examine selective modulation of these dynamics in humans undergoing invasive intracranial monitoring for treatment-resistant epilepsy and depression. Pursuing this signal from a novel platform with invasive intracranial recording electrodes provides much-needed spatial and temporal resolution to characterize the neural dynamics of socio-affective processing. We will leverage first-in-human intracranial neural recording opportunities created by a novel therapeutic platform termed “stereotactic electroencephalography-informed deep brain stimulation” (stereo-EEG-informed DBS; Parent Study UH3-NS103549), as well as the powerful platform of intracranial stereotactic recording and stimulation in patients undergoing epilepsy surgical evaluation at Baylor College of Medicine. The sEEG-informed DBS trial provides unique opportunities for intracranial recording of affect-relevant network regions in patients with treatment-resistant depression (TRD). Recordings in identical regions in epilepsy patients who themselves often demonstrate mild-moderate depressive symptoms will provide a wide dynamic range across the symptom spectrum. To provide critical data on the spatiotemporal dynamics of socio-affective processing we will leverage these two human intracranial recording and stimulation cohorts to study the precise structural (Aim 1), functional (Aim 2), and causal (Aim 3) properties of the affective salience network. Greater understanding of the social processing circuitry mediated by the affective salience network may be used to drive therapeutic innovation, pioneering a new paradigm that improves socio-emotional function across a wide variety of neuropsychiatric conditions. The results from this proposal have the potential to improve the lives of patients with dysfunction in social affective processing, with implications for a wide range of neuropsychiatric diseases.