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

摘要 解读人类面部表情是人类的一项核心社会能力，在不同的领域受到负面影响 神经精神疾病。人类社会认知障碍导致情绪疾病负担 精神障碍，以及自闭症和焦虑症，加强和加剧了社会孤立 以及不同诊断类别患者的绝望程度。拟议的研究审查了RDoC “面部沟通”的子结构和“负价系统”的领域 认知任务对理解情绪面部表情的能力提出了很高的要求。之前 努力为神经精神疾病的难治性病例开发神经调节范例 以社会情感障碍为特征的患者表现不足，部分原因是缺乏明确的神经 功能失调的状态信号。这个R01提案的总体目标是绘制出 社会情感加工，并检查这些动态的选择性调节在人类经历 治疗难治性癫痫和抑郁症的侵入性颅内监测。追寻这一信号来自一个 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加工的神经动力学。我们将利用 名为的新型治疗平台创造了首个人类颅内神经记录机会 《立体定向脑电信息脑深部刺激》(立体脑电信息DBS；家长 研究UH3-NS103549)，以及脑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通报的星展银行试验 提供了独特的机会记录患者的影响相关网络区域的颅内 难治性抑郁症(TRD)。癫痫患者在相同区域的记录 经常表现出轻到中度的抑郁症状将提供广泛的动态范围 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，我们 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 (目标1)、功能(目标2)和因果(目标3)的情感显著网络特性。更大 对情感显著网络所中介的社交处理电路的理解可用于 推动治疗创新，开创一种新的范式，在广泛的领域改善社会情绪功能 各种神经精神疾病。这项提案的结果有可能改善人们的生活 社交情感加工障碍患者与广泛的神经精神病学相关 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.