Targeting Cortical Dynamics: Rational Design of Individualized Brain Stimulation

描述（由申请人提供）：精神疾病的认知症状与大脑活动时间结构的变化有关。例如，皮质中伽马频带（>30 Hz）中的节律活动改变与精神症状有关，如幻觉、感觉门控减少和认知控制受损。尽管越来越多的认识到皮层振荡的功能作用，动力学，管理不同的节奏活动状态的发生（即皮层状态动力学）仍然未知。由于快节奏的状态可能会增强感觉处理，而慢节奏的状态会在休息时断开皮层与感觉输入的连接，因此了解皮层状态动力学对精神分裂症、自闭症和注意力缺陷障碍（如注意力和知觉受损）的认知症状的研究和治疗具有广泛的意义。长期目标是了解皮层状态动力学的电生理特征和行为相关性，并通过调节皮层状态动力学来开发个性化的脑刺激来治疗精神疾病。拟议的研究的目的是了解皮质状态动态响应于感觉输入，并调制这些动态与反馈刺激使用非侵入性经颅电流刺激在人类。这项工作的中心假设是，皮层网络表现出自发和诱导之间的缓慢和快速振荡活动状态，可以控制与非侵入性脑刺激的过渡。为了验证这一假设，本研究采用了一种跨学科的方法，该方法将计算机模拟、体内雪貂电生理学和无创经颅电流刺激与健康人类受试者的脑电图（EEG）相结合，以实现以下三个具体目标：（1）确定休息和感觉刺激期间皮层状态的电生理学底物，（2）识别作为皮层状态的函数的经颅电流刺激的最佳波形，以及（3）开发和评估反馈经颅脑刺激以控制皮层状态动力学并调节它们在人类中的行为相关性。这项工作是重要的，因为反馈脑刺激从根本上不同于今天流行的脑刺激， 通用的预编程刺激波形。这项工作的结果旨在催化精神疾病治疗的范式转变，以基于理性设计的有效，个性化的脑刺激。

DESCRIPTION (provided by applicant): Cognitive symptoms in psychiatric disorders are associated with changes in the temporal structure of brain activity. For example, altered rhythmic activity in the gamma frequency band (>30 Hz) in the cortex is implicated in psychiatric symptoms such as hallucinations, reduced sensory gating, and impaired cognitive control. Despite growing recognition of the functional roles of oscillations in cortex, the dynamics that govern the occurrence of different rhythmic activity states (i.e. cortical state dynamics) remain unknown. Since states with fast rhythms likely enhance sensory processing while states with slow rhythms disconnect cortex from sensory input during rest, understanding cortical state dynamics has broad implications for the study and treatment of cognitive symptoms in schizophrenia, autism, and attention-deficit disorder such as impaired attention and perception. The long-term goal is to understand the electrophysiological signatures and behavioral correlates of cortical state dynamics and to develop individualized brain stimulation to treat mental illness by modulating cortical state dynamics. The objective of the proposed research is to understand cortical state dynamics in response to sensory input and to modulate these dynamics with feedback stimulation using non-invasive transcranial current stimulation in humans. The central hypothesis of this work is that cortical networks exhibit spontaneous and induced transitions between slow and fast oscillatory activity states that can be controlled with non-invasive brain stimulation. In order to test this hypothesis, this work utilizes an interdisciplinary approach that integrates computer simulations, in vivo ferret electrophysiology, and non-invasive transcranial current stimulation coupled with electroen- cephalography (EEG) in healthy human subjects to pursue the following three specific aims: (1) to determine the electrophysiological substrate of cortical states during rest and sensory stimulation, (2) to identify optimal waveforms for transcranial current stimulation as a function of cortical state, an (3) to develop and evaluate feedback transcranial brain stimulation to control cortical state dynamics and modulate their behavioral correlates in humans. This work is significant because feedback brain stimulation radically differs from today's prevalent brain stimulation that utilizes generic, pre-programmed stimulation waveforms. The results of this work are intended to catalyze a paradigm shift in the treatment of mental illnesses to- wards effective, individualized brain stimulation based on rational design.