Targeting Cortical Dynamics: Rational Design of Individualized Brain Stimulation

描述（由申请人提供）：精神障碍的认知症状与大脑活动的颞叶结构变化有关。例如，大脑皮层伽马频段（bbb30 Hz）节律性活动的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。尽管人们越来越认识到皮层振荡的功能作用，但控制不同节律活动状态发生的动力学（即皮层状态动力学）仍然未知。由于快节奏状态可能会增强感觉加工，而慢节奏状态会在休息时切断皮层与感觉输入的联系，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。长期目标是了解脑皮层状态动力学的电生理特征和行为相关性，并通过调节脑皮层状态动力学发展个体化脑刺激来治疗精神疾病。本研究的目的是了解皮层状态对感觉输入的反应动态，并通过非侵入性经颅电流刺激对人类进行反馈刺激来调节这些动态。这项工作的中心假设是，皮层网络表现出自发和诱导的在慢速和快速振荡活动状态之间的转换，可以通过非侵入性脑刺激来控制。为了验证这一假设，本工作采用跨学科的方法，将计算机模拟、体内雪貂电生理学和健康人类受试者的无创经颅电流刺激与脑电图（EEG）相结合，以追求以下三个具体目标：(1)确定休息和感觉刺激时皮层状态的电生理基础；(2)确定经颅电流刺激的最佳波形作为皮层状态的函数；(3)开发和评估反馈经颅脑刺激来控制人类皮层状态动力学并调节其行为相关性。这项工作意义重大，因为反馈脑刺激与当今流行的脑刺激有根本的不同

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.