A neural population model-based characterization and modulation of neural oscillations underlying cognitive control in healthy and depressed/anxious human subjects

项目概要 认知控制，保留默认的、优先的反应以支持更具适应性的选择的能力 通常会因抑郁和焦虑等精神障碍而受到损害。因此，一种方法用于 改善认知控制对于治疗几乎没有有效治疗方法的疾病可能广泛有用。 成功解决冲突是一种认知控制形式，人们必须抑制自然反应 遵循不太直观的规则。冲突处理会引起扣带回和 内侧前额皮质 (PFC)，也可以通过侵入性颅内脑电图 (iEEG) 进行测量 作为额叶中线头皮脑电图。慢性以及间歇性高频短程列车 囊膜/纹状体刺激已被证明可以增强 theta 振荡，同时提高表现 在冲突任务上。此外，内囊或底丘脑的深部脑刺激（DBS） 外侧 PFC 的核和经颅电流刺激均可改善认知能力 控制任务。这些发现强烈表明我们可以调节认知控制及其神经 通过外部电刺激针对相关的大脑回路来产生特征。此举的目标 研究提案是对冲突解决背后的皮质振荡进行表征和建模 健康和焦虑/抑郁心理状态下的认知控制方面，为设计提供信息 用于恢复健康心理状态的神经调节干预措施。我们将采取三个 实现这一目标的互补方法。 1) 使用在接受治疗的癫痫患者中记录的 iEEG 用于手术评估的侵入性监测，我们将确定潜在的皮质神经振荡 冲突任务框架中的认知控制。我们还将用它来区分正常的 以及抑郁或焦虑的受试者。 2）我们将使用神经群体皮质模型来模拟和 表征 PFC 和观察到的时间皮层振荡背后的可行神经机制 在冲突处理过程中。我们将使用数据驱动的方法来估计相关模型参数。 3）我们将使用针对个体受试者校准的模型来设计皮质电刺激 将模拟振荡调节到所需的健康状态的范例。然后我们将验证 我们的模型通过在人类受试者中测试模型预测来确定我们是否可以成功 改变神经信号以及相关行为。总之，这将导致生物物理学 动机模型来模拟健康和病理状态下冲突处理的神经振荡 状态并允许我们设计刺激范式来调节它们。这也将提供新的见解 进入有针对性的神经调节，例如用于治疗目的的皮质刺激和知识 获得的信息可能会告知其他因情绪/焦虑障碍而受损的功能域。

Project Summary Cognitive control, the ability to withhold a default, prepotent response in favor of a more adaptive choice is often compromised across mental disorders such as depression and anxiety. Thus, a method for improving cognitive control could be broadly useful in disorders with few effective treatments. Successfully resolving conflicts is a form of cognitive control where one must suppress a natural response to follow a less intuitive rule. Conflict processing evokes theta (4-8 Hz) oscillations in the cingulate and medial prefrontal cortex (PFC) which can be measured through invasive intracranial EEG (iEEG) as well as frontal midline scalp EEG. Chronic as well as intermittent short trains of high frequency capsular/striatal stimulation have been shown to enhance theta oscillations while improving performance on a conflict task. Furthermore, deep brain stimulation (DBS) of the internal capsule or subthalamic nucleus and transcranial current stimulation of the lateral PFC all improve performance on cognitive control tasks. These findings strongly suggest that we can modulate both cognitive control and its neural signatures by targeting the relevant brain circuits with external electrical stimulation. The goal of this research proposal is to characterize and model cortical oscillations underlying the conflict resolution aspect of cognitive control in the healthy and anxious/depressed mental states to inform design of neuromodulation interventions for restoration towards healthy mental states. We will take three complimentary approaches to achieve this goal. 1) Using iEEG recorded in epilepsy patients undergoing invasive monitoring for surgical evaluation, we will determine cortical neural oscillations underlying cognitive control in the framework of a conflict task. We will also use this to differentiate between normal and depressed or anxious subjects. 2) We will use a neural population cortical model to simulate and characterize feasible neural mechanisms underlying PFC and temporal cortical oscillations observed during conflict processing. We will use a data driven approach for estimating relevant model parameters. 3) We will use the model calibrated to individual subjects to design a cortical electrical stimulation paradigm to modulate the simulated oscillations towards a desired healthy state. We will then validate our model by testing model predictions in our human subjects and determine if we can successfully change both neural signals as well as associated behavior. Together, this will lead to a biophysically motivated model to simulate neural oscillations underlying conflict processing in healthy and pathological states and allow us to design stimulation paradigms to modulate them. This will also provide new insight into targeted neuromodulation, such as cortical stimulation for therapeutic purposes and the knowledge gained will potentially inform other functional domains compromised in mood/anxiety disorders.