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

基于神经群体模型的健康和抑郁/焦虑人类受试者认知控制基础神经振荡的表征和调节

基本信息

批准号：
10594566
负责人：
Ishita Basu
金额：
$ 24.3万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

项目摘要

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.

项目摘要认知控制，保留默认的能力，有利于更适应的选择的优势反应在抑郁症和焦虑症等精神疾病中往往会受到影响。因此，一种用于改善认知控制可能在缺乏有效治疗的疾病中广泛有用。成功地解决冲突是一种认知控制的形式，其中一个人必须抑制自然反应遵循一个不那么直观的规则。冲突处理引起扣带回中的theta（4-8 Hz）振荡，内侧前额叶皮层（PFC），也可以通过侵入性颅内EEG（iEEG）进行测量额中线头皮脑电图慢性和间歇性高频短串囊/纹状体刺激已被证明可以增强θ振荡，同时提高性能冲突的任务。此外，内囊或底丘脑的深部脑刺激（DBS）也可用于脑内刺激。外侧前额叶皮层的经颅电流刺激和核团刺激都能提高认知能力，控制任务。这些发现有力地表明，我们可以调节认知控制及其神经功能，通过外部电刺激瞄准相关的大脑回路来识别信号。这个目标一项研究计划是描述和模拟冲突解决背后的皮层振荡在健康和焦虑/抑郁心理状态下的认知控制方面，神经调节干预，以恢复健康的精神状态。我们要三个为实现这一目标而采取的补充措施。1)应用iEEG记录癫痫患者接受手术评估的侵入性监测，我们将确定皮层神经振荡的基础冲突任务框架中的认知控制。我们还将使用它来区分正常的和抑郁或焦虑的受试者。2)我们将使用神经群体皮层模型来模拟和表征观察到的PFC和颞叶皮层振荡的潜在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的模型参数。 3)我们将使用校准到个体受试者的模型来设计皮层电刺激范例以朝向期望的健康状态调节模拟振荡。然后我们将验证通过在人类受试者中测试模型预测，改变神经信号和相关行为。总之，这将导致一个生物制药学上的动机模型来模拟神经振荡潜在的冲突处理在健康和病理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有针对性的神经调节，如用于治疗目的的皮层刺激，获得的信息将潜在地告知情绪/焦虑症中受损的其他功能域。