Neuronal and Network Mechanisms of Electrocortical Stimulation

皮层电刺激的神经元和网络机制

• 批准号: 10724958
• 负责人: Marc W. Slutzky
• 金额: $ 417.58万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724958
• 关键词: Affect; Amplifiers; Anatomy; Area; Behavior; Behavioral; Brain; Brain Mapping; Brain Neoplasms; Calcium; Cells; Clinical; Computer Models; Dementia; Diffusion; Disease; Electrical Stimulation of the Brain; Electrocorticogram; Electrodes; Elements; Ensure; Epilepsy; Etiology; Evoked Potentials; Excision; Functional Magnetic Resonance Imaging; Goals; Graph; Human; Image; Impairment; Individual; Investigation; Label; Language; Lesion; Location; Maps; Measures; Modeling; Morphologic artifacts; Mus; Neurology; Neurons; Neurosciences; Operative Surgical Procedures; Outcome; Pain; Pathway Analysis; Pattern; Persons; Postoperative Period; Recording of previous events; Research; Resolution; Role; Site; Speech; Stroke; Surgeon; Synapses; Testing; Time; Uncertainty; Work; behavioral study; brain dysfunction; cell type; chronic pain; density; electric field; excitatory neuron; experimental study; improved; inhibitory neuron; innovation; language impairment; millisecond; multimodality; nano; nervous system disorder; neural; neuroregulation; neurosurgery; novel; response; spatiotemporal; spectrograph; tumor; two-photon; white matter

Electrocortical stimulation (ECS) has been used for functional mapping for many decades to identify brain areas that are “critical” for speech and language (i.e., that impair function when stimulated) prior to epilepsy or tumor surgery. It also is used to modulate neural activity, e.g., in directly treating epilepsy or pain. However, despite its long history of clinical use, the precise mechanisms of ECS are poorly understood, both on neuronal and network scales. For example, it is not known how different cortical layers and cell types respond to ECS, nor whether ECS’ effects on behavior are due to affecting only the local cortex vs. underlying white matter. The long-term goal of this research is to understand how ECS interacts with the brain. The objectives of this proposal are to determine the local effects of ECS on cortical neurons, and to determine the effects of ECS on the cortical network and subcortical white matter. We will test the predictions of multiple computational modelling and indirect experimental studies. One of these that ECS preferentially activates cells in superficial cortical layers with broad projections, could help explain how focal stimulation causes widespread effects. We hypothesize that the anatomic and functional connectivity patterns of a cortical site determine its significance to the language network. That is, nodes that form connections among multiple regions are more likely to be critical. We also hypothesize that ECS causes behavioral changes by affecting both the cortex and underlying white matter. The specific aims of the project are 1) to determine the effects of ECS on a neuronal scale, 2) to determine the relationship between ECS’ effects and cortical connectivity patterns, and 3) to investigate the extent to which ECS’ effects are due to activating underlying white matter. This project is innovative in its use of nanomesh, µECoG (electrocorticography) arrays to enable simultaneous ECS and two-photon calcium imaging of neuronal responses, as well as its novel dynamic network metrics to analyze human cortical connectivity on a millisecond level. We have shown that focal cortical cooling only affects the cortex, and not the white matter, and will use cooling to probe the relative roles of cortex and white matter in ECS’ behavioral effects. Achieving our objectives will be significant because it will improve functional brain mapping and neuromodulation. We expect this to lead to better neurosurgical outcomes for a variety of neurologic disorders, including epilepsy, brain tumors, and chronic pain. We also expect this proposal will enable other studies using stimulation to investigate causality to be more precise in defining and understanding their outcomes. Finally, we anticipate this proposal will advance our understanding of how the brain encodes language.

几十年来，电皮层刺激（ECS）一直被用于功能定位，以确定癫痫或肿瘤手术前对言语和语言“至关重要”的大脑区域（即刺激时损害功能）。它也被用来调节神经活动，例如，直接治疗癫痫或疼痛。然而，尽管其临床应用历史悠久，但在神经元和网络尺度上，ECS的确切机制尚不清楚。例如，我们不知道不同的皮层层和细胞类型如何对ECS作出反应，也不知道ECS对行为的影响是由于只影响局部皮层还是潜在的白质。这项研究的长期目标是了解ECS如何与大脑相互作用。本提案的目的是确定ECS对皮质神经元的局部影响，以及确定ECS对皮层网络和皮层下白质的影响。我们将测试多种计算模型和间接实验研究的预测。其中之一是，ECS优先激活具有广泛投射的皮层浅层细胞，这可以帮助解释局灶性刺激如何引起广泛的影响。我们假设一个皮质部位的解剖和功能连接模式决定了它对语言网络的重要性。也就是说，在多个区域之间形成连接的节点更有可能是关键的。我们还假设ECS通过影响皮层和底层白质来引起行为改变。该项目的具体目标是1)确定ECS在神经元尺度上的作用，2)确定ECS的作用与皮层连接模式之间的关系，以及3)调查ECS的作用在多大程度上是由于激活潜在的白质。该项目的创新之处在于，它使用纳米网格、微ECoG（皮质电图）阵列，可以同时对神经元反应进行ECS和双光子钙成像，并采用新颖的动态网络指标，在毫秒级别上分析人类皮层的连通性。我们已经证明，局部皮层冷却只影响皮层，而不影响白质，并将利用冷却来探讨皮层和白质在ECS行为效应中的相对作用。实现我们的目标将是非常重要的，因为它将改善功能性脑绘图和神经调节。我们期望这将为包括癫痫、脑肿瘤和慢性疼痛在内的各种神经系统疾病带来更好的神经外科结果。我们也希望这一建议将使其他使用刺激来调查因果关系的研究能够更精确地定义和理解其结果。最后，我们期望这一提议将促进我们对大脑如何编码语言的理解。