Layer-specific manipulation to test feedforward/feedback cortical circuitry

用于测试前馈/反馈皮质电路的特定层操作

• 批准号: 10566631
• 负责人: EARL K MILLER
• 金额: $ 29.67万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10566631
• 关键词: AMPA Receptors; Affect; Attention; Attenuated; Back; Beta Rhythm; Brain; Code; Detection; Disease; Electric Stimulation; Electrodes; Failure; Feedback; Frequencies; Functional disorder; Glutamate Receptor; Glutamates; Infrastructure; Injections; Modeling; Monkeys; N-Methylaspartate; Neurons; Parietal Lobe; Pathway interactions; Pattern; Phase; Physiological; Prefrontal Cortex; Property; Psychoses; Reading; Role; Schizophrenia; Sensory; Signal Transduction; Site; Stimulus; System; Technology; Testing; Time; Training; Visual Cortex; Writing; antagonist; autism spectrum disorder; blind; density; experimental study; feeding; improved; insight; motor control; neural; neurophysiology; new technology; pharmacologic; predictive modeling; receptor; sensory input

The cortex must filter out the bulk of sensory inputs. Not enough or too much filtering may underlie a variety of disorders like autism and schizophrenia. Mounting evidence suggests that this depends on alpha/beta (~8-30 Hz) oscillations vs gamma (>35 Hz) with associated spiking. They are ubiquitous in cortex and anti-correlated. Gamma/spiking is high during sensory inputs while alpha/beta is high (and spiking is low) during conditions requiring top-down control. The central idea is alpha/beta (~8-30 Hz) rhythms in deep cortical layers inhibit the superficial layer activity (spiking and gamma, >35 Hz) that feed forward sensory inputs. Our testbed will be a model of Predictive Coding in which alpha/beta carries the top-down predictions from higher cortex that inhibit the feeding forward of bottom-up sensory inputs of predicted stimuli. We will test this hypothesis via direct cause-and-effect experiments, by manipulating the alpha/beta prediction rhythms in monkeys. We made this possible by developing a new ultra-fast latency (<10 ms) closed-loop system that can read the brain’s endogenous rhythms and phase-match electrical stimulation to them. We will also employ high-density “laminar” electrodes to record from all cortical layers and target stimulation to superficial vs deep layers. Laminar electrodes with injection ports will also allow selective pharmacological manipulation of deep vs superficial cortical layers. Monkeys will perform a local and global (patterned) oddball detection task. Our model makes specific predictions on how attenuating vs amplifying alpha/beta prediction signals will affect local physiological as well as feedforward vs feedback signaling of predictions and oddballs to higher vs lower cortex. Understanding neurophysiological properties, functions and interactions between cortical layers and their different dynamics can provide key insight into the control of cortical processing and the disorders that come from its dysfunction.

皮层必须过滤掉大部分感觉输入。不够或过多的过滤可能是 自闭症和精神分裂症等多种疾病。越来越多的证据表明，这取决于 alpha/beta（〜8-30 Hz）振荡与伽玛（> 35 Hz），并带有相关的尖峰。他们无处不在 皮质和抗相关。在感觉输入期间，伽马/峰值很高，而alpha/beta很高（并且 在需要自上而下控制的条件下，尖峰很低）。中心想法是alpha/beta（〜8-30 Hz） 深层皮质层中的节奏抑制了喂食的表面活性（尖峰和伽玛，> 35 Hz） 正向感觉输入。我们的测试平台将是一个预测编码的模型，其中alpha/beta带有 高层皮质的自上而下预测，抑制了自下而上感觉输入的喂养 预测刺激。我们将通过操纵直接因果实验来检验该假设 猴子中的alpha/beta预测节奏。 我们通过开发一个可以阅读的新的超快速潜伏期（<10 ms）闭环系统来实现这一目标 大脑的内源性节奏和对它们的相匹配电刺激。我们还将雇用 高密度“层流”电极从所有皮层层记录和靶刺激到表面 vs深层。带注射端口的层状电极也将允许选择性药理 操纵深层皮质层。猴子将执行本地和全球（图案） ODBALL检测任务。我们的模型对如何衰减与放大方式做出了具体预测 alpha/beta预测信号将影响当地的生理和馈送信号与反馈信号传导 对较高皮层的预测和ODBALL。了解神经生理特性， 皮质层及其不同动态之间的功能和相互作用可以提供关键的见解 控制皮质加工及其功能障碍的疾病。