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.

大脑皮层必须过滤掉大部分的感觉输入。不充分或过多的过滤可能是 各种障碍，如自闭症和精神分裂症。越来越多的证据表明，这取决于 阿尔法/贝塔(~8-30赫兹)振荡与伽马(&gt；35赫兹)振荡及相关尖峰。它们无处不在 皮质和反相关。在感觉输入期间伽马/峰高，而阿尔法/贝塔高(和 尖峰低)在需要自上而下控制的条件下。核心思想是α/β(约8-30赫兹) 皮层深层的节律抑制了表层的活动(尖峰和伽马，35赫兹) 前向感官输入。我们的试验床将是一个预测编码模型，其中阿尔法/贝塔携带 来自高级皮质的自上而下的预测，抑制了自下而上的感觉输入的前馈 可预测的刺激。我们将通过直接的因果实验来检验这一假设，通过操纵 猴子的阿尔法/贝塔预测节律。 我们开发了一种新的超快延迟(&lt；10ms)闭环系统，可以读取 大脑的内源性节律和相匹配的电刺激与之匹配。我们还将聘用 高密度“层流”电极记录从所有皮质和目标刺激到表层 VS深层。带有注射端口的层状电极也将允许选择性的药物 深部皮层与浅层皮质的操作。猴子将执行局部和全局(图案化) 古怪的检测任务。我们的模型对衰减和放大做了具体的预测 α/β预测信号将影响局部生理信号以及前馈和反馈信号 更高的皮质与更低的大脑皮层的预测和古怪。了解神经生理特性， 皮层之间的功能和相互作用及其不同的动力学可以提供关键的洞察力 控制大脑皮层的加工和由其功能障碍引起的疾病。