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量的感觉输入，过滤不足或过多可能是大脑皮层的基础。 越来越多的证据表明，这取决于自闭症和精神分裂症等各种疾病。 α/β（~8-30 Hz）振荡与伽玛（>35 Hz）振荡以及相关的尖峰它们普遍存在。 皮质和反相关的伽马/尖峰在感觉输入期间较高，而阿尔法/贝塔较高（并且 在需要自上而下控制的条件下，峰值较低），中心思想是 alpha/beta (~8-30 Hz)。 深层皮质层的节律抑制浅层活动（尖峰和伽马，>35 Hz） 我们的测试平台将是一个预测编码模型，其中 alpha/beta 带有 来自较高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 我们将通过直接因果实验，通过操纵来检验这个假设。 猴子的α/β预测节律。 我们通过开发一种新的超快延迟（<10 ms）闭环系统来实现这一点，该系统可以读取 我们还将采用大脑的内源性节律和相位匹配电刺激。 高密度“层状”电极可记录所有皮质层和浅层目标刺激 与深层电极相比，带有注射端口的层状电极也将允许选择性药理学。 深层与浅层皮质层的操纵将执行局部和全局（模式化）。 我们的模型对如何衰减与放大做出具体预测。 α/β 预测信号将影响局部生理以及前馈与反馈信号 了解神经生理学特性的预测和奇怪现象， 皮质层之间的功能和相互作用及其不同的动态可以提供关键的见解 大脑皮层处理的控制以及由其功能障碍引起的疾病。