Conserved thalamic mechanisms for attention and sleep

注意力和睡眠的保守丘脑机制

• 批准号: BB/X013634/1
• 负责人: Andrew Bagshaw
• 金额: $ 112.77万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX013634%2F1
• 关键词: Conserved; thalamic; mechanisms; attention; sleep

One of the defining characteristics of sleep is a change in the way the brain deals with external stimuli, like sights and sounds. While still being able to process information from the outside world (for example, if someone calls your name you may wake up), the complexity and nuance of the brain's response is considerably decreased. A similar process happens on a much shorter timescale when you are awake. Then, it is called attention, which refers to the ability to switch dynamically between reacting to or ignoring multiple co-occurring stimuli. To date, study of the brain networks underpinning these fundamental mechanisms of sleep and attention has been limited in humans. While insights from animal models provide us with crucial guidance, the ability to understand these processes in the human brain will provide rich new avenues of research in healthy brains and disorders like schizophrenia where these circuits are disrupted. Recent work in animals has suggested that the brain networks controlling responsiveness during sleep are the same as those responsible for attention during wakefulness. This project aims to study those networks in the human brain. This has not previously been possible, largely because the brain structures involved are difficult to visualise using MRI, the main technique to study structures that are deep within the human brain. However, in pilot data we have developed advanced brain imaging techniques which allow us to address these questions non-invasively and with unprecedented detail. Central to the control of sleep and attention, and the focus of this project, is a brain circuit involving the thalamus, the thalamic reticular nucleus (TRN) and the cortex. The thalamus is a deep brain structure that controls whether incoming information reaches the cerebral cortex. The TRN is a thin structure surrounding the thalamus which can block the transmission of signals from the senses to the cerebral cortex. Without access to this information, the computational power of the cerebral cortex is cut off from the environment, leading to the disengagement from the world that we experience during sleep. While small, around 3mm thick and 50-60mm long, the TRN therefore plays a role that is disproportionately important compared to its size. Functional MRI (fMRI) allows brain activity from throughout the brain to be recorded, and with current methods we can record from the thalamus and cortex. As it is smaller, the TRN is more difficult to see on MRI scans, but we have developed new MRI approaches which reliably identify it. These are based on MRI using a magnetic field strength more than twice that of a standard hospital scanner. With these cutting-edge techniques we can measure how the brain circuits identified from animal work are altered as people fall asleep or perform tasks which manipulate attention. Each participant will undergo an ultra-high field MRI scan to define their individual TRN. They will then take part in two sessions in a standard MRI scanner: one at night in which they will sleep, and another in the day in which they will perform an attention task that engages the thalamus-TRN-cortex circuit. They will wear a cap with electrodes to measure their electrical brain activity. This allows us to define when and how deeply they are sleeping and how their brain rhythms change with the task. Brain activity in the thalamus, TRN and cortex will be measured at the same time using fMRI. Despite the MRI scanner being an unusual place to sleep, we are experienced in this type of study and find that most people, if properly selected, are able to fall asleep. We will test the hypothesis that there is a common brain circuit underlying the change in responses to sensory stimulation during sleep and attention. It will provide fundamental new insights into the mechanisms by which information flow is controlled in the human brain, and open new ways to study brain disorders.

睡眠的一个决定性特征是大脑处理外部刺激的方式发生了变化，比如视觉和声音。虽然仍然能够处理来自外部世界的信息(例如，如果有人叫你的名字，你可能会被唤醒)，但大脑反应的复杂性和细微差别大大降低。当你醒着时，类似的过程发生的时间要短得多。然后，它被称为注意力，指的是在对多个共生刺激做出反应或忽略多个共同出现的刺激之间动态切换的能力。到目前为止，对支撑这些睡眠和注意力基本机制的大脑网络的研究一直局限于人类。虽然来自动物模型的洞察力为我们提供了至关重要的指导，但理解人脑中这些过程的能力将为研究健康的大脑和精神分裂症等疾病提供丰富的新途径，因为精神分裂症的这些回路会被破坏。最近在动物身上的研究表明，在睡眠中控制反应的大脑网络与在清醒时负责注意力的大脑网络是相同的。该项目旨在研究人脑中的这些网络。这在以前是不可能的，很大程度上是因为所涉及的大脑结构很难使用核磁共振成像来可视化，核磁共振是研究人类大脑深处结构的主要技术。然而，在试点数据中，我们开发了先进的大脑成像技术，使我们能够以非侵入性和前所未有的细节解决这些问题。控制睡眠和注意力的中心，也是这个项目的焦点，是一个涉及丘脑、丘脑网状核(TRN)和皮质的大脑回路。丘脑是一个深层的大脑结构，控制着传入的信息是否到达大脑皮层。TRN是围绕丘脑的一种薄结构，它可以阻止信号从感觉到大脑皮层的传输。如果不能获得这些信息，大脑皮层的计算能力就会与环境隔绝，导致我们在睡眠中体验到的与世界脱节。尽管TRN很小，大约3毫米厚，50-60毫米长，因此，与其大小相比，TRN扮演着不成比例的重要角色。功能磁共振成像(FMRI)可以记录整个大脑的大脑活动，利用目前的方法，我们可以从丘脑和皮质进行记录。由于TRN较小，在MRI扫描上更难看到，但我们已经开发了新的MRI方法，可以可靠地识别它。这是基于磁共振成像，使用的磁场强度是标准医院扫描仪的两倍以上。有了这些尖端技术，我们可以测量当人们入睡或执行操纵注意力的任务时，从动物工作中识别出的大脑回路是如何改变的。每个参与者都将接受超高场磁共振扫描，以确定他们各自的TRN。然后，他们将在标准的核磁共振扫描仪中参加两个阶段：一个在晚上，他们将在其中睡觉，另一个在白天，他们将执行一项涉及丘脑-TRN-皮质回路的注意力任务。他们将戴上有电极的帽子来测量他们的脑电活动。这使我们能够定义他们何时以及睡得有多深，以及他们的大脑节律如何随着任务的变化而变化。将使用功能磁共振技术同时测量丘脑、TRN和皮质的大脑活动。尽管核磁共振扫描仪是一个不同寻常的睡眠场所，但我们在这类研究中经验丰富，发现如果选择得当，大多数人都能入睡。我们将测试这一假设，即在睡眠和注意力集中期间，存在共同的大脑回路，潜在着对感觉刺激的反应的变化。它将为人类大脑中控制信息流的机制提供基本的新见解，并为研究大脑疾病开辟新的途径。