Laminar fMRI and resting state fMRI in the somatosensory system - effect of peripheral nerve injury on cortical circuits

了解信息是如何在大脑中处理的，以及它是如何在神经和精神疾病中受损的，是科学上最大的挑战之一。功能磁共振成像（fMRI）是一种研究脑功能的非侵入性方法。信息在由多个相互连接的大脑区域组成的皮层回路中流动的方式，以及这些回路对信息的处理是大脑功能的基础。能够测量信息在大脑中流动的方式将对周围神经损伤后的康复有很大的好处，在这种情况下，大脑会自我重组，但以一种不完美的方式，往往会阻止完全恢复或导致慢性疼痛。由于目前的成像方法过于粗糙，我们目前缺乏有效的方法来研究人类的大脑回路。常用的功能磁共振成像（fMRI）方法可以提供一个人在执行某项任务时哪个大脑区域是活跃的信息，但无法显示信息是如何在大脑中流动的。克服这些限制研究皮层回路的潜在方法是使用超高分辨率功能磁共振成像，即具有足够分辨率的功能磁共振成像来分辨皮层的层（层）。解析这些层对于理解皮层回路及其连通性至关重要，因为回路中的不同功能被分配给不同层的神经元。我们建议使用层流fMRI和层流静息状态（rs） fMRI来发展和完善fMRI，以获得足够的分辨率来提供关于不同层的功能激活和连接的信息。Rs-fMRI的原理是，如果两个区域连接在一起，它们的活动就会一起波动（它们是“功能连接”）。了解哪些皮质层是活跃的，以及它们是如何连接的，就有可能确定哪些是发送信息的，哪些是接收信息的。层流-功能磁共振成像将在超高磁场（7T）下对人体进行优化。我们将优化采集技术，提高分辨率并开发数据分析方法。我们将评估健康志愿者和周围神经损伤患者感觉运动皮层皮层的活动和功能连通性。周围神经损伤是常见的，并且非常痛苦。复杂的显微外科手术重建有帮助，但恢复缓慢且非常不完整，尽管神经再生，但功能恢复不完全。缺乏恢复被认为是因为大脑回路在神经愈合所需的较长时间内进行了重组。我们将使用层流功能磁共振成像（层流fMRI）来研究大脑回路的处理过程是如何变化的，通过比较受伤后的回路，并跟踪随着时间的推移，神经重新连接时皮层的变化。神经损伤后，最初会出现感觉输入的丧失，导致大脑重组。为了了解感觉剥夺后大脑回路的重组以及随后的神经重连是如何随时间变化的，我们将在受伤后的不同时间进行层流fMRI和rs-fMRI，并将其与手部功能恢复进行比较。然后，我们将研究大脑感觉运动回路在功能恢复良好或恢复不太理想的情况下如何进一步变化。皮层回路变化的时间将与回归功能的测量相关联。我们期望这项研究能够为非侵入性脑功能研究开辟新的途径，并提供有关脑感觉运动区功能的新信息。此外，它将阐明大脑中的可塑性机制，与理解适应性功能恢复、利用活动依赖可塑性的康复策略以及大脑可塑性对周围神经修复后功能恢复的限制高度相关。

Understanding how information is processed in the brain and how this is impaired in neurological and psychiatric conditions is one of the greatest challenges in science. Functional magnetic resonance imaging (fMRI) is a non-invasive method for investigating brain function. The way information flows in cortical circuits consisting of multiple interconnected brain areas, and the processing of information by these circuits is fundamental to brain function. Being able to measure how information flows in the brain would be of great advantage in rehabilitation after peripheral nerve injuries, where the brain reorganizes itself, but in an imperfect way that often prevents full recovery or leads to chronic pain. We currently lack effective ways to study brain circuits in humans because current imaging methods are too coarse. The commonly used fMRI methods can provide information about which brain areas are active when a person performs a certain task, but cannot show how information flows in the brain. A potential way of overcoming these limitations to the study of cortical circuits is the use of ultra high-resolution fMRI, that is fMRI that has sufficient resolution to resolve the layers (laminae) of the cortex. Resolving these layers is essential to understanding cortical circuits and their connectivity because different functions in the circuit are assigned to neurons in different layers. We propose to develop and refine fMRI to attain a resolution that is sufficient to provide information about functional activation and connectivity in the different layers using laminar fMRI and laminar resting state (rs) fMRI. Rs-fMRI is based on the principle that if two areas are connected, their activity fluctuates together (they are 'functionally connected'). Knowledge of which cortical layers are active and how they are connected makes it possible to establish those sending and those receiving information.Laminar rs-fMRI will be optimized in humans at ultra high magnetic field (7T). We will optimize the acquisition techniques, enhance resolution and develop methods for data analysis. We will evaluate activity and functional connectivity in the cortical layers of the sensorimotor cortex in healthy volunteers and in patients with peripheral nerve injury. Peripheral nerve injuries are common and intensely painful. Complex microsurgical reconstruction helps, but recovery is slow and very incomplete, with incomplete recovery of function, despite that the nerve regenerates. The lack of recovery is thought to be because brain circuitry has reorganized in the long time it takes for the nerve to heal. We will use laminar fMRI to investigate how the processing in the brain circuits changes by comparing the circuitry just after injury, and follow the changes in the cortex over time, as the nerve reconnects. Initially after nerve damage there is a loss of sensory input, which leads to brain reorganization. To understand how reorganization of brain circuits in response to sensory deprivation and the subsequent reconnection of the nerve change over time, we will carry out laminar fMRI and rs-fMRI at different times after injury and compare it to the recovery of function of the hand. We will then investigate how brain sensorimotor circuits further change in cases of good functional recovery or when recovery is less optimal. The timing of changes in cortical circuits will be correlated with measures of returning function.We expect the study to lead to new approaches for the non-invasive interrogation of brain function and provide new information about the function of brain sensorimotor areas. In addition, it will illuminate plastic mechanisms in the brain highly relevant to understanding adaptive functional recovery, rehabilitation strategies utilizing activity-dependent plasticity and the limitations that brain plasticity imposes on functional recovery after peripheral nerve repair.