What information does laminar fMRI provide about cortical sensorimotor circuits? Validation with electrophysiology and targeted nerve injuries

点击翻译按钮获取中文摘要

Understanding how the brain processes information and how this is impaired in disease is one of the great challenges in science. The way information flows in cortical circuits consisting of interconnected brain areas, and the processing of information by these circuits is fundamental to brain function. However, we lack effective ways to noninvasively study such 'neural circuits' in animals or humans, because current methods are either too coarse, or they are fine-grained and invasive but cover only a small part of the brain. Functional magnetic resonance imaging (fMRI) is widely used to investigate brain function, and it provides information about which brain areas are active when a person performs a task, but it does not show how information flows in the brain. Although standard fMRI is too coarse to show cortical circuits, they can potentially be studied using high-resolution fMRI at 7T. It has sufficiently high resolution to visualize the layers (laminae) of the cortex, which is essential to understand cortical activity and connectivity, because neurons in different cortical layers perform different functions in the circuit. For instance, information arrives in the middle layers, while deep layers send output to other brain areas. High resolution fMRI is starting to allow the visualization of cortical layers. However, fMRI measures blood flow and metabolism, and does not directly measure neural activity, and the understanding and validation of how these laminar fMRI signals relate to laminar neural activity measured with electrophysiology, is lagging behind. This information can only be gained from studying laminar circuits in animals using both methods. In this study, we compare laminar fMRI, resting state fMRI (rs-fMRI) and laminar electrophysiological recordings in rats to determine what information laminar fMRI provides about the neural computations in the layers. Rs-fMRI is based on the principle that if two areas are connected, their activity fluctuates together. Current rs-fMRI methods are too coarse to resolve how information flows, but laminar rs-fMRI can potentially solve this problem, because knowledge of which cortical layers are connected makes it possible to establish those sending and receiving information. We will first optimize the data acquisition methods and characterize the laminar signals in the somatosensory cortex of healthy animals. Subsequently we will investigate how cortical circuits respond to the withdrawal of sensory input, done by making injuries to the spinal cord and peripheral nerve. We will make lesions that selectively interrupt one of the main spinal cord pathways (dorsal columns) carrying sensory information from the body to the brain, and compare the response to this partial injury with the response to complete loss of sensory input caused by cutting the peripheral nerve. To understand how reorganization of brain circuits in response to sensory deprivation changes over time, we will carry out laminar fMRI and electrophysiology at different times after injury, under circumstances where there is no repair (dorsal column injuries do not spontaneously repair, nerve regeneration is prevented by ligation). We will then investigate how brain sensorimotor circuits further change under circumstances where there is successful regeneration of peripheral nerve fibres using a nerve crush model. The timing of changes in cortical circuits will be correlated with behavioral measures of returning function.We expect the study to lead to improved interpretation of (laminar) fMRI, and provide new information about the functional activity and connectivity of sensorimotor circuits. 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.