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

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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.