Magnetic resonance imaging (MRI) is a powerful tool that can map structure, function and connectivity of the brain noninvasively for understanding brain function and its deficit in disorders. As the same technique can be applied in both humans and animals, it allows direct translation of findings in animal models to humans, or vice versa. The laboratory aims to identify neuro-endophenotype of brain functions and disorders using advanced MRI techniques to improve our understanding of cognitive functions and to facilitate early diagnosis of diseases and evaluation of treatment.

Project 1: Understand neural basis of resting-state network

An interesting phenomenon of the brain is that certain brain areas form networks of synchronous oscillation at the resting (task-free) state. These resting-state networks can be detected by functional MRI (fMRI) noninvasively and their changes have been associated with attention, learning, memory, dementia and other disorders. While widely applied, the neural basis and function of resting-state networks are largely unknown. We aim to understand the neural basis underlies the resting-state networks, the axonal connectivity that supports the network topology and their relevance to behaviour, particularly learning and memory. We are setting up a fibre photometry system for simultaneous recording of neuronal calcium activity and fMRI to determine the neurophysiological origin of the large-scale oscillation and its plasticity after learning. Optogenetics will be used to manipulate the network activity to determine the function of the network oscillation in behaviour.

Project 2:  Understand interplay between blood flow, amyloid plaque and brain connectivity

Neurodegenerative diseases, such as dementia, are irreversible and generally incurable and hence early detection is essential so that interventions can be applied to slow down its progression. Impaired brain connectivity that colocalized with amyloid plaque, a major hallmark of Alzheimer’s dementia, has been found but its relationship with amyloid pathology is unknown. Furthermore, deficient cerebrovascular function has also been found in dementia, which may affect the brain network function due to reduced supply of nutrients; however, whether it involves in the pathogenesis is not clear. We aim to further understand the relationship among these factors using human brain imaging data and test hypothesis in animal models. This translational study would provide new ways for assessing brain function and indicate new directions for treatment development.

Project 3: Imaging brain connectome of learning and memory

How memory is formed and stored has been one of the most intriguing question in neuroscience. Besides cellular and synaptic changes in this process, recent studies indicate that learning shapes large-scale brain networks. Our previous work showed that maze training can induce long-lasting change in the spontaneous oscillation across the brain that can be detected by resting-state functional magnetic resonance imaging (fMRI). However, the relationship between large-scale brain network, synaptic plasticity and behaviour is still elusive. This project aims to identify connectivity signature of memory formation so as to determine key brain areas and pathways in this process. We will use advanced MRI, two-photon microscopy and calcium recording to characterise the structural and functional connectivity changes in memory consolidation in mouse models following behavioural training. Network analyses will be applied and correlated with behaviour. The behaviour-related brain networks identified will be validated by opto- and chemo-genetic methods.

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