Researcher biography

About

The Chuang laboratory is developing functional and molecular imaging to understand the neural activity, connectivity and metabolism of the brain and to determine neural endophenotypes of diseases. Identifying disease-specific patterns of brain activity and connectivity as biomarkers could improve the characterisation of diseases and their progress; the Chuang group aims to facilitate early and specific diagnosis, optimise treatment and develop drug therapeutics. 

A major focus of the laboratory is to map and understand the functional connectome in vivo. The brain connectome describes how neurons are wired and interact. It is a critical component for linking behaviour with cellular and molecular changes. Many neurodegenerative and psychiatric disorders show deficits in brain networks, suggesting that disease connectomes may underlie disease progression.

To determine brain connectivity associated with behaviour, the Chuang group developed various magnetic resonance imaging (MRI) techniques to track neuronal connections, map large-scale brain synchrony, quantify cerebral blood flow and metabolism in vivo in the rodent brain. They identified ongoing synchronous activity following a memory task and found that connectivity patterns reorganised toward the cortex over time, in line with current understanding of memory consolidation. The connectivity and behaviour performance can be enhanced by Aricept®, a drug for treating dementia.

The relationship between the functional connectome and memory performance indicates the potential of functional MRI for tracking cognitive function in diseases and to test drug effects. Now, the group is developing techniques for mapping neural metabolism (eg, dynamic nuclear polarization and chemical exchange saturation transfer), neuronal stimulation (eg, optogenetics, DREADD) and recording (optical and electrophysiology) together with MRI to track and intervene behaviour and disorders, which would be translated in human.

PhD Projects:

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: 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.

Project 3: Understand interplay between blood flow, metabolism and brain connectivity in Alzheimer’s dementia

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 or tau tangle, the two major hallmarks of Alzheimer’s dementia, have been found but their relationships with disease process and cognitive impairment are unknown. Furthermore, deficient metabolic and 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.