Researcher biography

The goal of the lab is to understand the neural endophenotype of diseases using functional and molecular imaging. Magnetic resonance imaging (MRI) is an excellent tool for in vivo imaging of brain structure, function, connectivity and metabolism. Together with molecular information by positron emission tomography (PET) and optical imaging, they could be biomarkers for characterising and tracking pathophysiological progression of diseases in vivo. These imaging biomarkers will be validated in rodent (especially transgenic mouse) models of brain disorders and translated to human to facilitate the understanding of mechanism, early detection, better prognosis and treatment development.

Especially, we focus on developing novel methods for imaging neural activity, connectivity and transmission. BOLD and perfusion-based functional MRI has been widely used to detect brain activation responding to task/stimulation or neural synchrony (aka, functional connectivity) in resting-state. We have successfully established arterial spin labeling (ASL) and resting-state fMRI in rats and mice to detect neuroplasticity and drug effects. Combined with optogenetic manipulation, we can map the entire activity and connectivity of specific neural pathway. To further understand the underlying neurotransmission change, magnetic resonance spectroscopy will be used for measuring GABA and glutamate. New methods based on chemical exchange saturation transfer (CEST) will be developed to allow imaging glucose metabolism and neurotransmission. In addition, functional contrast agents such as manganese will be explored to image Ca2+ dependent and neuronal connectivity. These techniques will be validated and compared using PET tracers, electrophysiology and optical imaging to have comprehensive view of the structural, functional and molecular process in the brain. We will apply these techniques to understand the functional connectomic signatures of neurodegenerative diseases and psychiatric disorders, as well as their relationship with genetics, neurotransmission, electrophysiology, behaviour and other disease phenotypes.

Currently Recruiting for New PhD Projects:

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.

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.

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.

Neuroinflammation, brain connectivity and neurodegeneration

Disease dependent derangement of brain connectivity has been found in various neurodegenerative and psychiatric disorders, indicating that impairment of structural and functional connectivity could be involved in the pathogenesis of the disease and the potential of using connectivity as a disease biomarker.  Furthermore, neuroinflammation has also been identified in various neurodegenerative and even psychiatric disorders. However, whether inflammation is involved in the pathogenesis and its relationship with impaired connectivity are not clear. We aim to further understand the role of neuroinflammation in the disease progression by combining imaging (PET scan of neuroinflammation and multimodal MRI) of human patients and animal models of Huntington disease to test hypothesis and validate in animal models. This translational study would provide new knowledge of the role of neuroinflammation in the pathogenesis and progression of disorders, new biomarkers for assessing pathology and new directions for treatment development.