The brain game unlocking the mysteries of human thought

Professor Ken Yung Kin-lam is the Associate Vice President (Research) and Chair Professor of Biology and Neuroscience at the Department of Science and Environmental Studies (SES). He is also the head of the recently opened University Research Facility of Human Behavioural Neuroscience (UHBN).

After graduating from Hong Kong Baptist College (now a university), Professor Yung obtained his MPhil degree from the University of Hong Kong and his DPhil from the University of Oxford. Prior to joining EdUHK, he served as the Ma Pak Leung Endowed Professor in Innovative Neuromedicine and Executive Associate Dean of the Graduate School at Hong Kong Baptist University.

Professor Yung has published over 190 SCI papers in internationally renowned journals. He has also served as Review Editor for Frontiers in Neural Circuits, and as a member of the Editorial Board of Research Integrity and Peer Review. He and his team have developed nanomaterial-based technologies for harvesting autologous neural stem cells and devices for cell differentiation. These technologies have won over 50 international innovation awards, including the Gold Medal and Gold Medal with Congratulations of the Jury at the International Exhibition of Inventions in Geneva. Many of his innovations have been patented in mainland China, the United States, Europe, and Hong Kong.

He has also served as a member of the International Brain Research Organisation and as President of the Hong Kong Movement Disorder Society. Currently, he is the Chairman of the Board of the Hong Kong New Generation Cultural Association and a member of the expert panel for the Ministry of Science and Technology of the People’s Republic of China.

FLASS FORWARD has spoken with this internationally renowned neuroscientist to understand how his research can assist patients with neurodegenerative diseases and what motivates him to persist in his decades-long research endeavour. He also offers some tips on how to keep our brains and nervous systems healthy.

A1: The human brain is estimated to contain approximately 86 billion neurons, which are the fundamental building blocks of the brain's neural network, responsible for processing and transmitting information throughout the body.

Neuroscience is a discipline that studies the brain and nervous system. In simplified terms, it can be divided into two main branches. The first branch covers fundamental studies on brains and neurons, focusing on the physiological properties of neurons. This branch typically involves research on animal nervous system and is closely related to biomedical research.

The second branch examines the biological bases of human cognition and behaviour. It investigates how neurons form networks and how nervous systems encode or decode information to command functions such as sensory perception, motor control, memory, and language. In other words, it explores how brain activities influence human behaviour, thoughts, language, emotions, and memory. This branch also includes research on neurological disorders such as Alzheimer's disease, Parkinson's disease, Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), as well as other mental illnesses like chronic depression and schizophrenia.

A2: Ageing plays a crucial role in the rise of neuroscience. It is a well-known fact that the world’s population is rapidly ageing. According to WHO, the proportion of people aged 60 years and above is expected to double from 12% in 2015 to 22% by 2050¹. Ageing leads to declines in health and performance, particularly noticeable in cognitive functions. Indeed, many neurological disorders, such as Alzheimer’s disease or other types of dementia, are closely connected to ageing. Research indicates that the risk of developing Alzheimer's disease significantly increases with age. Some statistics suggest that around 10% of individuals aged 80 and above suffer from it.

In response to an ageing population, many societies worldwide have invested substantial medical and social care resources to treat age-related illnesses and improve the wellbeing of the elderly. Many neuroscientists are contributing by devoting their research to discovering new solutions for these morbidities. This has become a fundamental driving force behind the exponential growth of the discipline over recent decades.

In addition to ageing, new enabling technologies are also propelling advancements in neuroscience. With more powerful equipment now available, research into nervous systems at a cellular level has made significant progress in recent decades. By employing methods such as neuroimaging and brain wave analysis, we have amassed considerable knowledge about various brain-related diseases like Parkinson's and Alzheimer's.

We have also made strides in understanding human cognition. Research into brain connectivity enables neuroscientists to better understand how different brain regions interact to produce complex thoughts and behaviours. However, there remains a noticeable gap that scientists must bridge before we can claim a comprehensive understanding of the biological bases of learning, behaviour, emotions, and memory.

A3: Many neuroscientists believe that understanding how the mind works is crucial for helping individuals with mental health issues. They are eager to employ neurological methods as alternative approaches for treating mental illnesses. The growing interest in neurological studies also stems from humanity’s enduring intellectual curiosity to understand our minds.

Mental illnesses, such as depression, anxiety disorders, or insomnia are indeed very common. According to some studies, approximately 20% people worldwide experience major depression at some point in their lives. Traditionally, medication has played a central role in treating various mental health conditions. When scientists discovered that antidepressants could regulate serotonin levels in individuals with depression², they began prescribing these medications to alleviate depressive symptoms. Medical research has shown that mental illnesses like Parkinson's Disease and ADHD are associated with lower dopamine³ levels; therefore psychiatrists administer drugs that stimulate dopamine secretion when treating patients with these conditions.

For many years, drug treatment has been mainstream; however, while there have been certain breakthroughs in drug therapy for mental patients over recent decades, overall progress has been slow. Furthermore, medications such as antidepressants, anti-anxiety drugs, and mood stabilisers can only reduce psychotic symptoms without addressing root causes. Many psychiatric disorders, like depression and Schizophrenia, have genetic underpinnings complicated by distorted thoughts and perceptions of reality alongside unfounded beliefs. To effectively treat these conditions, neuroscientists argue we need a deeper understanding of the human thoughts mechanisms.

Questions such as “Why can humans think?”, “How do humans think?”, and “What constitute human beliefs?” are age-old inquiries that generations of biologists, philosophers, psychologists, and cultural anthropologists have sought to answer throughout history. Despite their efforts, aspects like human cognition and self-reflection largely remain enigmatic. While no easy answers exists for these questions, an increasing number of neurological studies aim to unlock the mysteries behind human thoughts and beliefs. This quest is driven not only by a desire for better treatments for mental illnesses but also by our relentless curiosity about fundamental truths. There is considerable hope within the scientific community that neuroscience will eventually provide answers to these profound questions.

A4: Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, involve the progressive loss of specific neural cells. The currently available therapies such as drug treatments can only provide symptomatic relief but do not address the underlying causes of these diseases. In this sense, they are incurable at the moment.

In patients with Alzheimer’s disease, nerve cells in the brains are damaged, affecting normal cognitive functioning, speech, and movement. As the disease progresses, Alzheimer’s patients experience severe memory loss, even struggling to remember their close family members. Parkinson’s disease is a complex condition that primarily arises from the death of dopamine-producing neurons in the brain,⁴ resulting in stiffness or slowing of body movements.

Both Alzheimer’s disease and Parkinson’s disease are progressive. Currently, patients with these diseases take drugs to combat their illnesses. For example, patients with Parkinson's disease take L-DOPA to increase their dopamine concentrations in an attempt to reduce symptoms. While drugs can slow down the degenerative process for a period, their effectiveness reduces over time. Drug treatment can only relieve symptoms but cannot truly cure the root causes of the disease.

Deep Brain Stimulation (DBS) has also been used to combat Parkinson’s disease, Alzheimer’s disease, and other mental conditions. DBS is a surgical method that implants electrodes into specific areas of the brain to deliver electrical impulses to stimulate brain activity. Again, this method only alleviates symptoms but does not cure the disease.

As the root cause of all neurodegenerative diseases is the progressive death of neurons, if we can induce the regeneration of brain cells, specifically neural stem cells (NSCs), there is a high potential for curing these diseases. My previous research project aimed to retrieve NSCs from the lateral ventricles of patients, and then grow and implant new NSCs back into the patient’s brain.

The immediate difficulty we encountered was how to access the brain to obtain stem cells. We overcame this challenge by using magnetic nanoparticles (MNPs) coated with antibodies to harvest neural stem cells from the brain. As nano-sized devices are very small, their invasion into brain is minimal. Once we harvest neural stem cells from the brain, we culture them in a special medium so that they can proliferate. Finally, we implant the newly formed neutrons back into the patient’s brain to replace the damaged neurons. Since these new neural cells come from the patient’s own stem cells, they should be able to survive when transplanted back into the patient’s brain. This is called cell replacement therapy.

The project team has used animals to test this method of extracting and cultivating neural cells. The results have been satisfactory, and this approach called nanomaterial-based technologies for harvesting autologous neural stem cells is proven viable. Of course, we still need further adaptations and extensive clinical tests in humans before medical professionals can safely apply the technology to harvest NSCs from a human brain.

My previous research project also developed a nanomaterial-based cell differentiation device that can minimise the risk of tumorigenesis in stem cell therapy.⁵

A5: Obtaining NSCs in sufficient quantities for therapeutic applications has been challenging, as it often requires invasive procedures on the brain. Around ten years ago, I had a series of discussions with material scientists to find a novel approach to address this problem. We discovered that nano-scale devices are extremely small and can navigate through the body's vasculature and across the blood-brain barrier with minimal intrusion into the brain. Ultimately, we used magnetic nanoparticles (MNPs) in animal tests to retrieve NSCs from the brain. The tests have shown that this approach is feasible.

In the past decade or so, numerous studies have confirmed that nanomaterials have great potential in isolating, tracking, and manipulating stem cells. I still remember the joy of discovering how to use nanoparticles to retrieve NSCs. I am particularly delighted that this success was a result of cross-disciplinary collaboration.

A6: Like many other scientists, my thirst to understand fundamental truths about nature and human beings has motivated me to conduct research and ask questions. It is this desire to explore the unknown and seek new knowledge that drives us to persist on our academic paths.

As a scientist, I find engaging in academic research joyful and rewarding. There is a great sense of accomplishment when you publish your findings in international journals and receive appreciation for your presentations at international conferences from your peers. These are testaments to the rigor and significance of your research.

Today, scientific discoveries result from teamwork in which scientists from diverse backgrounds come together to tackle complex problems. New insights emerge as they exchange ideas and challenge each other's assumptions. Even your own students can play a vital role in your research. I have many experiences of being inspired by insightful questions from my students. Their questions stimulate me to approach old problems from new perspectives.

In the past three decades, I have been pleased to witness the growth of the research community in Hong Kong. The city has many talented researchers who are working hard on their projects. I feel proud and fulfilled to be part of both the scientific community here in Hong Kong and globally. Together, we are contributing to advancing scientific knowledge.

A7: As explained above, the ultimate purpose of neuroscience research is to develop effective treatments and therapies for neurological illnesses while keeping the nervous system healthy. Aside from remedial measures, there are many other ways to maintain our brain health.

Adequate exercise is certainly beneficial for our brains. Brain activity consumes a lot of energy, around 20% of the body's total oxygen supply. When engaging in physical exercises, especially aerobic activities like running, cycling, or swimming, our hearts pump faster and we breathe deeper to inhale more oxygen. In the long run, this improves our ability to take in and use oxygen, which enhances our brain performance.

Many studies have proven that cognitive activities help prevent cognitive decline. Activities such as reading, playing electronic games or chess and mahjong, listening to music, watching movies, or learning a new language stimulate our thinking, and improve our concentration and memory, keeping our brains sharp. ⁶

Sleep is also vital for our mental health. Scientists have discovered that sleep has a “waste removal function”. Damaged proteins are produced during normal bodily functions; when we sleep, these toxic proteins are removed from our bodies which aids in recovering brain cells.⁷ Some research even indicate that disturbances in sleep patterns along with poor sleep quality could lead to an increased risk of dementia as we age.