Meaning of the Mind

GRA Eminent Scholar Joe Tsien is unlocking how the brain works

Dr. Joe Tsien reads minds – at least, he’s working very hard to.

The neuroscientist and GRA Eminent Scholar heads an ambitious Brain Decoding Project at Georgia Regents University to unlock how the brain makes memories, perceptions, thoughts and behaviors. It’s an endeavor many scientists regard as a last frontier in the field.

To do this, Dr. Tsien and his colleagues in GRU’s Brain and Behavior Discovery Institute work with laboratory mice to decipher the meaning of hundreds of billions of neurons – nerve cells that send and receive electrical signals in the brain. By placing electrodes into the brains of mice, researchers literally can hear the pop-pop-pop of neurons firing. 

It is a sound that Dr. Tsien first heard in the 1980s as a sophomore at Shanghai’s East China Normal University. And he’s been listening to it ever since.

“The neurons generate electrical activity,” Dr. Tsien says. “Let’s say you see a picture, you hear a conversation, you have a thought. We look at how this electrical activity is generated at that particular moment. This is really reading the mind directly.” 

The researchers then look at how these moments form patterns. “So I can look at these patterns and say, ‘Oh, you are touching a banana.’ Not only that, but by reading the brain signals, I can tell if it is a ripe banana or a rotten banana,” Dr. Tsien says.  

The research initiative, known as the Brain Decoding Project, is like cracking a telegraph code, albeit an amazingly complex and elusive one. Unlocking how the brain works holds promise for everything from treating Alzheimer’s disease and schizophrenia to understanding what makes human beings human. 

The opportunity to focus on the Brain Decoding Project is what brought Dr. Tsien to GRU in November 2007. “I felt that GRU is a great place to do this type of work,” says Dr. Tsien, who co-directs the brain institute. So far, the medical college has built state-of-the-art lab space and hired three neuroscientists, and Dr. Tsien hopes to add another six to eight scientists in the next two years. Overall, GRA has committed $10 million to the project.

Dr. Tsien sees GRU as taking a lead role in the project but nowhere near the only role. “It is probably going to take the national and international scientific communities coming together. I don’t see this as a one-man, or even a 10-people, task,” he says.  

Over the years, collective research on how the brain works had yielded wide results. “People have been approaching this question of understanding the brain through various aspects: psychology, philosophy, molecular biology, genetics,” Dr. Tsien says. “We know that the hippocampus, when it is affected by stroke, produces memory loss. We know when there is a mutation of a gene, that leads to Alzheimer’s and Parkinson’s.”

However, scientists still don’t know how the brain functions at the most basic level. Dr. Tsien compares current knowledge about the brain to having the parts of a computer — the keyboard, monitor, etc., — but lacking the program needed to run the system. 

The key, he says, is understanding how memory is laid down – figuring out why we can remember hours later what we ate for breakfast or why we can put a name to a face we haven’t seen in years. 

“Memory is the bedrock of brain cognition,” he says. “Anything you do literally within a given framework, you need a memory.” 

Dr. Tsien has been at the forefront of research showing that manipulating a gene in mice can either enhance or impair memory. His follow-up on that research – which landed him on the cover of Time Magazine a decade ago – came with a 2010 study that showed how altering a gene that allows brain cells to communicate by just a fraction of a second longer improves memory.      

In the study, Dr. Tsien and colleagues also recently reported having deciphered conversations of neurons in the brains of mice as they form and recall memories. “I believe this is the first case where we’ve been able to decode this episodic memory in real time,” he says.  Even so, researchers still cannot answer the question, “What is memory?”   

For now, the GRU team is working to improve their ability to listen in on all of those chattering neurons. To the untrained ear, the sound of neurons firing is like listening to a crowd at a Braves game. “You need to figure out who is talking, almost like putting a listening device into a conference room,” Dr. Tsien says. “You try to figure out if there is some kind of structure or relationship in these neurons – who is the leader or who is doing what.”

The research could lead to a new day in artificial intelligence. “Knowing how the brain is able to turn bits and pieces into amazing processes — imagination, perception, creativities — could allow us to design the next generation of truly complete intelligent machines and networks,” Dr. Tsien says.

While such an idea captures the imagination, the implications of the brain decoding project for human beings are enormous. How it could eventually lead to treatments for Alzheimer’s or Parkinson’s, a degenerative disease that affects brain as well as motor function, seems obvious. “The brain is hundreds of billions of neurons and how they are connected,” Dr. Tsien says. “When the connections get degenerated, you morph into Azheimer’s disease or Parkinson’s.”

But the research also could bring new therapies to treat diseases and conditions that are virtually impossible to study in laboratory animals. 

Take schizophrenia, for example. Symptoms of the disorder typically include hallucinations and delusions. “Animals are not going to be able to tell you if they think someone is plotting against them,” Dr. Tsien says. Post-traumatic Stress Disorder (PTSD), which involves flashback memories and nightmares, also is very difficult to assess in laboratory animals. “With a lot of psychiatric disorders we are very limited in how we do research,” he says. The Brain Decoding Project “could really open the door to the systematic investigation of a lot of processes.”

How long all of this will take is unclear  — only it won’t be five years, even 10, Dr. Tsien says. It likely will be decades, if not longer. 

“It is such a complex problem,” he says, “but I am a patient man. It is so exciting. I can’t think of anything else more exciting than this.”