The day 14-year-old Christos Constantinidis finished reading Asimov's New Guide to Science, he knew he was going to be a scientist.
Today, the holder of the Stevenson Chair and associate director of the Vanderbilt Brain Institute runs the Constantinidis Lab at the Vanderbilt University School of Engineering. He studies what's actually happening in our brains when we're thinking.
His curiosity drives the core areas of his research-working memory, cognitive development and, most recently, an FDA-approved clinical study focused on improving memory in Alzheimer's patients. Additionally, Constantinidis' new book, Working Memory, was released earlier this summer.
Constantinidis' interest in neuroscience was piqued near the end of his undergraduate studies at the University of Athens in Greece. Wrestling with what his contribution to science might be, he settled on the puzzle that is the human brain.
"It was more of a romantic decision," Constantinidis said. "My undergraduate studies were very general-my degree was in biology-and when I was finishing, I thought, 'What is the biggest unanswered scientific question of our time? Wouldn't it be cool to study and try to understand the brain?' So, it was a new path of discovery. Since then, every day has been another interesting experience for me."
The decision took him from Athens to Baltimore, Maryland, where he earned his Ph.D. in neuroscience at Johns Hopkins University. He went on to Yale School of Medicine to train under legendary neuroscientist Patricia Goldman-Rakic. It was there that Constantinidis was able to really delve into working memory. The experience shaped his path significantly.
"Pat was one of my heroes," Constantinidis said. "She was a preeminent scientist-a towering figure of incredible stature in the field-and being in her lab was incredibly enriching. There were so many people there with diverse backgrounds and expertise in different areas of science who were all interested in the same question.
"I had the chance to be right there in the center of the scientific endeavor on understanding working memory," Constantinidis said, "and this has been the focus of my research ever since."
In his lab at Vanderbilt, Constantinidis studies how neurons-the cells that carry information through the brain-fire when we are thinking. He focuses on the prefrontal cortex, which is the part of our brain we use for keeping things in our train of thought (remembering a PIN code text message long enough to type it into a website), as well as executive functions like inhibiting impulses and making decisions. It's also a part of our brain that doesn't mature until adulthood.
Constantinidis' research zeroes in on what neuronal maturity in the prefrontal cortex actually looks like.
"Everyone knows that the prefrontal cortex takes time to mature … but what does that mean?" Constantinidis said.
"What does it mean for a neuron to be immature? How does it fire … differently than the mature neurons?"
"What we found was that neurons in the adult prefrontal cortex have more ability to generate what we call 'persistent activity.' From adolescence to adulthood, persistent activity increases," Constantinidis said.
Persistent neuronal activity is why we can remember stimuli after we see them. Neurons continue firing, holding that information in the brain for just a few critical seconds. This research has implications beyond adolescent development.
"In conditions such as aging-and more so in pathological conditions such as Alzheimer's-we see the opposite trajectory. The persistent activity declines," Constantinidis said. "We've studied this phenomenon for several years, and we understand it pretty well, so we were able to use our knowledge to develop a method of deep brain stimulation that can improve working memory."
By inserting microelectrodes into an area of the brain called the basal forebrain, the lab has found that electrical pulses can release a neurotransmitter called acetylcholine. The result is improved focus, attention and working memory.
Now Constantinidis and his team are setting up a three-year clinical study on Alzheimer's patients with profound memory deficits.
"Our plan is to track two initial patients over a period of three years and understand how this therapy potentially alleviates working memory symptoms," Constantinidis said.
For his research on working memory, Constantinidis, who is a professor of biomedical engineering, psychology and neuroscience, among other disciplines, has been elected a fellow of the American Association for the Advancement of Science, the prestigious scientific society behind the Science family of journals.
"I feel very honored and very humbled," Constantinidis said. "I feel this award recognizes the work of all of my trainees, more than anything else-all of the students who worked in my lab over the years, who dug deep into the questions and allowed our team to improve our understanding of these fundamental processes of the brain."
- Check out Constantinidis' new book Working Memory
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- Learn more about the Vanderbilt Brain Institute
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