Federal BRAIN Initiative Funds Two Princeton Neuroscience Studies
The 21st century has brought with it some amazing scientific advances: the first draft of the complete human genome, the successful induction of pluripotent stem cells and the discovery of the Higgs boson or “God Particle.” Yet, as President Barack Obama stated in 2013, though “we can [now] study particles smaller than the atom … we still haven’t unlocked the mystery of the three pounds of matter that sits between our ears.” This statement was made as part of the President’s announcement of a new federal funding effort focused on brain research entitled BRAIN (Brain Research Through Advancing Innovative Neurotechnologies). Just as the Human Genome Project provided a forum for collaboration, the BRAIN initiative aims to build a map of brain activity using research from many different universities and technology firms.
Two Princeton studies have been awarded millions of dollars through the National Institutes of Health as part of the BRAIN program. Both projects are in line with the initiative’s goal of understanding the activity of all of the brain’s neurons, cells which enable communication within the brain and send signals outwards to the rest of the body. Many neuroscience experiments involve studying how and when neurons respond to particular stimuli. Funds from the BRAIN initiative are already being used to create technological tools for the interpretation of normal and abnormal neuronal activity, and, ultimately, studying brain disorders. Both Princeton teams have been awarded over one million dollars each for their research projects. The first project is lead by Carlos Brody, William Bialek, Sebastian Seung, David Tank, Samuel Wang and Ilana Witten, all of whom are associated with the neuroscience department. Their project will focus on working memory, the brain’s ability to store and process relevant information in a way that makes it easily accessible for the short-term. According to Edward E. Smith, Professor of Psychology at Columbia University, working memory is like a “mental blackboard” because it keeps pieces of information available for tasks your brain is performing, until that information isn’t needed anymore and can be “erased” (1).
Past research has implicated the dorsolateral prefrontal cortex in the functioning of this mental blackboard. Some of the neurons in this functional brain region located at the top front of the cerebral cortex are active when the visual cue is presented while others become active once the cue is gone. It has been hypothesized that these alternating neuronal firing patterns provide the mechanism of remembering the cue and its location (1).
The project spearheaded by Bialek and others at Princeton University will use neurotechnological tools to record the activity of neurons all over the brain, not just the dorsolateral prefrontal cortex, during working memory tasks. The researchers hope to learn more about how other areas of the brain contribute to storage and processing required in the maintenance of short-term knowledge. In particular, they will look for neural circuits that are activated during working memory tasks. Neural circuits are pathways between two neurons that allow one neuron to excite or inhibit the activation of the second neuron. Thus, Princeton researchers may be able to map a network of neural circuits in the brain that help us to store small, but critical, pieces of information. Conditions like Alzheimer’s, schizophrenia and Post-Traumatic Stress Disorder affect working memory, and if more is learned about the cells involved in working memory, future treatments for these conditions may be more effective.
The second Princeton-based neuroscience research project receiving funding through the BRAIN Initiative is sure to intrigue video game fanatics. Professor Sebastian Seung, who teaches in both the computer science and neuroscience departments, developed an online game that has been played by over 160,000 Internet users from approximately 145 countries (2). The game, EyeWire, studies the connectome, which is the “full set of neurons and the synapses that link them, [with] one million times more connections than your genome has letters” (2).
EyeWire works by providing each player with a three-dimensional cube of tissue that has been developed using data from electron microscope images. The tissue is from the retina, an area at the back of the eye that is light sensitive and sends visual information to the brain (3). Each cube is only 4.5 microns (0.00004 inches) long on each side, yet it contains many neuron branches. Each gamer uses the EyeWire software to color in patterns of neuron branching in their cube. Computers aren’t adept at identifying these neuron branching patterns, but humans can see them easily. The more coloring you do, the more points you earn. EyeWire players can accumulate points and compete in individual or team contests.
A better understanding of the human connectome means that scientists can study how genes influence the connections in the brain as a whole, as well as how these connections can be “miswired” during development to result in brain disorders (4).
For every $1 the US government invested in the Human Genome Project (HGP) between 1988 and 2003, the economic return has been $141 (5). Since the BRAIN Initiative is modeled off of HGP, it is likely that these two Princeton research projects (and probably more) will contribute significantly to the physical and economic well-being of many Americans.