This is the time of March Madness, Daylight Savings Time, and what Emily Dickinson famously called the “month of expectation.” March is also Brain Awareness Month, an annual celebration with school visits, community lectures, and lab tours to introduce the public to the mind-blowing world of neuroscience. A list of Brain Awareness events can be found at http://www.dana.org/brainweek where you will also find that March 10 -16 is the peak for related public events around the world.
Since NIMH began focusing on mental disorders as brain disorders nearly two decades ago, educating people about the brain has been a priority for us.1 We often say that with the powerful tools of neuroscience, we can now use the brain to understand the mind, fulfilling the original vision that Freud had for a scientific psychology. But we have to remain humble about our understanding of the brain, because even our most powerful tools remain pretty blunt instruments for decoding the brain. In fact, we still do not know how to decipher the basic language of how the brain works.
A few numbers can help to define the challenge. The human brain is thought to have close to 86 billion neurons, each making on average about 10,000 connections. In contrast to most animals, our brains are largely made up of a heavily folded cortex, accounting for 80 percent of brain mass and about 100,000 miles of axons that provide the highways between neurons.2
How many different kinds of neurons are there in the brain? We really don’t know. Unlike the heart or kidney, which have a small, defined set of cell types, we still do not have a taxonomy of neurons and neuroscientists still argue about whether specific types of neurons are unique to humans. But there is no argument that neurons are only about 10 percent of the cells in the human brain. Most of our brain cells are glial cells, once thought to be mere support cells but now understood as having a critical role in brain function. Glial cells in the human brain are markedly different from glial cells in other brains, suggesting that they may be important in the evolution of brain function. As one hint to their function, an NIMH-supported study reported last week that human glial cells (but not mouse glial cells) transplanted into the mouse brain improve memory.3
How does the brain work? Again, we really don’t know. We have a very detailed understanding of how the heart pumps and the kidney filters, but how the brain encodes, stores, and retrieves information is still largely a mystery. We have known for over a century that most of the cortex is organized horizontally into six precise layers and much of the cortex has vertical mini-columns, but how this matrix of horizontal and vertical structures computes information is not really clear.
Neuroscientists talk a lot about brain circuits. In fact, the word “circuit” is probably misleading. We do not know where most circuits begin and end. And unlike an electrical circuit, brain connections are heavily reciprocal and recursive, so that a direction of information flow can be inferred but sometimes not proven. We believe there are “emergent properties” of the brain that convert electrical signals into memories or dreams, but how this happens is still a mystery. Recent studies have shown that diffuse waves of synchronization across the brain may be critical for attention or learning, but we are just learning about these slow waves of activity, and whether they occur at the “speed of thought” is still debated.4
Of course, the spectacular images from MRI and PET scans have already given us maps for perception and fear and language and many other functions. As scanners have improved their resolution from 1.5T (tesla) to 3T to recent 7T magnets and the protocols and analytic approaches have evolved, we now can map the cortical real estate associated with complex tasks like decision-making and face recognition. But these approaches even with the best current technology are still a 30,000 foot view of the action. Jay Giedd here at NIMH estimates that each gray matter voxel – the individual 3D pixels of 1 cubic mm that make up the scan – contains about 90,000 neurons, 400 meters of dendrites, and 4.5 million synapses. Each scan has over 650,000 voxels. And the actual measure is not neural activity per se but local blood flow, which changes slowly relative to the speed of thought.
In a sense, functional MRI is providing an image of something like the power grid of a city. fMRI slowly maps where and when different parts of the brain wake up, based on blood oxygen metabolism. By contrast, the street map of the brain is being mapped by the Human Connectome Project. Supported by the NIH Blueprint for Neuroscience Research, scientists working across the country are building something like a Google map for the human brain. In the first two years of the Human Connectome Project, scientists at Massachusetts General Hospital have created new MRI scanners with greatly enhanced resolution for looking at the geometric structure of the human brain.5 One remarkable claim from that work (still controversial) is that the fiber connections which heretofore looked like a bowl of spaghetti might actually have a relatively simple grid structure, allowing comparisons of connectomes between people. This kind of comparison is already underway at Washington University where the connectome group is obtaining the wiring diagrams of 1200 healthy adults, including 300 twin pairs. Last week, data from the first 68 volunteers were released on the Connectome website.
Whether March for you means basketball, changing clocks, or expectations, I hope you will check out some of the Brain Awareness events. Brain science has become one of the most exciting frontiers of science. When I was a kid, the scientific frontier was “outer space.” Today it seems to be “inner space” that fascinates the boldest and brightest young minds (or should we say young brains). We are still at the beginning of what could be an era of brain exploration, with great promise for understanding more about how each of us thinks and dreams and loves, but perhaps even greater promise for helping people with mental disorders.
1 Insel T. Mental disorders as brain disorders. TEDxCaltech talk 18 January 2013. California Institute of Technology, Pasadena, CA.
2 Lent R, Azevedo FA, Andrade-Moraes CH, Pinto AV. How many neurons do you have? Some dogmas of quantitative neuroscience under revision. Eur J Neurosci. 2012 Jan; 35(1):1-9. doi: 10.1111/ j.1460-9568. 2011. 07923.x.
3 Han X et al. Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell. 2013 Mar 7; 12: 342-353. doi: 10.1016/ j.stem. 2012. 12.015.
4 Salazar RF, Dotson NM, Bressler SL, Gray CM. Content-specific fronto-parietal synchronization during visual working memory. Science. 2012 Nov 23; 338(6110): 109-100. doi: 10.1126/ science.1224000.
5 Wedeen VJ et al. The geometric structure of the brain fiber pathways. Science. 2012 Mar 30; 335(6076): 1628-34. doi: 10.1126/ science. 1215280.