We’re about to start wondering how we ever managed without a map of the brain.
In 2016, researchers at Washington University (with partners at Oxford University and the University of Minnesota and contributions from Saint Louis University and several other institutions) completed their work on the Human Connectome Project. That means they’ve traced the brain’s pathways, illuminating, with unprecedented precision, patterns of connection among our 90 billion neurons as they send information across about 150 trillion synapses.
How’d they do it? With scans of more than 1,100 healthy young human brains, along with tons of information about how they think and live. A superpowered custom MRI machine imaged the subjects during tasks and at rest, and researchers layered in genetic and behavioral information, cognitive and motor and personality tests…
All that data’s now stored here, and it’s accessible at no cost to any researcher in the world.
Analysis is only beginning. Yet in the lab of principal investigator Dr. David Van Essen, who holds an endowed professorship in neuroscience at Wash. U., they’ve already mapped the cerebral cortex. Dr. Matthew Glasser used several methods at once, noting variations in the cerebral cortex’s thickness, measuring the myelin that insulates nerve fibers even in the gray matter, and using the HCP data to see which areas were functionally connected, their neurons firing together even when separated by long distances.
The cerebral cortex is a bit like a floppy pizza that’s been tossed in the air a few times too many: Thick in some places, thin in others, it has folds and ridges, as though it’d been crumpled to fit into a small bowl (like our skull). “Matt and I went over the entire convoluted cortical sheet and all the information we obtained and looked for sharp transitions,” Van Essen says. To switch metaphors, “It’s like looking for the political subdivisions instead of the mountains and valleys on the earth’s surface. The political subdivisions reflect the interactions among billions of neurons: who they’re talking to and how they interact. There are sharp differences between one group of neurons and the next.”
Not only a boon for research, the map will also help neurosurgeons avoid certain areas or intervene in others with unprecedented precision.
“We could conceivably reverse neurological disease.”
“As a neurosurgeon, I’ve never before had a wiring diagram for the machine I’m operating on,” says Dr. Richard Bucholz, the K.R. Smith Endowed Chair in Neurosurgery at the SLU School of Medicine.
Now he does.
Bucholz’s own part in the HCP was to study the electrophysiology of the brain—the magnetic signals generated by the nerve cells every millisecond—in 100 of the HCP subjects. He predicts that it will soon be possible to generate individual connectomes for all of us. Doctors will be able to look at a football player’s brain before he gets injured, then repeat the connectome to check for degradation. They’ll also be able to detect fine changes that indicate early Alzheimer’s disease or monitor a medication’s effectiveness or focus an intervention. “Say we’re dealing with Parkinson’s,” he suggests. “If you can come up with an accurate diagram and show where the wiring has started to fail, maybe you can do deep brain stimulation or [someday soon] tissue transplantation.
“We could conceivably reverse neurological disease,” he says.
So far, what’s most surprised Bucholz are the HCP data from sets of twins: Genetics plays a bigger role than he’d anticipated, encoding pathways of connection in the brain. “We tend to think that the neurological system responds more to environmental influences than anything else,” he says, “but there seems to be a high degree of concordance between identical twins. And these connections are the heart of the self: They define how one responds to the environment—emotionality, judgment, intelligence, everything that makes you human.”
Dr. Deanna Barch, who chairs the Department of Psychological and Brain Sciences at Wash. U., says she’s “been surprised in the opposite way, in terms of things I thought would be genetically influenced that were not. We do see patterns of brain connectivity, but some of the cognitive measures, like working memory and episodic memory, aren’t as genetically influenced as I would have thought.”
(It would be fascinating, the two agree, to see what the HCP brains look like a few decades from now, when the twins’ early shared environments are a smaller fraction of their life experience.)
Van Essen likes finding new clues: Little 55B, an area of the brain that had been largely ignored, turns out to be an intriguing part of a large, complex network involved in language, he reports. Like Barch, he’s fascinated by all the variability in the HCP results. Neighboring areas sometimes even swap positions. And though twins might receive identical genetic instructions, the folds in their cerebral cortexes look nothing alike. “There could be different landscapes but a lot more similarity in the actual circuitry.”
Branches are already shooting from the giant tree trunk of the HCP. The Lifespan Human Connectome Project, for example, will scan people from age 36 to 100-plus to see what healthy aging looks like, comparing brain scans over time and gathering lifestyle information to see what influences might be powerful.
A parallel project will be focused on childhood development, from age 5 to 21.
Meanwhile, the National Institutes of Health is funding 13 disease connectome projects. Schizophrenia, for example, is diagnosed basically by symptom. If Connectome scans reveal subdivisions of the disease, that could speed and focus treatment.
As for the lifespan data, it will show us whether the actual map of the brain changes over time or stays constant while its neurons’ pathways are rerouted. “My guess is that the biggest change will be in the wiring,” Van Essen says. “If I could hold my breath for all these questions we want to ask, my lungs would explode.”
A Deeper Look
Mind Rules Body
In a recent study, stroke patients used their minds to open and close a device fitted over their paralyzed hands, thus gaining more movement and control. Essentially, they were training the uninjured parts of their brains to take over functions previously performed by the injured areas.
Mapping Memory
The U.S. Department of Defense is funding a huge effort to model how we understand and remember events. The goal is to improve artificial intelligence. But the model could also illuminate various kinds of dementia and memory disorders.
Don't Get Your Bowels In An Uproar
Using both brain and gastro-intestinal imaging, scientists are realizing just how closely the brain’s nervous system is tied to the one in your gut.
Tune In, Turn Off
Last year, a study showed just how crucial it is to be able to turn off certain genes in the brain if you want to learn and remember something. Mice whose genes are stuck in the “on” position develop faulty wiring; their neurons respond abnormally to the environment, preventing the mice from learning new motor skills.
Risky Business
Scientists now know where uncertainty is processed in the brain, influencing us to take a risk or play it safe. We have “value-coding” neurons in this region that are excited by reward—but specifically suppressed before a risky decision. The findings could lead to treatments for anything that involves misjudging risk, whether it’s underestimating the risk (as in compulsive gambling) or overestimating it (anxiety disorders).
