The Quest To Decode The Brain

Thinking, moving, seeing—it all seems so easy. But the world’s smartest scientists are still grappling with basic questions about how we function. To gain more insights, researchers and engineers are developing more powerful and easier-to-use devices to study the brain. Some allow scientists to monitor more neurons than was previously possible in a living brain. Others grant researchers access to the hard-to-reach regions of the brain. Their big advantage: The tools can record the fast patterns of electrical signals the brain uses to convey information in more detail than before. It’s this neural Morse code scientists want to decipher. “The first step in understanding anything is able to measure it,” says Loren Frank, a neuroscientist at the University of California, San Francisco, who’s developing brain probes. “The technology we’ve had up ’til now hasn’t given us the measurement tools we need.” In recent years, academic, government and corporate efforts to develop more powerful tools have accelerated worldwide, thanks to the miniaturisation of hardware and improvements in manufacturing, neurotechnologists say. They’re spending billions on this research. Scientists hope these deeper data dives will help further the understanding of how networks of neurons work together during learning, memory, vision and movement. That could lead to better therapies for patients with brain-related diseases like dementia, epilepsy and Parkinson’s disease. “Before we understand what’s going on in disease, we need to understand how the brain as a machine works,” says Michael Hauser, a neuroscientist at University College London, who’s studying decision-making and movement.

Already, experiments leveraging new brain probes are giving neuroscientists novel insights—and opening up fresh questions—about how the brain shuttles information from one region to the next. In one, researchers monitor the brain activity of mice while the animals navigate what looks like a maze projected in front of them. (Most studies use animals for ethical reasons.) Scientists have traditionally thought of the brain as modular, where one region specialises in a certain function. But recent research enabled by new probes hint at a much more complex organ. In one study, a UCSF team used flexible, implantable electrodes—tools that measure the brain’s electrical signals—to examine how rats plan to move from one location to another. This involves memory, so the researchers zeroed in on the hippocampus, a seahorse-shaped region involved in memory formation. “We wanted to understand how the hippocampus forms and retrieves memories, which both involve linking patterns of brain activity across many regions,” says Dr Frank, who led the work. They found that bursts of activity across the hippocampus engage neurons everywhere they looked in the brain, including areas important for learning rules, decision-making and rewards, Dr Frank says. Scientists had previously found these “ripples” are important for strengthening memories, but hadn’t determined whether the patterns of activity were coordinated across many regions, he says. “It does look like a pretty brain-wide phenomenon,” says Dr Frank, whose lab developed the new probes in collaboration with the Lawrence Livermore National Laboratory in Livermore, Calif. The study is under review for publication. Parts of it were presented recently at a meeting of the U.S. Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. His team is doing further testing.

Other experiments are also pushing the field’s understanding of how the brain works, thanks to sharper reads on neural activity. When an animal moves, for instance, the brain’s motor cortex, which is responsible for generating movement, sends signals to the cerebellum, which helps with balance and coordination. Before those signals get there, they course through another region called the pons. But not all signals make it out, which surprised neuroscientist Adam Hantman. His team conducted the experiments at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Va. When an animal moves, the pons seems to be “a selective relay, where it lets some bits of information through, but it’s suppressing other bits,” Dr Hantman says. Why the brain does this remains a mystery, he says. “But the fact that it even happens? We just didn’t know.”

His team is using new, implantable probes called Neuropixels that allow scientists to record from hundreds of neurons in multiple brain regions at the same time. Within a year, his lab got “hundreds and hundreds” of neuron recordings in the pons. Without Neuropixels, the experiments would have been “very painful” or nearly impossible, he says. In living animals, the cortex’s surface layers are typically much more accessible than deep regions like the pons. The preliminary findings, he says, could help doctors understand the effects of cortical strokes, which affect signals sent to the cerebellum from the cortex. Likewise, at the Allen Institute for Brain Science in Seattle, scientists using Neuropixels are finding that many neurons in the cortex have a special type of signal that travels backwards along a neuron. Such signals are thought to convey to neighbouring cells “a sort of acknowledgement signal that yes, the neuron just fired,” says Christof Koch, the institute’s president. These are “probably critical for information processing” during learning, he says.

Scientists have observed such signals before in slivers of brain tissue, but know much less about them in living animals, he says. With Neuropixels, scientists have realised these signals are more common in the cortex than previously thought. That’s important because it’s in the cortex that high-level perception and thought arise, he says. Scientists are doing more experiments to figure out their exact role. HHMI and the Allen Institute, along with other foundations, have invested more than $12 million to develop and manufacture Neuropixels probes, which aren’t yet commercially available. Each will cost roughly $1,400 once they go on sale later this summer, according to Tim Harris, a fellow at Janelia who organised Neuropixels development. There is a wait list to get them. The Neuropixels development team and Dr Frank hope to one day test their probes in humans.

Credit: Daniela Hernandez for The Wall Street Journal, 15 June 2018.