• Newsletters

Scientists just drafted an incredibly detailed map of the human brain

A massive suite of papers offers a high-res view of the human and non-human primate brain.

  • Cassandra Willyard archive page

color lithograph of the rear cross-section of a brain and spine superimposed on an old map

This article first appeared in The Checkup, MIT Technology Review's weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first,  sign up here .

When scientists first looked at brain tissue under a microscope, they saw an impenetrable and jumbled mess. Santiago Ramon y Cajal, the father of modern neuroscience, likened the experience to walking into a forest with a hundred billion trees, “looking each day at blurry pieces of a few of those trees entangled with one another, and, after a few years of this, trying to write an illustrated field guide to the forest,” according to the authors of The Beautiful Brain , a book about Cajal’s work.

Today, scientists have a first draft of that guide. In a set of 21 new papers published across three journals, the teams report that they've developed large-scale whole-brain cell atlases for humans and non-human primates. This work, part of the National Institutes of Health  BRAIN Initiative , is the culmination of five years of research. “It's not just an atlas,” says Ed Lein, a neuroscientist at the  Allen Institute for Brain Science and one of the lead authors. “It's really opening up a whole new field, where you can now look with extremely high cellular resolution in brains of species where this typically hasn't been possible in the past.”

Welcome back to The Checkup. Let’s talk brains.

What is a brain atlas, and what makes this one different?

A brain atlas is a 3-D map of the brain. Some brain atlases already exist, but this new suite of papers provides unprecedented resolution of the whole brain for humans and non-human primates. The human brain atlas includes the location and function of more than 3,000 cell types in adult and developing individuals. “This is far and away the most complete description of the human brain at this kind of level, and the first description in many brain regions,”  Lein says. But it’s still a first draft. 

The work is part of the BRAIN Initiative Cell Census Network , which kicked off in 2017 with the aim of generating a comprehensive 3-D reference brain cell atlas for mice (that project is still in the works). The results reported on October 12 were part of a set of pilot studies to validate whether the methods used in mice would work for bigger brains. Spoiler: those methods did work. Really well, in fact.

What did these initial studies find?

The human brain is really, really complex. I know, shocker! Thus far, the teams have identified more than 3,300 cell types. And as the resolution gets even higher (that’s what they’re working on now), they’re likely to uncover many more. Efforts to develop an atlas of the mouse brain, which are further along, have identified 5,000 cell types. (For more, check out these preprints: 1 and 2 )

But underneath that complexity are some commonalities. Many regions, for example, share cell types, but they have them in different proportions. 

And the location of that complexity is surprising. Neuroscience has focused much of its research on the outer shell of the brain, which is responsible for memory, learning, language, and more. But the majority of cellular diversity is actually in older evolutionary structures deep inside the brain,  Lein says. 

How did they make these atlases?

The classic neuroscience approach to classifying cell types relies on either cell shape–think of star-shaped astrocytes –or the cells’ type of activity–such as fast-spiking interneurons. “These cell atlases capitalize on a new suite of technologies that come from genomics,”  Lein says, primarily a technique known as single-cell sequencing.

First, the researchers start with a small piece of frozen brain tissue from a biobank. “You take a tissue, you grind it up, you profile lots of cells to try to make sense of it,”  Lein says. They make sense of it by sequencing the cells’ nuclei to look at the genes that are being expressed. “Each cell type has a coherent set of genes that they typically use. And you can measure all these genes and then cluster all the types of cells on the basis of their overall gene expression pattern,” Lein says. Then, using imaging data from the donor brain, they can put this functional information where it belongs spatially.

How can scientists use these brain cell atlases?

So many ways. But one crucial use is to help understand the basis of brain diseases.  A reference human brain atlas that describes a normal or neurotypical brain could help researchers understand depression or schizophrenia or many other kinds of diseases, Lein says. Take Alzheimer’s as an example. You could apply these same methods to characterize the brains of people with differing levels of severity of Alzheimer’s, and then compare those brain maps with the reference atlas. “And now you can start to ask questions like, ‘Are certain kinds of cells vulnerable in disease, or are certain kinds of cells causal,” Lein says. (He’s part of a team that’s already working on this .) Rather than investigating plaques and tangles, researchers can ask questions about “very specific kinds of neurons that are the real circuit elements that are likely to be perturbed and have functional consequences,” he says. 

What’s the next step?

Better resolution. “The next phase is really moving into very comprehensive coverage of the human and non-human primate brain in adults and development.” In fact, that work has already begun with the BRAIN Initiative Cell Atlas Network , a five-year, $500 million project.  The aim is to generate a complete reference atlas of cell types in the human brain across the lifespan, and also to map cell interactions that underlie a wide range of brain disorders.

It’s a level of detail that Ramon y Cajal couldn’t have imagined. 

Another thing

Gene editing helped chickens resist bird flu. “It could take decades to work through the necessary technical and regulatory steps, but researchers say CRISPR gene editing could eventually save countless chickens’ lives—and transform animal farming,” writes Abdullahi Tsanni .  

Read more from Tech Review’s archive

Brain atlases have been around for a minute. In 2013, Courtney Humphries reported on the development of BigBrain , a human brain atlas based on MRI images of more than 7,000 brain slices. 

And in 2017, we flagged the Human Cell Atlas project, which aims to categorize all the cells of the human body, as a breakthrough technology . That project is still underway . 

Cell atlases could help provide the data needed for AI to build a virtual cell, argue Priscilla Chan and Mark Zuckerberg in an op-ed published last month . 

From around the web

An experimental RSV vaccine launched in the 1960s worsened symptoms of the illness rather than providing protection. A months-long investigation into the history of RSV research reveals that the families who participated in these trials knew little about the risks. This is a long one, but worth it. ( Undark )

A fascinating commentary on the new class of weight-loss drugs and the problems it can’t solve. Ozempic mania is “an example of how the American penchant for solving structural issues by fixing individual bodies is excellent at creating demand without solving social problems,” writes Tressie McMillan Cottom. ( New York Times )

The FDA is launching an advisory committee on digital health technologies. ( FDA )

One of the terrifying things we always hear about the 1918 flu is how hard it hit the young and healthy. But genetic research suggests that people with chronic diseases or nutritional deficiencies were twice as likely to die than healthy people. ( New York Times)

Biotechnology and health

Scientists are finding signals of long covid in blood. they could lead to new treatments..

Faults in a certain part of the immune system might be at the root of some long covid cases, new research suggests.

This baby with a head camera helped teach an AI how kids learn language

A neural network trained on the experiences of a single young child managed to learn one of the core components of language: how to match words to the objects they represent.

The first gene-editing treatment: 10 Breakthrough Technologies 2024

Sickle-cell disease is the first illness to be beaten by CRISPR, but the new treatment comes with an expected price tag of $2 to $3 million.

  • Antonio Regalado archive page

Weight-loss drugs: 10 Breakthrough Technologies 2024

Weight-loss drugs like Wegovy and Mounjaro are wildly popular and effective, but their long-term health impacts are still unknown.

  • Abdullahi Tsanni archive page

Stay connected

Get the latest updates from mit technology review.

Discover special offers, top stories, upcoming events, and more.

Thank you for submitting your email!

It looks like something went wrong.

We’re having trouble saving your preferences. Try refreshing this page and updating them one more time. If you continue to get this message, reach out to us at [email protected] with a list of newsletters you’d like to receive.

ScienceDaily

'A new era in brain science': Researchers unveil human brain cell atlas

The new research, part of the nih brain initiative, paves the way toward treating, preventing, and curing brain disorders.

Salk Institute researchers, as part of a larger collaboration with research teams around the world, analyzed more than half a million brain cells from three human brains to assemble an atlas of hundreds of cell types that make up a human brain in unprecedented detail.

The research, published in a special issue of the journal Science on October 13, 2023, is the first time that techniques to identify brain cell subtypes originally developed and applied in mice have been applied to human brains.

"These papers represent the first tests of whether these approaches can work in human brain samples, and we were excited at just how well they translated," says Professor Joseph Ecker, director of Salk's Genomic Analysis Laboratory and a Howard Hughes Medical Institute investigator. "This is really the beginning of a new era in brain science, where we will be able to better understand how brains develop, age, and are affected by disease."

The new work is part of the National Institute of Health's Brain Research Through Advancing Innovative Neurotechnologies Initiative , or The BRAIN Initiative, an effort launched in 2014 to describe the full plethora of cells -- as characterized by many different techniques -- in mammalian brains. Salk is one of three institutions awarded grants to act as central players in generating data for the NIH BRAIN Initiative Cell Census Network, BICCN.

Every cell in a human brain contains the same sequence of DNA, but in different cell types different genes are copied onto strands of RNA for use as protein blueprints. This ultimate variation in which proteins are found in which cells -- and at what levels -- allows the vast diversity in types of brain cells and the complexity of the brain. Knowing which cells rely on which DNA sequences to function is critical not only to understanding how the brain works, but also how mutations in DNA can cause brain disorders and, relatedly, how to treat those disorders.

"Once we scale up our techniques to a large number of brains, we can start to tackle questions that we haven't been able to in the past," says Margarita Behrens, a research professor in Salk's Computational Neurobiology Laboratory and a co-principal investigator of the new work.

In 2020, Ecker and Behrens led the Salk team that profiled 161 types of cells in the mouse brain, based on methyl chemical markers along DNA that specify when genes are turned on or off. This kind of DNA regulation, called methylation, is one level of cellular identity.

In the new paper, the researchers used the same tools to determine the methylation patterns of DNA in more than 500,000 brain cells from 46 regions in the brains of three healthy adult male organ donors. While mouse brains are largely the same from animal to animal, and contain about 80 million neurons, human brains vary much more and contain about 80 billion neurons.

"It's a big jump from mice to humans and also introduces some technical challenges that we had to overcome," says Behrens. "But we were able to adapt things that we had figured out in mice and still get very high quality results with human brains."

At the same time, the researchers also used a second technique, which analyzed the three-dimensional structure of DNA molecules in each cell to get additional information about what DNA sequences are being actively used. Areas of DNA that are exposed are more likely to be accessed by cells than stretches of DNA that are tightly folded up.

"This is the first time we've looked at these dynamic genome structures at a whole new level of cell type granularity in the brain, and how those structures may regulate which genes are active in which cell types," says Jingtian Zhou, co-first author of the new paper and a postdoctoral researcher in Ecker's lab.

Other research teams whose work is also published in the special issue of Science used cells from the same three human brains to test their own cell profiling techniques, including a group at UC San Diego led by Bing Ren -- also a co-author in Ecker and Behrens' study. Ren's team revealed a link between specific brain cell types and neuropsychiatric disorders, including schizophrenia, bipolar disorder, Alzheimer's disease, and major depression. Additionally, the team developed artificial intelligence deep learning models that predict risk for these disorders.

Other groups in the global collaboration focused on measuring levels of RNA to group cells together into subtypes. The groups found a high level of correspondence in each brain region between which genes were activated, based on the DNA studies by Ecker and Behrens' team, and which genes were found to be transcribed into RNA.

Since the new Salk research was intended as a pilot study to test the efficacy of the techniques in human brains, the researchers say they can't yet draw conclusions about how many cell types they might uncover in the human brain or how those types differ between mice and humans.

"The potential to find unique cell types in humans that we don't see in mice is really exciting," says Wei Tian, co-first author of the new paper and a staff scientist in Ecker's lab. "We've made amazing progress but there are always more questions to ask."

In 2022, the NIH Brain Initiative launched a new BRAIN Initiative Cell Atlas Network (BICAN), which will follow up the BICCN efforts. At Salk, a new Center for Multiomic Human Brain Cell Atlas funded through BICAN aims to study cells from over a dozen human brains and ask questions about how the brain changes during development, over people's lifespans, and with disease. That more detailed work on a larger number of brains, Ecker says, will pave the way toward a better understanding of how certain brain cell types go awry in brain disorders and diseases.

"We want to have a full understanding of the brain across the lifespan so that we can pinpoint exactly when, how, and in which cell types things go wrong with disease -- and potentially prevent or reverse those harmful changes," says Ecker.

Other authors of the paper are Anna Bartlett, Qiurui Zeng, Hanqing Liu, Rosa G. Castanon, Mia Kenworthy, Jordan Altshul, Cynthia Valadon, Andrew Aldridge, Joseph R. Nery, Huaming Chen, Jiaying Xu, Nicholas D. Johnson, Jacinta Lucero, Julia K. Osteen, Nora Emerson, Jon Rink, Jasper Lee, Michelle Liem, Naomi Claffey and Caz O'Connor of Salk; Yang Li and Bing Ren of the Ludwig Institute for Cancer Research at UC San Diego; Kimberly Siletti and Sten Linnarsson of the Karolinska Institutet; Anna Marie Yanny, Julie Nyhus, Nick Dee, Tamara Casper, Nadiya Shapovalova, Daniel Hirschstein, Rebecca Hodge, Boaz P. Levi and Ed Lein of the Allen Institute for Brain Science; and C. Dirk Keene of the University of Washington.

The work was supported by grants from the National Institute of Mental Health (U01MH121282, UM1 MH130994, NIMH U01MH114812), the National Institutes of Health BRAIN Initiative (NCI CCSG: P30 014195), the Nancy and Buster Alvord Endowment, and the Howard Hughes Medical Institute.

  • Brain Tumor
  • Nervous System
  • Human Biology
  • Brain-Computer Interfaces
  • Brain Injury
  • Intelligence
  • Neuroscience
  • Brain damage
  • Brain tumor
  • Embryonic stem cell
  • Optic nerve
  • Human brain

Story Source:

Materials provided by Salk Institute . Note: Content may be edited for style and length.

Journal Reference :

  • Wei Tian, Jingtian Zhou, Anna Bartlett, Qiurui Zeng, Hanqing Liu, Rosa G. Castanon, Mia Kenworthy, Jordan Altshul, Cynthia Valadon, Andrew Aldridge, Joseph R. Nery, Huaming Chen, Jiaying Xu, Nicholas D. Johnson, Jacinta Lucero, Julia K. Osteen, Nora Emerson, Jon Rink, Jasper Lee, Yang E. Li, Kimberly Siletti, Michelle Liem, Naomi Claffey, Carolyn O’Connor, Anna Marie Yanny, Julie Nyhus, Nick Dee, Tamara Casper, Nadiya Shapovalova, Daniel Hirschstein, Song-Lin Ding, Rebecca Hodge, Boaz P. Levi, C. Dirk Keene, Sten Linnarsson, Ed Lein, Bing Ren, M. Margarita Behrens, Joseph R. Ecker. Single-cell DNA methylation and 3D genome architecture in the human brain . Science , 2023; 382 (6667) DOI: 10.1126/science.adf5357

Cite This Page :

  • Extremely Efficiency Solar Cells
  • Earth's Freshwater Cycle out of Its Stable State
  • Secrets of One of the Most Distant Galaxies
  • Compact Fusion Power Plant
  • How Single Orca Hunts, Eats, Great White Shark
  • AI Scores Higher On 'Creative Potential'
  • How Radiation Shapes Planetary Systems
  • Heaviest Black Hole Pair Ever
  • 'Meat-Like' Proteins from Blue-Green Algae
  • Building Bionic Jellyfish for Ocean Exploration

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • View all journals
  • Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • 06 October 2021

Neuroscientists make strides towards deciphering the human brain

You have full access to this article via your institution.

Francis Collins and Barak Obama stand at a podium at a press conference beside a monitor displaying the words 'Brain Initiative'

Former US president Barack Obama at the 2013 launch of the BRAIN Initiative with Francis Collins, director of the National Institutes of Health. Credit: Jason Reed/Reuters/Alamy

In 2013, then-US president Barack Obama launched a US$5-billion project to improve our understanding of the human brain. The venture would take advantage of new techniques to probe the brain’s genetics and physiology. This week, Nature reports some of the results from the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

Although medical science continues to progress, the underlying causes of many brain disorders are not well understood at the cellular level. By the time the BRAIN Initiative ends in 2026, those involved say, it will have created a ‘gold mine’ for clinical researchers working on psychiatric, neurodegenerative and neurodevelopmental disorders.

new brain research

The BRAIN Initiative Cell Census Network—Motor Cortex

The lines of evidence described in the current papers are from the BRAIN Initiative Cell Census Network (BICCN). This work is expected to help scientists to identify suitable animal models of human brain conditions — such as Parkinson’s disease, motor neuron disease and Alzheimer’s disease — that share cellular characteristics.

The BICCN project’s findings also help to explain how neurons and brain circuits are involved in emotion, behaviour and learning. These are early steps towards a more complete understanding of the neural underpinnings of human cognitive abilities — such as language and reasoning — and will keep scientists busy for decades to come.

The BRAIN Initiative is a collaboration between hundreds of researchers around the world. The BICCN project’s foundational insights include a comparison of the cells of the primary motor cortex in three species: mice, marmosets and humans 1 . The primary motor cortex is the part of the brain responsible for skilled movements, and the findings will help to reveal which cellular mechanisms are conserved across species. This will aid researchers in establishing the most appropriate model organism for studying neurodegenerative conditions.

new brain research

A census of cell types in the brain’s motor cortex

Scientists have also created an atlas that reveals the locations of around 25 subclasses of cell in the primary motor cortex of the same three species 1 , 2 . The researchers report what neuroscientists call an input–output wiring diagram of this region in mice. This details all of the long-distance neural connections, known as axons, reaching into and out of this region; this will help neuroscientists in their investigations of how the brain exercises motor control 3 .

Researchers have also gained insight into how cells in the human neocortex — the thin outer layers of the two cerebral hemispheres — acquire their identities during embryonic development 4 . And the project is providing scientists with tools with which to visualize and mine vast new data sets. In addition, researchers have started to create a genetic ‘toolbox’ that exploits characteristic differences in gene expression in particular cell types to label and manipulate those cells 5 . In just a few years, scientists expect to be able to peruse an online atlas charting the type and location of every cell in the mouse brain. All of the data will be freely available.

However, it’s a big leap from creating what the researchers call a cell census to understanding the precise information that a particular network of neurons is processing. Scientists do not yet know how the brain processes the streams of sensory information that tell us that we’re hungry or cold, or that create a lifetime of memories.

new brain research

How the world’s biggest brain maps could transform neuroscience

Some neuroscientists think they will be able to crack the basis of these computations by breaking them down into their individual physiological and behavioural components. Others are pinning their hopes on a universal theory of brain function. One such theory, called active inference, visualizes the brain using predictive models to regulate physiology and behaviour 6 . It relies on a processing hierarchy with predictions flowing in one direction and prediction errors reported back in the opposite direction.

The BICCN researchers provide some of the tools needed to test the theory, including those required to identify and manipulate the cells that might be involved in such a circuit. But one of the experimental challenges will be to combine these cell-level tools with models of a particular aspect of perception, cognition or behaviour in live animals. Another challenge is determining the extent to which animal models might reveal useful insights about the human brain.

The BRAIN Initiative has already revealed a high degree of evolutionary conservation between the basic cellular components of the brain in different mammals. This is not surprising, given the extensive genetic overlap and similarities between species in behaviours such as eating and reproduction. But it is also reassuring, given the challenges we are already aware of regarding the extent to which animal models provide useful insights about the human brain. Whereas the mouse brain hosts around 70 million neurons, the human brain boasts some 86 billion, each one bristling with synapses, which allow them to connect to other cells. Many neurons have thousands of synaptic connections.

This difference in scale is among the reasons that Hongkui Zeng, an author of a number of the papers in this collection and director of the Allen Institute for Brain Science in Seattle, Washington, says it will take at least 50 years to create even a crude wiring diagram of a typical human brain. But as the papers published today show, scientists are making important inroads in deciphering the brain and creating tools that will one day unlock the secrets of our uniquely human cognitive attributes.

Nature 598 , 7 (2021)

doi: https://doi.org/10.1038/d41586-021-02660-x

Bakken, T. E. et al. Nature 598 , 111–119 (2021).

Article   Google Scholar  

BRAIN Initiative Cell Census Network (BICCN). Nature 598 , 86–102 (2021).

Muñoz-Castañeda, R. et al. Nature 598 , 159–166 (2021).

Bhaduri, A. et al. Nature 598 , 200–204 (2021).

Matho, K. S. et al. Nature 598 , 182–187 (2021).

Pezzulo, G., Rigoli, F. & Friston, K. Prog. Neurobiol. 134 , 17–35 (2015).

Article   PubMed   Google Scholar  

Download references

Reprints and permissions

Related Articles

new brain research

  • Neuroscience
  • Medical research

Why can’t researchers agree about consciousness? Because it’s all in the mind

Correspondence 05 MAR 24

Non-neuronal brain cells modulate behaviour

Non-neuronal brain cells modulate behaviour

News & Views 28 FEB 24

Synchronized neuronal activity drives waste fluid flow

Synchronized neuronal activity drives waste fluid flow

Multisensory gamma stimulation promotes glymphatic clearance of amyloid

Multisensory gamma stimulation promotes glymphatic clearance of amyloid

Article 28 FEB 24

Crym-positive striatal astrocytes gate perseverative behaviour

Crym-positive striatal astrocytes gate perseverative behaviour

Personalized cancer care can’t rely on molecular testing alone

Forget lung, breast or prostate cancer? Why we shouldn’t abandon tumour names yet

Here’s what many digital tools for chronic pain are doing wrong

Here’s what many digital tools for chronic pain are doing wrong

World View 05 MAR 24

Assistant/Associate Professor - Tenure Track (Cancer Research)

The Department of Cancer Biology & Pharmacology of UICOMP is now inviting applications for tenure-track Assistant/Associate Professor level positions.

Peoria, Illinois

University of Illinois College of Medicine at Peoria

new brain research

Associate or Senior Editor, Nature Machine Intelligence

Position: Associate or Senior Editor, Nature Machine Intelligence Location: Shanghai, Beijing, or New York- Hybrid working model Deadline: 31, Marc...

New York City, New York (US)

Springer Nature Ltd

new brain research

Associate or Senior Editor (Cancer epidemiology and imaging), Nature Communications

About Springer Nature Group Springer Nature opens the doors to discovery for researchers, educators, clinicians and other professionals. Every day,...

Postdoctoral Associate- Statistical Genetics

Houston, Texas (US)

Baylor College of Medicine (BCM)

new brain research

Head of Biology, Bio-island

Head of Biology to lead the discovery biology group.

Guangzhou, Guangdong, China

BeiGene Ltd.

new brain research

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Quick links

  • Explore articles by subject
  • Guide to authors
  • Editorial policies

Suggestions or feedback?

MIT News | Massachusetts Institute of Technology

  • Machine learning
  • Social justice
  • Black holes
  • Classes and programs

Departments

  • Aeronautics and Astronautics
  • Brain and Cognitive Sciences
  • Architecture
  • Political Science
  • Mechanical Engineering

Centers, Labs, & Programs

  • Abdul Latif Jameel Poverty Action Lab (J-PAL)
  • Picower Institute for Learning and Memory
  • Lincoln Laboratory
  • School of Architecture + Planning
  • School of Engineering
  • School of Humanities, Arts, and Social Sciences
  • Sloan School of Management
  • School of Science
  • MIT Schwarzman College of Computing

New MRI probe can reveal more of the brain’s inner workings

Press contact :, media download.

graphic of neurons being monitored

*Terms of Use:

Images for download on the MIT News office website are made available to non-commercial entities, press and the general public under a Creative Commons Attribution Non-Commercial No Derivatives license . You may not alter the images provided, other than to crop them to size. A credit line must be used when reproducing images; if one is not provided below, credit the images to "MIT."

graphic of neurons being monitored

Previous image Next image

Using a novel probe for functional magnetic resonance imaging (fMRI), MIT biological engineers have devised a way to monitor individual populations of neurons and reveal how they interact with each other.

Similar to how the gears of a clock interact in specific ways to turn the clock’s hands, different parts of the brain interact to perform a variety of tasks, such as generating behavior or interpreting the world around us. The new MRI probe could potentially allow scientists to map those networks of interactions.

“With regular fMRI, we see the action of all the gears at once. But with our new technique, we can pick up individual gears that are defined by their relationship to the other gears, and that's critical for building up a picture of the mechanism of the brain,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering.

Using this technique, which involves genetically targeting the MRI probe to specific populations of cells in animal models, the researchers were able to identify neural populations involved in a circuit that responds to rewarding stimuli. The new MRI probe could also enable studies of many other brain circuits, the researchers say.

Jasanoff is the senior author of the study , which appears today in Nature Neuroscience . The lead authors of the paper are recent MIT PhD recipient Souparno Ghosh and former MIT research scientist Nan Li.

Tracing connections

Traditional fMRI imaging measures changes to blood flow in the brain, as a proxy for neural activity. When neurons receive signals from other neurons, it triggers an influx of calcium, which causes a diffusible gas called nitric oxide to be released. Nitric oxide acts in part as a vasodilator that increases blood flow to the area.

Imaging calcium directly can offer a more precise picture of brain activity, but that type of imaging usually requires fluorescent chemicals and invasive procedures. The MIT team wanted to develop a method that could work across the brain without that type of invasiveness.

“If we want to figure out how brain-wide networks of cells and brain-wide mechanisms function, we need something that can be detected deep in tissue and preferably across the entire brain at once,” Jasanoff says. “The way that we chose to do that in this study was to essentially hijack the molecular basis of fMRI itself.”

The researchers created a genetic probe, delivered by viruses, that codes for a protein that sends out a signal whenever the neuron is active. This protein, which the researchers called NOSTIC (nitric oxide synthase for targeting image contrast), is an engineered form of an enzyme called nitric oxide synthase. The NOSTIC protein can detect elevated calcium levels that arise during neural activity; it then generates nitric oxide, leading to an artificial fMRI signal that arises only from cells that contain NOSTIC.

The probe is delivered by a virus that is injected into a particular site, after which it travels along axons of neurons that connect to that site. That way, the researchers can label every neural population that feeds into a particular location.

“When we use this virus to deliver our probe in this way, it causes the probe to be expressed in the cells that provide input to the location where we put the virus,” Jasanoff says. “Then, by performing functional imaging of those cells, we can start to measure what makes input to that region take place, or what types of input arrive at that region.”

Turning the gears

In the new study, the researchers used their probe to label populations of neurons that project to the striatum, a region that is involved in planning movement and responding to reward. In rats, they were able to determine which neural populations send input to the striatum during or immediately following a rewarding stimulus — in this case, deep brain stimulation of the lateral hypothalamus, a brain center that is involved in appetite and motivation, among other functions.

One question that researchers have had about deep brain stimulation of the lateral hypothalamus is how wide-ranging the effects are. In this study, the MIT team showed that several neural populations, located in regions including the motor cortex and the entorhinal cortex, which is involved in memory, send input into the striatum following deep brain stimulation.

“It's not simply input from the site of the deep brain stimulation or from the cells that carry dopamine. There are these other components, both distally and locally, that shape the response, and we can put our finger on them because of the use of this probe,” Jasanoff says.

During these experiments, neurons also generate regular fMRI signals, so in order to distinguish the signals that are coming specifically from the genetically altered neurons, the researchers perform each experiment twice: once with the probe on, and once following treatment with a drug that inhibits the probe. By measuring the difference in fMRI activity between these two conditions, they can determine how much activity is present in probe-containing cells specifically.

The researchers now hope to use this approach, which they call hemogenetics, to study other networks in the brain, beginning with an effort to identify some of the regions that receive input from the striatum following deep brain stimulation.

“One of the things that's exciting about the approach that we're introducing is that you can imagine applying the same tool at many sites in the brain and piecing together a network of interlocking gears, which consist of these input and output relationships,” Jasanoff says. “This can lead to a broad perspective on how the brain works as an integrated whole, at the level of neural populations.”

The research was funded by the National Institutes of Health and the MIT Simons Center for the Social Brain.

Share this news article on:

Related links.

  • Jasanoff Lab
  • Department of Biological Engineering
  • Department of Brain and Cognitive Sciences
  • McGovern Institute for Brain Research

Related Topics

  • Biological engineering
  • Brain and cognitive sciences
  • McGovern Institute
  • National Institutes of Health (NIH)
  • Neuroscience

Related Articles

MIT biological engineers have created a specialized sensor that allows them to track dopamine in the brain using magnetic resonance imaging (MRI), as shown in the bottom row. Images in the top row show overall brain activity, as measured by functional MRI.

How dopamine drives brain activity

MIT researchers have designed an MRI contrast agent that can detect calcium within neurons, allowing them to closely track brain activity.

New MRI sensor can image activity deep within the brain

MIT engineers have developed a sensor that can be used to measure optical and electrical signals in the brain, using MRI.

Monitoring electromagnetic signals in the brain with MRI

new brain research

New technique offers a more detailed view of brain activity

Previous item Next item

More MIT News

Decorative image of a laptop floating among abstract, grid-like charts and objects.

Using generative AI to improve software testing

Read full story →

One person stands behind a lectern with four seated panelists to her left. Above them, a screen displays "Sustainability connect 2024." Boston’s skyline fills the windows behind them.

At Sustainability Connect 2024, a look at how MIT is decarbonizing its campus

Picnic tables in MIT's Hockfield Court underneath trees with yellow leaves

School of Science announces 2024 Infinite Expansion Awards

Illustration of five diverse people wearing headphones or earphones. A curvy staff line with treble chef and notes are in background

Exposure to different kinds of music influences how the brain interprets rhythm

Close-up of large magnet inside a cryostat container

Tests show high-temperature superconducting magnets are ready for fusion

Rendering shows the Perseverance on the rocky brown surface of Mars. The Perseverance resembles a go-cart and has 6 wheels and an arm extending that houses the drill. The top of the Perseverance has a long neck and a camera on top.

Study determines the original orientations of rocks drilled on Mars

  • More news on MIT News homepage →

Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA, USA

  • Map (opens in new window)
  • Events (opens in new window)
  • People (opens in new window)
  • Careers (opens in new window)
  • Accessibility
  • Social Media Hub
  • MIT on Facebook
  • MIT on YouTube
  • MIT on Instagram

IMAGES

  1. Research: AI mimics the human brain’s subconscious

    new brain research

  2. Deep tech for brain research

    new brain research

  3. GPS for the brain? New brain atlas wows scientists

    new brain research

  4. Human Brain Research Project

    new brain research

  5. Stanford scientist joins call for major brain research project

    new brain research

  6. New research: Brain implant can objectively measure chronic pain severity

    new brain research

VIDEO

  1. The Brain

  2. Unraveling Brain Health

COMMENTS

  1. New brain atlas offers comprehensive map of the human brain

    New brain atlas offers comprehensive map of the human brain | MIT Technology Review. Biotechnology and health. Scientists just drafted an incredibly detailed map of the human brain. A...

  2. 'A new era in brain science': Researchers unveil human brain

    The new research, part of the NIH BRAIN Initiative, paves the way toward treating, preventing, and curing brain disorders. Date: October 12, 2023. Source: Salk Institute. Summary:...

  3. Neuroscientists make strides towards deciphering the human brain

    06 October 2021. Neuroscientists make strides towards deciphering the human brain. Early findings from the BRAIN Initiative are exciting, but researchers still have a way to go in their quest...

  4. New frontiers in neuroscience

    New frontiers in neuroscience. Recent discoveries about the biological underpinnings of human behavior are helping psychologists find new ways to improve people’s lives. By Ashley Abramson Date created: January 1, 2022 9 min read. Vol. 53 No. 1. Print version: page 62. Cognition and the Brain. Neuropsychology. 16. Cite This Article.

  5. New MRI probe can reveal more of the brain’s inner workings

    March 3, 2022. Press Inquiries. Caption. Using a novel probe (in light blue) for functional magnetic resonance imaging (fMRI), MIT biological engineers have devised a way to monitor individual populations of neurons and reveal how they interact with each other. Credits. Courtesy of the researchers.