The Biggest Brain Maps Ever Created Are Pushing the Frontiers of Neuroscience

By Shelly Fan / SingularityHub / Dec 28, 2021

neuron

A neuron is a nerve cell that is the basic building block of the nervous system. Neurons are similar to other cells in the human body in a number of ways, but there is one key difference between neurons and other cells. Neurons are specialized to transmit information throughout the body.

These highly specialized nerve cells are responsible for communicating information in both chemical and electrical forms. There are also several different types of neurons responsible for different tasks in the human body.

Sensory neurons carry information from the sensory receptor cells throughout the body to the brain. Motor neurons transmit information from the brain to the muscles of the body. Interneurons are responsible for communicating information between different neurons in the body.

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ここから本文です。

Our quest to understand the brain’s connections is a bit like aliens trying to understand Earthlings (人間、地球人/ə́ːθliŋ) from outer space. Imagine having to track down every single person and their conversations across different continents, reconstruct noisy snippets (小片、切れ端、断片/snípit) into coherent messages, and from that data, infer the zeitgeist (時代精神/záitgàist) of the human race.

That, essentially, is what neuroscientists are trying to achieve with brain maps. Massive projects are racing to trace connections among the brain’s data-crunching (〔データを〕高速処理する/krʌntʃ) inhabitants, neurons—collectively called the connectome. And if we can “listen in” on those conversations, we can decipher the brain’s inner workings which power our memories, thoughts, and behaviors.

The idea isn’t without controversy. The brain is a highly flexible, adjustable, and adaptive being. One main contention (主張、論点/kənténʃən) is that a connectome—any connectome—is just a snapshot in time, with little potential to reflect a broader population. To skeptics, tracing a connectome is like predicting traffic patterns by staring at a paper map: utterly impossible.

This year overhauled (徹底的に点検する、追い付く、追い抜く/òuvərhɔ́ːl) that criticism. For the first time, scientists were able to predict reproductive behaviors of one animal, the lab-darling (好まれる) roundworm C. elegans, using an algorithm based on its connectome. A book-length map of another lab-favorite critter, the fruit fly, dazzled (驚嘆させる/dǽzəl) neuroscientists with new insights into spatial navigation, with implications from virtual reality (VR) to robotics.

Also in play are hefty (大変な努力がいる、ひどく骨が折れる、高額の、べらぼうに高い/héfti) projects to map our own brains, across ages and for diverse neurological disorders. Even Google is on board, providing computational resources to deal with an explosion of data and processing requirements, eyeing (目を付ける) potential input for advancing AI.

A New Era

Mapping the brain is an unenviable (〔困難なことなので〕気の進まない、やりたくない/ʌnénviəbəl) task with a staggering scale of complexity.

The first step in the venture took stock of the brain’s hardware—the types of neurons that form the basis of neural computation. The second traced where neurons branch out to connect with others—either immediate neighbors or far-off partners across brain regions. For connectomics, the next sprint forward (全速力で走る、ダッシュする) is less about hardware and more about hard questions: what can brain maps actually tell us about how the brain works?

Here’s where this year’s studies shone.

Take C. elegans, the lowly worm with just 302 neurons—and the only animal with a fully sequenced connectome. In one recent study, a team used the map to trace the worm’s mating behavior. The trick was to superimpose a map of activated neural networks to the connectome map—like overlaying traffic patterns onto Google Maps. With just eight connectomes from different worms, the team was able to find a pattern that predicts mating behaviors of a ninth worm. Disrupt a single neuron in the connectome, and the worm’s mating behavior broke down.

“It was really striking how clear the link was,” said study author Dr. Vladislav Susoy.

Another years-long project came to fruition with fruit flies. A favorite model animal in neuroscience, flies are smart navigators and fierce warriors eager to tussle (激しく格闘［闘争］する/tʌ́sl) when faced with a foe. Yet how their poppy seed-sized brain, with hundreds of thousands of neuronal branches that tangle into a cotton ball, powers those behaviors remains unsolved. This year, a team traced a tiny chunk of the fly’s brain used for navigation—a huge step up from C. elegans. The work mapped roughly 25,000 neurons and 20 million connections, resulting in a trove of (宝庫) data that’s already led to new theories on spatial navigation.

“It’s really extraordinary,” said Dr. Clay Reid at the Allen Institute to the New York Times. “I think anyone who looks at it will say connectomics is a tool that we need in neuroscience—full stop (終止符、ピリオド、完結、終わり).”

A Connectomics Future

Worms and flies may seem “meh (別に大したことはない、期待ほとではない、凡庸な/me),” but they’re indispensable for studying basic neuron function and physiology. They also provide a peek (垣間見る) of what’s to come. As the studies show, the brain’s wiring diagrams (図形/dáiəgræ̀m) are instrumental in helping scientists investigate existing theories and explore new ones. And connectomes are readily scaling up to mice and men.

For example, the MouseLight Project is mapping connections across the mammalian brain. MICrONS is creating one of the largest roadmaps of neural connections in mice, distilling (抽出する、抜き出す) algorithms that power the cortex, with the aim of engineering better AI.

“What we’re trying to do here is understand the brain on its own terms,” said Reid, who works on the MICrONS project.

For human brains this year, the decade-long Human Connectome Project (HCP) expanded brain maps from healthy people to those with early psychosis. In an effort to battle age-related brain issues, they also began synthesizing brain maps in people as they age.

These maps are rough. Unlike animal studies, the data are captured with fMRI (functional Magnetic Resonance Imaging), with far less resolution than mapping single neurons and their connections. It’s much more seeing the forest rather than the trees.

Yet that may be the fastest way forward. Jumping from flies to mice to men will require a leap in data processing technologies. To build a connectome, brains are generally sliced into wafer-thin sections, chemically treated, and imaged independently under a microscope. Reconstructing individual images into a brain region, or whole brain, is like using the panorama (全景) feature on a smartphone, and a behemoth (巨大) computational task. It’s also high stakes—mess up one brain section, and it derails the whole project.

But there’s hope. A few months back, a Harvard-Google collaboration revealed an enormous high-resolution scan of the human brain. Their secret sauce was to tap into supercomputers to speed up the image stitching (縫い合わせる) process, automating what was traditionally a giant pain point.

“It’s a great challenge for supercomputing—that’s what makes it exciting,” said Dr. Sebastian Seung, a prominent supporter of connectomics. “You don’t want to build a supercomputer and let it sit there. You need to find problems at the frontier.”

New brain mapping technologies are in the works. One strategy, called Tomo-SEM, uses a technique similar to a CT scan to image a brain, one slice at a time, without the need to chop it up. Another, TEM (transmission electron microscopy), images brain slices under a special microscope that is far cheaper and has outstanding resolution. Similar to genome sequencing, scientists are hopeful that the cost—both in terms of time and funds—will rapidly decline as new technologies are developed.

Although they’re a great start, the maps by themselves won’t be enough to decode brain function. As the fly study thoroughly showed, translating connections into behavior will take enormous analyses. For example, a physical connection between neurons doesn’t necessarily mean a functional one. Like a defunct (機能していない、現存しない、使われていない/difʌ́ŋkt) road on Google Earth, it may be an unfortunate fluke (偶然の出来事、不測の事態/flúːk).

The brain’s connections are also highly plastic (可塑性の/plǽstik), in that depending on age and experience, they’ll change. For some, this calls into question how valuable connectomes are, as they only capture a snapshot. Adding to the debate is whose connectome we should sequence first. Differences in age, gender, socioeconomic status, and health could massively change a person’s neural connections. Who gets to be the “reference point” for all human brains?

As the young field of connectomics reaches its teenage years, many details still need ironing out (〔問題などを〕解決する). But to Dr. Ken Hayworth at Janelia, “What’s exciting about connectomics is / instead of waving your hand and thinking this circuit is how the brain computes, / now you get the actual circuitry behind it.”

コネクトーム（connectome）

コネクトーム（connectome）とは、生物の神経系内の各要素（ニューロン、ニューロン群、領野など）の間の詳細な接続状態を表した地図、つまり神経回路の地図のこと。つながる、接続するといった意味を持つ英語のコネクト（connect）という言葉と、「全体」を表す-オーム（-ome）という接尾語から作られた言葉。人間の神経回路地図全体のことを言うときは特にヒト・コネクトーム（Human connectome）と名付けられている。また、コネクトームの調査、研究を行う分野はコネクトミクス (connectomics)と呼ばれる。

研究の現状

ヒトゲノムの解読は2003年に終了が宣言されたが、ヒト・コネクトームの解読はまだ端緒についたばかりである。人間の脳には1000億ほどの神経細胞があり、それらの間に1兆ほどの接続が存在すると考えられている。これは30億ほどの塩基対（2-3万の遺伝子）で構成されているヒトゲノムよりはるかに複雑な対象であり、ヒト・コネクトームの研究の発展には技術的な進歩が欠かせない。神経系の詳細な接続状態が良く分かっている生物は単純な種のみで、こうした種の例としてたとえばセンチュウ（C. elegans）がいる。C. elegans は体長1mmほどの大きさを持つ線虫の一種で、302個の神経細胞を持つ。近年、ショウジョウバエの全脳の接続状態も細胞レベルの解像度での解明も進んでいる。哺乳類では、網膜、大脳皮質などにおいて、部分的に解明され始めている。センチュウやハエのような無脊椎生物では、神経系の成り立ちがどの個体でも共通性があるので、コネクトームという実体のおよその把握も可能である。しかし、哺乳類においては、神経細胞やそのつながりには個体差があり、学習や記憶など環境との相互作用によって、神経回路の様相が常に変化しているため、コネクトームは「ゲノム」のようには定義できない。