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Studying the Brain at Rest Is Really Hard

Neuroscientist Daniel Margulies studies the brain when it's not really doing anything specific, but still has a lot going on.

Try to think of nothing. Just let your brain rest. Now, what are you thinking about?

When the brain is in a resting state—that is, it's not being told to do a specific task—it doesn't just go blank; there's still activity going on.

This is the brain state neuroscientist Daniel Margulies is interested in. He leads the Neuroanatomy and Connectivity Research Group at the Max Planck Institute for Human Cognitive and Brain Sciences in Germany, where his work currently focuses on the resting brain and what it might tell us about brain connectivity.

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He's also a member of the Hubbub group, an interdisciplinary project looking at the idea of rest and busyness that has just taken up the first residency at the Hub, a new space at the Wellcome Collection in London. Margulies told us more about how he looks at the brain when it's not doing anything in particular, but still has a lot going on.

Daniel Margulies. Image: Daniel Margulies/Hubbub Group

MOTHERBOARD: So you're looking at the brain in its resting state. What does that even mean?
Daniel Margulies: It's a field that began developing almost 20 years ago now, and it emerged from a cognitive question. In general, our goal is to understand brain function underlying cognitive processing; we want to localise areas of the brain as they're involved in performing specific tasks, and to differentiate regions of the brain and what they do.

The way that was traditionally done was by taking a certain task—like tapping your fingers or reading a list of words—and then you would contrast that specific state with another one. You would subtract two different mental states to look at the brain regions involved in the function you were interested in looking at. Where the resting-state field emerged is that one of the states used as a contrast was a resting condition, where you had people do nothing more than stare at a crosshair. It was assumed that brain activity was composed of nothing more than noise in that state.

But what was found over several years by a couple of different groups is there's actually a remarkable amount of coordinated activity taking place in the brain even when you don't have a specific externally-driven task. From that point on, interest increased in trying to understand what dynamics are present when we're in this resting condition; when we're supposedly not doing anything, but our brains are not only active but organised and coordinated.

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How do you go about studying the brain in that state?
It's really much simpler than a lot of other ways to study the brain. We put people in an MRI scanner, and you might have a little plus sign, a crosshair, up on the screen, or you might not. You simply ask people to hold as still as possible and relax in the scanner, and let their mind wander.

An MRI scan of a resting brain

The reason this works and is of interest is because the amount of activity change that's induced by a specific cognitive task—for instance, counting numbers, remembering song lyrics, going through a grocery list, walking mentally through your home, or even any of those things your mind might be doing when not asked to do something else—actually only changes brain activity by a very small percentage: one or two percent. Whereas the spontaneous fluctuations we see in brain activity that seem to be intrinsic and aren't actually related to the demands of the environment or to cognitive experience—the variance they account for is much higher at around 10 percent.

So we're able to study the resting activity in the brain partly because, no matter what you do, you really can't change your brain activity as much as when it's just spontaneously doing what it does.

It sounds like this is quite a new way of thinking about the resting brain. What's the hardest part of working in this area?
Well, it has a little bit of a Wild West feel. What I mean by that is I started working in the field around 2005-2006 and there weren't so many groups that were doing this research, so the terrain was wide open.

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It was heavily criticized from the traditional cognitive neuroscience community, and because we were already kind of marginalised there was a lot of flexibility in new kinds of analytic techniques that could be tried, and the tools that were being developed could be applied to numerous topics in new ways. You could start to study health and disease, you could start to look at different mental states, how pharmacology would impact on brain activity…

One of the challenges is dealing with the methodological criticisms. What can you really understand about cognition? What can you really understand about brain organisation if you're not having the brain do something specific, or you're not aware of the cognitive state someone's in? And then another challenge is, what is the gold standard that we're dealing with?

No matter what you do, you really can't change your brain activity as much as when it's just spontaneously doing what it does

One of the major applications of this is looking at brain connectivity, and that's primarily what I focus on. We're taking advantage of the fact that brain areas that are connected to each other seem to be somehow communicating in coordinated, spontaneous activity at rest. We can take advantage of that to map connectivity between regions. One of the challenges we face in that specific subfield is that we don't really know if there are actually axonal connections between the regions we find to be connected. All that we know is that these areas of the brain are showing synchronised activity at rest.

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While in many cases that appears to be highly correlated with what we know about connectivity patterns, we don't actually have a gold standard, and so there's a great need for validation and furthering our understanding of the mechanisms underlying the spontaneous brain activity we observe.

Were you always interested in this particular area?
No, it's been a long, funny trajectory. I met somebody at a bus stop in New York and she offered to introduce me to her husband that afternoon… Long story short, ten years later, here we are.

I started off in the humanities actually, in French literature and philosophy. I was interested in psychoanalysis and I'll give you the short version: I'd been living in France and I came back to the States and I was really surprised to see the influence of biomedical models on psychiatry, as it was quite different in France when I was there. I thought the best way to understand how this was operating was to just go into a lab and see what it's like on the research side, and I just fell in love with lab work, with the way people collaborate with this communal goal in a lab. I liked the environment so much I stuck with it.

And what's next?
My lab mainly focuses on using resting brain activity to try to understand connectivity patterns underlying basic brain organisation, but in addition to that one of the questions that comes up is: If two people's brains are slightly different, does that impact on differences they might have in behaviour, personality, cognitive ability? So we also look at that.

The other question is: Can we understand how moment to moment changes in these dynamics relate to moment to moment changes in mental experience? To address that question I've been working with Jonny Smallwood, who's a psychologist at York focusing on mind-wandering, trying to understand, what do people think about when we leave them to do nothing? And how does one go from a state of focused attention to a self-generated thought kind of state where you're no longer invested in the environment around you but in your own preoccupations?

So the other half of what the lab's been doing is collaborating with Jonny and his lab on studies looking at how we can relate brain dynamics to the dynamics of mental experience.

Science Is Really Hard is a new series where Motherboard asks scientists about the real work that goes on behind scientific discoveries and what their jobs actually involve.