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An Interview with Neurovariability Expert Stephanie Forkel

A interview about the Science special issue on brain connectivity


In the morgue. That’s where Stephanie Forkel, a researcher whose work focuses on neuroviability, first realized that there are differences between what people’s brains look like.


“The first time I saw a brain, I was like, ‘hang on a minute!’ I thought my neuroanatomy was good, but this doesn't look like the textbook,” she says, laughing. “So that was my ‘aha moment’ of realizing that there is a huge degree of variability in anatomy that we didn't capture in textbooks.”


The mismatch between what Forkel had studied, and what she was seeing in real life, is partially due to the fact that neuroimaging, the scientific method used to learn more about the brain through scans, was occupied with the question of how the brain works, examining the so called “gray matter, where the neuronal cells bodies are. As a result, it largely disregarded the importance of the brain’s “white matter” — the deep tissue that stores the pathways for connection between the brain’s areas. That’s where a lot of the variability takes place, Forkel says.


With more accurate methods and larger swaths of data collected thanks to advancements in technology over the years, now neuroimaging allows scientists like Forkel to upend many of the early misconceptions prior scientific research birthed. In fact, she recently published a paper in a special issue of the journal Science arguing that neuroscience needs a new framework for better understanding the brain. Brain connectivity is at the heart of what makes our brains different from other species, and what makes our brains different from each other.


She is now a Donders Principle Investigator and Assistant Professor at Radboud University. I’m a science journalist, and my work — which has appeared in the New York Times, Guardian, BBC, and National Geographic — is all about telling stories of how the mind works. On the day of the Science special issue’s release, I had the pleasure of chatting with Forkel for my first ITM column called “Behind the Science”, where I unpack the behind-the-scenes of science that’s changing the way we think about the world of mental health and neuroscioence.


We talked about what her work means for the field of neuroscience, and how it can be a game changer for research, clinical practice, and pop culture.


Collage featuring representations of brain-scans, a technology often used by researchers to examine patients' cerebral functions, made by the author.

Can you tell me a little bit about yourself, and why you started doing this kind of work?


During my psychology studies, I got fascinated with the mechanistic of how the human brain works to allow for such rich functions, such as language, to emerge. That was when I switched to studying neurosciences. I love my field of research because it is interactive and multidisciplinary — clinical work, biomedical engineering, physics, maths, linguistics, and much more. It’s also a multipotential field that allows us to explore many different interests with the possibility to live in different parts of the world and interact with brilliant minds to push the boundaries of what we currently know.


Can you walk me through how research over the years really dispels the whole pop culture myth of “the right brain, the left brain,”, and our modular understanding of brain function?


The “modular view” of the brain — this part of the brain does this and that part does that — is founded in the history of our discipline, which is based on a handful of famous single cases. For example, patients who back in the time suffered a lesion to a specific part of their brain and lost the ability to do certain things, or lost inhibition or memory. Those patients really became the foundation and the bedrock of our discipline. For example, Phineas Gage had an iron rod shot through his brain, or Patient H, who lost the ability to form new memories and was stuck in a constant present. That was the first time we could actually associate a lesion in the brain with a specific change in behavior.


Now, with neuroimaging, we can actually look at many more patients and scan them over time, following the trajectory of how they heal. This is what actually first highlighted that it's not a simple modular system, but actually, it's a lot more complex: there is this entire white matter network behind those regions that orchestrates how the brain functions.


In your research, you say “circuits create networks by stringing together many brain regions to orchestrate a brain symphony.” You argue that brain connections are critical for the brain to work, and they’re basically entirely responsible for some functions. So how do these connections really have an impact on cognitive functions?


We make an example with language because classically, we have this “modular view” of the language process. Different parts of the brain carry out different functions: the frontal lobe does the articulation of language, the temporal lobe does the comprehension of language, and the parietal lobe does the concept and meaning of words. Obviously those parts of the brain are quite distant from each other, so language as we know it wouldn't work unless all these different brain areas actually communicate with each other. They have to be connected and orchestrated because, in the end, language is so much more than just a sum of words. We get so many cues and information from communicating through language that is far beyond just articulation, comprehension, and concepts. This is a perfect example of why the modular view is incomplete, and connections are a really important part of how the brain works, and why we should learn more about them.


And there are differences between the strength and number of connections in people’s brains, and that is also what causes variability among different people in how they perform cognitive functions… correct?


Yes, exactly. So there’s a question of, how different are we from each other? And what is the consequence of that? Like if you have a stronger connection for, say, language networks, does that mean you're better at learning a second language, or does that mean that you can recover better when you lose your language after a stroke? We still don’t have the answers to that, but this new way of looking at the brain — focusing on its connections — can help to start addressing these questions.


Other elements we’re also interested in learning more about are: how different are we from our older self? So how does our brain, and brain connectivity, change across the lifespan?


This also puts brain evolution into a new framework. Because your research notes that parts of the brain that have evolved later on are a little bit more variable between people, correct?


We compared the variability in the white matter between humans, macaques, and chimps. We found that the deeper structures in the brain that are older are also more alike between us. Then the areas more on the surface — the areas which tend to be associated with more complex cognitive functions — those are more variable. And so, this is the evolutionary component: when did this actually separate us, humans, from other species? And is variability a driving force behind that separation? Is there a cognitive advantage to being more variable? These are all questions that we can start to look into.


Like all good research, this actually gives us more questions than answers, but what are the clinical implications of these new findings?


We have formed a lot of models of how the brain functions in healthy 20-year-old white university students. And then, when you bring that back to an individual patient, we see quite often that the models don't fit — they don't predict well long-term outcomes after a stroke, or explain why some people recover better than others. This is where this new model focusing more on brain connections could have quite a huge impact in the real world.


For example, awareness of the connections between brain areas becomes important and can help us explain “atypical cases”. Cases of injuries where you have a lesion in a certain area, but no symptom, or you have a symptom, but the lesion is in a place different from where you’d expect. And that would then be explained by a network that actually connects those two areas.


In conclusion, how long do you reckon it could take to filter this new way of thinking about the brain into research, education and pop-culture?


I guess there will be differential trajectories. Take-up in the clinic always takes a bit longer because obviously, you can't just put out a new theory or method and then expect clinicians to jump on it and just apply that to patients. It has to go through a rigorous testing and evaluation period.


On the other hand, textbooks and educational changes could be much quicker, maybe in a matter of a couple of years. And being that there are a lot more initiatives of scientists actually going into schools, or teaching outside of school environments, I think there is a huge potential for these results and initiatives to actually come to fruition.


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This interview, like all interviews of Behind the Science, was edited for clarity.


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