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A genius among us: UCSF neuroscientist William Seeley

UCSF neuroscientist William Seeley was named a 2011 MacArthur fellow
UCSF neuroscientist William Seeley was named a 2011 MacArthur fellow

“Genius” is a pretty loaded title. But the John D. and Catherine T. MacArthur Foundation began bestowing that honor on American luminaries who shine in a variety of respective fields. They no longer call the recipients “geniuses,” but they do still award half-a-million dollars to 20 or so every year to support their work. No strings attached.

Two of this year’s MacArthur fellows are from the Bay Area – former poet laureate Kay Ryan from Fairfax, and William Seeley, an associate professor of neurology at the UCSF Memory and Aging Center here in San Francisco.

KALW’s Ben Trefny met up with Seeley at his lab in UCSF to talk with him about his significant study of frontotemporal dementia, and on being recognized for his particular genius.


WILLIAM SEELEY: These are devastating illnesses, and patients come in usually with a family member because they are having a new loss of neurological function, and the function that's lost depends on which part of the brain is affected by the illness. If they have Alzheimer's disease, they may complain about progressive loss of recent memory. If they have Parkinson's they'll say that their movements are slower, less fluid, or maybe they have a tremor. If they have frontotemporal dementia, they usually won't complain of anything and it will require a spouse to bring them to the clinic because their behavior and personality have changed so profoundly that they're not even aware of the change, but they can no longer behave normally in a social environment.

BEN TREFNY: So how many people are affected by frontotemporal dementia in the U.S.?

SEELEY: Well, the estimates are about 1.5 in 100,000.

TREFNY: How about Alzheimer's disease?

SEELEY: About 150 in 100,000, so significantly a higher proportion. FTD is particularly tragic because it strikes when people are younger, maybe still have kids at home, they're still working, there are a lot of years in front of them. In contrast to Alzheimer's disease, still just an incredibly devastating and important illness, but it occurs later in life so the number of years in front of folks confronted by that disease is fewer.

TREFNY: Tell me about the research that you do into frontotemporal dementia?

SEELEY: Well, we're interested in the neural anatomy of the disease – brain cells and neural networks that are affected in that illness. And our plan going forward is to take that information and try to translate it into some really fundamental biology – how and why those particular cells and circuits are affected in the disease.

TREFY: So you're taking a map of the brain, looking at the specific parts, and even kind of, if we were in a Google maps of the brain, then you're getting closer and closer into it to see the streets and even the addresses?

SEELEY: Yeah, we're trying to get down to the level of the core units of computation in the brain which are the brain cells themselves. We think that both the wide angle Google map, Google Earth map – I guess it should be called "Google Brain Map" – is important for following and tracking the disease, but also the very kind of focused-in, granular level so we can understand the initial target inside the brain cell and why those cells are targeted.

TREFNY: You are an expert on brain mapping and on the brain, certainly as much as anybody who I've ever met, what do we really know about how we think? How the brain moves thoughts around, the parts of the brain that think about anything – whether it's disease, or how I'm going to get from here to my house, driving home, how am I going to notice that car that's coming and this other thought in my head about my laundry list, etc.?

SEELEY: Well, we know quite a bit about all that actually. And we can watch the brain change dynamically in the context of those sorts of shifts in thought. We can watch different areas that are responsible for those functions light up or change their conductivity strength to each other. For example, if you were thinking about the route you took riding over here today, you would see activation in spatial areas of the brain, regions for the rain that look up information about 3D space. If you were thinking about something else, like an overdue bill, or something like that, we'd see an entirely different signature when we looked at your brain. In action we'd see probably a little bit of a memory circuit that called to mind the fact that that bill was still not paid and then a little bit of an emotional kick.

TREFNY: Do we know then what kind of exercises or procedures, or Sudoku, or whatever, helps us to keep our brain healthy or build up parts where we might be less strong in thought?

SEELEY: Well, you can change your brain by what you do – there's no question about that. And focused training does change the brain. What we'd all love is some kind of a pill, something you could do in a kind of a brain workout every day that would protect all of the aspects of your brain, that would improve the longevity of those neural networks and circuits. We don't have something like that, but I think it's a reasonable thing to keep looking for and a lot of people are looking for that kind of strategy.

TREFNY: Well we could do that kind of thing with our physical bodies by exercising every day. Say, we spend an hour in the gym or we bike to work, or something like that, then is there something that's comparable for the brain you put into practice, or would if you had time?

SEELEY: Well I think that analogy to the gym workout is perfect. When you go to the gym and you lift weights in a certain way, you are trying to improve the function of specific muscle groups that are put under the stress of that weight by the way you are holding it. Now, you know, a workout, a brain workout, a dedicated workout, could do that same thing that you do in the gym with your muscles – you could improve in that one specific thing. But I think you would agree with me that if you go to the gym and you do bicep curls with your right arm it doesn't make your left arm any stronger, nor does it make your toe any stronger, or help in any other way except for strengthening that right arm. So I think if I had to give other aging brains out there in the audience, like mine, some advice, I'd say keep doing the things you enjoy most, and do them with vigor. I think the worst thing you can do for your brain is not use it as much as you should. So, get off the couch, do things that you find invigorating.

TREFNY: Do you know if there is anything that you know are detrimental to the brain that can help the generation that leads to different diseases that one can get whether its Alzheimer's or whether it is ALS or something else like excessive alcohol, drug use, or traumatic brain injuries or things like that that end up affecting it? Or is it primarily something that’s hereditary or something that’s passed down genetically? How do you see those balanced out?

SEELEY: Well one’s risk for developing one of these illnesses that I study is a very complex, multi-factorial calculation but there are controllable risks and those are probably worth the time and the focus here. So the things to avoid are things that work against the integrity of the blood vessels to the brain and those are things like smoking, probably number one, high blood pressure, high cholesterol diabetes due to weight control problems, lack of exercise. Those all are the enemies of blood vessels that feed the brain during life and the more wear and tear those blood vessels see over time the higher ones risk for cognitive impairment in old age such as Alzheimer's disease or vascular diseases of the brain. There seems to be a vicious cycle that people can be pulled into due to those factors. On the other hand lack of education, lack of mental engagement are also risks and so: Stay in school, use your brain during your lifespan, and increase your chances of holding on to your marbles late in life.

Ben was hired as Interim Executive Director of KALW in November, 2021.