Paul Rand: When someone we’ve known forever suddenly starts behaving in ways that we can’t explain, our minds instinctively reach for psychological answers.

Bruce Miller: Have they become apathetic? Have they lost empathy for other people? Have they started to overeat? Have they developed compulsive behavior?

Paul Rand: That’s Bruce Miller, a professor of neurology at the University of California, San Francisco.

Bruce Miller: When you see a dramatic change in someone’s personality or behavior in mid or late life, you should assume that the brain is changing. And so that for me was always a paradigm shift. These are not things that people, when they see these symptoms in someone they love immediately jump to the idea that this is neurodegenerative.

Paul Rand: But after years of treating and studying patients with a special kind of neurodegenerative disease, when Miller sees these changes, he immediately thinks of the brain.

Bruce Miller: When we look at the brain with an MRI, we see loss of these relatively silent areas in the brain. If someone suddenly becomes addictive with alcohol or drugs, my assumption is not that this is psychological, and I think our whole medical system, if we’re going to recognize this, has to shift.

Paul Rand: Anyone who’s experienced a loved one with Alzheimer’s knows how it changes their brain and sometimes turns them into unrecognizable people.

Bruce Miller: I think it’s easy to understand when someone develops a memory problem that it relates to an area in the brain, the hippocampus, but it’s not easy for people when there is a psychological issue to attribute it to a degenerative disease.

Paul Rand: The brain disturbance that Miller has focused on in his career is a relatively rare disease called frontotemporal dementia.

Bruce Miller: FTD or frontotemporal dementia is the most common neurodegenerative disease in people under the age of 65.

Paul Rand: This kind of dementia doesn’t start with forgetting people’s names or routinely losing our keys, but instead it attacks the very fabric of our personalities.

What is FTD?

Bruce Miller: This is kind of shocking to hear because people, most have never heard about this illness. The average age of onset in the populations I’ve studied is around 50. This is a bit younger. These are people who are at work, have big expectations in work and family, and suddenly start to decline in ways that people find very unsettling and mysterious.

Paul Rand: And what he’s discovered researching this disease is fascinating for our understanding of what makes us who we are, how much control we have over our own actions, and how our society may need to change to acknowledge this biology.

Bruce Miller: So we have to begin to recognize that changes in who someone is do not happen unless there’s a chemical or a structural disturbance in the brain.

Paul Rand: From the University of Chicago Podcast Network, welcome to Big Brains where we explore the groundbreaking research and discoveries that are transforming our world. I’m your host, Paul Rand. Join me as we meet the minds behind the breakthroughs. On today’s episode, the social brain and how we can better understand human behavior through science.

The University of Chicago Leadership and Society Initiative guides accomplished executive leaders in transitioning from their long-standing careers into purposeful encore chapters of leadership for society. The initiative is currently accepting candidates for its next cohort of fellows. Your next chapter matters for you and for society. Learn more about this unique fellowship experience at Leadforsociety.uchicago.edu.

While we understand that things like our memory and mood come from the structure of our brains, we don’t often think that things like our personality and our character come from the very same place.

Bruce Miller: People, I think tend to dissociate the parts of the brain that are involved with social engagement as being something not in the brain and something psychological that has nothing to do with very specific brain circuits.

Paul Rand: But Miller’s research has shown that these social aspects of our lives are actually directly tied to the biology in our minds.

Bruce Miller: I’ve become interested through my work in large expanse in the brain that is responsible for our abilities to talk with, relate to, sometimes soothe and heal other people.

Paul Rand: He calls these parts of the collective brain, the quote unquote social brain.

Bruce Miller: And I think this is a part of the brain that is largely ignored by the neuroscience and also our society. A massive parts of the right hemisphere in the anterior regions, the frontal lobe and the anterior temporal lobe, are strongly devoted to seeing other people’s faces, recognizing their pain or joy, being able to walk in that person’s shoes, think about ways that we can interact successfully with that person. And I think altruism is a big part of what this part of the brain does. And wow, is that ever an important part of a human society.

Paul Rand: Now, the way you really start digging into this and exploring the social brain is through our neurodegenerative disease called FTD. And I wonder if you could explain what FTD is and just give us a good tight definition and understanding of it.

Bruce Miller: What is different about this than Alzheimer’s disease, which tends to start in memory areas, frontotemporal dementia attacks in a relentless way, the anterior frontal lobes and the anterior temporal lobes, which make up this very important circuit, which allows us to put off reward, stop from doing things that we shouldn’t do, prevent us from drinking things that we shouldn’t, empathize with other people. So what we see is a decay, I think of it as a moral decay, but it’s a decay related to the loss of function in this very specific area.

Paul Rand: One of the things I really liked what you did in the book is you brought in real world stories. It’s not just a scientific study, but you really helped make it relatable by giving personal type stories. And one of the first that you had is with Jamie, and I wonder if you can give us the Jamie story, if you would please.

Bruce Miller: I think the most striking aspect of Jamie was her cruelty. She had one of the most remarkable caregivers that I had ever seen, a man who had been in the army and looked after Jamie in an exquisitely beautiful fashion, but Jamie was unbelievably cruel to him.

Paul Rand: What was so striking about Jamie’s cruelty wasn’t just its intensity, but that she wasn’t always like this.

Bruce Miller: She said things that were cruel sometimes she even did physically cruel things like throw coffee at her husband. She lost interest in her business. She lost interest in her finances and actually got into financial trouble.

Paul Rand: Wow. Okay. So let’s talk about what was going on in her brain that was causing this.

Bruce Miller: So when I looked at Jamie’s brain, it was most loss of tissue I had ever seen in the front of brain in my relatively young career at that time. In particular, the right anterior temporal lobe was just shrunken as was the right frontal lobe.

Paul Rand: Jamie had what is called the behavioral variant of frontotemporal dementia.

Bruce Miller: So that is the behavioral variant. And I also have found, watch this remarkable story roll out in my lifetime where one gene after another, a mutation in the gene will cause the expression of this disease, not when someone’s a child or a young adult, but in midlife.

Is FTD hereditary?

Paul Rand: I hadn’t been thinking about this genetically, but it sounds like there certainly is a genetic linkage, at least in this case.

Bruce Miller: When we say about 20% of our cases have a gene that is highly penetrant, that means you are likely to get this disease when you reach your 50s or 60s and sometimes even younger. So sometimes with these mutations, people can develop us in their 20s or 30s, and you can imagine almost no one thinks that a 20-year-old who is suddenly misbehaving has a degenerative disease in the brain.

Paul Rand: Another one of Miller’s patients who experienced the behavioral variant of FTD was named Thomas.

Bruce Miller: So Thomas was a gentleman whose major symptoms related to rigidity, remarkable rigidity and a loss of empathy.

Paul Rand: From most of Thomas’s life, he was known as a kind and caring person. That is until...

Bruce Miller: Thomas was a very religious man. And like a lot of people whose disease begins in the right interior temporal lobe become more rigid in their beliefs. If they’re atheists, they’re more rigidly atheistic if they’re religious Christian, more rigid. So here’s an example of Thomas’s rigidity. There’s a major flood in his rural town. It’s Sunday. All of the people, including the minister of his church are down at the river with sandbags trying to protect the city from a flood. Thomas is the only one in the church infuriated, he talked to me about this many times, that everyone had lost their religion and he was the only one in church on that day. Really, he could not understand why people on Sunday where it was a time of worship needed to be there. During the Super Bowl, good friends of his had a small betting pool for $5. Thomas raged at his friends about this irreligiosity on Super Bowl Day, how wrong it was, and you can imagine lost many of his friends.

Paul Rand: And so what did you see when you looked at his brain and you did an MRI? What did you see?

Bruce Miller: One of the things about the brain in these patients is sometimes the damage is very small and very focal. And I think that’s what astounded all of us about Thomas was most of the brain worked well, and in fact, he worked in IT very effectively until his behavioral problems became so disabling that he could no longer do this. So most of the brain worked fine, language, perception, but he lost the ability to experience emotion the way we do. Loss of empathy for his wife was astounding.

One morning she cut off the tip of her finger. We all feel a sense of sadness and horror when we hear about this. Thomas didn’t react that way. Thomas walked back into the house, said, “I’m going to get my wallet because I don’t want to get a ticket on the way to the hospital.” He comes out of the house, his wife is crying, he asks her to stop. “You’re embarrassing me with our neighbors.” Then suddenly stops again, picks up the clippers, walks across the street to the neighbor, gives the neighbor the clippers and says, “Here you go. I’m going to be gone for a while. You can use these while we’re not around.” The remarkable thing about this is all of the doctors and psychologists who saw Thomas thought that the problem was in his wife, not in Thomas. It shows you how we tend to see behavior.

Paul Rand: And all of this raises important ethical implications. And in the case of one of Miller’s patients, even legal implications.

Bruce Miller: As we’ve studied these diseases, we’ve learned that many people because of their loss of judgment and their what we would call disinhibition, about 40% of people with this commit antisocial acts that either do or could lead them to be arrested. And it shows you that we don’t entirely have free will. And our free will is really taken from us in particular if the frontal lobes are not working. And so Clark was driving under the influence and actually took a swing at a female policeman. And so his wife came to me and wanted to know whether Clark was really responsible for the crimes that he committed. And again, Clark had massive atrophy in the frontal lobes, very disturbed.

Paul Rand: Now you make the case in this part of the book where our legal system isn’t necessarily taking into account a defendant’s brain functioning. And should that be happening more, and if so, how do you enable that?

Bruce Miller: I think it’s really a great question on a double-edged sword. So for my patients, the answer is almost always the crimes they commit, they would not be responsible for. They don’t have the apparatus in the brain to prevent them from committing these crimes. Most of them are petty and silly, driving through a red light, even though a policeman was watching. They’re a combination of disinhibition and poor judgment, but some of them can be more serious and the frontal lobes are very important for our ability to inhibit a crime.

Paul Rand: But not all of the changes in the brains of people with FTD lead to negative outcomes. It’s often the case that when certain parts of the brain atrophy, other parts actually increase. Many people with FTD experience incredible changes in their capacity for creativity, which Miller learned when he met Marcus.

Bruce Miller: So Marcus was the first patient I ever saw. He had eventually what we called a semantic form of progressive aphasia. No idea what that was at that point. Semantic is, I think it’s a little bit elusive, but the story is we have two anterior temporal lobes. The left side is really critical for understanding words and concepts. So over time we learn that there are animals, then we learn the more specificity, there are birds, then we learn there are pigeons and hawks, and then red-tailed hawks. So in that area of the brain, the left anterior temporal lobe starts to disintegrate, we lose this knowledge, we lose these facts. We have trouble understanding what a word means. And so Marcus came in and he was losing language in a very peculiar way. He didn’t know the meaning of many words. He’d been very successful banker. Suddenly he became obsessed with colors.

He said, “I see purple, I feel purple.” And much to the surprise of his son, he became an artist. He actually won local awards in his state for this art that emerged later in life. This visual preoccupation and enhancement accompanied this journey of visual creativity. Marcus began my effort to understand why someone with a degenerative disease would become a visual artist. Everyone told me this was just a coincidence that had no meaning, but I wasn’t quite sure. So I started seeing people and started, unlike most neurologists, asking about strengths or new things that had emerged that were positive in the setting of their illness, and began to collect now a large number of my patients and their beautiful art. More recently, Bill Seeley, one of my colleagues and Adit Friedberg, showed that in these people there was increased activation in the posterior parts of brain that are involved with visual processing. So we started to have a physiological and anatomic explanation for this change. So the loss of language seemed to release circuits in the back of the brain that were responsible for their painting.

Paul Rand: FTD is one window into the social brain that makes us who we are. We can better understand how our personalities are built in healthy brains by observing what happens when they deteriorate. So how prevalent is this disease and are there treatments and a way to keep our social brains healthy? That is after the break.

If you’re enjoying the discussions that we’re having on this program, there’s another University of Chicago podcast network show that you should check out. It’s called The Pie. Economists are always talking about the pie, how it grows and shrinks, how it’s sliced, and who gets the biggest share. Join veteran NPR host Tess Vigeland, and she talks with leading economists about their cutting edge research and key events of the day. Hear how the economic pie is at the heart of issues like the aftermath of a global pandemic, jobs, energy, policy, and much more.

How prevalent, if you had to talk about FTD, and again, coming earlier in people’s lives, what percentage of the population, if you had to guesstimate, would you say are impacted by this? At least I’m sitting here thinking, “Gosh, I forgot something recently,” or everybody’s going to start thinking saying, “Well, do I need to have this checked out?”

Bruce Miller: I think there are about a hundred thousand cases in the United States a year. It’s not trivial. It’s not trivial. I think we’re just grappling with is this a relatively uncommon disease? I’d still call it an orphan disease with profound implications for society though. Or is this a disease with lots of manifestations later in life as well? And I don’t think we have the answer yet.

Paul Rand: And I’m assuming at this stage there’s nothing that could be done to reverse the damage that’s been done.

Bruce Miller: We don’t have really great therapies yet for frontotemporal dementia. Still today, most of the cases that we see go unrecognized.

Paul Rand: Oh, my gosh.

Bruce Miller: But I would also add that this is the most exciting time in my lifetime in terms of getting basic scientists to think about these genes and thinking about ways of curing the illness associated with the gene. We work with a young neurologist named Claire Clelland and who is mentored by our Nobel laureate, Jennifer Doudna. And we think that with the CRISPR technology, we can cut out these bad genes and absolutely eliminate this disorder. Polio disappeared. We think these diseases can disappear with the right therapy.

Paul Rand: As we think through it, and again, when you talk about addressing this using CRISPR technology, where are we in the whole mix of not only the understanding but progressing in different levels or types of treatment?

Bruce Miller: The first, the question is can we recognize these illnesses early? And then even more important, can we recognize the molecule in the brain responsible for that person’s change in behavior or language? And these are called biomarkers. In Alzheimer’s disease, we now have really splendid biomarkers that can detect even the very early stages of the illness before someone is really, truly having trouble with memory.

So for all of the different molecular causes of neurodegenerative conditions, we are working extensively on biomarkers. Some of it is the clinical story. What is for certain this particular cause of disease? Is there a gene that we can measure? Are there proteins in the blood that may tell us that this person is in the early stages of this degenerative disease? So I think that the theme with Alzheimer’s where we have a lot more treatment experience is that if we don’t get in early, if we don’t treat people before they’re really sick with a memory disorder, our treatments aren’t going to work. But there probably are, just as language therapy helps a lot of our patients, I think we need to develop social cognitive therapies that will help these patients and also help their loved ones as they engage and understand what they can do and what they can’t do in this dyad that is so important.

Paul Rand: So if there’s no treatment for Miller’s patients like Thomas, what can families and friends do to make their lives better?

Bruce Miller: I think for that family, there were two or three things that we did were incredibly important and are still important today. One is explaining to his wife that this was not her fault. This is not caused by you. This is a degenerative disease. The second point was to help her to understand, and it was explained to the whole family unit that this is a neurologic disease. This is not anything that Thomas can help. The third thing we did was with this disease, we spent a lot of time with the family protecting resources. Because you can imagine somebody with a disease like this is unbelievably irresponsible. And for every patient I see, probably half have lost very significant amounts of their resources by bad decision making. And then finally, eventually protecting the family. We had medicines that calmed to Thomas down. So there were little things we could do, but for me that was one of the beginnings of the journey at really moving this from diagnosis, which we’re still not very good at, to thinking about ways of treating it and preventing it.

Paul Rand: While there may be no way to treat or prevent FTD, are there things we can do for our social brain to keep it healthy throughout our lives? Well, Miller says yes.

Bruce Miller: I think really important to be socially engaged. One of the remarkable things about frontotemporal dimension gene carriers that we’ve studied is a lot of the times they become socially withdrawn, even become hermits. So the illness not only is a degeneration in the circuits that make us want to be social, but also it is exacerbated by the lack of stimulation of those social circuits. So we have a lot of good data, Caitlin Casaletto from UCSF has written about this, that social engagement, even if you’re a gene carrier, is associated with probably less likelihood of the disease happening at a young age. So I think we’re starting to believe that cognitive stimulation, exercise, social engagement, are all important.

I talked with a university president once and I was talking to him about this and he said, Well, I don’t think we can teach values and we can’t teach empathy.” I think this is the myth of the social brain. This is different than learning how to play a violin. Acts of empathy tied to altruism are the most beautiful things that we can do as a human society. I think empathy is everything in our lives, kindness. The Dalai Lama talks about this, whenever possible, be kind. We can always be kind as the comment Dalai Lama makes. So these principles have really changed the way I engage with people, treat people, my likelihood of responding to someone who is down on the street, someone who has a problem on an airplane, which I just recently dealt with. I think engagement and socially positive activities, whether it’s in your own family, whether it’s people in need. I think these are the ways that we develop our empathy circuit.

But we have rarely touched the surface to understanding your question, and I think more and more, I think as we learn about the empathy circuit, we’re going to learn how to make the best of this and teach children the right ways. But I think a lot of it, just like shooting a basketball, it’s engaging, it’s doing, doing it over and over again.

Matt Hodapp: Big Brains is a production of the University of Chicago Podcast Network. We are sponsored by the Graham School. Are you a lifelong learner with an insatiable curiosity? Access more than 50 open enrollment courses every quarter. Learn more at graham.uchicago.edu/bigbrains. If you like what you heard on our podcast, please leave us a rating and review. The show is hosted by Paul M. Rand, and produced by Lea Ceasrine and me, Matt Hodapp. Thanks for listening.