Prefrontal Damage Linked to Depression

In this episode, Richie Davidson and Cortland Dahl deeply explore the science of the emotional brain: why the mind is a storyteller, what split-brain research reveals about consciousness, how brain asymmetry shapes emotion, why some people approach opportunity with optimism while others withdraw, and what meditation may do to the brain and immune system. Enjoy!

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Podcast Chapter List

(00:00:00) – The brain is a storyteller

(00:01:03) – Welcome to Dharma Lab

(00:04:05) – Norman Geschwind and behavioral neurology

(00:06:31) – The thumbtack story: emotional memory without conscious memory

(00:12:12) – Language, the left hemisphere, and the corpus callosum

(00:19:04) – Brain asymmetry and emotion

(00:22:54) – Why emotion was so understudied

(00:29:26) – Brain asymmetry, attachment, and aversion

(00:31:19) – The prefrontal cortex and the old divide between thought and feeling

(00:37:07) – Studying emotion in newborn infants

(00:42:37) – Meditation, brain asymmetry, and the immune system

(00:47:04) – Why “it’s not so simple”

Written transcript for those who prefer to read

Lightly edited for clarity and readability.

The Brain Is a Storyteller (00:00:00)

Cortland Dahl:The example you gave earlier, with Broca’s area and the split-brain findings, points to something fascinating. Parts of the brain are not always talking to each other. One part of the brain clearly knows something, but the part that communicates doesn’t. And it doesn’t stay silent. It makes something up.

That’s the funny thing. In the absence of information, we don’t just stay silent. When we don’t know something, we are not comfortable with not knowing. Some instinctual part of us fills in the blanks almost all the time.

Richard Davidson:Exactly. The human mind and brain is a storyteller. This is how we make sense of our world. We create these narratives.

Welcome to Dharma Lab (00:01:03)

Cortland Dahl:Welcome everyone to another episode of Dharma Lab. I’m Cortland Dahl, and I’m here with Dr. Richard Davidson, who we all lovingly call Richie.

As many of you know, Richie is one of the most pioneering and widely studied neuroscientists on the planet. It’s a gift to be in conversation with him.

Today we’re going to have a conversation I’ve wanted to have for a long time. I moved to Madison, Wisconsin in 2012 to study with Richie, and over the years I’ve heard many conversations at the Center for Healthy Minds about neuroscience, meditation, and the mind. But one thing that has never really happened, even for those of us who work closely with Richie, is a kind of broad “download” from him about the amazing body of work he has contributed to over the decades.

Many people know Richie as a pioneer of contemplative science and contemplative neuroscience, the scientific study of how practices like meditation affect the mind, the brain, and our biology. But he is also a pioneer of affective neuroscience, which you might think of as the neuroscience of emotion.

To be a pioneer in one field is extraordinary. To be a pioneer in two is kind of mind-boggling.

So today I want to dig into some of those key insights, especially around neural asymmetry, which was a huge part of Richie’s early career and a central theme in affective neuroscience.

Norman Geschwind and Behavioral Neurology (00:04:05)

Richard Davidson:This topic is near and dear to my heart. It still is something I’m extremely interested in. It really began when I was a graduate student and had the opportunity to study with Norman Geschwind at Harvard Medical School.

Geschwind was one of the great towering figures in what we now call behavioral neurology. I took a course with him on functional neuroanatomy, which is basically how different parts of the brain are connected to different behavioral functions.

He was a neurologist, so he looked at people’s behavior as an external reflection of what was going on in the brain. He was an extremely keen observer of behavior, and he was also very demanding. He was what we would now call a localizationist, someone who believed in the specific localization of different functions in different parts of the brain.

He used to say that if you don’t believe in localization, it’s because you don’t know neuroanatomy well enough. That pushed me to learn neuroanatomy deeply, including doing a human brain dissection.

I also went on rounds with him, where he would visit neurological patients in the hospital. He would do these bedside exams that were incredible, using clever ways of interacting with patients to reveal what might be different about their brains.

The Thumbtack Story: Emotional Memory Without Conscious Memory (00:06:31)

Richard Davidson:One of the most famous demonstrations I saw involved a technique associated with Korsakoff, who described a syndrome of dementia related to alcoholism.

Korsakoff showed that there can be a separation between memory for declarative information and memory for emotional information.

A person with severe dementia might not recognize you if you came back the day after seeing them. They may have no conscious memory of who you are. But the question was whether the same was true for emotional information.

The demonstration was this: a doctor would put a thumbtack in his hand and shake the patient’s hand. The patient would feel the prick and withdraw. The next day, the doctor would return and ask, “Do you know who I am?” The patient would say no. The doctor would identify himself and offer his hand again.

But the patient refused to shake his hand.

When asked why, the patient confabulated. He said something like, “I think your hand is dirty, and I don’t want to shake your hand.”

That’s a beautiful demonstration of the dissociation between declarative memory and emotional memory. The declarative memory was gone. The patient did not recognize the doctor’s face or name and had no conscious memory of having seen him. But the emotional memory remained.

Cortland Dahl:That one point has huge implications for life. We often have an interpretation of something and we are completely convinced of it. It seems so real that it doesn’t occur to us that it’s an interpretation.

And yet the mind may have limited information, or may not be conscious of something, and it creates a whole story. In some cases, the story is flat-out wrong. But in the moment, it feels like reality.

Richard Davidson:Exactly. And this is not just occurring in patients with frank brain damage. This is happening in all of us all the time. This is how our minds work. The mind creates a story about the world, and it’s from that story that we operate.

It is not from some veridical perception of things in the world. There is no such thing as that. Our minds are constantly creating these stories.

This relates directly to our insight pillar of well-being, which is about the narratives we are constantly creating about ourselves.

Language, the Left Hemisphere, and the Corpus Callosum (00:12:12)

Richard Davidson:One of Geschwind’s great contributions was his work on language-related lateralization in the human brain.

In virtually all right-handed people, which is about 85 to 90 percent of the population, it is the left hemisphere that can speak, while the right hemisphere cannot.

There is a key region called Broca’s area, named after Paul Broca. Damage to this area, often through stroke, can impair a person’s ability to speak. What is interesting is that this is one of the most clearly lateralized functions in the human brain. If this area in the left hemisphere is damaged, the corresponding area in the right hemisphere does not simply take over.

The two hemispheres of the brain are very similar in many ways, but they have important differences. They are connected by the corpus callosum, a massive bundle of white matter that connects neurons in one hemisphere to corresponding neurons in the other. It is the largest pathway of connection in the human brain.

In the past, for some patients with severe epilepsy, surgeons would cut the corpus callosum to prevent seizures from spreading from one hemisphere to the other. This left people with two disconnected hemispheres.

When that happens, you can demonstrate strange dissociations. For example, if a split-brain patient is blindfolded and holds a glass in the left hand, the sensory information goes to the right hemisphere. But because the right hemisphere cannot speak, and the information cannot cross to the left hemisphere, the person may not be able to verbally identify the object. If you give them multiple-choice pictures, though, they can point to the glass.

Cortland Dahl:That’s the same basic finding. One part of the brain clearly knows something, but the part that communicates doesn’t. And it doesn’t stay silent. It makes something up.

Brain Asymmetry and Emotion (00:19:04)

Richard Davidson:Most early research on brain asymmetry focused on the back of the brain, where language and some perceptual differences were located. The left hemisphere was specialized for speech and language. The right hemisphere seemed better at certain visual-spatial skills.

But another early observation was especially interesting: when patients had damage to the left hemisphere, especially including the left prefrontal region, they were more likely to show depression after the brain damage. Two people could have comparable amounts of damage, but if the damage was in different hemispheres, the emotional consequences could be different.

That led to the conjecture that the left hemisphere might play some role in emotions that are antithetical to depression. These patients often seemed anhedonic, meaning they were not experiencing much pleasure.

There were also clinical reports of patients with right-hemisphere damage, whose left hemisphere was intact, showing inappropriate laughter or joy in situations where that would not normally occur.

These were early clues that there might be interesting emotional differences between the hemispheres.

Why Emotion Was So Understudied (00:22:54)

Richard Davidson:In those days, emotion was very understudied. Almost all the research on the brain and emotion was done in rats. It was focused mostly on the hypothalamus and basic drives like hunger and sex.

But these neurological patients were showing emotional changes from cortical damage, without frank damage to subcortical structures. That was fascinating to me.

I began thinking about ways to frame this theoretically. One important point is that asymmetries are not restricted to humans. You see asymmetries in other species. So maybe asymmetry is not fundamentally tied to language. Maybe language is one component of a deeper biological system.

There was a famous but obscure paper from 1959 by an ethologist, someone who studies animal behavior in natural environments. The paper traced approach and withdrawal behavior across the whole span of evolution, even in single-cell organisms.

The basic claim was that if an organism behaves at all, it will approach and withdraw. That is the fundamental behavioral decision an organism makes with respect to its environment.

In a moment of loose but creative insight, it occurred to me that asymmetry is a fundamental property of nervous systems, and approach and withdrawal are fundamental behavioral patterns. Maybe they are connected. Maybe the observations about depression and euphoria in brain-damaged patients had something to do with this.

Brain Asymmetry, Attachment, and Aversion (00:29:26)

Cortland Dahl:That’s fascinating from a Buddhist perspective. In Tibetan Buddhism, there is not the same kind of biological mapping, but there is an incredibly sophisticated understanding of the mind, psychology, and what is called the subtle body. Asymmetry shows up all over the place. And while the terms approach and avoidance are not used in the same way, attachment and aversion are central terms. You can see the correlation.

Richard Davidson:Yes. I’ve thought about that too. There are breathing practices, such as unilateral nostril breathing, that may differentially activate each hemisphere. There is research on that as well.

This was the beginning of my theory of brain asymmetry and its relation to approach and withdrawal, or perhaps attachment and aversion.

The Prefrontal Cortex and the Old Divide Between Thought and Feeling (00:31:19)

Richard Davidson:This was happening in the late 1970s. I became especially interested in the prefrontal cortex.

Another major influence on me was Walle Nauta, one of the great neuroanatomists of the 20th century. He was at MIT, and I took his neuroanatomy course while I was a graduate student at Harvard. His area of focus was the prefrontal cortex.

He wrote a paper called “The Frontal Lobes and the Regulation of Mood.” It was the first time I had read someone speculating that the prefrontal cortex had something to do with emotion, not just cognition.

Historically, the prefrontal cortex was thought of as part of the brain’s cognitive machinery. Emotion and cognition were often seen as separate. This was really a byproduct of a philosophical dogma: rational thought on one side, emotion and feeling on the other, with the two considered independent and often at war.

The idea that thought and feeling could be working synergistically together was not in the lexicon or imagination of scientists in those days.

Studying Emotion in Newborn Infants (00:37:07)

Richard Davidson:When we began, the only noninvasive way to study the human brain was EEG, which records electrical activity from the scalp. We began recording brain electrical activity in the prefrontal regions while trying to activate emotions associated with approach and withdrawal.

We thought that if these patterns were truly fundamental, they should appear very early in life. So we studied babies, including newborn infants.

How do you elicit emotional responses in newborns? It turns out to be pretty easy. We gave them a small squirt of sugar water, which they loved, and a small squirt of lemon juice, which produced a very different facial response.

Charles Darwin had written about facial expressions of emotion in humans and animals, and he claimed that expressions of pleasure and disgust were innate and present from birth. We tested this by recording the infants’ facial expressions and brain activity.

Even 72 hours after birth, you could clearly see different facial responses to sugar water and lemon juice. We also saw differences in brain asymmetry in the predicted direction.

There were big individual differences. People differ in their asymmetry at baseline, before you do anything.

People with greater left-sided prefrontal activation tend to be more approach-oriented. They tend to be more optimistic and ready to go when an opportunity presents itself. People with greater activation in the same regions of the right hemisphere tend to be more avoidant and shy.

Meditation, Brain Asymmetry, and the Immune System (00:42:37)

Cortland Dahl:What are the takeaways from this research? Beyond just being interesting neuroscience, how does this help us understand our own minds and navigate our inner terrain?

Richard Davidson:There are many things to say, but one concrete project led to my most highly cited scientific publication. It was published in 2003, and to the best of our knowledge, it was the first randomized controlled trial of mindfulness-based stress reduction, or MBSR, that had ever been done.

MBSR was developed by Jon Kabat-Zinn as an eight-week intervention to give people initial training in awareness practices. We studied MBSR in a group of very stressed employees at a tech company in Madison, Wisconsin.

We brought participants into the lab before and after the eight-week program and measured asymmetry in their brain. We wondered whether beginning meditators might show a shift toward more left-sided activation, which we associated with a more optimistic, approach-oriented style.

The study also happened to end around Thanksgiving, which is when many people receive flu vaccines. We asked participants not to get a flu vaccine before the study ended. Instead, we gave them the flu vaccine ourselves and took blood samples before and after, which allowed us to measure antibody response.

We hypothesized that people who went through the meditation training might show a more robust response to the vaccine.

That is what we found. People showed a greater increase in left-sided activation over the course of training, and they also showed a more robust antibody response to the flu vaccine compared to untreated controls.

At the time, these were very novel findings. The study has limitations. It was not a large sample, and the methodology was not perfect. But it was the first study of its kind.

Why “It’s Not So Simple” (00:47:04)

Richard Davidson:There is a lot more to say about asymmetry. I’ll conclude with a puzzle.

We measured brain electrical activity in very long-term practitioners who had been meditating for decades and had tens of thousands of hours of practice. They did not show extreme left prefrontal activation.

So it is not so simple.

That raised all kinds of questions about what this metric is actually reflecting. It is clearly reflecting something interesting, and it seems to be associated with early stages of meditation practice. But there may be an inverted U-shaped function, and the story is more complicated than we originally thought.

We originally thought about this in terms of approach and withdrawal, positive and negative emotion. But deeper reflection on Buddhist psychology suggests that the way we parse emotion may be imperfect.

There may be a better way to think about emotion: not simply positive versus negative, but virtuous or unvirtuous. In other words, some emotions lead us toward greater awareness, connection, insight, and purpose, while others detract from those qualities.

That gives the framework much more nuance and complexity. It became clear to us that this complexity had to be taken into account.

Closing (00:49:17)

Cortland Dahl:I think we just mapped out about ten future Dharma Lab episodes. This was fantastic.

I’ve wanted to have this conversation for a long time, just to geek out on these questions and these lines of research, because they are so fascinating and have so many implications.

I have even more questions now than when we began. I especially want to talk about the 1990s, when asymmetry caught the popular imagination through ideas like “left brain” and “right brain.” As one of the pioneers of that field, I’d love to hear how you think about the ways it was popularized, simplified, and maybe misrepresented.

But that’s another conversation.

Thank you, Richie. And thank you everyone for listening. This will not be the last conversation of this kind. Take care, and see you soon.

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