Healthy Brain, Happy Life (10 page)

Recording the activity of individual cells in the brain is a little like fishing. First, you set yourself up in a good part of the lake (or brain) where you think there will be some nice big fish (or brain cells), and then you wait. I was recording with a very thin microelectrode as it passed hundreds, probably thousands of cells through other parts of the brain before it reached the hippocampus. I sampled the electrical activity of the brain cells as the electrode passed by, and the brief burst of electrical activity registered as little “pops,” which you can hear on an audio monitor. My goal was to figure out if the pattern of this firing from a given cell had anything to do with the animal learning a new association between a picture and a reward. But there were no guarantees. There were plenty of days when I listened to the activity of many cells with the electrode, and not a one did anything much at all. It just sounded like a bunch of radio hash with no rhyme or reason to the pattern of firing. Other days, however, I got lucky and caught a nice big fish in the form of a cell that had interesting activity—for example, cells that seemed to fire only when a particular picture was shown or cells that fired a lot during the blank delay interval of the task between the presentation of the picture and when the animal made a response to one of the targets.

I kept fishing in the hippocampus with the hope of finding something interesting, and over the first few months of recording something did start to emerge. I noticed that a particular cell we were monitoring seemed to have little or no firing associated with the task early in the trial when the animal had not learned any of the associations. But then, the cell seemed to increase its firing rate later in the session when more associations were learned. I didn’t fully appreciate the pattern until we analyzed the data later. Then it was as obvious as the nose on your face.

Just as I had noticed when listening to the cells during the experiment, these cells had little or no specific firing related to the task early in the learning session when the association had not been formed. But as the animal learned a new association, certain cells would dramatically increase their firing to double or sometimes triple their earlier rate. The increase in activity didn’t happen when all associations were learned, just during particular associations. This suggested that there were particular groups of cells in the hippocampus that signaled the learning of new associations by changing their firing rate. I realized I had been listening to the birth of a new memory in the firing of these neurons! Nobody had ever characterized learning in the hippocampus in quite this way before. We were seeing exactly how hippocampal cells encoded newly learned associations, and because we know that damage to this brain region impairs the creation of such associations, the study suggested that this pattern of brain activity was the key to the new associative learning process.

This was not only exciting for my research partners and me but for the field of neuroscience in general. Ours was one of only a handful of demonstrations of brain plasticity occurring in real time and directly associated with a change in behavior, in this case, new associative learning! Diamond had shown that rat brains had more synapses in general if the animal was raised in an enriched environment relative to an impoverished environment, but her studies did not measure behavior while learning was occurring or while a memory was forming. It was kind of assumed that if your brain got bigger, this was generally a good thing for behavior or performance. The long-term implication of our work is that if we understand this functionality in the brain, we might be able to replicate it when a brain is handicapped by various neurological problems. In other words, these findings showed us how cells in a normal hippocampus work as new memories are being formed. Because this brain area was missing in H.M., he was not able to form new memories. Importantly,
these results are also key first steps to developing possible therapies for the associative or episodic memory deficits that occur in Alzheimer’s disease, traumatic brain injury, and normal aging.
We must understand how the normal brain works to form new memories before we can fix what goes wrong with them in these neurological conditions.

TAKE-AWAYS: FORMING NEW MEMORIES

•  Parts of the temporal lobe, including the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (one on each side) are critical for a fundamental form of memory called declarative memory.

•  Declarative memory is named for its ability to be consciously declared and includes memory for our life experiences (episodic memory) as well as memory for facts (semantic memory).

•  For a new declarative memory to be laid down, these key temporal lobe regions must be working. These regions are also required as this new memory is repeatedly recalled and possibly associated with other information on its way to becoming a long-term memory.

•  Once these temporal lobe areas do their job of forming a long-term memory, the areas are no longer required. The memories are then thought to reside in complex networks of cells in the cortex.

•  If you damage your hippocampus as an adult, there are no other brain areas that can take over. So there is no plasticity left if you lose this area of the brain.

•  We now know that cells in the hippocampus can signal the formation of new associative memories by changing their firing rate in response to particular learned associations. Learn someone’s name and there will be a group of cells in the hippocampus that are firing specifically to that newly learned name–face association.

THE MYSTERY OF MEMORY HITS HOME:
Memories Mean More Than Neurons

I
t was a beautiful clear Wednesday morning in New York City. I had been a faculty member at NYU for a while by that time. That morning I was eager to dig into the Wednesday food section of the
New York Times
—my favorite section of the week. I was excited to see an article about the world-renowned chef Thomas Keller. With my parents, I had been to both of Keller’s five-star restaurants, the French Laundry in Yountville, California, in the Napa Valley and the equally amazing Per Se, overlooking Central Park. I was looking forward to a fun article about specialty butter or rare wild mushrooms, so I was surprised when I found that the article was about Keller’s later-in-life revived relationship with his father, who left the family when Keller was five years old.

Since that time, Keller had had only sporadic contact with his father. It was not until the chef was in his forties that son and father had established a real relationship. They enjoyed each other’s company so much that the elder Keller moved to Yountville to live near his son. Both loved their new relationship, eating and enjoying life to its fullest—no doubt the wonderful food and the beautiful surroundings of the Napa Valley only added to the joyful intensity of their reunion. But a tragic car accident left Keller’s father a paraplegic, requiring constant care and monitoring. Keller threw himself and all of his resources into helping his father heal and begin a new life from his now ubiquitous wheelchair. Under the careful watch of his son, the elder Keller survived with at least some of his old gusto intact for another year, before passing away.

It was a moving article. I could feel the pain that Keller experienced in losing the father whom he had only just gotten to know so late in life.

But the kicker was a quote by Keller who summed it all up when he said, “At the end of the day when we think about what we have, it’s memories.” I actually started to cry.

I cried not just because the story was moving. I cried because the story made me realize something important about myself. I had spent the last sixteen plus years studying the mechanics of memory, without truly thinking about what memories mean to me. Yes, I thought about patient H.M. and all that he lost without his medial temporal lobes. But I had spent no time thinking about how precious my own memories were to me. What memories were they? In a flash, the memories that came to mind were about studying; doing lab work; and earning degrees, prizes, and grants. I realized that my recent memories were all about science.

But I also had all sorts of memories about being a child, growing up in California with my parents and brother. If I concentrated, a slideshow of these moments began to unfold inside my head. Wasn’t Thomas Keller right? Aren’t our memories our most precious possession?

MEMORY LOSS AT HOME

While overt damage to the brain leading to amnesia is relatively rare, the brain regions damaged in those patients are also damaged in patients suffering from dementia and Alzheimer’s disease. One January a few months after that Thomas Keller article had been published, I got a call from my mother. She told me that Dad wasn’t feeling well and that he told her he couldn’t remember how to get to the convenience store where he had been going to get his coffee for the last thirty plus years. Quite suddenly, my father’s memory had evaporated.

I’m not a neurologist, but I knew my father’s symptoms were not just the forgetfulness that comes with age, when the brain’s memory centers begin to gradually slow down. I jumped into action and through my colleagues at Stanford, I got my dad an appointment with a top-notch neurologist. I flew out to go to the appointment with my parents. I was there when my father was given a diagnosis of general dementia.

I can’t even put into words how helpless I felt. I was considered an expert on the brain areas important for memory, and yet I was completely and utterly powerless to do anything to help my dad. What was all my education good for if I couldn’t help my own father? It was devastating.

I decided that even if I couldn’t cure his memory problem, I would find a way to help him. In the process, I helped my mother and myself as well.

Before that fateful January, I had been on a mission (much like Thomas Keller) to improve and enrich my own relationship with both my parents. While we were never estranged, we were not close either. For many years, my parents and I spoke only once every few months. We had gotten into a habit of not speaking regularly. On my end, I was too busy trying to attain my dream of earning tenure as a professor of neuroscience. On their end, I think my parents just accepted the sparse communication as part of the package of having a daughter with the kind of high-powered academic career that had been expected of her.

But as I entered my forties, I decided that I wanted to close the distance between us. I first started by making a point to call every week, a change that they both embraced. So, I was already talking to Dad more regularly before and after his memory problem appeared. And after the diagnosis, Dad was still Dad: he had the same sweetness and sense of humor, loved to ask me if I had seen any good Broadway shows, and always loved to hear about the new restaurants in New York. He just couldn’t remember what he had for lunch that day or who was at the family gathering last week.

But memory can also work in mysterious ways. Sometime after Dad’s diagnosis, I decided I wanted to try to change another one of our family traditions. While my Japanese American family was unwaveringly polite and always friendly, one thing we were not was affectionate. I like to tell people to think of us like a Japanese American version of
Downton Abbey
without the accent, the servants, or the real estate.

While there was no question that my mom and dad loved my brother and me, the reality was that we never said it. That just wasn’t done in the culture of our family. After we learned that my father had dementia, I realized that I wanted to start saying those three words, to both of my parents. I guess I wanted (or needed) them both to know that I
did
love them.

But then I had a problem. I knew I could not just start saying it without any explanation. It would be like suddenly starting to speak Russian to them instead of English for no reason.

So I decided I would have to ask permission.

Then I thought, Wait a minute! I’m a grown woman and I have to ask my parents’ permission to say I love you? That’s ridiculous, awkward, and uncomfortable. But then I realized that it wasn’t the awkwardness of asking permission that was bothering me. It was the fear that they might say no. And I knew that would make me feel awful.