The distinguished psychologist Randy Gallistel had written eloquently about the whole phenomenon of probability matching and how deeply biological it all seemed to be.3 Imagine an organism foraging for food that has to pick between two trees. One of the trees has a 70 percent probability of having fruit while the other has only a 30 percent chance. It would be natural for the organism to choose the one with the higher payoff for food. As the organism nibbled away at the tree, however, the probabilities would be changing and at some point that other tree would become the hot property; thus one would expect that a highly evolved organism would also have built into it the constant monitoring of the other possibility. In this light, guessing probabilities becomes a basic structure, and then, once a probability is noted, maximizing would be the appropriate smart response.
As is so often the case in science, while an initial observation remains true, the initial interpretation can be completely wrong. Mike Miller had dogged it and wrestled it to the ground. It now seemed as though both hemispheres had these basic mechanisms, and what was lateralized was the interpreter, that unique device that tries to make sense of our thoughts, emotions, and behavior. Thanks to his efforts, and after putting in lots of work, we understood the mechanisms of hemisphere function more clearly.
BIG SCIENCE, SMALL COLLEGE
Dartmouth still needed an extra push in building up our new Center for Cognitive Neuroscience. We had been working in antiquated space with no real modern labs available. The college had been aware of this for some time—in fact, for some twenty years. Finally, some action was imminent. There would be a new building for psychology, and cognitive neuroscience would get the entire fourth floor. I was delighted, but I also knew we needed to move into the era of brain imaging. In order to even think about having the capability of brain imaging in the new building, the right kind of basement addition would have to be constructed.
I decided to mobilize the faculty and to make a bold push to the dean: establish a brain imaging center with a new MRI machine right there in the new psychology building. No psychology department in the world had an MRI of its very own in its own building. Dartmouth should be the first! The dean at the time was a biologist and was very friendly to the idea of making the field of psychology more biological. Still, we were talking big-time money for a small liberal arts college. In truth, I thought it would remain a fantasy.
Dean Ed Berger called me with his decision. While he couldn’t meet the whole nut, he could contribute $450,000 toward the additional basement costs. I had learned from days at Davis, one always takes any largesse made available for a project, even though it might not be the whole amount. In fact, it rarely is. I also knew, however, that it was not logical to spend that amount of money on a basement and not put anything in it.
There was another issue. No one on the faculty had the faintest idea how to run an fMRI machine. While some of us had been part of studies that included brain imaging measurements, we didn’t know how to actually manage these extremely complex machines and their environment. That meant getting the dean to approve a full professorship and a national search. We knew we needed a leader in the field, but at the time, we didn’t have a machine or the firm commitment of one. In 1999, while all of this was going on, I was running the two-week summer institute in cognitive neuroscience. One of the guest speakers was Scott T. Grafton, a brain imaging expert up from Emory. His work was fascinating, and his sense of a scientific problem was always right on. He was a neuroscientist in his own right as well as being a technical expert in imaging.
That afternoon, I dropped by the Hanover Inn—one of the most idyllic spots in America. Scott had changed into jogging clothes, which alarmed me: I hadn’t seen mine since the aborted climb on Mount Rainier. The idea flickered through my mind that he might not be my kind of guy after all. We sat on a couple of cane rocking chairs on the front porch of the inn, overlooking the college campus that Dwight Eisenhower once noted looked exactly like what a college should look like. After a few thises and thats, I blurted out, How would you like a job here? He looked at me and simply said, “Why not?” I asked if his wife could come up for a visit in the near future. She was a general surgeon specializing in oncology, which meant we were talking two jobs. While I was not dissuaded, I was beginning to see hiring complexities. Although Dartmouth was small and purportedly under the aegis of one administration, the College of Arts and Sciences had little to do with the medical school and hospital and there would need to be a job open.
Two weeks later the Graftons pulled back into town to take a serious look at moving to Hanover. It took about two seconds to realize all would work out. Kim is one of those magical people. After she met with the surgeons, she was offered a job on the spot. Ironically, it was the college that had to go through some paperwork to get the offer out the door to Scott. Still, it was all done in record time, houses were bought and sold, and by New Year’s Eve of 1999, the Graftons were in town to greet the spanking-new year and the spanking-new scanner.
The presence of the machine led to a change in the whole intellectual level and activity of the place. Having Grafton, a true authority at the helm, meant we were instantly taken seriously throughout the brain imaging community. Postdoctoral fellows from all over the world flocked to Dartmouth. Hiring new assistant professors became much easier. New kinds of funding were made available. The place was hopping. Again, it all worked because of Scott Grafton. Not only did he understand all the math, the physics, the computer science, and the data analysis issues, but at his core he was a psychological scientist. He wanted to know about how the brain plans action, perhaps the key question of all cognitive neuroscience.
Yet Scott had still another dimension. He was an M.D., a neurologist, working in a Ph.D. environment. Prior to switching to basic research full-time, he had practiced medicine for twenty years. He had walked the wards, declared people brain dead, seen suffering, treated all the patients that walked in the door, and done all the rest that goes with medicine. Dealing with the bumps and squeaks of a psychology department were only minor annoyances in comparison and simply didn’t cause him any major anxiety or concern. His equanimity was almost unheard of and was widely appreciated.
What came with this posture was also a huge appetite for ideas and a willingness to help novices learn how to do complex brain imaging. As a result, when a social psychologist approached him about examining the multiple dimensions of the self, or the workings of the emotional brain, or the possible pathways of the brain involved in transferring a visual image from one area of the brain to another, or any one of dozens of other projects, Scott was there to make sure the science was done correctly.
CORRECTING SCIENTIFIC ERRORS
The last time I had used a scanner was in New York and it was to examine the extent to which our patient V.P. was truly split. That study was done with an earlier version of an MRI magnet, something called a 0.5 Tesla machine. It provided remarkable images, and, at the time, we swooned. At Dartmouth, our new machine was 1.5 Tesla in strength, which meant the signals being captured from the brain tissues were clearer and more detailed. Today, the everyday machines are 3 Tesla, and the experimental machines for humans are up to 7 Tesla. The stronger the magnet, the greater the signals, allowing for crisper images and more anatomical detail.
When V.P. came up to Dartmouth for one of her testing sessions, we thought it might be good to rescan her. We wanted to double-check her images to see if the fibers that we thought had been spared in her split-brain surgery had indeed been spared. For several years we believed that the surgeon had missed some fibers in the posterior region of the callosum, thereby possibly allowing for some kind of visual information to be communicated between the hemispheres. She also had some fibers spared in the farthest anterior regions of the callosum. No one knew what these regions might be communicating.
A few years earlier, Alan Kingston had come up with a dramatic finding that suggested V.P. had some unique capacities. When compound words were
presented to J.W. and V.P., they responded differently. There was no ambiguity about remnant fibers in J.W. His postoperative MRI was clean as a whistle. When he was presented with a compound word, neatly separated, such that sky was flashed to the right hemisphere and scraper to the left hemisphere, J.W. drew a picture of scraper (serrated knife) with his right hand and a picture of the sky with clouds with his left. There was no integration, no picture of a tall building. V.P., on the other hand, integrated the information on every trial (Figure 45).
FIGURE 45. We tested Case V.P.’s ability to integrate visual information. Because her callosum fibers had been inadvertently spared during her surgery, she was able to do this in a unique way.
(Courtesy of the author)
With this knowledge and because we were sure that those early imaging results were not only cool but accurate, we began to study what kind of visual information might be transmitted over those remaining posterior fibers. We assumed from all of our earlier work that the posterior fibers were doing the work. In poking around on this problem, Margaret Funnell came up with another puzzling result. V.P. seemed as split as anyone for 99 percent of the tests we ran on her. She could not cross-compare color, pattern, size, or anything else we could think of between her two hemispheres. Then, one day after trying various combinations of stimuli, Margaret presented a phrase to one hemisphere, “red square,” and its corresponding colored geometric shape to the other hemisphere. Specifically, Margaret flashed the words to the right brain and, about a tenth of second later, a picture of a red square along with another shape to the left brain. Thus the task for V.P. was simple: After one half brain saw a word pair, such as “red square,” all the other half brain had to do was to pick out a red square instead of the alternative, say, a blue circle. On this sort of trial she responded correctly. What was so mystifying was that for the comparison task, one of the half brains had to have the comparison stimulus printed out as a “word.” If we flashed an actual red square, and not the words “red square,” V.P. could not do the simple task! We were flabbergasted. Could it be possible that some of those remnant posterior fibers were selectively transmitting information about words?
My graduate student friend from Caltech days, Charles Hamilton, had been carrying out some intricate work on the callosal system in monkeys. Chuck had been showing that the posterior region of the callosum was segregated into areas that seemed to subserve different aspects of the visual experience.4 It was intricate and fascinating work, and we quickly believed that with V.P.’s results we might have stumbled on to a homologue* in humans, pathways not directly related to simple sensory experience, but specific pathways dedicated to higher-order information. We wrote this up and gleefully sent it off for publication. It was quickly accepted and published.5 It was after this that V.P. was scanned by the new machine.
You guessed it. The new scans told a different story about V.P. Those pesky remaining fibers in the splenium—the visual areas of the posterior callosum that we thought we had seen—were gone! It was the fibers in the anterior segments of the callosum that were crystal clear in the new images. The earlier image had produced an artifact, which we wrongly interpreted as remaining fibers in the splenium. We immediately put out a second, short article correcting the earlier claim (Figure 46).6 In fact, with the correction, the results were just as intriguing. Now, the part of the brain that we know encodes complex information, the frontal lobes, was actually doing the communicating, not the posterior sensory regions. In other words it wasn’t a carbon copy sort of thing where the basic sensory regions of one half brain were communicating with the basic sensory regions of the other half brain. Instead, some kind of more abstract representation was being communicated.
FIGURE 46. Images taken from MRI scans of the patient taken in 1984 and 2000. The white squares mark regions of bright signal observed at both ends of the corpus callosum in the 1984 scan (panel 1) and at the rostral end in the 2000 scan (panel 2). The arrows in panel 2 indicate the locations of the coronal slices shown in panels 3 and 4. Panel 3 shows a slice through the region of bright signal found in the anterior callosum, where the spared fibers can clearly be seen. Panel 4 shows a slice taken from the posterior end of the callosum, in the region where bright signal had been observed in 1984. The callosal fibers in this slice are clearly severed.
(Courtesy of the author)
GETTING AHEAD OF A SOCIAL NORM
When I returned to Dartmouth from UC Davis, I had the good fortune to get to know a professor of mathematics, Dan Rockmore. Harvard- and Princeton-trained, and restless like me, Dan introduced me to the world of computer science. I had my Mac and that had been good enough for me, but Dan is one of those people who can’t help themselves. He understands stuff, lots of stuff. He was a bachelor at the time and so had extra time to hang out and talk about ideas and possible new projects. He could easily understand my thinking, and I could trust he knew what he was talking about. Together we launched many new ideas.
One day we were hanging out at the Dirt Cowboy, the local coffee shop, when I told him we needed a database for all the brain imaging experiments being done all around the world. Brain imaging experiments are expensive, and the data generated from them could be used and reused if people shared their data. Scientists are always thinking of different ways to analyze a data set as time goes by. And making them available to anyone interested in the topic would be extremely productive. This was a well-recognized issue, and one of the leading researchers in the brain imaging field, Marc Raichle, was among many pushing for it. A National Institutes of Health official, Steve Koslow, was trying to identify funds for what would be called a neuroinformatics program. The highly influential editor of Science magazine, Floyd Bloom, was a very active supporter. There were many, many more and yet no one was doing anything about it.
Rockmore began to unpack the problem and explain how he thought it was a doable task. For a neuroscientist, the amount of data in any one experiment seemed huge and overwhelming. It caused a sort of paralysis in thinking and action. How could gigabytes of data be managed? I mean, the computers would have to store maybe a terabyte! Holy cow. Over the next few weeks, Rockmore reinforced my salutary view of interdisciplinary collaborations. To him and his colleagues, large data sets were no problem at all. He soon brought in other mathematicians and computer scientists. Before I knew it, we were submitting a large grant to open up a national functional brain imaging data center (fMRIDC). Raichle agreed to serve as chairman of our external advisory board, Koslow said he would keep an eye on the application as it wound its way through the government review bureaucracy, and we started the spadework. We thought we were heroes, especially after we were actually funded by not only the National Science Foundation but also the Keck Foundation.
Of course, achieving that first goal involved a lot of footwork. First and foremost was the huge sociological problem that scientists do not like to share their data. Turf is king. At that point in scientific history, physicists, astronomers, geneticists, protein chemists, and more were commonly sharing their data, but neuroscientists had never been asked to do so. None of the disciplines that were currently cooperating had liked the idea at first. They all fought it until the norm in the field switched, usually led by one of its intellectual leaders. Quickly enough, the journals in the field would only publish a paper on the condition that the underlying data from the paper was made publicly available. This whole process was not always swift, and we had to submit our grant within months. How were we going to convince the grant agencies that researchers would hand over their data?
Conveniently, I was editor in chief of the Journal of Cognitive Neuroscience, so I decided the journal should have a new mandatory policy about data submission. In order to publish in JOCN, you would be required to submit your data to our new database system. Naturally, we wrote to all the major journals and asked for the same requirement, and all agreed at first.
As the project rolled on, it generated a lot of heat. As my colleague Jac
k Van Horn, who managed the project with great skill and care, recently noted:
. . . [U]pon becoming aware of our efforts and goals, fMRI researchers angered by journal requirements to provide copies of the fMRI data from their published articles began a letter writing campaign seeking to muster opposition against the fMRIDC—an effort which was featured in the news and editorial sections of several influential journals (Aldhous, 2000; Bookheimer, 2000). Commentaries over fMRI data sharing were aired in the pages of Science (Marshall, 2000), Nature (Editorial, 2000b), Nature Neuroscience (Editorial, 2000a), as well as in the journal NeuroImage (Toga, 2002) expressing concern over the data sharing requirement, over what possession of the data implied, human subject concerns, and, if databasing was to be conducted at all, how it should be conducted “properly.” Leadership groups in the field argued that fMRI was not mature enough to begin archiving its data (Governing Council of the Organization for Human Brain Mapping, 2001), conjecturing that until the BOLD response* was better understood, it was too early to consider databasing the images of published studies. People privately complained away, that those who collected the data owned it, that they would be remiss in simply giving it and that a small team at a modest Ivy League institution was not the best group to take on the task of archiving it. As a result of the apparent magnitude of these concerns, many of the journals, who had initially been so supportive, decided not to require submission of data from the fMRI studies they published. Instead they hoped to wait out the controversy and let the community itself resolve the issue.7
Tales from Both Sides of the Brain : A Life in Neuroscience (9780062228819) Page 30
