Hanna and Antonio Damasio with the functional MRI scanner in USC’s Dornsife Cognitive Neuroscience Imaging Center, which she directs. Photographs by Tim Rue

Issue: Summer 2006

Emotional Rescue

Time to retire that old adage about “not thinking with your heart but your head.” Two USC neuroscientists have proven just how essential emotions are to the well-ordered intellect.

By Carl Marziali

Consider all the decisions you make, or might make, by following your gut. You marry for love. The stock market crashes - you sell. The stock market crashes - you buy. A business associate proposes a deal that sounds too good to be true - you pass. Or you bite. You live your life based on faith in a God you cannot see.

When gut feelings shape so much of our lives, isn't it time someone studied them seriously?

Antonio and Hanna Damasio thought so. Starting in the 1980s, neuroscience's pre-eminent married couple opened a new frontier for the field with a long-ignored question: How do emotions influence the way we think?

The quest for the answer has led the Damasios down a tangled path of neurological mysteries, from the blown-out skull of a 19th-century railroad worker, to studies of brain-injured patients who failed in life but passed every psychological test, to the exploration of so-called "social emotions" in a stunningly ambitious research program at USC's new Brain and Creativity Institute.

Housed in the USC College of Letters, Arts and Sciences, the institute opened last fall to coincide with the Damasios' arrival on campus from the University of Iowa. Here, the researchers hope to scientifically dissect the complex emotions that some consider uniquely human: pride, respect, admiration, elevation, embarrassment, shame, contempt, generosity.

"These emotions are very important because they really form the scaffolding for a lot of our social activity," says Antonio Damasio, the institute's director. "We want to study behaviors, we want to study what happens in people's faces when these are being engaged, and we want to study what happens in the brain when they're having these emotions. Armed with advances in imaging technology and analysis, and excited by the interdisciplinary collaborations available at USC, the Damasios are set to embark on a program that, some traditionalists worry, threatens to usurp philosophy as a route of inquiry into the human essence.

Yes, philosophy - which René Descartes practiced while lying in bed, and Socrates developed in leisurely walks on warm Mediterranean evenings - might someday be subject to experimental verification.

How did neuroscience get to this point?

The starting gun fired in 1848, next to a new railroad siding somewhere in Vermont. Phineas Gage, a 25-year-old construction foreman, was leading a crew laying tracks for the Rutland & Burlington Railroad. Antonio Damasio, who opens his groundbreaking book Descartes' Error with an account of Gage's life, describes him as a skilled and respected leader. Someone people looked up to.

But on this hot summer day, Gage had a fateful moment of distraction. The crew was about to blast a rocky outcropping that stood in the way of progress. A hole was drilled; explosives were deposited. Gage's job was to wait for sand to be poured into the hole and then to pack the sand with an iron rod.

Instead, Gage pushed the rod straight into the dynamite.

The explosion launched the thing like a rocket. The entire rod - more than 3 feet long, and 1.25 inches across - shot through Gage's head and landed a hundred feet away.

The force of the blast was no surprise. The surprise lay in Gage's recovery. Within an hour he was talking normally and describing the gory episode in detail to doctors. Within two months he was "cured."

But something had changed. It didn't take long for friends and relatives to notice new and unpleasant personality traits: rudeness, profanity, unreliability, boastfulness. A man once admired by his crew for good sense and steadfastness had become a windbag. He never held a steady job again.

Risk and reward Antoine Bechara's Iowa Gambling Task was the first to replicate frontal-damaged patients' real-world problem - a disastrous inability to learn from their mistakes.

The problem was not in Gage's mental powers but in the way he used them, the Damasios believe. The accident had destroyed his character. It had deleted the store of wisdom and emotional memory that had made him such a respected worker and friend.

The fact that Gage was pronounced cured in the first place shows how much our culture identifies the brain with rational thought. Gage could speak and reason normally. Therefore his brain had to be working normally, doctors concluded - overlooking the inconvenient evidence of a gaping hole in the skull and a bloody, 13-pound iron rod.

"To understand Gage's behavioral change would have meant believing that normal social conduct required a particular corresponding brain region, and this concept was far more unthinkable than its equivalent for movement, the senses, or even language," Damasio writes in Descartes' Error.

At the University of Iowa, the Damasios had seen patients with similar behavioral problems: an inability to make sound decisions, to hold a job, to manage money, to keep friends.

The patients' brain scans often showed damage in the ventromedial region of the frontal lobes, behind the lower forehead and between the eyes.

Could Gage's brain have been damaged in the same region?

In a virtuoso display of imaging technique, Hanna Damasio and colleagues in 1993 reconstructed Gage's brain scan.

"Brains are very different [from one another]," she grants, "but the shape of the brain - the main constraint of that shape - is the skull. And we had the skull of Phineas."

Hanna Damasio obtained measurements of Gage's skull, which has been preserved in a museum. Using the CT scan of a normal brain and skull as a starting point, her research team manipulated the scan until it matched the dimensions of Gage's skull.

This modified CT scan could be compared to scans of real brains. Hanna Damasio, who now directs the USC Dornsife Cognitive Neuroscience Imaging Center, chose a handful of close matches - living patients whose skulls were close to Gage's in shape and size.

The researchers ran computer simulations of Gage's accident to understand the rod's trajectory. In every scenario, the rod severely damaged the ventromedial region of the frontal lobes.

The Gage experiment, combined with extensive studies of patients with frontal damage, led the Damasios to surmise that the frontal lobes interconnected emotion, social conduct and decision-making.

These early observations and conjectures led to the formulation of the Somatic Marker Hypothesis: the notion that emotion plays a critical role in decision-making. But how to verify this hypothesis? The living patients were as inscrutable as the perforated skull of a 19th- century foreman.

Just as Phineas Gage had fooled his doctors, patients with frontal lobe damage showed exasperating normalcy in the laboratory. Anyone could tell something was wrong with these people - except by using the very tests designed to spot mental problems. On those tests, the patients soared.

The Wechsler Adult Intelligence Scale (IQ), the Rey-Osterrieth complex figure, the Multilingual Aphasia Examination, the Wisconsin Card Sorting Test, the Minnesota Multiphasic Personality Inventory. A psychopath trying to deceive his parole board could only dream of the normal numbers these brain-damaged people put up effortlessly.

For almost a century, mainstream neuroscience had considered feelings irrelevant to the study of reason, and here was the result: a gaping blind spot where emotion hits the brain.

The Damasios set about shining light on that blind spot.

First, with University of Iowa experimental neuropsychologist Daniel Tranel, Antonio Damasio carried out a landmark series of skin conductance tests on patients with ventromedial lesions.

Though the purposes and the techniques differ, skin conductance tests resemble the lie detector in their tracking of real-time emotional responses to stimuli.

Patients and a control group were shown a series of images, some graphic and powerful, others bland and unremarkable. Skin conductance readings of subjects in the control group rose and fell as the images changed. But the brain-damaged subjects showed hardly any response.

At last, a measurable difference.

The experiment did not explain the patients' real-world problems, but it did indicate a strange emotional flatness. Several patients said they knew how they should feel in certain situations; still, they could not feel that way.

Enter Antoine Bechara - then the Damasios' postdoctoral student, now an associate professor of psychology in USC College.

Bechara invented what has come to be known as the Iowa Gambling Task. Working with Hanna Damasio, he set out to design the most lifelike laboratory test he could imagine. Having written his dissertation on addiction and decision-making, Bechara turned to gambling.

The task was brilliant in its simplicity. Subjects were given a pile of money and four decks of cards. They were asked to turn over one card at a time from the deck of their choice. Most of the cards paid out to the player. Some required the player to pay the bank.

Two of the decks were risky, with higher winnings but also much higher losses - so much higher that players were almost sure to go broke. The other decks paid less, but also had lower penalties.

The difference between normal and frontal-damaged subjects was striking. As the game went on, normal players drifted to the safer decks. Frontal patients did the opposite, even after they were broke and borrowing from the bank.

The reason, Bechara and the Damasios concluded, lay at the core of the frontal patients' problem. They had intellectual memories of huge losses, but learned no emotional lessons from those experiences. So they kept repeating their mistakes.

The Iowa Gambling Task was the first to replicate the frontal patients' real-world problem: a disastrous inability to decide.

"This area of the brain is really important for linking memory to an emotional tug," says Bechara. Without an emotional weight, he says, memories have no power to change our actions.

From these experiments and other observations, Antonio Damasio further developed his Somatic Marker Hypothesis. He concluded that each potential choice is tagged with a feeling (a somatic marker) making that choice more or less desirable. To be conscious of the marker is to have a gut feeling.

Somatic markers don't guarantee happiness - who hasn't been on a bad date or picked a poor investment? - but without some kind of innate weighting system, all choices appear equal and overwhelming. Somatic markers winnow the field.

"We're not saying that emotion is always good," says Antonio Damasio. "But we're certainly not saying that emotion is always bad. In fact, if one would have to choose, it's probably more often good than bad.

"What are the great opportunities that you face as a living creature? They have to do with food or sex. Most of the emotional apparatus is in fact designed to signal positively when there is a good mating opportunity, or when there is low-lying fruit. You are definitely led by somatic markers, and they propel you in the direction of food and sex, and by extension to money, which symbolizes both."

Ralph Adolphs, now professor of biology, psychology and neuroscience at Caltech, learned about the Somatic Marker Hypothesis chapter by chapter as a young post-doc in the Damasios' lab at Iowa, when Antonio Damasio asked him to critique drafts of what would become Descartes' Error. "It was an exciting time," Adolphs says. "You really got the sense that there was new theoretical ground being broken."

The Somatic Marker Hypothesis provoked much debate when it was published in 1994, and remains a battleground to this day.

"The general idea of it has been borne out by the data," Adolphs says, although "some of the specifics one could quibble with. It continues to be a very provocative hypothesis. Its impact has been huge."

Dozen of labs around the world were inspired by the research, with theoretical spillover into psychology, education and other areas.

For Antonio Damasio, the Somatic Marker Hypothesis was a single achievement in a prolific career, albeit an achievement that opened an entire new field of study.

Last year, he was the sole winner in the scientific category of the Prince of Asturias Award - one of the world's most selective honors, and one generally awarded to teams of two to five investigators. Past recipients include Craig Venter, who led the team that mapped the human genome, and Robert Gallo and Luc Montangier, who identified the AIDS retrovirus.

"Antonio Damasio occupies a unique position in the world of neuroscience," says Joseph Aoun, dean of USC College. "His research on the neurobiology of the mind has had a major influence on current understanding of the neural systems that underlie emotion, memory, language, decision-making and consciousness."

Hanna Damasio is considered a pioneer of the use of brain imaging technology in cognitive neuroscience. Her book Lesion Analysis in Neuropsychology, first published in 1989, remains a classic text in worldwide use. Her 1995 Human Brain Anatomy in Computerized Images was the first brain atlas based entirely on computer reconstructions of living human brains - "autopsy in vivo," as she likes to describe it. (A second and entirely new edition has just been published.)

The reconstructions were done in Brainvox, a sophisticated brain imaging program that she co-developed and employed in her study of Phineas Gage's skull.

Signing the couple is a recruiter's dream, according to Eric R. Kandel, a Columbia University neuroscientist and 2000 Nobel laureate. "It's an enormous coup for the University of Southern California," he says, calling Hanna Damasio "a phenomenal imager" and Antonio Damasio "one of the great modern thinkers about the brain."

"They are giants in the field," he adds. "I followed them very closely while they were at Iowa, and they transformed the neurology department there."

At USC, the Damasios are already collaborating with researchers across campus, from Adrian Raine (criminal pathology), to Laura Baker (psychology of twins), to Zhong-Lin Lu (social communication). The growing research team includes graduate and even undergraduate students in fields from international relations to music.

There are pragmatic as well as theoretical reasons for such collaborations, says Hanna Damasio. Neuroscientists studying social emotions do not necessarily know what are the best questions to ask, and social scientists may not be familiar with the highly unnatural environment of a brain imaging experiment.

"There are things you can do and there are other things that you just can't," she says. "We know the constraints, and by working together with colleagues in other fields we can ask the good questions and with luck find the answers."

The back-and-forth is not limited to scientists. Soon, the institute will be welcoming influential British director Peter Brook (The Lord of the Flies) and virtuoso pianist Pierre-Laurent Aimard as visitors.

Antonio Damasio describes such visits as the start of a dialogue between neuroscience and the arts. In fact, the USC Brain and Creativity Institute might just as well be called the Institute for the Study of How We Think. Its goals are that sweeping.

So sweeping, perhaps, as to update and refresh the traditional methods of intellectual inquiry. In particular, Antonio Damasio suggests the existence of neurobiological roots behind the processes studied for centuries by philosophy - a prospect variously exhilarating, neutral or repulsive to philosophers.

He questions the great Immanuel Kant and his idealistic views of rationality, and finds more evidence for the equally extreme but intriguing ideas of David Hume, who championed emotion as the wellspring for all human thought.

"Some of the very beautiful inquiries of the past are either favored or disfavored by current science," he says. "In the debate between Hume and Kant, I believe that Hume wins hands down."

We are at an interesting moment in history, Antonio Damasio believes, equipped with powerful new scientific tools, yet attached to centuries of honored intellectual traditions. "You would have to be very foolish not to take the opportunity" he says, to employ these tools to test the validity of traditional beliefs.

The institute's ultimate mission, as he articulates it, is to "take the classical forms of inquiry about human nature and the human mind, and see how you can join these classical forms and approaches with modern neurobiology."

"Just a very small agenda. Not ambitious at all," he jokes.

This is the type of project that will last decades, if not centuries - and in some ways it is already in progress, Damasio says in earnest. A couple of neuroscientists will get nowhere on their own. But what science teaches you, Damasio says, is that if an idea is good, others will join.

"Once you start the project, lots of people will come in and want to do it," he says, "and the project will no longer be your own."

Where the project will lead is anybody's guess. Maybe to a kind of self-knowledge that humanity has never known.