"... More than any other researcher, [Joseph] LeDoux has put the amygdala - two nubbins of neural tissue (one on either side of the brain) - at the center of what he calls the Wheel of Fear. Located near the center of the skull, the amygdala belongs to an archaic part of the brain, a part found in birds and reptiles, often referred to as the "limbic system," although LeDoux doesn't much care for the term. It has long been associated with emotion, especially fear. There are a handful of patients in the United States and Europe who have totally lost the use of the amygdala. While they are not, as might be expected, fearless, they do display subtle social quirks, according to Ralph Adolphs of the University of Iowa, like an unusually trusting manner and an inability to recognize fear in other people's faces."LeDoux is not the only biologist to have homed in on the amygdala. Bruce Kapp of the University of Vermont started by studying one of the signature aspects of fear, changes in heart rate, and worked back to the brain. Beginning in 1979, he focused on the part of the brain stem that controls heart rate in rabbits. Following the nerve filaments like a spent fuse back into the brain, he discovered that these fibers lead to the amygdala. Not only that, they also lead to a small hive of related nerve cells in the amygdala, a bit larger than the head of a pin, known as the central nucleus.
"What was found to be true in rabbits, and later in rats, now appears to be true in humans as well. The central nucleus is the part of your brain that instantaneously looses the hounds of fear when you hear a loud bang, feel an earthquake, see Alan Arkin lunge for Audrey Hepburn that last time in "Wait Until Dark." Nerves running out from this little knot of excitation carry the messages that control heart rate, blood pressure, sweating, respiration, freezing, increased jumpiness - all the engines that get revved in a fearful situation. But the wiring doesn't stop there. Other nerve fibers from the amygdala thread their way back (or "project") into the upper parts of the brain, to regions that control the release of stress hormones (which may play a major role in the reign of irrational fears), to the cortex and to sensory areas. So when a threat occurs, when imminent danger needs to be sorted out right away, alarms go off throughout the brain - and a result of this richly thatched neural alarm system, says Kapp, is a very alert individual. "one of our hypotheses is that a number of these projections enhance arousal; you open your sensory gates and process information more efficiently." So fear, in this telling, has a kind of distinctly modern responsibility: it instantly primes animals, presumably including us, to notice novelty and pay special attention to, indeed, the shock of the new.
"LeDoux came at the amygdala from a different direction. He set up an experiment in rats known as fear conditioning, which works like this: You give the animal a tone, followed shortly by a mild shock, so that the animal is "conditioned" to have a fear response to the sound alone. Then you try to trace the circuit by which the brain converts the sound into a fear response.
"Over the last decade or so, LeDoux and others have worked out this circuitry in lab rats step by step, each accreted detail sending a small ripple through the world of human psychology. His laboratory has been able to show that as soon as conditioned animals hear the tone that precedes a shock, the auditory information travels to a way station in the brain known as the sensory thalmus, an essential stop for any incoming information about the world, and then immediately continues on to the amygdala. In rats, a fear-inducing sound goes from the ear to the amygdala in 12 milliseconds - that is, 12 one-thousands of a second. Moreover, LeDoux says, cells in this corner of the amygdala, known as the lateral nucleus,"learn" and memorize the fearful stimulus with incredible rapidity and tenacity. The research suggests that all it takes is one terrifying experience to form a lifelong emotional memory, one that is extremely difficult to erase.
"While LeDoux's lab has concentrated on this downstairs circuit, the laboratory of Michael Davis, now at Emory University in Atlanta after 29 years at Yale, has sketched out what might be considered the high road in the processing of fear, one that may more closely mirror the routine processing of fearful information in humans. It passes from the sensory organs, like eyes and ears, and lingers in the cortex, where conscious memories are formed, before threading down to the amygdala. Davis has also tentatively identified a separate destination, called the bed nucleus of the stria terminalis, which is heavily connected to the amygdala and seems to control chronic states of fear like anxiety and worry.
"This may sound like a lot of dense neural cartography, but the significance for psychiatry, if the same dual circuitry pertains to humans, would be profound. It suggests that because there are two different neural routes to the amygdala, two different kinds of fear-related memory can form. Indeed, one of the provocative things about LeDoux's circuit is where it doesn't go. It doesn't go to the thinking part of the brain first. And what that implies - certainly in rats, and almost certainly in humans ... is that we experience, learn and unconsciously commit to emotional memory many fearful situations, without ever being aware of what has triggered the racing heart and quick pulse.
"One hallmark of a panic attack, for example, is that its victim cannot understand what has triggered such a powerful reaction. The implication of fear-conditioning experiments in animals is that we have a separate memory of a fearful stimulus, be it a bear or a dinner party, lodged in the amygdala, probably informed by things we have heard or seen but do not consciously remember. So it's as if we walk through the world half-blind, bumping into archival stimuli, things we never knew scared us, things that we can't consciously remember but that nevertheless set in motion inexplicable and disturbing sensations of dread. Freudian analysts who have followed the work of LeDoux and others have been quick to point out that neuroscience's version of unconscious fear, in the words of Dr. Jean Roiphe, a Manhattan analyst, "strongly corresponds with the Freudian notion that it's indelible and never goes away."
"Indeed, the sheer amount of environmental information pouring into the brain at any given moment - not to mention at terrifying moments - is probably more than consciousness can keep up with. This notion underpins one of the most startling messages to come out of the neurosciences in recent years: that most of what the brain does occurs outside of, and inaccessible to, our awareness. "Consciousness," says LeDoux, "is the weird thing, the unusual thing."
"The big question, of course, is just how much delivering shocks to lab rats can tell us about human behavior. It clearly doesn't tell the whole story, everyone agrees, but it's beginning to tell us quite a bit. Just within the past year, the first returns from the neuroimaging suite support the idea that human fears and anxiety can form subconsciously. In a PET study just published, Dr. Ray Dolan of the Wellcome Department of Cognitive Neurology in London has demonstrated that in humans, as in LeDoux's rats, a fear-conditioning route bypases the cognitive part of the brain. Elizabeth Phelps of Yale and her co-workers have also recently demonstrated that fear conditioning in humans activates the amygdala in the same way it does in rats.
"And Paul Whalen, Dr. Scott Rauch and their co-workers at Massachusetts General Hospital recently reported a clever experiment confirming that humans can indeed activate their fear circuitry without ever being aware of it. The Mass General researchers used an approach suggestive of subliminal advertising known as "masking"; they showed subjects in an M.R.I. machine photographs of fearful faces for a mere 33 milliseconds, followed by a longer, masking exposure to expressionless faces for 167 millieconds. The subjects had no conscious memory of seeing the fearful face, yet their brains unequivocally did; the amygdala lighted up even during the brief flash of a fearful face, but not afterward and not during the similarly brief exposure of a happy face. "So it's a very fast and preferential way to get information," says Whalen. "Anxiety is about hypervigilance, and this is a vigilance system. ....."