The Tell-Tale Brain

physiological signal from a subject’s body or brain is tracked by a machine and represented back to the subject through some sort of external display. The goal is for the subject to concentrate on nudging that signal up or down and thereby gain some measure of conscious control over it. For example, a biofeedback system can show a person his heart rate, represented as a bouncing, beeping dot on a display screen; most people, with practice, can use this feedback to learn how to slow their hearts at will. Brain waves can also be used for biofeedback. For example, Stanford University professor Sean Mackey put chronic pain patients in a brain-imaging scanner and showed them a computer-animated image of a flame. The size of the flame at any given moment was a representation of the neural activity in each patient’s anterior cingulate (a cortical region involved in pain perception), and was thus proportional to the subjective amount of pain he or she was in. By concentrating on the flame, most of the patients were able to gain some control over its size and to keep it small, and ipso facto to reduce the amount of pain they were experiencing. By the same token, one could monitor mu waves on an autistic child’s scalp and display them on a screen in front of her, perhaps in the guise of a simple thought-controlled video game, to see if she can somehow learn to suppress them. Assuming her mirror-neuron function is weak or dormant rather than absent, this kind of exercise might boost her ability to see through to the intentionality of others, and bring her a step closer to joining the social world that swirls invisibly around her. As this book went to press, this approach was being pursued by our colleague Jaime Pineda at UC San Diego.

A third possibility—one that I suggested in an article for Scientific American that I coauthored with my graduate student Lindsay Oberman—would be to try certain drugs. There is a great deal of anecdotal evidence that MDMA (the party drug ecstasy) enhances empathy, which it may do by increasing the abundance of neurotransmitters called empathogens, which naturally occur in the brains of highly social creatures such as primates. Could a deficiency in such transmitters contribute to the symptoms of autism? If so, could MDMA (with its molecule suitably modified) ameliorate some of the most troubling symptoms of the disorder? It is also known that prolactin and oxytocin—so-called affiliation hormones—promote social bonding. Perhaps this connection, too, could be exploited therapeutically. If administered sufficiently early, cocktails of such drugs might help tide over some early symptom manifestations enough to minimize the subsequent cascade of events that lead to the full spectrum of autistic symptoms.

Speaking of prolactin and oxytocin, we recently encountered an autistic child whose brain MRI showed a substantial reduction in the size of the olfactory bulb, which receives smell signals from the nose. Given that smell is a major factor in the regulation of social behavior in most mammals, we wondered, Is it conceivable that olfactory-bulb malfunction plays a major role in the genesis of autism? Reduced olfactory-bulb activity would diminish oxytocin and prolactin, which in turn might reduce empathy and compassion. Needless to say, this is all pure speculation on my part, but in science, fancy is often the mother of fact—at least often enough that premature censorship of speculation is never a good idea.

One final option for reviving dormant mirror neurons in autism would be to take advantage of the great delight that all humans—including autistics—take in dancing to a rhythm. Although such dance therapy using rhythmic music has been tried with autistic children, no attempt has been made to directly tap into the known properties of the mirror-neuron system. One way to do this might be, for example, to have several model dancers moving simultaneously to rhythm and having the child mime the same dance in synchrony. Immersing all of them in a hall of multiply reflecting mirrors might also help by multiplying the impact on the mirror-neuron system. It seems like a far-fetched possibility, but then so was the idea of using vaccines to prevent rabies or diphtheria.³

THE MIRROR-NEURON HYPOTHESIS does a good job of accounting for the defining features of autism: lack of empathy, pretend play, imitation, and a theory of mind.⁴ However, it is not a complete account, because there are some other common (though not defining) symptoms of autism that mirror neurons do not have any apparent bearing on. For example, some autistics display a rocking to-and-fro movement, avoid eye contact, show hypersensitivity and aversion to certain sounds, and often engage in tactile self-stimulation—sometimes even beating themselves—which seems intended to dampen this hypersensitivity. These symptoms are common enough that they too need to be explained in any full account of autism. Perhaps beating themselves is a way of enhancing the salience of the body, thereby helping anchor the self and reaffirming its existence. But can we put this idea in the context of the rest of what we have said so far about autism?

In the early 1990s our group (in collaboration with Bill Hirstein, my postdoctoral colleague; and Portia Iversen, cofounder of Cure Autism Now, an organization devoted to autism) thought a lot about how to account for these other symptoms of autism. We came up with what we called the “salience landscape theory”: When a person looks at the world, she is confronted with a potentially bewildering sensory overload. As we saw in Chapter 2 when we considered the two branches of the “what” stream in the visual cortex, information about the world is first discriminated in the brain’s sensory areas and then relayed to the amygdala. As the gateway to the emotional core of your brain, the amygdala performs an emotional surveillance of the world you inhabit, gauges the emotional significance of everything you see, and decides whether it is trivial and humdrum or something worth getting emotional over. If the latter, the amygdala tells the hypothalamus to activate the autonomic nervous system in proportion to the arousal worthiness of the triggering sight—it could be anything from mildly interesting to downright terrifying. Thus the amygdala is able to create a “salience landscape” of your world, with hills and valleys corresponding to high and low salience.

It is sometimes possible for this circuit to go haywire. Your autonomic response to something arousing manifests as increased sweating, heart rate, muscular readiness, and so on, to prepare your body for action. In extreme cases this surge of physiological arousal can feed back into your brain and prompt your amygdala to say, in effect, “Wow, it’s even more dangerous than I thought. We’ll need more arousal to get out of this!” The result is an autonomic blitzkrieg. Many adults are prone to such panic attacks, but most of us, most of the time, are not in danger of getting swept away by such autonomic maelstroms.

With all this in mind, our group explored the possibility that children with autism have a distorted salience landscape. This may be partially due to indiscriminately enhanced (or reduced) connections between sensory cortices and the amygdala, and possibly between limbic structures and the frontal lobes. As a result of these abnormal connections, every trivial event or object sets off an uncontrollable autonomic storm, which would explain autistics’ preference for sameness and routine. If the emotional arousal is less florid, on the other hand, the child might attach abnormally high significance to certain unusual stimuli, which could account for their strange preoccupations, including their sometimes savant-like skills. Conversely, if some of the connections from the sensory cortex to the amygdala are partially effaced by the distortions in salience landscape, the child might ignore things, like eyes, that most normal children find highly attention grabbing.

To test the salience landscape hypothesis we measured galvanic skin response (GSR) in a group of 37 autistic and 25 normal children. The normal children showed arousal for certain categories of stimuli as expected but not for others. For example, they had GSR responses to photos of parents but not of pencils. The children with autism, on the other hand, showed a more generally heightened autonomic arousal that was further amplified by the most trivial objects and events, whereas some highly salient stimuli such as eyes were completely ineffective.

If salience landscape theory is on the right track, one would expect to find abnormalities in visual pathway 3 of autistic brains. Pathway 3 not only projects to the amygdala, but it routes through the superior temporal sulcus, which—along with its neighboring region, the insula—is rich in mirror neurons. In the insula, mirror neurons have been shown to be involved in perceiving as well as expressing certain emotions—like disgust, including social and moral disgust—in an empathetic manner. Thus damage to these areas, or perhaps a deficiency of mirror neurons within them, might not only distort the salience landscape, but also diminish empathy, social interaction, imitation, and pretend play.