Autism's smoking gun?

People with autism often appear to be trapped in their own world, unable to forge the interpersonal connections that others make almost effortlessly. While normally developing infants constantly interact with adults--smiling when smiled at, making eye contact with others, following the direction of other people's gaze--infants with autism often seem more interested in objects than people, many have observed.

In the 1990s, scientists discovered mirror neurons--potentially the neurological basis for making such connections. The neurons--which were found in monkeys--fired both when the animals performed an action, and when they saw the same action performed. (See page 49.) Soon after, researchers posited that a dysfunction in the mirror-neuron system might underpin autism.

"If you imagine the behavioral and social deficits that would come from a failure of the mirror neurons, you imagine a pathology just like autism," says Hugo Théoret, PhD, a psychology professor at the University of Montreal.

But while many in the field follow that logic for autism's social impairments, there is less agreement on whether the disorder's mental retardation and repetitive behaviors could arise from a mirror-neuron system gone awry. Theoret posits that faulty mirror neurons could lead to repetitive behavior, and researchers such as Marco Iacoboni, MD, PhD--a neuroscience professor at the University of California, Los Angeles--believe an inability to imitate could lead to mental retardation. However, other researchers, such as Helen Tager-Flusberg, PhD, professor of anatomy, neurobiology and psychology at Boston University, argue that only social deficits could result from faulty mirror neurons.

While scientists have yet to pinpoint the precise function of the mirror-neuron system in humans--and what problems a dysfunction could cause--a flurry of new research suggests that autistic people's mirror systems are not as active as those of normal adults. For example, a study by Théoret, Tager-Flusberg and their colleagues, published in the February issue of Current Biology (Vol. 15, No. 3, pages 84-85), shows that when autistic people watch the hand movements of other people, their brains' mirror-neuron areas activate less than the mirror-neuron areas in normal adults' brains.

"This [research] could help us understand better the early development of autism," says Tager-Flusberg. And, perhaps further down the line, research on mirror neurons could inform behavioral treatments that could retrain the neurons or help people with autism develop compensatory systems, she says.

Developing theories about the human brain's mirroring system suggest that faulty mirror neurons could lead to serious social dysfunction, learning disability and maybe even involuntary repetitive behaviors, such as hand flapping and repeating the words of others.

Imitation appears to be the primary function of mirror neurons. People without working mirror neurons would need to analyze a movement before attempting to copy it, while those with a working mirror system can do so automatically. In line with this theory, a decade of research has shown that people with autism tend to have difficulty imitating others, especially when those movements are complex, says Tager-Flusberg.

Because imitation provides a rich source of learning, deficits in imitation could lead to the mental retardation that co-occurs with autism 75 percent of the time, says Iacoboni.

Imitation might also provide the foundation for understanding the behavior and emotions of others, he notes.

"When you see someone else express sadness, what you do is simulate in your brain the same neural activity you would if you were expressing sadness with your face," says Iacoboni. "The motor neurons then communicate to your emotion centers and you feel a little sad too."

As-yet-unpublished research by Iacoboni and his colleagues suggests that, when instructed to, high-functioning people with autism can imitate the facial expressions of others, but they do not appear to use the brain's mirror system. Instead they may consciously analyze the action to imitate it, says Iacoboni.

Moreover, the study found that as the mirror areas of normal adults activated, so did their limbic systems--brain areas associated with emotion. Mirror-system activity seems to touch off an imitation of other people's actual emotional state, Iacoboni says. People with autism, however, do not show limbic activation as they mimic the facial expressions of others, he found.

Such differences in brain functioning could underpin the difficulty many people with autism seem to have relating to and understanding others, Iacoboni notes.

While many researchers agree that mirror-system dysfunction may underpin the social isolation of autism, Théoret breaks ranks and posits that the neurons' malfunction has more extensive effects: He makes the controversial claim that the repetitious behaviors characteristic of autism may arise from an unregulated mirror system.

In normal adults, the brain probably counteracts mirror-neuron activation with overriding signals further down the motor pathway, researchers say. In fact, involuntary mimicking among people with brain injuries suggests that override signals may occur in the prefrontal cortex, according to research by University of California, Los Angeles, professor Mario Mendez, MD, PhD, and others. People with autism and some people with brain damage may have a faulty override system, resulting in hand-flapping or other stereotyped behavior, Théoret says.

Other researchers argue that dysfunctional mirror neurons underpin only the social deficits of autism.

"The mirror-neuron system is fascinating because it has quite a focused function," says Tager-Flusberg. "If you start relating everything to it, it loses any kind of theoretical significance."

The repetition, self-injury, compulsive habits and limited interests evidenced by many people with autism could not be easily explained by mirror-neuron dysfunction, she argues.

Additionally, researchers have yet to theorize how mirror neurons might sustain a concentrated hit, leaving other areas of the brain unaffected, says Sally Rogers, PhD, a professor of psychiatry and behavioral sciences at the University of California, Davis.

"Mirror neurons aren't located in a particular brain structure--they don't develop at one particular time," she says.

While research on mirroring systems is in its infancy, the possibility that dysfunctional mirror neurons could be responsible for the striking social deficits of autism has many researchers excited.

"Whenever we find something that is not working well, that does open up possibilities for how we could make the system better functioning," says Théoret. "But we are a long way off from that now."