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Like all preliminary studies, this one is... preliminary. In other words, it has not been replicated, and the findings may turn out to be misleading.

Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. “The LC-NA system is the only brain system involved both in producing fever and controlling behavior,” says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.

The locus coeruleus has widespread connections to brain regions that process sensory information.

It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another).

“What is unique about the locus coeruleus is that it activates almost all higher-order brain centers that are involved in complex cognitive tasks,” says Dr. Mehler.

Drs. Purpura and Mehler hypothesize that in autism, the LC-NA system is dysregulated by the interplay of environment, genetic, and epigenetic factors (chemical substances both within as well as outside the genome that regulate the expression of genes). They believe that stress plays a central role in dysregulation of the LC-NA system, especially in the latter stages of prenatal development when the fetal brain is particularly vulnerable.

Drs. Purpura and Mehler believe that, in autistic children, fever stimulates the LC-NA system, temporarily restoring its normal regulatory function.

the future of autism treatment probably lies in drugs that selectively target certain types of noradrenergic brain receptors or, more likely, in epigenetic therapies targeting genes of the LC-NA system.

“You can’t take a complex neuropsychiatric disease that has escaped our understanding for 50 years and in one fell swoop have a therapy that is going to reverse it — that’s folly. On the other hand, we now have clues to the neurobiology, the genetics, and the epigenetics of autism. To move forward, we need to invest more money in basic science to look at the genome and the epigenome in a more focused way.”

This study documented that autistic children experience behavior changes during fever.

Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. "The LC-NA system is the only brain system involved both in producing fever and controlling behavior," says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.

The locus coeruleus has widespread connections to brain regions that process sensory information. It secretes most of the brain's noradrenaline, a neurotransmitter that plays a key role in arousal mechanisms, such as the "fight or flight" response. It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another). Poor attentional focusing is a defining characteristic of autism.

"What is unique about the locus coeruleus is that it activates almost all higher-order brain centers that are involved in complex cognitive tasks," says Dr. Mehler.

autism, the LC-NA system is dysregulated by the interplay of environment, genetic, and epigenetic factors

They believe that stress plays a central role in dysregulation of the LC-NA system, especially in the latter stages of prenatal development when the fetal brain is particularly vulnerable.

a higher incidence of autism among children whose mothers had been exposed to hurricanes and tropical storms during pregnancy.

autistic children, fever stimulates the LC-NA system, temporarily restoring its normal regulatory function. "This could not happen if autism was caused by a lesion or some structural abnormality of the brain," says Dr. Purpura.

future of autism treatment probably lies in drugs that selectively target certain types of noradrenergic brain receptors or, more likely, in epigenetic therapies targeting genes of the LC-NA system.

If the locus coeruleus is impaired in autism, it is probably because tens or hundreds, maybe even thousands, of genes are dysregulated in subtle and complex ways," says Dr. Mehler. "The only way you can reverse this process is with epigenetic therapies, which, we are beginning to learn, have the ability to coordinate very large integrated gene networks."

"You can't take a complex neuropsychiatric disease that has escaped our understanding for 50 years and in one fell swoop have a therapy that is going to reverse it — that's folly. On the other hand, we now have clues to the neurobiology, the genetics, and the epigenetics of autism. To move forward, we need to invest more money in basic science to look at the genome and the epigenome in a more focused way."

In 2006 your lab published a paper in Nature Neuroscience linking a mirror neuron dysfunction to autism. How might reduced mirror neuron activity explain the symptoms of autism?

Reduced mirror neuron activity obviously weakens the ability of these patients to experience immediately and effortlessly what other people are experiencing, thus making social interactions particularly difficult for these patients. Patients with autism have also often motor problems and language problems. It turns out that a deficit in mirror neurons can in principle explain also these other major symptoms. The motor deficits in autism can be easily explained because mirror neurons are just special types of premotor neurons, brain cells essential for planning and selecting actions. It has been also hypothesized that mirror neurons may be important in language evolution and language acquisition.

Thus, a deficit in mirror neurons can in principle account for three major symptoms of autism, the social, motor and language problems.

There is convincing behavioral evidence linking media violence with imitative violence. Mirror neurons provide a plausible neurobiological mechanism that explains why being exposed to media violence leads to imitative violence.

I think there are two key points to keep in mind. The first one is the one we started with: mirror neurons are brain cells specialized for actions. They are obviously critical cells for social interactions but they can’t explain non-social cognition. The second point to keep in mind is that every brain cell and every neural system does not operate in a vacuum. Everything in the brain is interconnected, so that the activity of each cell reflects the dynamic interactions with other brain cells and other neural systems.

The upshot of these differences is that the columns in an autistic brain seem to be more connected than normal with their close neighbours, and less connected with their distant ones. Though it is an interpretative stretch, that pattern of connection might reduce a person’s ability to generalise (since disparate data are less easily integrated) and increase his ability to concentrate (by drawing together similar inputs).

Dr Snyder argues that savant skills are latent in everyone, but that access to them is inhibited in non-savants by other neurological processes. He is able to remove this inhibition using a technique called repetitive transcranial magnetic stimulation.

However, among the individuals with HFA, NAA was significantly associated with communication impairments, as measured by the ADI. In addition, Cre and NAA were associated with restrictive interests, and Cre alone was associated with social difficulties. The results therefore, indicate that those with the lowest concentrations of these metabolites tended to have more severe clinical symptoms as reported by the ADI.

The results of this study provide support for the need to conduct examinations that go beyond simple group comparisons.

key metabolites, while observed at normative levels, play a key role in the clinical presentation of the disorder.

presence of normative functioning in a particular domain or brain process (when compared to typical peers) does not necessarily indicate that such domain is not implicated in the phenomenology of the condition.

"Although these are early days, we think this difference in stress hormone levels could be really significant in explaining why children with AS are less able to react and cope with unexpected change,"

If these Asperger symptoms are caused primarily by stress, caregivers could learn to steer children away from situations that would add to anxiety, the researchers said.

"This study suggests that children with AS may not adjust normally to the challenge of a new environment on waking,"

The researchers, whose findings were published in the journal Psychoneuroendocrinology, will next study if this lack of cortisol upon waking also occurs in children with other types of autism.