Neuroimaging tools offer new ways to study autism

Different techniques help researchers examine diverse aspects of autism.

By Hugh McIntosh

Functional magnetic resonance imaging (fMRI) may be the hottest new tool in brain research, but it is only one of the neuroimaging advances that offer new opportunities for studying autism. Here are three others:

? Positron emission tomography (PET) is being used to explore serotonin synthesis and other aspects of autism in children, says pharmacologist Diane Chugani, PhD, at Wayne State University in Detroit. Researchers have been curious about serotonin ever since the discovery that many people with autism have abnormally high levels of this neurotransmitter in the blood. Studies of serotonin synthesis in the brain became possible only last year with the development of a substance called AMT, which allows the PET scanner to trace a precursor of serotonin and, by extrapolation, gives researchers an estimate of how much serotonin the brain is producing.

Chugani and colleagues are using AMT and PET to study serotonin synthesis in autistic children ages 2 to 14. The researchers have already reported finding abnormalities in serotonin synthesis in specific brain areas in children with autism. The areas affected are part of a pathway responsible for fine sensory discrimination, and autistic children often have sensory abnormalities, Chugani says. It is possible that these areas of the brain may be particularly vulnerable if there is an imbalance in serotonin or a lack of serotonin regulation during development.

? Magnetic resonance spectroscopy (MRS) is opening a new chapter on brain chemistry by identifying and quantifying various brain chemicals via their characteristic patterns of radio signals emitted during MRS. Scientists are using this technique to explore the observation that people with autism often have enlarged brains. One study is focusing on brain chemicals that contain phosphorus, says child neurologist Nancy Minshew, MD, at the University of Pittsburgh. These include phosphomon-oesters, which are membrane building blocks, and phosphodiesters, which are degradation products. Initial research on the frontal lobe found that as a patient?s autism grew worse, membrane production decreased and degradation increased.

In another study, researchers are using MRS to examine whether the normal processes of synaptic pruning and programmed cell death (apoptosis) in early child development proceed normally in children with autism. Failure of either of these processes could lead to an enlarged brain, says psychiatrist Stephen Dager, MD, at the University of Washington in Seattle. He and his colleagues are studying autistic children at ages 3 and 6 to look for changes in levels of N-acetylspartate (NEA), choline, creatine and lactate. NEA provides a measure of neuronal density, and choline, creatine and lactate can be used to measure membrane breakdown.

Changes in the proportions of these brain chemicals over time in children with autism, compared with changes in children without autism, can tell researchers whether apoptosis and synaptic pruning are proceeding normally, says Dager.

? Magnetoencephalography (MEG) measures the tiny magnetic fields around the electrical currents that flow through neurons near the brain?s surface. At the University of Colorado in Denver, researchers are using MEG to study signal processing in the primary sensory cortex, which may be impaired in people with autism, says psychiatrist Martin Reite, MD. 'If the earliest sensory processing is disturbed, then it?s clear that there?s going to be disturbance in the down-stream?stages of processing,' Reite says. 'MEG is the only tool that we have that gives us resolution in that early time domain.'

MEG is also being used at the University of Utah to investigate the association between epileptic activity and autism. About one-third of children with autism develop seizures. But they don?t begin until around adolescence, suggesting that epileptic activity does not cause autism.

MEG studies, however, indicate that many autistic children who do not have seizures show epilep-tiform activity in the brain, especially when asleep, says Utah neurophysiologist Jeffrey David Lewine, PhD. He and his colleagues hypothesize that epileptic activity disrupts the formation of neural networks in the language areas and frontal lobes of the brain, resulting in autistic symptoms.

Hugh McIntosh is a writer in Chicago.