A small study found that male children with autism had larger brain weights and 67% more prefrontal brain neurons than children without autism, scientists from the NIH-UCSD School of Medicine Autism Center of Excellence, La Jolla, Calif., reported in JAMA (Journal of the American Medical Association). The small preliminary study compared 7 children with autism to 6 healthy controls - they were aged from 2 to 16 years.

The authors explained that head overgrowth and larger brain size are evident in children with autism. Neural dysfunctions have been identified in several brain regions, including PFC (prefrontal cortex). This part of the brain plays a key part in communication, cognitive development, and higher-order social development.

As background information, the scientists wrote:

"Therefore, knowledge of the neural basis of overgrowth could point to early causal mechanisms in autism and elucidate the neural functional defects that engender autistic symptoms. In the first magnetic resonance imaging (MRI) report of early brain overgrowth in autism a decade ago, it was theorized that excess numbers of neurons could be an underlying cause, perhaps due to prenatal dysregulation of proliferation, apoptosis [cell death], or both.

However, the neural basis of early overgrowth remains unknown and can only be known from direct quantitative studies of the young postmortem autistic brain."

Eric Courchesne, Ph.D., and team set out to find out whether brain overgrowth early in life for children with autism also involves abnormal PFC neuron numbers. They carried out post-mortems on 13 boys aged from 2 to 16 years. 7 of them had had an autism spectrum disorder (ASD) and 6 had been autism-free (controls). The expert anatomists who examined the children did not know about the boys' diagnosis status.

Neuron size and numbers were measured and quantified in the DL-PFC (dorsolateral) and M-PFC (mesial) subdivisions of the PFC. The boys had died between 2000 and 2006 and were from the southeastern and eastern USA.


Prefrontal cortex
PFC is the anterior part of the frontal lobes of the brain; in front of the motor and premotor areas


The scientists found that:
  • DL-PFC - the children with autism had 79% more neurons
  • M-PFC - the children with autism had 29% more neurons
  • DL-PFC - there were (average) 1.57 billion neurons in the children with autism, compared to 0.88 billion in the other children
  • M-PFC - there were (average) 0.36 billion neurons in the children with autism compared to 0.28 billion in the other children
  • Brain weight deviated from normal ranges by 17.6% among the children with autism, compared to 0.2% among those without autism
The authors explained:

"Together, these 2 subdivisions gave a total combined prefrontal neuron count that was 67 percent greater in the autistic children compared with controls.

Our sample of autistic children was not large enough to statistically examine brain-behavior relationships. Future studies with many more cases of autistic children might reveal important relationships between neuron counts and symptom severity or intellectual ability."

To our knowledge, this study is the first direct quantitative test and confirmation of the theory that a pathological overabundance of neurons in critical brain regions is present at a young age in autism.

Because cortical neurons are generated in prenatal, not postnatal life, pathological overabundance of neurons indicates early developmental disturbances in molecular and genetic mechanisms that govern proliferation, cell cycle regulation, and apoptosis. Therefore, the finding has significance for understanding the etiological and neural development and functional origins of autism."

Editorial - Head Size and Larger Neuron Numbers in Autism

In an Accompanying Editorial in the same journal, Janet E. Lainhart, M.D., of the University of Utah, Salt Lake City, and Nicholas Lange, Sc.D., of the Harvard University Schools of Medicine and Public Health, Boston, wrote:

"The results of the study by Courchesne et al show that the relationship between increased neuron count, brain overgrowth, and increased brain weight in autism is complex."

Prefrontal neuron number and brain weight were increased in the autism group but were not significantly correlated. Future studies of prefrontal neuron numbers are needed in children and adolescents with autism who do not have brain overgrowth and in nonautistic children with benign megalencephaly [an abnormally large brain] to determine if increased prefrontal neuron count in autism is associated with autism only, brain overgrowth only, or some combination of both.

Neuroimaging studies suggest that other regions of the brain, including the temporal lobe, deserve further investigation by postmortem tissue analysis. Because neurons in all brain areas except the olfactory bulb and hippocampus are generated before birth, the present findings add significantly to mounting biological evidence that the developmental neuropathology of idiopathic autism begins before birth in some, possibly all, cases.

The study by Courchesne et al also adds to frequently reported findings in neuroanatomical studies of autism, including increased variance and loss of typical relationships between measured components of the brain. Factors that normally organize the brain appear to be disrupted."

Written by Christian Nordqvist