Scientists at Children’s Hospital Los Angeles Investigate How Blood Flow in the Brain is Affected by Autism

With autism diagnoses on the rise, science is on the hunt for answers.


LOS ANGELES–(BUSINESS WIRE)–Each year, one in 59 children are diagnosed with Autism Spectrum
Disorder (ASD), a condition that impacts a child’s social, emotional,
and behavioral development. The rate of diagnosis has grown, tripling in
the last 15 years. While genetic and environmental influences have been
implicated as potential causes of ASD, little is known about its
neurobiology.

Now, researchers at Children’s Hospital Los Angeles have brought us one
step closer.

In a study published recently in the journal Biological Psychiatry,
CHLA’s Bradley
Peterson, MD
, uncovers a direct link between altered brain activity
and social deficits in ASD. Peterson’s group studied 44 individuals with
ASD and compared them with 66 typically-developing participants. Groups
were matched for age, sex, and IQ.

Peterson’s team used advanced imaging techniques to acquire two types of
information. First, the group used a method called arterial spin
labeling, which measures blood flow through the vessels of the brain.
Because active parts of the brain need the most oxygen and nutrients,
more blood flow to an area signals increased brain activity. Second, the
team measured levels of NAA, an amino acid byproduct commonly used as a
marker of healthy neurons.

This is a multimodal imaging data set,” explains Peterson, Director of
the Institute
for the Developing Mind
at CHLA and Professor of Pediatrics at the
Keck School of Medicine of USC. “Each modality gives us a different
window into the brain. We are able to look through both windows at once
to tell us much more about what’s going on in the brains of these
individuals.”

Scans revealed a striking pattern in the part of the brain called the
white matter.

Our brains have about 100 billion cells, which communicate with each
other through long, wire-like branches called axons. These axons are
coated with myelin, a specialized wrapping – like wire insulation – that
helps the messages flow faster from one cell to another. Because myelin
appears white, communication pathways between cells are collectively
called white matter. Cell bodies, or gray matter, are not coated
as extensively in myelin and therefore do not appear white.

Studies show that communication between distant brain cells is disrupted
in ASD due to fewer long-range connections between cells and thinner
myelin. Given these differences in white matter, decreased blood flow
and activity in this region would make sense.

Yet, Peterson and his team found exactly the opposite.

In the study, the researchers found what is called hyperperfusion
– increased blood flow, indicating more brain activity – throughout
large portions of white matter in participants with ASD. Perhaps even
more striking, these activity rates were correlated with ADOS scores;
ADOS is a tool used by doctors to help diagnose ASD.

If white matter is compromised in ASD, one might expect decreased
activity in this region, not increased. Peterson explains that
this finding likely reveals an attempt to compensate for underlying
white matter problems. “If the drive train in your car is compromised,
you have to hit the gas harder to achieve the same speed,” he explains.
Similarly, supporting cells in the brain that create and maintain the
myelin wrapping seem to be working overtime to counteract deficits in
the underlying axon. This compensatory mechanism may partially explain
why many individuals with ASD are high functioning. “This correlation of
perfusion and ADOS is absolutely key,” emphasizes Peterson, “because it
shows that the higher the blood flow, the more ASD symptoms the
participants have. This very solidly supports the idea of compensation.”

Looking in the second window – measuring NAA concentrations as a marker
for healthy neurons – revealed support for this idea of compensation.
We found that in participants with autism, the lower the NAA
concentrations were, the higher their perfusion was at those points in
the brain,” Peterson says. In other words, areas with the lowest levels
of healthy neurons were also the ones with the highest activity and
blood flow.

The majority of autism research has focused on other parts of neurons,
as opposed to axons. Peterson’s study marks the first to correlate
widespread white matter hyperperfusion, healthy neuron biomarkers, and
symptom scores. The study paves the way for understanding more about how
the brain may compensate for compromised white matter signaling. “Axons
and their supporting cells have not been a major focus in autism
research,” Peterson says. “My hope is that this study will help to
refocus attention on the cell types and brain areas that are critical in
understanding the neurological basis for ASD.”

Additional authors on the study include Ariana Zargarian, Jarod B.
Peterson, Suzanne Goh, Siddhant Sawardekar, Steven C. R. Williams, David
J. Lythgoe, Fernando O. Zelaya, and Ravi Bansal.

This study was supported by National Institute of Mental Health grant
R01 MH089582 and funding from Children’s Hospital Los Angeles and the
University of Southern California.

About Children’s Hospital Los Angeles

Children’s Hospital Los Angeles has been ranked the top children’s
hospital in California and sixth in the nation for clinical excellence
by the prestigious U.S. News & World Report Honor Roll. The
Saban Research Institute at CHLA is one of the largest and most
productive pediatric research facilities in the United States. CHLA also
is one of America’s premier teaching hospitals through its affiliation
since 1932 with the Keck School of Medicine of the University of
Southern California. For more, visit CHLA.org, the child
health blog
and the research
blog
.

Contacts

Melinda Smith
(323) 361-7236
msmith@chla.usc.edu