Analyses of FAS/FAE Deficits
Investigator: Ann Streissguth
Funded by the
National Institute on Alcohol
Abuse & Alcoholism (NIAAA)
This research proposed
to quantify and link the neuroanatomic and neuropsychological abnormalities
in people with brain damage caused by prenatal alcohol exposure.
Prior to this study, there were few methods for quantifying the
brain damage caused by alcohol and its relation to dysfunctional
behavior in the individual patient, and none that used modern morphometric
methods measuring neuroanatomic shape variation as discernible from
MRI scans. Traditionally the only "quantification" of
this brain damage was indirect, and lies in the diagnostic category
called Fetal Alcohol Syndrome (FAS). Unfortunately, FAS is a very
insensitive guide to the extent of underlying brain pathology, even
though it is specific for alcohol. People with FAS vary widely in
many channels of behavior, and many other heavily exposed people
who do not meet criteria for an FAS diagnosis show neurobehavioral
deficits that may be as severe as FAS. Such patients are often referred
to as having Fetal Alcohol Effects (FAE) or Alcohol Related Neurodevelopmental
Although we hypothesized
that our image analysis methods would reveal significant mean differences
in brain form between FAS/FAE and Controls, we were surprised to
find that the most significant finding was a hypervariation of form
of the Corpus Callosum (CC: a white matter pathway connecting the
two hemispheres of the brain). Subjects with FAS and FAE had callosa
that were generally thicker or thinner than control counterparts.
In addition 3, of the subjects with FAS/FAE showed frank dysgenesis
(incomplete development) of the corpus callosum. This study also
found that there was a complete intermingling of (lack of discrimination
between) the alcohol exposed subjects with and without the facial
features of FAS in terms of representations of the shape of the
CC. There was no difference in CC neuroanatomy between subjects
with FAS and those with FAE or ARND.
When the shape measurement
of the Corpus Callosum was combined with results of neuropsychological
testing, we found further surprising results. The variation in the
shape of the corpus callosum was related to two specific patterns
of neuropsychological performance. Those subjects with FAS/FAE whose
callosa were thinner than controls demonstrated deficits in motor
coordination but had relatively normal executive function abilities.
Conversely, those subjects with FAS/FAE whose callosa were thicker
than controls demonstrated relatively normal motor coordination
but had deficits in executive function abilities. Utilizing neuroanatomy
and neuropsychology together, we could discriminate between FAS/FAE
subjects and control subjects; with 100% sensitivity and 93% specificity.
Again the two exposed groups were completely intermingled demonstrating
that there is no difference in neuroanatomy and neuropsychology
between subjects diagnosed FAS and those with FAE or ARND. Future
research will use the same methodology to study other brain regions
thought to be associated with the damaging effects of prenatal alcohol
The potential role of
these findings suggests that MRI screening of extent of damage in
FAS/FAE would be of great benefit. For those without the full stigmata
of the disorder, but with characteristic dysfunctional behaviors,
the detection of neuroanatomic anomalies may permit proper identification
and service delivery prior to the development of debilitating secondary
consequences. Also, it will become possible to draw much finer distinctions
among the clinical samples currently diagnosed as "FAS"
or "FAE". Prognoses would thereby become more accurate,
and the provision of therapeutic intervention or special education
would become both more effective and more humane. Further work is
appropriate in order to extend these correlated dimensions of structural-functional
deficit downward into childhood or even infancy.
The Center on Human Development
and Disability's summary
of Ann Streissguth's brain study.
here for a list of selected publications.