Fetal Alcohol and Drug Unit

Neuroanatomic/Neuropsychologic Studies Among Adults and Infants

Principal Investigator: Ann Streissguth, Ph.D.

Funded by the National Institute on Alcohol Abuse & Alcoholism (NIAAA)

Adults

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, 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 lay in the diagnostic category called Fetal Alcohol Syndrome (FAS). However, 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 individuals are often referred to as having Fetal Alcohol Effects (FAE) or Alcohol Related Neurodevelopmental Disorders (ARND).

Although we hypothesized that our image analysis methods would reveal significant mean differences in brain form between FAS/FAE and controls, the most significant finding was a hypervariation in the form of the Corpus Callosum (CC; a white matter pathway connecting the two hemispheres of the brain). Subjects with FAS and FAE had CC that were generally thicker or thinner than control counterparts. In addition three of the subjects with FAS/FAE showed frank CC dysgenesis (incomplete development). 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 CC was combined with results of neuropsychological testing, we found further surprising results. The variation in the shape of the CC was related to two specific patterns of neuropsychological performance. Those subjects with FAS/FAE whose CC were thinner than controls demonstrated deficits in motor coordination but had relatively normal executive function abilities. Conversely, those subjects with FAS/FAE whose CC 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 exposure.

Infants

Our previous work with adolescent and adult brain imaging suggested that early imaging of the CC using ultrasound might be useful to evaluate central nervous system (CNS) abnormalities related to prenatal alcohol exposure in infant. Diagnostic ultrasound is widely available, easier to administer, and less expensive than structural MRI. An ultrasound protocol to detect neuroanatomic anaomalies would allow for very early identification of infants at risk for Fetal Alcohol Spectrum Disorders (FASD) and lead to early intervention. Our unit developed a postnatal cranial ultrasound protocol that can be administered from birth to four months of age. We conducted an exploratory study (N=44) and detected 12 babies out of 23 in a high alcohol exposed group, while misclassifying only one in 21 in the unexposed group. The detection was based on a “sickle-shaped” splenium angle in the corpus callosum (angle > 90o). Further research is needed to confirm the splenium angle’s sensitivity/specificity for detecting CNS abnormalities related to prenatal alcohol exposure and its use identifying infants at risk for FASD.