Using brain imaging to track FAS
by Edward Riley and Sarah Mattson
Ever since Jones and Smith identified fetal alcohol syndrome in
1973, we have been aware that prenatal alcohol exposure could have
a negative effect on normal brain development. One had only to look
at the early autopsy reports of infants and children with FAS to
see the widespread damage that could occur. However, since most
of these reports represented extreme cases of FAS, it was difficult
to generalize to the typical case of FAS, let alone cases of FAE.
But, about ten years ago we began to work with Terry Jernigan from
the University of California San Diego to use magnetic resonance
imaging (MRI) to study the living brains of alcohol-affected children
in a relatively non-invasive fashion, giving us a better picture
of the FAS mind.
Our imaging studies have revealed several brain areas that seem
to be particularly affected by prenatal alcohol exposure. For example,
the first child that we imaged had a thin corpus callosum, which
is the major pathway between the two hemispheres of the brain. The
left and right hemispheres coordinate their functions by communicating
across the corpus callosum and if this structure isn't functioning
appropriately, the two hemispheres can't coordinate effectively.
Abnormalities of the corpus callosum have been linked to deficits
in attention, reading, learning, memory, planning, decision-making,
and psychosocial functioning, all of which are impaired in alcohol-exposed
people. The next child that we imaged, to our surprise, was missing
the corpus callosum altogether, a condition known as agenesis of
the corpus callosum. In this child, the major connection between
the two hemispheres of the brain was missing. We have identified
three other children with FAS in San Diego with agenesis in their
FAS subjects. However, like the first child that we scanned, most
people with FAS and FAE do have an intact corpus callosum, but as
in this child, we found that it tends to be smaller, particularly
at the front and back parts.
Recently, in collaboration with Elizabeth Sowell and her colleagues
at UCLA, we have analyzed the shape and location of the corpus callosum
following prenatal alcohol exposure. Again, the corpus callosum
was reduced in size, specifically in the back part, but it was also
displaced in three-dimensional space. The average location of the
corpus callosum for the children with FAS and FAE was displaced
compared with the control children, with the biggest differences
in the part of the corpus callosum closest to the back of the brain.
Furthermore, this displacement was related to the children's performance
on a verbal learning task.
One area of the brain that we have been particularly intrigued
with is a group of subcortical structures known as the basal ganglia.
Our studies have shown that the caudate, a part of the basal ganglia
is disproportionately reduced in volume in children with FAS and
FAE. The caudate is involved in cognitive functions, such as in
the ability to shift from one task to another; inhibition of inappropriate
behavior; and spatial memory, which are impaired in people with
prenatal alcohol exposure. We believe that the reductions in the
caudate account for some of the cognitive deficits seen in people
with prenatal alcohol exposure. This notion is appealing because
the caudate also has extensive connections to the frontal lobes
of the brain, which traditionally are thought of as mediating higher
cognitive functions.
Finally, we have shown that the cerebellum is also particularly
sensitive to prenatal alcohol. The cerebellum or "little brain"
is located at the base of the brain. It is involved in both motor
and cognitive skills. for example, damage to the cerebellum has
been implicated in deficits in learning as well as in balance and
coordination, all of which are impaired by prenatal alcohol exposure.
We recently found that the volume of the cerebellum was reduced
in people with FAS compared with controls, in part replicating our
previous reports.
Most recently, we have been looking at new ways of analyzing our
brain data to provide additional insights about the damaging effects
of prenatal alcohol exposure. using a technique known as brain mapping,
we can now study the whole brain at one time, rather than focusing
in on specific brain regions. Elizabeth Sowell and her colleagues
have used this brain mapping technique to analyze and compare brain
images of people with FAS and FAE and non-alcohol-exposed control
subjects. We are showing greater reductions in the brain's white
matter, which contains the nerve cells extensions (i.e., axons)
that connect nerve cells with each other. These findings were particularly
pronounced in the parietal love, an area that is involved in visual-spatial
processing and the integration of sensory information.
One important point has to be made regarding our studies. We have
always examined alcohol-exposed children with and without the facial
features of FAS. while our findings are most prominent in the FAS
or dysmorphic children, we also find effects in the non-dysmorphic
children. While the facial features might provide some indication
of brain changes, the absence of the FAS facial features does not
preclude alternations in brain and behavior.
What are our current plans and where are we going in the future?
We are currently trying to correlate our brain changes with the
changes that we see in behavior. For example, how does having a
small caudate relate to the ability to shift from one task to another?
Our preliminarily findings indicate that in children with alcohol
exposure histories, the reduction in the size of the caudate predicts
overall performance on tests that require the ability to inhibit
responding, as well as lean and recall verbal information. In the
future we hope to utilize other imaging techniques such as functional
MRI (see related article on page 4), where one examines not the
size or volume of a particular structure, but rather how that structure
functions. Normal size doesn't necessarily mean normal function,
and reduced size doesn't always mean abnormal function. fMRI is
a powerful technique to examine how the brain is working. We are
also examining the possibility of using MRI spectroscopy to examine
the brains of children with FAS. This technique provides additional
information about the functioning of the brain. The use of new technology
and refined use of existing techniques will allow us to continue
to learn more about how prenatal alcohol affects brain development,
what effect this has on behavior, and perhaps push us closer to
developing adequate treatment and intervention strategies.
Edward Riley, Ph.D., and Sarah Mattson, Ph.D., are
affiliated with the Center for Behavioral Teratology and the Department
of Psychology at San Diego State University.
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24/7 vs. letting go
by Marceil Ten Eyck
Eleven years go, when my daughter was diagnosed with fetal alcohol
syndrome, there was not much information about effectively parenting
an individual with this disability. A fellow pioneer in the search
for parenting tools said, "Parenting a child with FAS using
available parenting information is like trying to get around Seattle
with a map of San Francisco." How true! Since then, we parents
have been struggling along using intuition, our best reasoning abilities,
ideas from other parents, ideas from professionals, whatever we
could find that might fit any given situation. I have heard many
parents wish for a parenting recipe or a parenting map for FAS/E;
I have been one of the loudest wishers.
Sidney, my daughter, is now 26 years old. She struggles daily to
deep up with world that is too intricate, complicated, and moving
too fast for her. She continues to amaze me with her determination
and courage to be the best she can be. When I am asked how I parented
her, I try to talk about strategies that worked for her and the
many things I did that didn't work, the mistakes I made. I also
believe it is important for me to say, over and over, she is only
one individual with this diagnosis and generalizing to all individuals
with this diagnosis can be dangerous as well as useless.
- All individuals with FAS/E are alike.
- All individuals with FAS/E are different.
Both these statements are true.
So what about the recipe book, the map that many of us have wished
for? So far, I believe there is no one map or recipe that will fit
all. What we now have is a wonderful bank of ideas to draw from.
These ideas come from parents and professionals who have tried them
and have had successes with them, and although one idea does not
work for all, we can certainly mix and match to find those that
will work for us.
So what about 24/7 (24 hours a day, 7 days a week) parenting and
observation versus just letting go? Recently I heard radio advice
host Dr. Laura Schessinger criticize a mother who called in about
a daughter with FAS who had become pregnant while at a church picnic.
Dr. Laura chastised the mother for letting her 16-year-old daughter
out of her sight, for any length of time, anywhere. I was appalled
that Dr. Laura presumed to criticize a mom for allowing her teenage
daughter to go on a church picnic without her, FAS or no. A recent
article I read about parenting noted that 24/y supervision would
"be needed for a lifetime due to poor judgment and lack of
impulse control." On the other hand, in an article in F.A.S.
Times, Josie DeVries describes the alternative: "to abdicate
our duties as parents—to let him go merrily on his way and
allow him to make his own choices about how/where he would spend
his future."
Although some individuals with FAS/E undoubltedly will need supervision
24/7, others will need some level of "letting go" in order
to become successful and separate adults. This letting go might
put us out of our comfort zone, knowing that we cannot keep our
children safe every minute of every day.
Dr. Kieran O'Malley at the Fetal Alcohol and Drug Unit in Seattle
told me about a young man who was being supervised 24/7 who ran
away from home because he said it was the only way he could get
out from under restrictions that were to tight for him. I suspect
the parents supervising their son were being careful, concerned
parents, wanting safety and the best for their son. If I had to
do it over again, I would do more supervision of a junior-high-age
daughter. I wanted my daughter to be safe, and to be the best parent
I could be. Yet, each of us was parenting differently, and each
child/adult may well be successful.
Finding the place between supervision 24/7 and "letting him
go merrily along his way" may be one of the most difficult
parenting tasks we face. The need to keep our challenged individuals
safe can be overwhelming, keeping us from allowing them the risks
they need to take to grow. At the same time, knowing when to surround
them with safety can be problematic too. When they are children,
it is easy. When a child becomes an adolescent, then an adult, the
choices become much harder. There is no tried and true recipe, there
is no map here. I also believe it is important not to criticize
parents who may be parenting differently than us, even if it is
only done indirectly by saying, "my way is the right way."
It is tough enough to be a pioneer in this endeavor without other
pioneers telling us we did it the wrong way.
Marceil Ten Eyck is a founder of Iceberg and has
a daughter with FAS and a daughter with FAE.
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Using active imaging to unlock the secrets
of FASD
by Paul D. Connor, Ph.D.
An important aspect of researching Fetal Alcohol Spectrum Disorders
(FASD) has always been listening. The knowledge that we gain by
listening to those who lives are affected by FASD can be used to
design studies that will both contribute to our understanding of
FAS and assist those who live with this syndrome. One of the major
hurdles that those dealing with FASD often face is the challenge
of obtaining appropriate services. One effective way of gaining
services is to demonstrate the presence of brain damage.
A number of studies are currently being conducted in Seattle and
San Diego that use structural brain imaging in an attempt to determine
whether or not there are significant structural changes in the brains
of people with FASD. Using a combination of structural Magnetic
Resonance Imaging (MRI) and neuropsychological testing, researchers
can compare physical changes in the brain (obtained from the MRI)
to changes in cognitive functioning measure separately by neuropsychological
testing. This approach has been and continues to be very effective;
however, the information we gain from combining these two sets of
data provides only an indirect measure of how the brain is functioning.
Ideally, we would like to get a more direct picture of the brain's
activity while the neuropsychological testing is being performed.
For that, we need to turn to imaging methods that allow us to observe
brain functioning while neuropsychological testing is being performed.
One way to do this is to use a relatively new technology called
functional Magnetic Resonance Imaging (fMRI).
Functional MRI uses the same equipment as structural MRI, a sophisticated
computer that uses a very large magnet to excite the molecules in
the body and then record how long it takes for those molecules to
"relax." However, unlike structural MRI that looks at
molecules such as hydrogen to build a picture of the structure of
the brain, fMRI looks at blood oxy generation to see the function
of the brain while a person does a task. The theory behind fMRI
is that when the brain is active on a task, it needs more oxygen
than when at rest. The fMRI scanner can detect those regions of
increased oxygen use and show pictures of them. We wanted to use
this technology to look at the functioning of brains of people with
FASD, something that has not previously been done.
We have recently conducted a small pilot study to look a the activity
of the brain of four subjects with FASD and two control subjects
by having them do a working memory task while scanning their brains.
Working memory is a complicated task that requires the person to
remember information and in some way manipulate that information
for short periods of time. For example, keep a running memory of
letters that are shown to you on a computer screen and decide if
the letter you just saw was the same as one you saw two letters
ago.
Because fMRI works by looking at the difference in blood oxygen
of the brain between actively doing a test and when resting, we
also had the subjects doing a "rest" task. The goal of
the study was to see how the brains of subjects were performing
on a working memory test, but we were not really interested in the
parts of the brain responsible for seeing the letters, recognizing
them as letters, and moving their hands when responding. However,
if we simply had the subject close their eyes and do nothing during
the "rest" period, all of these areas would be seen as
active in the final functional image. So we needed to devise a task
that had almost all of the same requirements as the working memory
test but not the actual working memory part. We did this by asking
the subject to watch a series of letters and respond when he or
she saw a particular letter.
Other studies have shown that when performing this task in the
fMRI a certain part of the frontal lobes of the brain called the
dorsolateral prefrontal cortex (DLPFC) becomes active. In our study
we found that all of the subjects with FASD showed significant activations
in this part of the brain. In fact, at least two of the subjects
with FASD showed activation of this area in both hemispheres, suggesting
that they needed to recruit more brain tissue in order to complete
the task. By contrast, neither of the control subjects showed significant
activations of the DLPFC when performing this task. Initially we
thought this finding was a little odd. However, other researchers
have found that when a working memory test is not very challenging,
the DLPFC does not get involved with the tasks and only with increased
difficulty of the task will these regions become activated. This
seems to be the case with the control subjects in this study.
All of the subjects with FASD had difficulty with this task and
thus needed to use the DLPFC quite a bit, but the control subjects
found this task relatively easy and thus didn't need to involve
this region of the brain. With a more complicated task (remembering
letters presented three previously, for example) control subjects
would probably need to activate this region. However, with that
increased difficulty, would subjects with FASD recruit even more
brain tissue or would the task be so great that their brains "shut
down" or give up on the task thus resulting in less activation?
These are questions that will be posted with follow-up studies that
we have submitted for funding from the National Institute on Alcohol
Abuse and Alcoholism.
Our small pilot study has shown that there appears to be differences
in activation of regions of the brain between control subjects and
those with FASD. This finding is very promising and hopefully, with
replication in larger samples and on other tasks that subjects with
FASD have difficulty with (such as arithmetic, disinhibition, attention,
and motor coordination), more light can be shed on the brain functioning
of people damaged by prenatal exposure. This information can then
be used to better advocate for much needed services. Also, once
we have established that there are differences in the way that the
brains of patients with FASD function, we can use fMRI as a technique
to evaluate the effectiveness of treatment by seeing if there is
a change in brain function following treatment. This has been used
in a number of other populations including ADHD. The future is looking
very active indeed! Stay tuned.
Paul D. Connor, Ph.D., is affiliated with the Fetal
Alcohol and Drug Unit at the University of Washington Department
of Psychiatry and Behavioral Sciences.
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New book offers insights
by Julie Gelo
It was with a true sense of honor that I was given the opportunity
to review the new book, Watch for the Rainbows. The first
edition was published in May 2001 and is a collection of true stories
for educators and other caregivers of children with Fetal Alcohol
Spectrum Disorder (FASD). The stories are written as a unique and
special collaboration between the education system and the medical
system. Dr. O'Malley wrote, "It is my hope that these clinical
vignettes will serve as a lesson and guide for educators, patients,
and other caregivers to seek 'the hidden rainbow' in the child,
and celebrate and strengthen its appearance."
Watch for the Rainbows: True Stories for Educators and
Other Caregivers of Children with Fetal Alcohol Spectrum Disorders
by Frances M. E. Kapp, B.Ed., M.A. Ph.D., and Kieran
D. O'Malley, M.B., D.A.B.P.N. (P)
Frances Kapp Education, Calgary, Alberta, Canada
First Edition, May 2001
I think that most of the professionals and the caregivers of those
special individuals who have been diagnosed with Fetal Alcohol Syndrome
and Related Conditions or FASD clearly agree that it is not primarily
a dysmorphic disorder, but a central nervous system disorder and
that the effects of prenatal alcohol exposure on the central nervous
system can be wide ranging.
The book is formatted using true stories that were related to Dr.
Kapp by parents, teachers, and physicians that she interviewed during
the data collection process for her doctoral dissertation about
FASD. Her hope was to illustrate some of the traits that are common
to many children with FASD and that caregivers will have greater
insight into more patient means of helping these children if they
realize that certain behaviors are a natural part of the syndrome.
She does, however, remind us all to bear in mind that each of these
children, like all other children, has his or her own unique personality.
Dr. Kapp resides in Calgary, Alberta, Canada, and has been in the
educational field for a number of years and has received the Community
Achievement in Education Award and Gonzaga University's prestigious
School of Education Leadership Award for the Doctoral Programs.
She has her own business, Fances Kapp Education, which specializes
in all phases of FASD.
Following the specific stories or vignettes are then comments by
Dr. O'Malley explaining and exploring these vignettes from a medical
and psychiatric arena. Dr. O'Malley is a board certified psychiatrist
and board eligible child psychiatrist. Currently, he is an acting
assistant professor in the Department of Psychiatry and Behavioral
Sciences and the Jackson School of International Studies at the
University of Washington in Seattle, Washington, and also maintains
a small community psychiatric consultation practice in Calgary,
seeing only patients with FASD or autistic spectrum disorders.
The vignettes that are covered in the book include topics of "The
Joy of Creativity," "Physical Fats Without Fear,"
"Dealing With Stress," "A Sensitive Nature,"
"Extroverted Children," "Detour!: The Need for Supervision,"
"The Issue of Lying," and "Teaching Strategies."
These are followed by recommendations for further reading and a
summary of recommendations by parents, physicians, and teachers
for caregivers of children who have FASD compiled by Dr. Kapp along
with explanations of the neuropsychiatry of FASD by Dr. O'Malley.
As the birth, foster, and adoptive mother of many children with
FASD, I would highly recommend this book for all those whose lives
are touched by individuals with FASD. It offers wonderfully sensitive
and positive stories of our children along with a medial and psychiatric
explanation of these behaviors that we can all understand. It truly
reminds us that our children are the "rainbows" behind
the storms of their behaviors.
To order
In Canada:
Frances Kapp Education
Suite #335
305-4625 Varsity Drive NW
Calgary, AB T3A 0Z9
$19.50 + $6.50 shipping and handling for one copy
In the U.S.:
Dr. Kieran D. O'Malley
UW Dept of Psychiatric & Behavioral Sciences
Fetal Alcohol & Drug Unit
180 Nickerson St, Suite 309
Seattle, WA 98109
$14.95 + $5.00 shipping and handling for one copy
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