Brain Development: Normal Processes and the Effects of Alcohol ...

to speculat e tha t n o particula r patter n o f behavioral
or intellectual functioning is characteristic of individuals
with FAS (Clarren, 1986) . Yet, neuropsychological
studies suggest a syndrome-specific pattern o f cognitive
and behavioral deficits associated with fetal alcohol exposure
(Mattso n an d Riley , 1998) . Th e subject s that
comprise autops y studie s likely represen t th e mos t severe
cases of prenatal alcohol exposure, i.e. , those with
damage incompatibl e with life . Thus , finding s fro m
autopsy studies may not be representative of the major -
ity of individuals with fetal alcohol effects. This is especially
true in the case of FAS, because mos t of the brain
damage cause d by fetal alcoho l exposur e doe s not preclude
viability (Clarren, 1986) .
IMAGING STUDIE S
Medical imagin g technologie s detec t inheren t differ -
ences i n biological tissu e density (e.g., gray brain matter
vs. white brain matter vs. bone), displayin g them a s
images with contrast differences. Imagin g technologie s
offer th e abilit y to examine structural brain damage i n
vivo an d includ e larger , more representativ e sample s
than the descriptions of brain structure provided by autopsy.
Give n tha t CNS deficit s ar e a hallmark feature
of FASD, brain matter quantification through imaging
studies provide s a crucia l insigh t int o specifyin g ho w
normative brain-behavio r relationship s migh t b e af -
fected by alcohol exposure. In contrast to autopsy, magnetic
resonanc e imagin g (MRI ) an d othe r i n viv o
techniques provid e information, albeit indirectly, of living
tissue. Moreover, a s there i s no inheren t selectio n
bias, the findings of these studies are likely more repre -
sentative of the populatio n o f interest.
Structural brai n imag e analyse s revea l tha t chil -
dren an d adolescent s prenatall y expose d t o alcohol,
with o r without dysmorphi c facial features, hav e pat -
terns of brain structure malformations consistent with
the neuropsychologica l an d behaviora l effect s foun d
in thi s population . Mos t o f the existin g researc h o n
neurostructural change s associate d wit h prenata l alcohol
exposur e relies on structural MRI techniques .
Total Brain Volume and Shape
Early MR I Studies
Most MRI studies of individuals prenatally exposed to
alcohol hav e focuse d o n measure s of brain volume .
ALCOHOL AN D THE DEVELOPIN G HUMA N BRAIN 14 5
Reliably, quantitativ e volumetri c analyse s have con -
firmed the overal l reductions i n size of the brai n an d
the cerebra l vaul t (Swayz e e t al. , 1997 ; Archibal d
et al, 2001 ; Autti-Ramo e t al, 2002) . Analytic tech -
niques examining regional variations in brain size and
shape have suggested tha t fetal alcoho l exposur e pro -
duces a pattern o f differential brai n damage. Specifi -
cally, th e corpu s callosum , cerebella r vermis , basa l
ganglia, and parietal regions may show particular sensitivity
to the effect s o f prenatal alcohol . A discussion
of findings from specifi c studies follows.
A series o f imaging studies from a group o f collaborators
in San Diego has focused on images collected
from a sample o f children an d adolescent s prenatall y
exposed t o alcohol , bot h wit h an d withou t dysmor -
phic feature s (ALC ) (Archibal d e t al., 2001). Analysis
of total brain volume show s that there are lobar differ -
ences between AL C and contro l groups . After statisti -
cally controllin g fo r overal l brai n reduction s i n th e
ALC group, the parieta l lobe is disproportionately reduced,
suggestin g tha t thi s regio n i s particularly vulnerable
t o alcoho l exposur e durin g development .
Such data parallel findings in the mature rat, in which
parietal corte x i s reduced b y one-third followin g prenatal
exposure to ethanol (Mille r and Potempa, 1990 ;
Mooney an d Napper , 2005) , but occipita l corte x is
unaffected.
The regiona l tissue composition i s affected b y prenatal
exposure to ethanol. Ra w volume reductions are
evident for both gra y and whit e matte r when FA S individuals
are compared with controls. Yet , when over -
all reduction s i n brai n volum e wer e statisticall y
accounted for, only white matte r reduction s reache d
statistical significance . Thus, global whit e matte r hy -
poplasia appear s t o b e mor e sever e tha n globa l gra y
matter hypoplasi a i n brain s o f individuals with FAS .
In addition, exploratio n o f proportional tissu e composition
i n eac h lob e reveale d tha t parieta l gra y an d
white matte r volume s ar e disproportionately reduce d
in individual s with FA S relative to controls , wherea s
occipital lob e whit e matte r i s proportionally larger in
FAS subjects. These finding s sugges t relative sparing
of white matter in this region.
Voxel-Based Morphometry
Whole-brain voxel-base d morphometry (VBM ) aims
to localize cortica l abnormalitie s by examining eac h
voxel, o r point, o n th e brai n image . Thi s methodol -
ogy avoid s th e nee d t o defin e boundarie s o n eac h