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

148 ETHANOL-AFFECTE D DEVELOPMENT
A subsampl e fro m th e Seattl e studie s wa s use d
to examin e th e relationshi p betwee n th e alcohol -
induced callosa l hypervarianc e an d decrease d neu -
ropsychological performance (Bookstein et al., 2002b).
The relatio n o f callosal shap e an d neuropsychologi -
cal performanc e wa s analyze d usin g partia l least -
squares (PLS) analysis. Briefly, a PLS analysi s applies
traditional multiple regression methods to latent variables
(LVs), which are variables created fro m a factor
analytic procedure to combine and summarize multiple
measure s o f a construct . Th e dat a reductio n capabilities
o f PL S ca n b e use d t o comba t bot h th e
complexity brough t abou t b y larg e number s o f out -
come variables and the statistical problems (e.g., multicollinearity)
associate d wit h multiple , indirec t
measurement o f complex constructs. On th e basi s of
this analysis , exces s shap e variatio n correlates with
two different profiles of cognitive deficit that are unrelated
t o IQ o r the dysmophic/nondysmoprhi c grou p
distinction. A relatively thick callosa l trac t i s associated
with deficits in executive function, whereas a relatively
thin callosum is related to motor deficits .
The effec t o f ethanol o n the corpu s callosum has
been examine d in nonhuman primates (Miller et al.,
1999). MRI studies and analyses of postmortem tissue
show tha t th e callosu m i s large r i n som e ethanol -
exposed animals, the most affected segmen t being the
anterior par t (includin g the rostrum) . This segmen t
interconnects th e fronta l cortice s and i s involved in
executive function . Moreover, th e numbe r o f axons
in th e anterio r callosu m i s increase d i n ethanol -
exposed monkeys . I t i s importan t t o not e (a ) tha t
these ethanol-inducec l change s ar e dose-dependen t
and (b) that they are evident in monkeys with dysmorphic
and nondysmorphic FASD.
Basal Gangli a
MRI studies show that the volume of the basal ganglia
is reduced i n individual s prenatally expose d t o alco -
hol (Mattson et al, 1996) . Although both the caudat e
and the lenticular nuclei are reduced in volume, only
the caudat e i s reduced afte r brai n size i s taken int o
account. A larger study that further delineates subcortical
structure s (Archibal d et al., 2001 ) describe s sig -
nificant difference s i n childre n wit h FAS . N o
differences ar e eviden t i n childre n wit h nondysmorphic
FASD . Th e latte r data concu r wit h findings of
a MR I analysi s o f th e basa l gangli a showin g n o
abnormalities i n childre n wit h dysmorphi c an d
nondysmorphic FASD (Autti-Ramo et al., 2002).
Hippocampus
The hippocampu s i s associated wit h short-term mem -
ory an d learning . Accordin g t o neuropsychologica l
studies of children with FASD, it appears that the hip -
pocampus is damaged by prenatal alcohol exposure. In
a recent study, evaluating spatial learning and memory
in childre n wit h feta l alcoho l exposur e (Hamilto n
et al. , 2003) , a virtual Morri s maz e tas k based o n ap -
proaches routinely used in animal studies was used as a
measure o f hippocampal functio n (Sutherlan d e t al. ,
2001; Johnso n an d Goodlett , 2002) . Alcohol-exposed
children have impaired place learning relative to controls
bu t ar e equall y proficien t durin g th e cue -
navigation phase . Thu s th e result s o f th e huma n
studies, like those with animals, implicate tha t ethano l
interferes with hippocampal-mediated place learning .
Imaging studie s sho w hippocampa l damag e i n
alcohol-exposed subjects , althoug h no t al l studie s
confirm thi s finding . I n a smal l sampl e o f Finnis h
adolescents prenatally exposed to alcohol, some chil -
dren hav e hippocampa l abnormalitie s includin g hy -
poplasia an d regiona l thinnin g (Autti-Ram o e t al ,
2002). Moreover , i t appear s that th e hippocamp i i n
these individuals is asymmetrical; specifically, the right
hippocampus are significantly larger than the lef t hippocampus
(Riikonen et al., 1999) . No lateralization is
evident in controls. In contrast, another study describes
relative sparing of the alcohol-exposed hippocampu s i n
an otherwise hypoplastic brain (Archibald et al., 2001).
Attempts to replicate existing MRI studies are neede d
to clarify such conflicting findings. Particularly, longitudinal
studie s will assis t i n assessin g developmental
trends; i t i s difficul t t o meaningfull y compare cross -
sectional sample s that differ o n crucial variables such
as age.
Optic Nerv e
Eye abnormalities are frequently documented i n individuals
with FAS . Optic nerve hypoplasia i s the mos t
frequent for m o f ocula r dysmorpholog y associate d
with prenata l alcoho l exposur e (Stròmlan d an d
Pinazo-Durân, 2002) . Ten o f 1 1 childre n diagnose d
with FA S showed evidenc e o f optic nerv e hypoplasia
when evaluated with MRI, ophthamological examinations,
an d electroretinogra m (ERG ) (Hu g e t al. ,
2000). In addition to the structural damage to the optic
nerve , visual acuit y was decreased i n al l but on e
subject. Report s o f the frequenc y o f vision problem s
in FA S vary ; ove r hal f o f th e childre n studie d i n