Alcohol and the 


Developing Brain:


Neuroanatomical Studies


Wei-Jung A. Chen, Ph.D., Susan E. Maier, Ph.D., 

Scott E. Parnell, and James R. West, Ph.D. 

One of the distinguishing features of prenatal alcohol exposure is impaired cognitive and behavioral 

function resulting from damage to the central nervous system. Information available from the small 

number of autopsied cases in humans indicates that the offspring of mothers who abused alcohol 

during pregnancy have various neuroanatomical alterations ranging from gross reductions in brain 

size to cellular alterations. Recent neuroimaging technology provides the most powerful tool for 

assessing the neurotoxic effects of fetal alcohol exposure in living organisms and for exploring the 

relationship between behavioral dysfunction and brain damage at the regional level. Recently, animal research has suggested that the damaging effects of alcohol exposure during brain development 

could be prevented or attenuated by various pharmacological manipulations or by complex motor 

training. These promising findings provide directions for developing future prevention or intervention strategies. KEY WORDS: prenatal alcohol exposure; neuroimaging; neurotoxicity; fetal alcohol 

effects; brain damage; cognitive development; AODR (alcohol and other drug related) behavioral 

problem; prevention strategy; drug therapy; CNS function; cell adhesion molecules; mitochondria 

Prenatal alcohol exposure adversely tion of symptoms known as fetal alcohol in the communications among cells. 

affects the developing anatomical syndrome (FAS). The criteria for diag- These alterations can have a long-term structures of the body and brain, nosing FAS include facial dysmorphology, detrimental impact on behavioral and leading to a range of physical, cognitive, growth retardation, and central nervous cognitive development. and behavioral effects. The term “anatom- system (CNS) dysfunction. Facial dysical structures” encompasses both the morphology results from anatomical 

components of the major body systems changes occurring during weeks 4 to 8 Human Neuroanatomical 

(e.g., heart, blood vessels, bones, muscles) of gestational development that affect Studies and the cellular and molecular structures how tissues merge under the facial 

within these major components. Any prominences. Of all anomalies associ- Since FAS was defined several decades alterations to the body’s anatomical ated with FAS, growth retardation is ago, researchers have learned a signifi­ structures, regardless of the level at which the most obvious form of anatomical cant amount about the nature of the they occur (gross or microscopic), may change. People who are not professionally 

negatively affect an organism’s function. trained to analyze facial dysmorphology 

This article reviews changes in brain can easily recognize this anomaly WEI-JUNG A. CHEN, PH.D., is an assisanatomy (i.e., neuroanatomy) that occur because the weight and size of FAS tant professor; SUSAN E. MAIER, PH.D., 

following developmental (prenatal and/or infants are distinctly smaller than nor- is a research assistant professor; SCOTT E. 

early postnatal) alcohol exposure in both mal. Anatomical alterations associated PARNELL is a graduate student; and 

humans and animal models. It also dis- with CNS dysfunction may range from JAMES R. WEST, PH.D., is a distincusses promising techniques to prevent gross reduction in brain volume (i.e., guished professor; all in the Department of 

or reverse alcohol-induced neuroanatom- microencephaly), to deficits in cell Human Anatomy and Medical 

ical changes. number in a particular brain region, Neurobiology, College of Medicine, Texas 

The most serious consequence of to cellular modifications of individual A&M University System Health Science 

prenatal alcohol exposure is a constella- nerve cells (i.e., neurons), to alterations Center, College Station, Texas. 

174 Alcohol Research & Health 
xxx xxx xxx xxx xxx xxx xxx

behavioral, cognitive, and physical features of FAS and related diagnoses. Until 

recently, not much was known about 

the actual anatomical injury to the brains 

of children with FAS and the relationships 

between risk factors and behavioral/ 

cognitive outcomes and brain injury. 

This information could only be acquired 

at autopsy, and because FAS generally is 

not life threatening, there were few cases 

available for study. Researchers had to 

use caution when reviewing the autopsy 

data derived from children with FAS 

who died for reasons other than accidents 

because brain tissues may be severely 

affected by other life-threatening diseases. 

Therefore, researchers had to rely on 

animal models to address most of these 

questions. Now that magnetic resonance 

imaging (MRI) and functional MRI 

(fMRI) are available for use with living 

subjects, researchers are generating new 

data that can lead to a better understanding of brain and behavior relationships 

in humans, as well as a better interpretation 

of findings from animal studies. This 

new information will guide researchers 

working with animals in their attempts 

to target mechanisms and potential 

therapeutic interventions for humans. 

Microcephaly 

Microcephaly is defined as having a 

small head relative to body size and is 

based on the ratio of body weight to 

head circumference or height-to-head 

circumference (not to be confused with 

microencephaly, which refers to the size 

of the brain). Early studies showed that 

microcephaly was related to alcohol use 

throughout pregnancy (Ernhart et al. 

1985; Rosett et al. 1983). Coles (1994) 

reported that children whose mothers 

stopped drinking before the end of the 

second trimester had larger head circumferences on average than children whose 

mothers continued to drink throughout 

pregnancy. This finding suggests that a 

pregnant woman may be able to avoid 

additional injury to her baby’s brain if 

she stops drinking before the third trimester. 

These data are useful for counseling 

pregnant women about the benefits to 

their unborn children of reducing or 

ceasing their alcohol consumption as 

soon as their pregnancy is identified. 

Neuroimaging 

In recent years, researchers have used 

both anatomical MRI and functional 

MRI to determine the nature of brain 

injury in living offspring with FAS. 

Early seminal MRI studies by Riley 

and colleagues (reviewed by Roebuck 

et al. 1998) showed reductions in the 

volume of several brain regions in children who were affected by heavy1 

maternal drinking. These studies were 

significant because they showed a 

reduction in the size of specific brain 

regions independent of any reduction 

in total brain volume. 

More recently, Archibald and colleagues (2001) found that, in children 

with FAS, the fibers carrying information between brain cells (i.e., white 

matter) appear to be more susceptible 

to reductions in volume than the outer, 

convoluted layer of brain tissue called 

the cerebral cortex. Within the cerebral 

cortex, the parietal lobe (situated at the 

upper middle of the cerebrum) is reduced 

by prenatal alcohol exposure, whereas 

the temporal and occipital lobes 

(located on the sides and back of the 

brain, respectively) are not. These 

anatomical data clearly show that alcohol’s effect on the developing brain is 

not uniform but varies depending on 

the brain region. Wass and colleagues 

(2001) used ultrasound sonography to 

examine living fetuses exposed to alcohol and found a reduction in the size 

of the frontal cortex, but not other cortices, of the cerebrum. 

Clark and colleagues (2000) used 

MRI to examine the brains of adults 

who had been exposed to alcohol in 

utero and were classified as nonretarded (as assessed by IQ score). They 

found only one abnormal case, a thinning corpus callosum in the adult with 

the lowest IQ. (The corpus callosum is 

a bundle of fibers through which the 

two cerebral hemispheres communicate.) 

Otherwise, the MRIs of all other study 

participants were considered to be in 

the normal range. Some of the partici1 Heavy drinking is defined as 7 to 13.99 ounces (oz) 

absolute alcohol per week or 14 to 27.9 standard drinks 

per week (approximately 12 oz beer, 5 oz wine, 1.25 oz 

liquor) in the NIH 1988 National Health Interview Survey 

(USDHHS 1988). 

Alcohol and the Developing Brain 

pants from this study were examined 

further using positron emission tomography (PET). These scans revealed 

changes in metabolic rate in the thalamus and the head of the caudate 

nucleus (two brain structures important for communication within the 

brain) (Clark et al. 2000). The authors 

suggest that the functional findings 

may be related to the regional vulnerability of the brain to prenatal alcohol 

exposure, which is consistent with the 

conclusion of an earlier PET study 

(Hannigan et al. 1995). 

More recently, Bookstein and colleagues (2002a,b) explored the relationship between the shape of the corpus 

callosum in adolescents and adults 

(assessed with MRI) exposed to alcohol 

prenatally and the degree of their cognitive impairment, to see if the shape 

of the corpus callosum was an indicator 

of heavy in utero alcohol exposure. 

Although the volume of the corpus 

callosum in the alcohol-exposed study 

participants was not different from that 

in the control participants, the variability in the shape of the corpus callosum 

was much higher in the alcohol-exposed 

group. The authors suggest that variations in corpus callosum size, volume, 

and shape revealed by MRI can be 

used as diagnostic criteria for FAS and 

related brain disorders. Thus, MRI 

could be used to solicit more social 

support services, which often are lacking for adolescents and adults affected 

by prenatal alcohol exposure. 

Autopsy Studies 

Anatomical changes occurring at the 

cellular level in humans can best be 

revealed with autopsy material. Although 

only a very small number of brains are 

available for this level of analysis, finding any microscopic changes in the 

brain lends considerable support to the 

claim that developmental alcohol exposure induces neuronal injury, which 

ultimately may be responsible for the 

behavioral and cognitive changes 

observed in children exposed to alcohol 

prenatally. 

Clarren and associates (1978) found 

changes in the structure of the autopsied brains of four children diagnosed 

Vol. 27, No. 2, 2003 175 
with FAS. The most prevalent findings 

in these brains were incorrectly located 

(i.e., ectopic) neurons in the white matter, suggesting errors in the migration 

of neurons throughout the brain. In 

one case there was a complete absence 

of the corpus callosum and anterior 

commissure, another fiber bundle that 

connects regions of the brain. Ferrer 

and Galofre (1987) found that the 

short, hair-like projections (i.e., dendritic spines) on fibers called dendrites, 

which extend from neurons to receive 

information from other neurons, also 

were affected. They reported that the 

brain from a 4-month-old infant with 

FAS showed a significant decrease in the 

number of dendritic spines on nerve 

cells projecting from the cortex to 

other parts of the brain and spinal 

cord. Another autopsy case, of a 2-

month-old infant born to a mother who 

binge drank during pregnancy (primarily during the first trimester), revealed 

absent olfactory bulbs and tracts (which 

the brain uses to sense odors); poorly 

developed optic tracts; fused anterior 

brain structures such as the septum, 

thalamus, and the head of the caudate 

nucleus; fewer cells in the dentate gyrus, 

which is part of the hippocampus (an 

area crucial for memory); and fewer 

nerve cells in the cerebellum (which regulates balance, posture, movement, and 

muscle coordination) known as Purkinje 

cells, and disorientation of these cells 

(Coulter et al. 1993). Although these 

autopsy data are based on a small number of subjects, they seem to show that 

prenatal alcohol exposure does have a 

damaging effect on the structural organization of the developing human brain. 

Animal Neuroanatomical 

Studies 

Most of the current information on 

how developmental exposure to alcohol 

induces brain damage comes from animal 

studies. Because of the obvious ethical 

constraints of performing certain procedures on humans, the retrospective nature 

of the human data, and numerous confounding variables, human studies cannot 

address issues that can be addressed with 

animal studies. Researchers are able to 

control factors such as dose, timing, and 

pattern of alcohol exposure in animal 

studies. And because there are so few 

human autopsy cases, researchers have 

performed most neuroanatomical 

assessments, particularly at the cellular 

level, on animals. The following sections 

briefly summarize several hallmark findings related to neuroanatomical studies 

of the effects of developmental alcohol 

exposure in animals. 

Microencephaly 

Microencephaly, defined in animal subjects as having a small brain relative to 

body size, is a gross neuroanatomical 

anomaly associated with heavy alcohol 

exposure during development. As 

described above, such an anomaly in 

humans is inferred by deficits in head 

circumference because we cannot 

remove and weigh the human brain. 

However, in animals, the most common 

and traditional means of measuring 

microencephaly is brain weight. 

Numerous reports have shown that 

alcohol exposure during the brain growth 

spurt (a period of most intense brain 

growth) in rats significantly reduces 

the weight of the forebrain, brain stem, 

and cerebellum (Maier et al. 1997). 

Importantly, in the microencephalic 

brain, not every brain region is affected 

equally. Using state-of-the-art threedimensional stereological techniques, 

researchers can estimate the volume 

(size) of various brain regions to 

demonstrate microencephaly. Many of 

these stereological studies have demonstrated that developmental alcohol exposure leads to reductions both in brain 

weight and volume in a rat model (Maier 

et al. 1997; Chen et al. 1998). It appears 

that heavy alcohol exposure during the 

brain growth spurt (early postnatal 

period in rats, and third trimester and 

early infancy in humans) leads to the 

most severe and pronounced microencephaly compared with exposure during 

other developmental stages. Surprisingly, 

in rats, even 1 day of alcohol exposure 

at a high dose (6.6 grams per kilogram 

body weight) is sufficient to cause 

growth deficits in specific brain regions, 

such as the cerebellum (Goodlett et al. 

1990). Olney and colleagues (2002) 

recently have suggested that these alcohol-induced reductions in brain volume and neuronal loss may be attributed to alcohol-induced neurodegeneration via programmed cell death (i.e., 

apoptosis). 

Neuronal Loss 

One of the most devastating and extreme 

consequences of developmental alcohol 

exposure is the loss of neurons, and the 

data documenting neuronal loss are 

derived mostly from animal studies. 

Although selective programmed neuronal death is a normal aspect of CNS 

development, excessive neuronal death 

disrupts the development of normal 

neural networks and may lead to cognitive and behavioral dysfunctions (in 

both humans and animals). Distinct 

regions and specific cell types appear to 

be affected by alcohol-induced neuronal 

loss. Studies in rats have clearly demonstrated that alcohol causes a reduction 

of cerebellar Purkinje cells, cells of the 

olfactory bulb, and pyramidal cells in a 

part of the hippocampus known as the 

CA1 region (Chen et al. 1998, 1999a; 

Livy et al. 2003). In other neuronal 

populations, however, such as those in 

the ventrolateral nucleus of the thalamus (an area important for voluntary 

movement) and the locus coeruleus (a 

group of nerve cells involved in arousal 

and vigilance), alcohol does not cause 

cell loss (Chen et al. 1999b; Livy et al. 

2001). This pattern of alcohol-induced 

loss of neurons is important for two 

reasons: (1) it establishes a correlation 

between the severity of neuronal loss of 

a specific neuronal population and the 

degree of behavioral deficits associated 

with such a cell population, and (2) it 

provides insight into the specific characteristics of neuronal populations that 

are most vulnerable or most resistant to 

alcohol-induced neuronal loss. 

Fewer Dendritic Spines 

Proper CNS communication depends 

on an adequate number of dendritic 

spines and dendritic branching, because 

dendrites are the sites of contact for 

neurons. Animal studies, both in vivo 

and in vitro, have demonstrated that 

176 Alcohol Research & Health 
developmental alcohol exposure negatively affects the structural integrity of 

the dendrites and the number of dendritic spines in neurons located in the 

substantia nigra (a group of nerve cells 

involved in movement), the cortex, and 

the hippocampus (Tarelo-Acuna et al. 

2000; Yanni and Lindsley 2000; Shetty 

et al. 1993; Fabregues et al. 1985). For 

example, Tarelo-Acuna and colleagues 

(2000) showed that prenatal and postnatal alcohol exposure alters the proportions of different spine shapes in the 

long (apical) dendrites of hippocampal 

CA1 pyramidal cells. 

Changes in the dendritic morphology 

and reductions in dendritic spines in the 

hippocampus interfere with the optimal 

transmission of the neural impulse. 

Relating these data to humans, it is possible that these changes could contribute 

to the cognitive problems seen in children 

with FAS, because the hippocampus is 

involved in learning and memory. 

Disrupted Mitochondrial 

Membrane 

The mitochondria are subcellular structures that produce energy for the cell. 

Changes in the structural integrity of 

the mitochondrial membrane and its 

associated proteins have been shown to 

initiate apoptosis or necrosis, two possible forms of cell death (Kroemer et al. 

1997). Ramachandran (2001) demonstrated that alcohol exposure in utero 

significantly elevates cytochrome c and 

apoptosis-inducing factor (AIF) levels 

in mitochondria in the fetal rat brain. 

Light and colleagues (2002) showed 

that 1 day of alcohol exposure (6.0 

g/kg on postnatal day 4) leads to apoptotic Purkinje cells in early generated 

cerebellar lobules. The observation of 

these apoptotic neurons coincides with 

the release of cytochrome c from the 

mitochondria of the Purkinje cells. These 

studies suggest that alcohol-induced 

neuronal loss may occur via disruption 

of mitochondria within those neurons. 

Changes in Cell Adhesion Molecule 

Properties 

The extracellular matrix (ECM), a filamentlike structure on the surface of the 

Alcohol and the Developing Brain 

cell, is crucial for proper adhesion, 

migration, and differentiation of neurons 

in the developing CNS. Therefore, disruptions in the ECM can have severe 

negative ramifications for developing 

neurons. One such disruption of the 

ECM is evident in alcohol’s effects on 

the L1 cell adhesion molecule (L1CAM), 

a cell surface protein that promotes 

cell-to-cell binding. Charness and 

coworkers (1994) demonstrated that 

alcohol inhibits the adhesive properties 

of L1CAM in cell cultures, preventing 

neurons from properly adhering to each 

other or to the ECM. Bearer and colleagues (1999) reported that alcohol 

inhibited L1CAM-mediated outgrowth 

of the connective fibers from early postnatal rat cerebellar neurons. Collectively, 

these results suggest that developmental 

alcohol exposure may alter cellular 

components, such as L1CAM, and that 

the consequences of a change in L1CAM 

function could be detrimental to brain 

development. 

Neural Circuitry Modifications 

A complete, intact, and functional 

neural circuitry requires proper connections between regions of the brain. 

Developmental alcohol exposure has 

been shown to cause aberrant wiring 

patterns or abnormalities in fiber bundles 

in the developing brain. For instance, 

the size of the corpus callosum, one of 

the largest fiber bundles in the brain, is 

significantly reduced following prenatal 

alcohol exposure in rats (Zimmerberg 

and Scalzi 1989). Further research has 

shown that, in rats, in utero alcohol 

exposure alters the distribution of neurons 

from cortical areas projecting through 

the corpus callosum into the somatosensory cortex, which receives tactile information from the body (Miller 1997). 

Recently, Elberger and associates found 

that alcohol exposure during the period 

equivalent to the second trimester in 

rats resulted in an abnormal dendritic 

branching of corpus callosal projection 

neurons in the visual cortex (Qiang et 

al. 2002). These findings demonstrate 

that the interhemispheric connections 

are affected by prenatal alcohol exposure. 

Furthermore, early findings indicated 

that the topographic organization of 

hippocampal mossy fibers (neuron 

extensions that terminate in mosslike 

branchings) was affected by developmental alcohol exposure (West et al. 

1981; West and Hodges-Savola 1983). 

Prenatal alcohol exposure also may 

significantly interrupt the development 

of the cortical circuitry by interfering 

with the proliferation and migration of 

the cortical neurons. Miller (1986, 1993) 

demonstrated that prenatal alcohol 

exposure delays the migration of neurons 

from the zone where they are produced 

to their final destinations, and the rate 

of migration of these cortical neurons 

was decreased as well. Such errors in 

proliferation and migration disrupt 

synchronized developmental events, 

which results in ectopic clusters of cortical neurons and abnormal neuronal 

circuitry. In sum, because of the critical 

role of integrated neural circuits within 

the brain, it is obvious that abnormalities 

in any component of a neuroanatomical circuit resulting from developmental alcohol exposure would have severe 

consequences for CNS functions. 

Implications for 

Prevention and 

Intervention 

Recently, several studies have shown 

that complex motor training and pharmacological treatments are able to 

prevent or ameliorate developmental 

alcohol-induced alterations in specific 

anatomical structures. These studies are 

based on the assumption that restoring 

neuroanatomical integrity would result 

in subsequent functional recovery. 

Therefore, identifying the structural 

alterations associated with prenatal alcohol 

exposure and understanding the underlying mechanisms of these changes are 

critical steps in developing both prevention and intervention strategies. 

Complex Motor Training 

Using a paradigm that involves complex 

motor training (see figure 1), Klintsova 

and colleagues (2002) convincingly 

demonstrated structural reorganization 

in rat cerebellum following early postnatal alcohol exposure. The most striking 

Vol. 27, No. 2, 2003 177 
and profound aspect of these studies 

was that, although the complex motor 

skill training was initiated during adulthood (180 days of age), it was able to 

successfully stimulate the creation of 

new connections between Purkinje cells 

and the long connecting fibers (i.e., 

parallel fibers) of other neurons in animals 

that were exposed to alcohol between 

postnatal days 4 and 9. Although the 

number of Purkinje cells was unchanged 

following the complex motor training, 

the increased volume of the paramedian lobule of the cerebellar cortex and 

the increased number of parallel fiber 

synapses per Purkinje cell were sufficient 

anatomical changes to result in improved 

motor skills. These findings have relevant clinical significance and important 

therapeutic implications. They suggest 

that complex rehabilitative motor training can improve motor performance 

of children, or even adults, with FAS. 

However, at present it is unclear whether 

recovery or reorganization of neural 

connections is possible in regions other 

than the cerebellum and motor cortex of 

the nervous system. Moreover, it remains 

to be seen whether the improvement in 

motor skills and anatomical alteration in 

synapses following complex motor 

training is permanent. 

Pharmacological Treatments 

Antioxidant therapy has been reported 

to be effective in reducing early postnatal alcohol-induced neurotoxicity in 

animal studies. Heaton and colleagues 

(2000) showed that vitamin E protects 

against early postnatal alcohol-induced 

cerebellar Purkinje cell loss in lobule I, 

a lobule that is most sensitive to alcohol during development. Although it 

has not yet been documented, researchers 

speculate that antioxidant treatment 

would protect the functions of the 

cerebellum from early postnatal alcohol 

exposure because the antioxidant prevents 

the formation of harmful free radicals. 

In contrast to complex motor training, 

which is an intervention, administering 

vitamin E during pregnancy is a preventive effort. Prevention in many ways 

is more effective and economical than 

intervention in attenuating the detrimental effects of alcohol exposure during 

development. Recent data show that 

melatonin, a known and effective antioxidant, when given to neonatal rat pups 

simultaneously with alcohol, does not 

prevent the early postnatal alcoholinduced Purkinje cell loss in either the 

part of the cerebellum known as the 

cerebellar vermis or in lobule I (Edwards 

et al. 2002). Taken together, these data 

suggest that preserving the intact neural 

structures depends on the type of 

antioxidant used and possibly the timing of antioxidant administration. 

Treatment with antioxidants before 

alcohol exposure may be critical for the 

antioxidant to be available in an amount 

that would most effectively inhibit 

alcohol-induced generation of free 

radicals. Recently, two peptides derived 

from growth factors that are associated 

with normal development (i.e., 

NAPVSIPQ [NAP] and SALLRSIPA 

[SAL, also called ADNF–9]) have been 

shown to be effective in preventing prenatal alcohol-induced somatic and brain 

growth retardation in a mouse model 

(Spong et al. 2001). In addition, supporting evidence indicated that the levels of 

these peptides were reduced in mouse 

embryos which were exposed to alcohol 

prenatally (Spong et al. 2002). More 

recently, these peptides have been shown 

to reverse alcohol-induced inhibition 

of L1-mediated cell-to-cell adhesion in 

vitro (Wilkemeyer et al. 2002). Despite 

the promising findings that these peptides 

prevent some aspects of fetal alcoholinduced damage, their ability to prevent 

damage to specific neural anatomical 

structures has not been examined. 

Recent data suggest that administering MK–801, a compound that blocks 

receptors for the brain chemical glutamate, during alcohol withdrawal reduces 

the loss of hippocampal pyramidal cells 

in the CA1 region in a neonatal rat 

model. However, the most profound 

effect of this pharmacological treatment 

is its ability to reverse the behavioral 

impairment in a specific learning task 

that was induced by early postnatal 

alcohol exposure (Thomas et al. 2002). 

These findings demonstrate that preserving the integrity of neural structures 

is important for upholding function. 

Figure 1 A rat undergoing complex motor training. This training consists of prodding the rat to traverse an elevated course with multiple obstacles and 

challenges without falling off. Each rat runs the course five times per day 

for 12 days, and each run is timed. Over time, the rat will learn to traverse 

the course in less time without falling. Such motor training experiences 

during adulthood stimulate connections between nerve cells in animals 

that received alcohol during the early postnatal period (i.e., during the 

brain growth spurt). The resulting improved performance on the obstacle 

SOURCE: Photograph courtesy of Dr. Anna Klintsova, Binghamton University, Binghamton, New York. 

course suggests a potential intervention that may attenuate the severity of 

developmental alcohol–induced brain injury. 

178 Alcohol Research & Health 
Further evidence for the effectiveness 

of certain pharmacological treatments 

involves the ability of the eight-carbon 

long-chain alcohol known as 1-octanol 

to attenuate alcohol-induced damage. 

Recent data show that a low dose of 1­

octanol interacts with the L1CAM to 

block an alcohol-induced mechanism 

of abnormal physical development in a 

mouse embryo model (Wilkemeyer et 

al. 2000; Chen et al. 2001). As shown 

in figure 2, it appears that l-octanol 

significantly reduces the severity of 

alcohol’s effects. Although it is unclear 

whether treatment with 1-octanol in vivo 

would be just as effective as in vitro, 

or whether 1-octanol protects against 

alcohol-induced brain damage, this 

treatment holds promise for developing 

pharmacological agents to prevent alcoholinduced injury during development. In 

sum, these anatomical studies of developmental alcohol effects provide opportunities to assess the effectiveness of 

prevention and intervention methods. 

Conclusion 

Identifying specific neuroanatomical 

anomalies as adverse effects of heavy alcohol exposure during development has 

Alcohol and the Developing Brain 

been a significant contribution to the 

fetal alcohol field. Animal studies have 

been important in the following ways: 

• They have demonstrated that alco­


hol exposure during development,


even without polydrug use or


undernourishment, can induce


significant structural changes to


the developing brain.


• They have demonstrated that vari­


ous regions of the developing brain


are not uniformly vulnerable, and


that the brain is not equally vulner­


able throughout its developmental


period. Demonstrating so-called


regional and temporal vulnerabil­


ity, as well as other potential risk


factors, has helped researchers to


understand the considerable vari­


ability observed in children prena­


tally exposed to alcohol. 


• The quantifiable nature of specific


neuroanatomical anomalies offers


a direct measure for future studies


to use in assessing the efficacy of


putative neuroprotective agents.


Similarly, important advances also 

have been made in human studies. 

Noninvasive MRI studies in children 

exposed to alcohol in utero have been 

much more instructive than autopsy 

studies. They allow neuroanatomical 

deficits to be correlated with functional 

deficits. MRI, fMRI, PET, and other 

neuroimaging techniques offer the 

potential to help direct future research 

into pharmacological intervention and 

treatment strategies with fetal 

alcohol–exposed patients. 

Taken together, human and animal 

neuroanatomical studies have provided 

both an experimental foundation for a 

better understanding of the behavioral 

impairments associated with heavy maternal drinking, and an important means 

of evaluating potential neuroprotective 

and therapeutic interventions. ■ 

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