DEVELOPMENTAL NEUROPSYCHOLOGY, 18(3), 281–296

Copyright © 2000, Lawrence Erlbaum Associates, Inc.

Long-Term Sequelae of
Prefrontal Cortex Damage Acquired in
Early Childhood
Steven W. Anderson, Hanna Damasio, Daniel Tranel, and
Antonio R. Damasio
Department of Neurology
Division of Behavioral Neurology and Cognitive Neuroscience
University of Iowa

Frontal lobe dysfunction is often invoked as a contributing factor in developmental dis-

orders characterized by chronic maladaptive behavior, but interpretation of relevant
neuropsychological findings has been hampered by the limited information available
regarding the consequences of focal prefrontal damage early in life. We describe here
the long-term behavioral and cognitive sequelae of damage to prefrontal cortex in two
young adult patients who had sustained their brain damage prior to 16 months of age. In
the context of normal neurological examinations, both cases had remarkable histories
of impaired decision making, behavioral dyscontrol, social defects, and abnormal emo-
tion. Performances were primarily normal on a broad range of neuropsychological mea-
sures (intellect, memory, language, academic achievement, visual perception, and
visuoconstruction), but selective impairments of executive function were evident.
Early dysfunction in the prefrontal region may result in severe and chronic social mal-
adjustment despite largely normal cognitive abilities. These findings can help inform
neuropsychological evaluation of patients with possible prefrontal dysfunction in the
setting of developmental disabilities or early brain trauma.

Benton recently noted that, “A review of the literature discloses a surprising paucity
of cases that can be utilized to evaluate the behavioral effects of prefrontal disease in
children” (1991, p. 275). The few cases which have been described tend to be limited
by restricted duration of follow-up and inconclusive neuroanatomical findings.
Even more sparse is information regarding the effects of focal prefrontal damage in-

Requests for reprints should be sent to Steven W. Anderson, Department of Neurology, University of
Iowa Hospitals and Clinics, Iowa City, IA 52242. E-mail: steven-anderson@uiowa.edu
282 ANDERSON, DAMASIO, TRANEL, DAMASIO

curred in the first months and years of life, as nearly all cases in the literature involve
onset of damage after 3 years of age. Exceptions include the case of Ackerly and
Benton (1947) and Case 1 of Price, Daffner, Stowe, and Mesulam (1990).
There is reason to suspect that the impact of prefrontal damage incurred at a very
early age is likely to be substantial. Focal damage to specific regions of the prefrontal
cortex in adulthood or later childhood can have devastating consequences for the
ability to navigate the complexities of human social interaction, and studies of infant
monkeys and rodents with prefrontal ablations also have found substantial defects in
aspects of the animals’ learning and social behavior (for reviews, see Damasio &
Anderson, 1993; Eslinger, Biddle, & Grattan, 1997; Finger, 1991; Kolb & Gibb,
1990). Although some young children make remarkable recoveries from brain dam-
age (e.g., in the realms of language or motor function), consistent with the notion of
greater neuronal and functional plasticity early in life, caution is warranted in gener-
alizing from these findings to defects in social behavior and decision making result-
ing from prefrontal damage. It is likely that the ability to functionally compensate for
early injury varies across brain regions and cognitive domains. Teuber and Rudel
(1962) postulated that complex cognitive–behavioral activity is more likely to be
chronically disrupted by early onset of brain damage, whereas simple functions
(motor, sensory) are more likely to recover.
Much of the existing research on nonfocal brain injury suggests that develop-
ment of cognitive and behavioral competencies may be more adversely affected
the earlier in life an injury is incurred (e.g., Taylor and Alden, 1997). For some
realms of cognitive function, earlier injury may disrupt acquisition of basic com-
petencies which provide necessary foundations for later development, and it is
possible that damage to multiple systems may interact to produce greater disabil-
ity. Investigation of the long-term consequences of focal prefrontal damage ac-
quired in early childhood may be useful in understanding the consequences of
childhood traumatic brain injury, which often involves damage to prefrontal re-
gions in the context of more widespread damage. Many of the sequelae of trau-
matic brain injury which prove to be most disabling bear considerable similarity to
descriptions of patients with frontal lobe lesions. Similarly, the consequences of
prenatal alcohol exposure are suggestive of prefrontal dysfunction in the setting of
more widespread brain damage (see Connor, Sampson, Bookstein, Barr, &
Streissguth, this issue).
It also is likely that understanding of certain developmental behavioral disor-
ders, including psychopathy, will depend on further elucidation of mechanisms of
dysfunction in prefrontal cortex. The behavioral syndrome resulting from
adult-onset damage to orbital and mesial prefrontal regions has been termed ac-
quired sociopathy because of similarities to the condition of developmental
sociopathy or psychopathy (Damasio, Tranel, & Damasio, 1990). Abnormalities
of psychophysiological arousal and reactivity have been reported both in persons
with antisocial behavior and in patients with prefrontal lesions (Bechara, Damasio,
 EARLY PREFRONTAL CORTEX DAMAGE 283

Tranel, & Damasio, 1997; Damasio et al., 1990; Scarpa & Raine, 1997), and there
is increasing evidence that prefrontal dysfunction may contribute to at least some
cases of psychopathy (e.g., Raine, Lencz, Bihrle, LaCasse, & Colletti, 2000;
Raine, Staoddard, Bihrle, & Buchsbaum, 1998). However, there also are differ-
ences between the two conditions, such as the general lack of malevolent intent
and criminality in acquired sociopathy.
We present descriptions of two children with circumscribed prefrontal damage
acquired prior to age 16 months and evaluated in young adulthood. Both patients
were raised in stable, middle-class homes by college-educated parents, and they
had normal siblings. Neither child had a family history of psychiatric disease or
risk factors for behavioral disturbance other than their brain injury. Detailed histo-
ries were obtained from medical, academic, and legal documents, as well as inter-
views with the children’s parents. The children participated in comprehensive
neuropsychological evaluations, and neuroanatomical analyses were performed
with three-dimensional MRI brain imaging.

CASE 1: HISTORY AND BEHAVIOR

Case 1 (patient “FD”) had a normal birth, and she attained developmental mile-
stones in speech and walking at normal ages. Her history was unremarkable until
age 15 months, when her head was run over by one wheel of a pickup truck. She ex-
perienced momentary loss of consciousness, followed by apparent confusion and
lethargy. On admission to the hospital, she had a normal Glasgow Coma Scale
score and was not in acute distress. There were tread marks across the right side of
her face. Skull X-rays showed an 8 cm linear left parietal skull fracture without de-
pression, and possible slight displacement of the left coronal suture. Within 2 days,
she was eating well, and was bright, alert, and active. There were no focal motor or
sensory defects. She was discharged, and at follow-up 2 months later was consid-
ered neurologically and behaviorally normal. This event was largely forgotten or
ignored in subsequent years, even as numerous mental health professionals at-
tempted to diagnose and treat her emerging behavior problems.
FD showed a mixed pattern of hand preference (+40 on the modified
Geschwind-Oldfield Questionnaire). She would draw with either hand, usually
wrote with her left hand, and preferred her right hand for throwing. Her mother re-
ported that the girl never had shown a significant right-hand preference. There was
a family history of sinistrality (left-handed father, ambidextrous mother). She had
one sibling, a right-handed younger brother, and he had no behavior difficulties.
The patient’s mother first noted behavioral problems in the girl around the age
of 3, when she observed that her daughter seemed to be largely unaffected by pun-
ishment. Neither physical intervention, such as slapping her fingers or spanking,
nor withholding of privileges, appeared to reduce the probability of recurrence of
284 ANDERSON, DAMASIO, TRANEL, DAMASIO

the undesired behaviors. A second behavior abnormality noted in FD’s early home
life was her tendency to pick up and carry off any object in the house as if it were
her own. She would take decorative items, her sibling’s toys, food items, kitchen
utensils, parents’ personal possessions, tools, and seemingly anything else which
she found attractive or interesting and bring it to her room or other location where
she would be playing. The items often were found broken or abused. By age 4, this
behavior was so pervasive that her parents installed locks on all closets and cup-
boards, the refrigerator, and the doors to several rooms to protect the child’s safety
and their possessions.
FD attended a highly structured school until the sixth grade. Beginning in Kin-
dergarten, her teachers noted difficulty in controlling her behavior. She was, how-
ever, able to obtain average grades until the sixth grade, when her behavior
problems escalated and her grades declined following transfer to a less structured
school. She first saw a school counselor and a psychiatrist regarding her disruptive
classroom behavior in third grade. It was observed that she rarely completed as-
signments unless someone worked with her and kept her on task. She was diag-
nosed with Attention Deficit Disorder at that time, and Ritalin was prescribed.
FD ran away from home for the first time while she was in the fourth grade, and
was returned home after she was caught shoplifting. Her behavior problems in
school worsened over the next few years. She failed to turn in assignments, lied
blatantly and frequently, and often was tardy or absent. She was described as un-
able to focus her attention, easily agitated, and aggressive (usually verbal aggres-
sion, but occasionally physical). She repeatedly forged her mother’s signature on
permission and absentee slips. Her grades declined, until by age 14 she was failing
most classes. Ritalin had been discontinued by this time because it seemed to
worsen her behavior problems.
She became too disruptive in classrooms to continue in the public school sys-
tem, and was placed in the first of a series of treatment facilities at age 14. She was
arrested for shoplifting on two occasions, and her family found evidence of theft
on several additional occasions.
She generally was rejected by her peers throughout her school years, and never
had close friends. She stole from other children and lied to them. The lies were a
near daily occurrence, with some clearly motivated by an attempt to get out of
trouble, but often without apparent purpose other than perhaps drawing attention
to herself. She occasionally dated boys, was sexually active by age 14, and became
pregnant at age 18. Her maternal behavior was marked by dangerous insensitivity
to the infant’s needs. She appeared to experience little or no empathy.
She had been placed in six different treatment facilities by age 16. The treat-
ment programs all involved some form of contingency management, which
seemed to have limited effects on the targeted behavior, and no lasting conse-
quences. She typically was discharged for repeatedly running away, rules viola-
tions, and failure to progress toward treatment goals. She had been reprimanded
 EARLY PREFRONTAL CORTEX DAMAGE 285

for theft, intimidation, confidentiality violations, destruction of property, and pos-

session of contraband. It was repeatedly noted in her records that she was often
friendly, pleasant, and charming toward adults in authority positions, but also ob-
viously manipulative. She required prodding to sustain acceptable personal hy-
giene. In childhood and continuing at the treatment facilities and into adulthood,
she would hide food items in her locker or bedroom and leave them until the odor
of decay led someone else to initiate cleaning. She was disinclined to throw any-
thing away and accumulated large quantities of useless objects (empty boxes, gum
wrappers, old papers). Whenever an object turned up missing at the treatment fa-
cilities, the search would begin in FD’s room, where it often would be found in the
back of her closet or in a drawer. Her crime strategies were poorly thought out. For
example, she stole jewelry from another girl at the facility, then openly appeared
wearing the jewelry and adamantly claimed that it had been sent by her mother,
even though she was well aware that all incoming mail was monitored and re-
corded by the staff.
Her emotions were described by her family and caretakers as labile and often
poorly matched to the situation. She was easily provoked to angry verbal out-
bursts, and just as easily to loud laughter. Often her mood changed without appar-
ent provocation. She would sometimes cry when she was angry, but most affective
states were fleeting. Her reactions during the frequent discussions of her misbe-
havior suggested she experienced little or no guilt or remorse.
By the time she was referred to us, she had variously been diagnosed with At-
tention Deficit Disorder, Oppositional Defiant Disorder—Unidifferentiated Type,
and “limited intellectual ability.” She had been placed on multiple medications for
treatment of attentional problems, aggression, and emotional difficulties, none of
which seem to have had an appreciable beneficial effect on her behavior.
At that time, her neurological evaluation was normal except for the behavioral
disturbance. Behavior during our evaluations was variable, ranging from sullen
and withdrawn to outgoing and expansive. Her demeanor would change quickly.
She denied or greatly minimized the significance of any behavior problems. She
was unable to articulate any plans for the future, other than a strong desire to es-
cape the restrictions and regulations of treatment facilities and her family.

CASE 2: HISTORY AND BEHAVIOR

Case 2 (patient “ML”) had a normal birth, but at age 3 months, he displayed vomit-
ing and a bulging fontanel, which led to a craniotomy for resection of a malignancy
in the right frontal region. Surgery was not followed by radiation or chemotherapy,
but there has been no indication of recurrence.
He went on to experience developmental milestones atarelativelynormalpace.He
showed a consistent left-hand preference (–100 on the modified Geschwind-Oldfield
286 ANDERSON, DAMASIO, TRANEL, DAMASIO

Questionnaire); his parents and siblings all were right-handed. He began Kindergar-
ten at age 5. Although his behavior was not considered grossly abnormal at that time,
his first teacher’s records foreshadowed problems to come, noting difficulty adjust-
ing to new situations, a need for frequent reminders to stay on task and to complete
assignments, and problems interacting with other students. By the fourth grade, it
was recommended that he receive special education assistance for his poor work
habits (poor focus of attention, impulsive responses, not bringing appropriate mate-
rials to class, not turning in assignments), but he did not qualify for this service be-
cause of normal performances on standardized tests of academic achievement.
Standardized testing in the eighth grade for similar reasons again revealed primarily
normal performances, except for a defective score on reasoning subtests (concept
formation, integration of two visual cues, complex rule detection). Throughout the
upper grades, he received generally below-average grades, but was passed each year
to the next grade until his senior year, which took him two years to pass. Records
from the school years indicated that he was disruptive in class and usually failed to
turn in assignments on time, despite high average to average IQ scores obtained at
various points during his school years.
Outside of the school setting, behavior in childhood was notable for impulsive-
ness and poor judgment. Personal hygiene was poor unless closely supervised. He
ate large quantities of food and inappropriate foods, and he was obese.
His behavior problems became more apparent following graduation from high
school, likely due to the loss of the daily structure provided by the school setting.
He remained dependent on his parents following graduation. A brief attempt at liv-
ing independently was a resounding failure. After quitting or being fired from mul-
tiple jobs, he was able to maintain part-time employment in a restaurant with major
support from his parents. If left to his own devices, ML typically would watch TV,
listen to music, or read all day long.
He was not able to manage his monetary resources; he would quickly spend all
available funds with no consideration of his financial obligations. He repeatedly
bought items on credit and then failed to make payments, and he engaged in petty
thievery. When briefly living independently, he accumulated large debts. Much of
his income went to support a child he fathered; he had little contact with the child
or his mother. He had few if any friends, but occasionally dated socially marginal
women. He had a strong interest in pornography. He lied frequently, usually to
cover some misbehavior, but often for no apparent motive. He would not admit to
wrongdoing, even when his guilt was evident. He would occasionally consume al-
cohol and marijuana, and smoked one to two packs of cigarettes per day.
ML’s eating behavior remained abnormal in adulthood, in that he would eat vir-
tually any food item he could find, for example, frozen fish sticks directly out of
the freezer, or condiments such as mayonnaise straight from the jar. Personal hy-
giene also remained poor. He often would wear soiled clothing and not dress ap-
propriately for the weather. His living space was generally filthy, despite
 EARLY PREFRONTAL CORTEX DAMAGE 287

contingencies for cleaning. He collected quantities of useless objects such as food

containers and empty matchbooks.
Failure to consider future consequences of his actions was a stable feature of
ML’s daily behavior. He appeared to engage in virtually no adaptive planning for
the future. He was unable to generate any feasible response to questions regarding
future employment or other personal goals.
His parents described him as showing little or no worry, guilt, empathy, re-
morse, or fear. Against a backdrop of emotional neutrality and unconcern, he dis-
played occasional sudden bursts of anger which would quickly dissipate. When
angry, he would swear violently and make threatening gestures, and he infre-
quently became physically violent. During our evaluation, ML was alert, coopera-
tive, and well oriented. The neurological evaluation was normal except for his
behavioral problems. Affect was unusually cheerful for the situation, and he was
socially outgoing. His manner was pleasant and relaxed, and effort was good on
formal testing. Speech was notable for being loquacious and rambling.

STANDARDIZED NEUROPSYCHOLOGICAL FINDINGS

The scores on standardized neuropsychological tests for both cases are presented in
the appendix. There was considerable similarity in the cognitive profiles of the two
patients. Both performed primarily in the average range on the Wechsler Adult In-
telligence Scale for Children–Revised (WAIS–R) subtests of intellectual function.
Academic achievement was consistent with normal expectations for high school
graduates. Anterograde memory was normal, as indexed by recall and recognition
tasks 30 min after acquisition of new information. The learning curve on the Rey
Auditory Verbal Learning Test was uneven for Case 2, likely due to mildly com-
promised attention. Performances on measures of language, visuoperceptual dis-
crimination, visuospatial ability, visuomotor coordination, and visuoconstruction
all were within normal limits.
Performances on tests of executive function were variable and in some in-
stances significantly impaired. There was no evidence of excessive susceptibility
to interference on the Stroop color–word task, and no difficulty alternating be-
tween two sets of stimuli on the Trail Making Test. Although both participants
were able to complete six categories on the Wisconsin Card Sorting Test (WCST),
patient FD made 33 perseverative errors (defective range), whereas ML commit-
ted only eight perseverative errors (normal). Both had severely impaired perfor-
mances on the Tower of Hanoi. On a Design Fluency test, they created few unique
figures and showed perseverative tendencies.
Performances on measures which placed demands on sustained attention and
working memory (i.e., the ability to briefly maintain information in accessible
storage while performing another task) were primarily normal, but with some vari-
288 ANDERSON, DAMASIO, TRANEL, DAMASIO

ability. Both participants were able to maintain adequate attention over several hours of
testing, but occasional attentional lapses were noted. Four tasks in particular can be ex-
amined for evidence of working memory defects: (a) WAIS–R digit repetition (back-
ward condition), which requires maintenance of a digit string while performing a
reversal task; (b) WAIS–R arithmetic, which requires maintenance of the key numerical
facts while performing mental arithmetic calculations; (c) the Benton Visual Retention
Test (BVRT), which requires maintenance of a representation of geometric stimuli
while performing a drawing task; and (d) Part B of the Trailmaking Test, which requires
maintenance of serial position in a letter string while performing a number search, and
visa versa. Performances of both participants were normal on these tasks, except for
mild impairments on digits backward (Case 1) and the BVRT (Case 2). Overall, the
neuropsychological profiles suggested slight difficulties with working memory and at-
tention, but these were not salient problems in their daily activities.
FD’s Minnesota Multiphasic Personality Inventory–2 (MMPI–2) profile in-
cluded six scales with T scores above 75 (scales F, 4, 6, 7, 8, & 9), suggesting consid-
erable psychological distress, with marked distrust of others and alienation, together
with a disregard of societal norms. The profile was generally consistent with her ex-
pressed anger and resentment regarding the confinement and rules under which she
was forced to live. She felt that her interpersonal difficulties were a result of unfair
rules and undue persecution by her parents, treatment facility personnel, and the
mental health and legal systems. She also endorsed severe depressive
symptomatology, including suicidal intent, on the Beck Depression Inventory. This
was consistent with her frequently dramatic but brief expressions of despair and sui-
cidal intent, which were at odds with her general behavior and appeared to reflect at-
tempts to manipulate her situation. ML’s responses on self-report personality
questionnaires, on the other hand, did not suggest any subjective psychological dis-
tress, consistent with his easygoing and content attitude. His MMPI–2 profile con-
tained only one elevated scale (scale 9 = 70), which likely reflected his difficulties
with anger control and his willingness to participate in virtually any activity sug-
gested to him, rather than his actual level of behavioral activity, which was quite low.

NEUROIMAGING FINDINGS

Figure 1 shows three-dimensional reconstructions of the brains of the two individu-

als from thin cut MRI using BRAINVOX, an interactive brain imaging software
package (Damasio & Frank, 1992). As can be seen, both individuals had focal dam-
age in prefrontal regions.

DISCUSSION

The behavioral descriptions and neuropsychological data presented here are in-
tended to serve as an index of relatively “pure” prefrontal damage acquired early in
 EARLY PREFRONTAL CORTEX DAMAGE 289

FIGURE 1 Three-dimensional reconstructions of the brains of the two cases from thin cut
MRI using BRAINVOX (Damasio & Frank, 1992). For FD (Case 1), there is a cystic formation
occupying the polar region of both frontal lobes. This cyst displaces and compresses prefrontal
regions, especially in the anterior orbital sector, more so on the left than on the right. Addi-
tionally, there is structural damage in the right mesial orbital sector and the left polar cortices.
For ML (Case 2), there is extensive damage to the right frontal lobe, encompassing prefrontal
cortices in mesial, polar, and lateral sectors. Both the lateral half of the orbital gyri and the ante-
rior sector of the cingulate gyrus are damaged. The cortex of the inferior frontal gyrus is intact,
but the underlying white matter is damaged, especially in the anterior sector.

life. These cases, which appear to be free of unusual genetic or environmental influ-
ences or damage to nonfrontal brain areas, can help provide an interpretive base for
neuropsychological evaluations in which early frontal lobe dysfunction is consid-
ered, such as closed head injury, fetal alcohol exposure, or developmental behavior
disorders. The sample size clearly is small, and conclusions must be regarded as
tentative, but the findings are consistent with the notion that early damage to
prefrontal regions can lead to severe disruption of adaptive behavior, while not sig-
nificantly affecting many aspects of cognition tapped by standard educational, psy-
chological, or neuropsychological tests.
The dissociation between severe dysfunction in daily activities and good per-
formances on standardized cognitive tests provides both an important diagnostic
indicator as well as a major challenge in the evaluation of persons with prefrontal
dysfunction (e.g., Anderson, Damasio, Jones, & Tranel, 1991; Damasio & Ander-
son, 1993; Eslinger & Damasio, 1985). As previously described, it is not unusual
for remedial or rehabilitative services to be denied to such individuals on the basis
of normal performances on standardized tests. Both individuals did have impair-
ments on measures of executive functions, although it was necessary to evaluate a
range of such abilities for this to be apparent. For example, ML performed within
normal limits on the Trail Making Test, the WCST, the Stroop test, and the Con-
290 ANDERSON, DAMASIO, TRANEL, DAMASIO

trolled Oral Word Association, which could be considered a reasonable battery of

executive function tests. The importance of supplementing standardized test data
with a detailed history from sources other than the patient is evident. There also
may be benefits in using specialized tests such as measures of moral reasoning and
decision making (Anderson, Bechara, Damasio, Tranel, & Damasio, 1999).
The behavior problems in these cases appeared in a relatively subtle form at an
early age, and escalated throughout development into adulthood, despite normal
home environments and attempts at intervention. There is evidence that prefrontal
lesions placed in nonhuman primates early in development do not affect perfor-
mance on tasks subserved by prefrontal cortex until that part of the brain matures
(e.g., Franzen & Myers, 1973; Goldman-Rakic, 1987; Málková, Bachevalier,
Webster, & Mishkin, this issue). The first reported behavioral abnormalities in our
two cases were an insensitivity to negative contingencies at 3 years of age (Case
1), and difficulty staying on task and interacting with peers at age 5 (Case 2). Al-
though based on unsystematic observations and the potential distortions of
long-term recall, the evidence in our cases also suggests a period of a few years in
which the frontal lobe damage had no appreciable impact on behavior (for further
discussion of delayed effects of early prefrontal damage, see Eslinger et al., 1997;
Goldman, 1974; Kolb & Gibb, 1990).
There was considerable similarity between the long-term effects of prefrontal
damage acquired by these patients in early childhood and similar damage acquired
in adulthood (e.g., Damasio, 1994; Damasio & Anderson, 1993; Grattan &
Eslinger, 1991), despite that in the present cases the impairments largely reflect a
failure to ever develop specific cognitive and behavioral competencies, whereas in
the adult-onset cases the defects arose through deterioration or loss of normally de-
veloped abilities. In both instances, the primary impairments occurred in the do-
mains of emotion, social behavior, and decision making, with most other cognitive
abilities being essentially normal. The behavior of the early-onset prefrontal dam-
age cases appeared more dysfunctional than that of the adult-onset prefrontal le-
sion patients we have studied, possibly due to their inability to ever acquire aspects
of socially relevant knowledge, which in the case of adult-onset lesions was ac-
quired normally and tends to be preserved (Anderson et al., 1999; Saver &
Damasio, 1991). Similar findings, including apparently greater severity of deficits
relative to patients with adult-onset lesions, have been reported in children who
sustained frontal lobe injuries in later childhood (Eslinger et al., 1992; Marlowe,
1992; Mateer & Williams, 1991; Price et al., 1990).
The magnitude and intractability of the defects incurred by injury at an early
age suggest that there may be limited neuronal plasticity in the sectors of the
prefrontal circuitry which contribute to emotional modulation and the linkage of
emotion and decision making. Yet, it would seem possible that with the right inter-
vention, the behavioral problems resulting from early prefrontal damage might be
remediable, at least to some degree. Given the extent of recovery of elementary
 EARLY PREFRONTAL CORTEX DAMAGE 291

sensory and motor abilities following early damage, as well as the early plasticity
evident in the language system, why would impairments of social behavior, emo-
tion, and decision making be resistant to recovery? One possible answer is sug-
gested by the different patterns of neuronal development observed in prefrontal
cortex compared to other brain regions. For example, the massive reorganization
of infant sensory cortex in response to environmental manipulation is well-known
(Weisel & Hubel, 1963). However, several aspects of prefrontal neuronal organi-
zation appear to be relatively well-specified very early in development, suggesting
they are determined by influences other than environmental stimulation (Schwartz
& Goldman-Rakic, 1990). Clearly, in the cases previously described, the behavior
problems persisted despite greater-than-normal instruction in social conduct and
decision making. Even so, the apparent intractability of these behavioral problems
in no way implies that intervention should not be attempted. Aspects of prefrontal
circuitry continue to mature into late adolescence or adulthood (e.g., Sowell,
Thompson, Holmes, Jernigan, & Toga, 1999), and likely are subject to modifica-
tion by experience. Mateer and Williams (1991) offered several practical sugges-
tions for managing the behavior problems resulting from early prefrontal damage.
The finding that early damage limited to the prefrontal region results in severe
and chronic social maladjustment is consistent with the notion that dysfunction in
this area may play an important role in certain developmental behavioral disorders.
There was strong resemblance between the behavior of our patients and that of in-
dividuals with psychopathy (“Conduct Disorder” or “Antisocial Personality Dis-
order,” according to Diagnostic and Statistical Manual of Mental Disorders, 4th
ed., nosology). There also is evidence of cognitive impairments in psychopathic
children and adults, which raises the question of prefrontal dysfunction (e.g.,
Fisher & Blair, 1998; Lapierre, Braiun, & Hodgins, 1995; Morgan & Lilienfeld,
2000; Newman et al., 1987; but see Pennington & Ozonoff, 1996, for discussion of
conflicting findings). Together with evidence of prefrontal abnormalities in
neuroimaging and EEG studies of psychopathy and childhood behavior disorders
(e.g., Deckel, Hesselbrock, & Bauer, 1996; Raine et al., 2000; Raine et al., 1998),
these findings provide growing reason to believe that the early onset of dysfunc-
tion in prefrontal regions may underlie at least some cases of psychopathy.

ACKNOWLEDGMENT

This study was supported by National Institute of Neurological Diseases and

Stroke Grant PO1 NS19632 and the Mathers Foundation.

REFERENCES

Ackerly, S. S., & Benton, A. L. (1947). Report of case of bilateral frontal lobe defect. Association for Re-
search in Nervous and Mental Disease, 27, 479–504.
292 ANDERSON, DAMASIO, TRANEL, DAMASIO

Anderson, S. W., Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (1999). Impairment of social
and moral behavior related to early damage in the human prefrontal cortex. Nature Neuroscience, 2,
1032–1037.
Anderson, S. W., Damasio, H., Jones, R. D., & Tranel, D. (1991). Wisconsin Card Sorting Test perfor-
mance as a measure of frontal lobe damage. Journal of Clinical and Experimental Neuropsychology,
13, 909–922.
Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (1997). Deciding advantageously before know-
ing the advantageous strategy. Science, 275, 1293–1295.
Benton, A. L. (1991). Prefrontal injury and behavior in children. Developmental Neuropsychology, 7,
275–281.
Connor, P. D., Sampson, P. D., Bookstein, F. L., Barr, H. M., & Streissguth, A. P. (2000/this issue). Di-
rect and indirect effects of prenatal alcohol damage on executive function. Developmental
Neuropsychology, 18, 331–354.
Damasio, A. R. (1994). Descartes’ Error. New York: Grosset & Dunlap.
Damasio, A. R., & Anderson, S. W. (1993). The frontal lobes. In K. M. Heilman & E. Valenstein (Eds.),
Clinical neuropsychology, third edition (pp. 409–460). New York: Oxford University Press.
Damasio, H., & Frank, R. (1992). Three-dimensional in vivo mapping of brain lesions in humans. Ar-
chives of Neurology, 49, 137–143.
Damasio, A. R., Tranel, D., & Damasio, H. (1990). Individuals with sociopathic behavior caused by
frontal lobe damage fail to respond autonomically to social stimuli. Behavioral Brain Research, 41,
81–94.
Deckel, A. W., Hesselbrock, V., & Bauer, L. (1996). Antisocial personality disorder, childhood delin-
quency, and frontal brain functioning: EEG and neuropsychological findings. Journal of Clinical
Psychology, 52, 639–650.
Eslinger, P. J., Biddle, K. R., & Grattan, L. M. (1997). Cognitive and social development in children
with prefrontal cortex lesions. In N. A. Krasnegor, G. R. Lyon, & P. S. Goldman-Rakic (Eds.), De-
velopment of the prefrontal cortex (pp. 295–335). Baltimore: Brookes.
Eslinger, P. J., & Damasio, A. R. (1985). Severe disturbances of higher cognition after bilateral frontal
lobe ablation: Patient EVR. Neurology, 34, 1731–1741.
Eslinger, P. J., Grattan, L. M., Damasio, H., & Damasio, A. R. (1992). Developmental consequences of
childhood frontal lobe damage. Archives of Neurology, 49, 764–769.
Finger, S. (1991). Brain damage, development and behavior: Early findings. Developmental
Neuropsychology, 7, 261–274.
Fisher, L., & Blair, R. J. R. (1998). Cognitive impairment and its relationship to psychopathic tendencies
in children with emotional and behavioral difficulties. Journal of Abnormal Child Psychology, 26,
511–519.
Franzen, E. A., & Myers, R. E. (1973). Age effects on social behavior deficits following prefrontal le-
sions in monkeys. Brain Research, 54, 277–286.
Goldman, P. S. (1974). An alternative to developmental plasticity: Heterology of CNS structures in in-
fants and adults. In D. G. Stein, J. J. Rosen, and N. Butters (Eds.), Plasticity and recovery of function
in the central nervous system (pp. 149–174). New York: Academic.
Goldman-Rakic, P. S. (1987). Development of cortical circuitry and cognitive function. Child Develop-
ment, 58, 601–622.
Grattan, L. M., & Eslinger, P. J. (1991). Frontal lobe damage in children and adults: A comparative re-
view. Developmental Neuropsychology, 7, 283–326.
Kolb, B., & Gibb, R. (1990). Anatomical correlates of behavioural change after neonatal prefrontal le-
sions in rats. Progress in Brain Research, 85, 241–256.
Lapierre, D., Braiun, C. M., & Hodgins, S. (1995). Ventral frontal deficits in psychopathy:
Neuropsychological test findings. Neuropsychologia, 33, 139–151.
 EARLY PREFRONTAL CORTEX DAMAGE 293

Málková, L., Bachevalier, J., Webster, M., & Mishkin, M. (2000/this issue). Effects of neonatal inferior
prefrontal and medial temporal lesions on learning the for delayed nonmatching-to sample. Devel-
opmental Neuropsychology, 18, 399–421.
Marlowe, W. B. (1992). The impact of a right prefrontal lesion on the developing brain. Brain and Cog-
nition, 20, 205–213.
Mateer, C.A., & Williams, D. (1991). Effects of frontal lobe injury in childhood. Developmental
Neuropsychology, 7, 359–376.
Morgan, A. B., & Lilienfeld, S. O. (2000). A meta-analytic review of the relation between antisocial be-
havior and neuropsychological measures of executive function. Clinical Psychology Review, 20,
113–136.
Newman, J. P., Patterson, C. M., & Kosson, D. S. (1987). Response perseveration in psychopaths. Jour-
nal of Abnormal Psychology, 96, 145–148.
Pennington, B.F., & Ozonoff, S. (1996). Executive functions and developmental psychopathology.
Journal of Child Psychology and Psychiatry, 37, 51–87.
Price, B. H., Daffner, K. R., Stowe, R. M., & Mesulam, M. M. (1990). The comportmental learning dis-
abilities of early frontal lobe damage. Brain, 113, 1383–1393.
Raine, A., Lencz, T., Bihrle, S., LaCasse, L., & Colletti, P. (2000). Reduced prefrontal gray volume and
reduced autonomic activity in antisocial personality disorder. Archives of General Psychiatry, 57,
119–127.
Raine, A., Staoddard, J., Bihrle, S., & Buchsbaum, M. (1998). Prefrontal glucose deficits in murderers
lacking psychosocial deprivation. Neuropsychiatry, Neuropsychology, and Behavioral Neurology,
11, 1–7.
Saver, J., & Damasio, A. R. (1991). Preserved access and processing of social knowledge in a patient
with acquired sociopathy due to ventromedial frontal damage. Neuropsychologia, 29, 1241–1249.
Scarpa, A., & Raine, A. (1997). Psychophysiology of anger and violent behavior. Psychiatric Clinics of
North America, 20, 375–394.
Schwartz, M. L., & Goldman-Rakic, P. (1990). Development and plasticity of the primate cerebral cor-
tex. Clinics in Perinatology, 17, 83–102.
Sowell, E. R., Thompson, P. M., Holmes, C. J., Jernigan, T. L., & Toga, A. W. (1999). In vivo evidence
for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience, 2,
859–861.
Taylor, H. B., & Alden, J. (1997). Age-related differences in outcomes following childhood brain in-
sults. Journal of the International Neuropsychological Society, 3, 555–567.
Teuber, H-L., & Rudel, R. G. (1962). Behaviour after cerebral lesions in children and adults. Develop-
mental Medicine and Child Neurology, 4, 3–20.
Wiesel, T. N., & Hubel, D. H. (1963). Single cell response in striate cortex of kittens deprived of vision
in one eye. Journal of Neurophysiology, 26, 1003–1017.
 APPENDIX
Standardized Neuropsychological Test Scores

Age Corrected Scale Scores

Intellectual Abilities Case 1 Case 2

Wechsler Adult Intelligence Scale–Revised

Subtest
Information 9 11
Digit Span 8 9
Vocabulary 7 11
Arithmetic 9 11
Comprehension 5 8
Similarities 9 8
Picture Completion 11 8
Picture Arrangement 10 14
Block Design 12 12
Object Assembly 8 12
Digit Symbol 8 8
Verbal IQ 85 94
Performance IQ 98 104
Full Scale IQ 90 98

Academic Achievement Scaled Score (Percentile)

Wide Range Achievement Test–3

Reading 116 (86) 105 (63)
Spelling 113 (81) 105 (63)
Arithmetic 93 (32) 103 (58)

Memory and Attention Number Recalled

Rey Auditory Verbal Learning Test

Learning Trials
1 6 6
2 11 6
3 11 10
4 11 8
5 14 11
30 min delayed recall 15 12
30 min delayed recognition 30 30

Raw Scores

Benton Visual Retention Test

Number correct 8 6
Number of errors 3 5
Complex Figure Test 30-Min Delayed Recall
Raw Score 19 24

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 APPENDIX (Continued)

Language Raw Scores

Controlled Oral Word Association

Percentile 43 15
Category fluency
Raw score 54 51
Expected score; M = 58, SD = 9.6
Benton Laboratory Writing Assessment
Copy, dictation, and spontaneous Normal Normal
Boston Naming Test
Raw score 52 57

Visual Perception and Visuomotor Functions Percentiles

Facial Recognition Test 15 49

Judgment of Line Orientation 40 57
Complex Figure Test Copy
Raw score 29 31
Time 3 min, 47 sec 3 min, 50 sec

Standard Score

Grooved Pegboard
Right hand 10 7
Left hand 10 6

Executive Functions Standard Score

Trailmaking Test
Part A 8 9
Part B 10 10
Wisconsin Card Sorting Test
Categories 6 6
Perseverative errors 33 8

Number of Moves

Tower of Hanoi
Trial
1 120 120
2 120 60
3 120 120
4 120 120
Minimum possible moves, 31; maximum number allowed, 120

Raw Score

Design fluency (expected score)

Unique designs (12) 3 8
Perseverations (0) 2 1
Namable objects (0) 1 0

(continued)

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296 ANDERSON, DAMASIO, TRANEL, DAMASIO

APPENDIX (Continued)

t scores

Stroop Color Word Test

Word 35 36
Color 38 37
Interference 52 43

Mood t scores

Beck Depression Inventory (raw score) 36 5

Beck Anxiety Inventory (raw score) 37 8