The ability of rhesus monkeys to master the rule for delayed nonmatching to sample (DNMS), a measure of object recognition, has a protracted development, reaching adult levels of proficiency around 4-5 years of age. To test the possibility that this slow development could be due, at least in part, to immaturity of the prefrontal component of a temporo-prefrontal circuit important for DNMS rule learning, monkeys with neonatal lesions of the inferior prefrontal convexity were compared on DNMS with both normal controls and animals given neonatal lesions of the medial temporal lobe (MTL). Consistent with our previous results, the neonatal MTL lesions led to marked impairment in rule learning (as well as in recognition memory with long delays and list lengths) at both 3 months and 2 years of age. By contrast, the neonatal inferior convexity lesions yielded no impairment in rule-learning at 3 months and only mild impairment at 2 years, a finding that contrasts sharply with the marked effects of the same lesions made in adulthood. This pattern of sparing closely resembles the one found earlier after neonatal lesions to the cortical visual area TE. The functional sparing at 3 months probably reflects the fact that the temporo-prefrontal circuit is nonfunctional at this early age, resulting in a total dependency on medial temporal contributions to rule learning. With further development, however, this circuit begins to provide a supplementary route for learning. Neonatal MTL lesions in monkeys not only impair learning and memory but also produce severe losses in social interactions as well as increases in locomotor stereotypies. These behavioral abnormalities emerged at about 6 months of age and persisted into adulthood. Recent evidence in children has indicated that early insult to the ventral prefrontal cortex show significant changes in the modulation of social behaviors (see next paragraph), suggesting that this prefrontal cortical region, like the MTL, may be crucial for the regulation of social skills early in life. In the present study, we investigated the effects of neonatal lesions of the inferior prefrontal convexity (IC), a part of the ventral prefrontal cortex, on the development of social skills in infant monkeys and compared these effects to those found in infant monkeys with neonatal MTL lesions. At 2 and 6 months, each operated animal was paired in a play cage with an age-matched control with which it was reared (MTL+C or IC+C), and the pairs' behavior was videorecorded for short intervals across five consecutive days. Similarly, each normal control was paired with another normal animal with which it was reared (N+N). Unlike monkeys in the MTL+C dyads, which displayed reduced social contact at both ages compared to N+N dyads, those in the IC+C dyads showed a normal amount of social contact. In addition, only animals with early MTL lesions showed significant increases in locomotor stereotypies. The findings suggest either that the part of the ventral prefrontal cortex that regulates social skills does not include the inferior prefrontal convexity, or that the latter region is included but that the socioemotional effects of damaging this region do not emerge until later in life. Ventral frontal damage in adults produces impairment in social behavior while leaving intelligence and many other aspects of cognition intact. Two previous studies (Price et al., Brain 1990; Anderson et al., Nature Neurosci., 1999) suggest that comparable damage in early childhood, when the frontal lobes are immature, still lead to the same outcome as that seen after damage in adulthood. We have confirmed those findings in two new childhood cases. Case I, in a traffic accident at age 6, sustained focal atrophy and encephalomalacia in the right frontal lobe rostrally and left frontal pole. Case II, with a closed head injury at age 4, sustained damage extending laterally from the anterior horn of the left lateral ventricle to the cortex just anterior to the left coronal suture; no damage was visible on the right. The most striking symptom in each case is delinquent behavior, this having become pronounced during secondary school and leading eventually to appearances before the courts. When investigated at ages 15 and 11-17 years, respectively, both were found to have IQs below normal (Case I, 84; Case II, 65), with memory, language, and academic attainments being consistent with, or higher than, their IQs. Both suffer from somatic complaints, anxiety and/or depression, severe attentional problems, and pronounced impairments on tests of self-monitoring, feedback utilization, and problem solving. The results corroborate the conclusion that, despite prefrontal functional immaturity and neural plasticity early in life, early damage to ventral frontal cortex, even rostrally or unilaterally, leads with further development to chronic sociopathic behavior and associated deficits.
