Birth order and left-handedness revisited: some recent findings in chimpanzees (Pan troglodytes) and their implications for developmental and evolutionary models of human handedness

Neuropsychologia 38 (2000) 1626 – 1633 www.elsevier.com/locate/neuropsychologia

Birth order and left-handedness revisited: some recent findings in chimpanzees (Pan troglodytes) and their implications for developmental and evolutionary models of human handedness William D. Hopkins a, b,*, Jeremy F. Dahl b, Dawn Pilcher b b

a Department of Psychology, Berry College, PO Box 455019, Mount Berry, GA 30149 -5019, USA Di6ision of Psychobiology, Yerkes Regional Primate Research Center, Emory Uni6ersity, Atlanta, Georgia 30322, USA

Received 15 December 1999; received in revised form 24 March 2000; accepted 3 April 2000

Abstract This paper examines the relationship between parity, pregnancy outcome, and handedness in a sample of captive chimpanzees (Pan troglodytes). The relation between parity, maternal age and positive or negative pregnancy outcome was assessed from life history data for 536 chimpanzees housed at the Yerkes Regional Primate Research Center. The incidences of negative pregnancy outcome (notably spontaneous abortions and stillbirths) were significantly higher in parities of 8 or higher compared to all other parities. In a sub-sample of 165 chimpanzees, the relation between parity, maternal age and handedness was assessed to determine whether left handedness may serve as a marker of prenatal pathology. These analyses indicated that left-handedness was more prevalent in 1st and 8 or higher parities compared to parities between 2 and 7, respectively. Possible prenatal hormonal and periparturitional factors are discussed as possible mechanisms for the observed findings. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: Champanzee; Birth order; Handedness; Hormones; Evolution

1. Introduction It is well known in humans that maternal age and parity are risk factors associated with higher incidences of birth defects, genetic disorders and reproductive pathology. For example, several cross-cultural epidemiological studies have reported that the incidences of infant mortality and stillbirths are higher in older females as well as in multiparous compared to primiparous females [18,22,23,35,36,46,48,53]. The evidence of increased risks for neonatal pathology in young primiparous and older, high parity, females is not restricted to humans but is similarly reported for non-human primates [24,38] and other mammals such as cows and pigs [10,42]. Parity and maternal age have also been reported to be associated with hand preference suggesting the possi* Corresponding author. Tel.: +1-706-290-2152; fax: + 1-706-2387827. E-mail address: [email protected] (W.D. Hopkins).

bility that common biological mechanisms influence both perinatal pathologies and handedness. Some but not all previous studies in humans have reported that there are higher incidences of left-handedness in firstand latter-born subjects (defined as parities \ 4) compared to middle-born subjects [1–6,9,20,30,42,50,52,54], a finding that mirrors the incidences of reproductive pathology in relation to parity. The correspondence between the high frequency of both perinatal pathology and left-handedness suggest that left-handedness at particular parities may be a marker of prenatal pathology [49]. In humans, however, parity is confounded with many sociological and economic factors that may or may not directly influence the incidences of both left-handedness and reproductive pathology. For instance, less well off individuals typically have poorer diets, higher rates of pregnancy, poorer prenatal care, and increased incidences of substance abuse, all of which may contribute to reproductive pathology [5,52]. Thus, the potential role that parity or maternal age play in the expression of repro-

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W.D. Hopkins et al. / Neuropsychologia 38 (2000) 1626–1633

ductive pathology is not always clear when working with human populations. Recently, Hopkins and Dahl [33] have reported that parity is associated with hand preference in a sample of 165 captive chimpanzees. Specifically, we reported that first and latter-born subjects, exhibit higher incidences of left-handedness compared to middle-born chimpanzees. The significance of these findings are that they cannot be explained on the basis of sociological or economic factors which suggests a biological explanation for the observed effects. In this paper, we report a series of findings on the association between handedness, birth order (or parity) and reproductive biology in a sample of captive chimpanzees. There were three specific aims of the study. First, we sought to determine whether the incidences of non-right-handedness mirror the incidences of puerperal pathology in chimpanzees, as may be the case in humans. Second, we sought to examine which of the two variables, parity or maternal age, best explained variation in handedness and puerperal pathology. If similar mechanisms influence the expression of non-right-handedness and reproductive pathology then it can be hypothesized that the same variables will account for variation in the outcome measures. Finally, we sought to explore some possible mechanisms that may explain the association between birth order, hand preference and puerperal pathology in chimpanzees (and possibly humans). Bakan [3] proposed that the pattern of non-righthandedness observed in first- and latter-born humans are due to perinatal birth trauma experienced by the fetus. To date, results from human subjects do not fully support this interpretation (see [52] for review). As an alternative hypothesis, it is well known that there are changes in reproductive physiology in older human females, particularly as it pertains to variations in sex steroid concentrations, notably estrogen. One possible mechanism that might explain the pervasiveness of non-right-handedness, particularly in latter-born subjects, may be the concentration or effectiveness of circulating sex steroids of pregnancy that have been hypothesized to influence the development of cerebral lateralization in humans and animals [21,25,58]. Chimpanzees and other apes exhibit swelling or tumescence of their perineal tissue that can be reliably and objectively quantified by observers [16,60]. Higher perineal swelling (PS) scores are associated with increasing concentrations of circulating estrogen during the follicular phase of the ovarian cycle, and detumescence with increasing levels of progesterone during the luteal phase [28,29,43 – 45]. The variation in the swelling of the perineal tissue is therefore known to be a marker of underlying changes in levels of gonadotropins during ovarian cycles. In addition, several species exhibit swelling during pregnancy including the orangutan, gibbon, common chimpanzee and pygmy chimpanzee [11–

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14,40,51,55]. A recent study of 107 chimpanzee pregnancies showed that, just as the pattern and degree of swelling during ovarian cycles in common chimpanzees clearly and closely act as external indicators of gonadotropin concentrations, fluctuations in swelling during pregnancy is similarly indicative of maternal steroid fluctuations (albeit the principal source of the hormones is the feto-placental unit rather than the ovary for much of the pregnancy) [13,15]. Of particular interest in the current context is that previous studies indicate that low PS scores during pregnancy lead to an increased likelihood of maternal rejection of the offspring, neonatal fatality and stillbirths [13]. Depicted in Fig. 1 are the mean PS scores during pregnancies leading to different outcomes measured by Dahl [13]. Dahl [13] reported that low PS scores during pregnancy are associated with high incidences of stillbirths and maternal incompetence. Thus, low PS scores are associated with negative pregnancy outcome. In humans, decreased concentrations in estrogens are seen in human pregnancies leading to stillbirth and neonatal fatality [19]. More recently, Hopkins and Dahl [34] have examined the relationship between PS scores during pregnancy and hand preference. Hopkins and Dahl [34] found that pregnancies leading to offspring, which exhibit left-hand preferences as juveniles or adults, have significantly lower PS scores compared to pregnancies leading to right-handed offspring. It is

Fig. 1. Mean PS scores during pregnancies leading to different outcomes including stillbirth, neonatal fatality, maternal incompetence, and normal.

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important to emphasize that these effects were observed in pregnancies leading to both mother- and nurseryreared chimpanzees so that the influence of PS scores on hand preference is not confounded by rearing outcome. Given these findings, it follows that increasing parity or maternal age would be associated with decreasing cumulative PS scores because of its association with left-handedness. In this study, we tested this hypothesis by examining PS scores in relation to parity and maternal age in a sample of chimpanzees. It was hypothesized that high parity, older females would show lower PS scores compared to low parity, younger female chimpanzees.

2. Method

2.1. Subjects In the initial analysis, we sought to examine the association between parity, maternal age and puerperal pathology. To accomplish this aim, we went through the animal records of the Yerkes Regional Primate Research Center (YRPRC) of Emory University, Atlanta, Georgia and Orange Park, Florida which have been kept since the early 1930s. Based on the animal records for the past 59 years, 536 pregnancies were documented each with known outcomes, known parities and maternal ages (see below). For the offspring of 165 of these pregnancies, hand preferences were known, including 95 females and 70 males. Over the course of the past 25 years, PS scores have been obtained daily through out the entire duration of the pregnancy in a sample of 164 pregnant female chimpanzees. Of these 164 pregnancies, hand preferences were known for 92 offspring.

2.2. Procedure 2.2.1. Birth outcome Pregnancy outcomes were categorized into (a) positive outcomes that were defined as the vaginal delivery of a living fetus and (b) negative outcomes which consisted of either spontaneous abortions, stillbirths, premature births, caesarian-section delivery or general dystocia. Stillbirths were confirmed at necropsy by noting whether the lungs were filled with fluid, with the presence of fluids indicating that the fetus never took a breath. Spontaneous abortions were based on confirmed pregnancies that were aborted at any point in the pregnancy. No effort was made to identify the point during the pregnancy that abortions occurred. Premature birth’s, caesarian-sections and general dystocia were noted from the veterinary reports made at the time of delivery. Within the positive outcome category, a further distinction was made based on the finding that

the external indicator of hormones varies with maternal competence [13]. The outcomes were classified as (a) exhibited appropriate maternal behavior and raised by their mother (mother-reared) and (b) exhibited maternal incompetence that required the removal of the offspring to be raised by humans (nursery-reared). For certain offspring, no assignment could be made.

2.2.2. Handedness Hand preferences were assessed using a coordinated bimanual task referred to as the TUBE task which has been described in detail elsewhere [31,32]. Briefly, peanut butter is placed on the inside edges of PVC pipe that are given to the chimpanzees in their home cages. The hand used to extract the peanut butter is recorded as left or right during a series of responses. A minimum of 20 responses were collected from each subject. In a previous study, Hopkins and Dahl [33] reported that the mean handedness index (calculated as the number of right hand responses minus the number of left-hand responses divided by the total) in first- and latter-born subjects are significantly lower than in middle-born. Indeed, population-level right handedness was found only in the middle-born subjects. In this study, the chimpanzees were classified as right- or non-righthanded using the cut-point of 0 from the HI scores. Chimpanzees with negative HI values were classified as non-right-handed while subjects with positive HI values were classified as right-handed. 2.2.3. Perineal swelling (PS) scores The subjects were observed daily and the degree of edema of the perineal region was scored on a five-point scale ranging from 0 to 4. This follows on from earlier work [62], more recent studies [28], and the development of a highly comparative method with greater precision and accuracy [11,16,26,27]. This last approach allows for the documentation of quite subtle variation and testing for inter-observer reliability through the use of an expanded 13 point scale (0–12) [16]. Using this 13-point scale, tests between observers revealed that in about 75% of observations there was complete concordance and concordance of 95% at plus or minus one. This demonstrates that the coarser scoring scale of 0–4 is extremely robust and variation due to differences in scoring between trained observers is negligible. 2.3. Maternal age and parity For all analyses, age of the mother at the termination of each pregnancy (i.e., maternal age) was assessed in years and months of age. The parity variable was converted from rank to categorical data. Four cutpoints were used to define the parity variable and were psychometrically derived based on the overall parity data from the colony. Specifically, the mean parity for

W.D. Hopkins et al. / Neuropsychologia 38 (2000) 1626–1633

all pregnancies was 4.48 with a standard deviation of 3.41. From these data, we defined one group as 1st born chimpanzees, all of whom having parities equal to 1. Another group was comprised (2nd – 4th) of the chimpanzees with parities of 2, 3 or 4 and represented individuals that were within one standard deviation below the mean parity. Another group was defined (5th to 7th) as chimpanzees with parities of 5, 6, or 7 and represented individuals within one standard deviation above the mean parity. Finally, the last group was defined (8th+) as chimpanzees with parities that were more than one standard deviation from the mean.

3. Results

3.1. Descripti6e results for hand use Using the categorical data, 65% of the sample was classified as right-handed and 35% were classified as non-right-handed, a distribution that differed significantly from chance x 2 (1, N =165) = 14.55, p B0.01. Two 2× 2 chi-square test of independence failed to reveal a significant interaction between sex and hand use x 2 (1, N = 165)= 1.42, ns and rearing history and hand use x 2 (1, N = 165) = 0.69, ns. Finally, a one-sample t-test was used to assess whether the distribution in HI values differed from a normal distribution. The mean HI value was 0.170 and this value differed significantly from zero t(164) = 4.08, p B0.001. These results are consistent with the chi-square goodness-of-fit results with both findings indicating population-level right handedness for this measure of hand use.

3.2. Parity and pregnancy outcome The frequency of stillbirths, spontaneous abortions, premature births, caesarian-sections and dystocia were 54, 31, 19, 5, and 1, respectively. There were 426 positive outcomes that constituted live, vaginal deliveries. A 2× 4 chi-square analysis indicated a significant interaction between parity and pregnancy outcome x 2 (3, N =537)=12.79, p B0.009. Subsequent 2× 2 chisquare tests of independence indicated that proportion of negative outcomes were significantly higher in 8th+ parity offspring compared to 2nd – 4th x 2 (1, N= 310)= 12.20, pB0.001, and 5th – 7th born subjects x 2 (1, N= 212)=5.73, p B0.02. In short, pregnancies of parities 8 or higher have a two-fold increase in termination or fatality compared to the middle-born parity sub-groups. The proportion of positive and negative pregnancy outcomes at each birth order group are shown in Table 1. The next analyses examined the association between parity and different positive maternal outcomes including mother- and nursery-rearing (see Table 1). For

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Table 1 Pregnancy outcome and parity in chimpanzees Parity 1st Pregnancy outcome Negative Positive Rearing history Nursery Mother

2nd “ 4th

5th “7th

8th+

22 78

16 82

17 83

34 64

59 41

38 62

51 49

78 22

these analyses, the chimpanzees that were taken from their biological mothers for the purposes of experimental protocols were excluded because the outcome was not objectively evaluated with respect to maternal behavior. A 2× 4 chi-square test of independence revealed a significant interaction between parity and positive outcome type x 2 (3, N= 273)= 20.17, pB 0.001. Subsequent analyses indicated that the proportion of nursery-reared subjects was significantly higher in the 8th+ born subjects compared to the 2nd“4th x 2 (1, N= 151)= 18.22, pB0.001, 5th“ 7th x 2 (1, N= 101)= 8.77, pB 0.01 and 1st born subjects x 2 (1, N= 92)= 4.03, pB 0.05. In addition, the proportion of nursery-reared subjects was higher in the 1st compared to the 2nd“4th born chimpanzees x 2 (1, N=172)= 6.49, pB0.02.

3.3. Parity, handedness and PS scores A 4 × 2 chi-square test of independence indicated a significant interaction between parity and hand preference x 2 (3, N= 165)= 12.87, pB 0.03. Subsequent 2× 2 chi-square tests indicated that the proportion of left-handed subjects was higher in 1st born x 2 (1, N= 102)=8.30, pB0.004 and 8th+born x 2 (1, N= 107)= 8.54, pB 0.004 compared to 2nd“ 4th born subjects. For the purposes of comparison, the incidences of negative pregnancy outcomes and left-handedness as a function of the same parity classifications are depicted in Fig. 2. As can be seen, the increased incidence of left-handedness mirrors the incidences of negative pregnancy outcomes, a finding that suggests that left-handedness may be a marker of reduced fitness of the developing fetus. It should be emphasized that these results cannot be explained on the basis of socioeconomic variables and suggests that biological factors related to increasing parity or maternal age likely explain these results. For the PS scores, two analyses were performed. For both analyses, parity and sex were the independent variables with the total PS scores for the entire pregnancy serving as the dependent variable. In one analysis, there were no covariates while in the second,

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maternal age was a covariate. Analysis of variance of the PS scores revealed significant effects for parity with F(3,138)= 5.99, pB0.003 or without F(3,140) =8.50, p B 0.009 maternal age being statistically controlled for in the analysis. The mean PS scores for 1st, 2nd“ 4th, 5th “7th and 8th+ born subjects were 149.20, 151.12, 68.87, and 46.10, respectively. Tukey’s Honestly Significant Difference (HSD) post-hoc analysis indicated that 1st and 2nd“4th born subjects had significantly higher PS scores than 5th “7th and 8th +born subjects. No other post-hoc analyses were significant.

3.4. Predictors of left-handedness, negati6e pregnancy outcome and PS scores Maternal age positively correlated with parity in this sample of chimpanzees (r =0.83, df=390, p B 0.001), therefore the issue of which factor is the better predictor of pregnancy outcome, PS scores and hand preference is not clear. Assuming that a similar mechanism explains these various findings then it can be hypothesized that the same variable or variables would predict handedness, PS scores and pregnancy outcome. To address this issue, trend analyses were performed for the parity and maternal age variables. Specifically, we attempted to fit either a linear or quadratic line for the parity and maternal age variables to the distributions of hand use, PS scores and pregnancy outcome data. The influence of parity and maternal age on the dependent measures were analyzed separately because trend analyses, like multiple regression, requires that the predictor variables be uncorrelated which was not the case for these two predictor variables. Shown in Table 2 are the beta values and associated t-values for each predictor variable in relation to the outcome measures of handedness, pregnancy outcome and PS scores.

Table 2 Results from trend analyses Measures Handedness Parity Linear Quadratic Maternal age Linear Quadratic PS scores Parity Linear Quadratic Maternal age Linear Quadratic Pregnancy outcome Parity Linear Quadratic Maternal age Linear Quadratic

beta

t

p-level

0.614 −0.751

2.29 −2.81

0.03 0.006

0.466 −0.467

1.17 −1.18

0.22 0.22

−0.693 0.340

−2.46 1.21

0.02 0.23

−0.978 0.704

2.59 1.87

0.01 0.06

0.181 −0.308

1.19 −2.03

0.23 0.04

0.408 −0.567

1.77 −2.40

0.07 0.01

With respect to the handedness variables, a significant proportion of the variance was accounted for by parity R 2 = 0.067, F(2,159)=2.72, pB 0.04 but not maternal age R 2 = 0.001, F(4,259)=0.70, ns. A quadratic trend explained the highest proportion of variance in the handedness data. For the PS scores, a significant proportion of variance was accounted for by the parity R 2 = 0.141, F(2,154)= 12.64, pB 0.005 and maternal age R 2 = 0.103, F(2,154)=8.86, pB0.005 variables. The linear equations for the parity and maternal age variables were the only significant predictors. Finally, for pregnancy outcome, a significant proportion of variance was accounted for by parity R 2 = 0.020, F(2, 523)= 5.54, pB 0.001 and maternal age R 2 = 0.033, F(2,523)= 8.90, pB 0.005. For both variables, a quadratic trend accounted for a significant proportion of the variance.

3.5. The association between PS scores, parity, and hand preference

Fig. 2. The proportion of negative pregnancy outcomes and lefthandedness as a function of birth order (parity) in a sample of chimpanzees.

Finally, we were interested in directly comparing the relationship between hand preference and PS scores in relation to parity in our sample. Because PS scores and handedness were assessed on different scales of measurement, the individual scores for each measure were normalized by use of a standardized z-score transformation. We subsequently performed a series of onesample t-test to assess whether the degree of handedness and PS scores within a parity cohort deviated significantly from the normative data for the population of subjects. Depicted in Fig. 3 are the mean

W.D. Hopkins et al. / Neuropsychologia 38 (2000) 1626–1633

standardized z-scores for the HI and PS scores as a function of birth order group. With respect to hand preferences, the mean z-score for the first born group were significantly lower than the population mean t(26) = 2.03, pB 0.05 while they were significantly higher for the 2nd– 4th born subjects t(79) = 2.31, pB 0.01. The mean z-scores for the 5th – 7th and 8th + group did not significantly differ from the population mean. For the PS scores, the mean z-scores did not significantly differ from the population mean for the 1st- and 2nd–4th born groups. However, the mean PS z-scores were significantly lower than the population mean for the 5th– 8th t(29) = −3.39, p B 0.01 and 8th +born t(27)= 6.90, p B 0.001 groups.

4. Discussion The cumulative evidence presented here indicates that biological factors associated with increasing parity account for individual variation in hand preference, maternal behavior as well as perineal swelling scores in chimpanzees. Handedness and PS scores are distributed differently in relation to parity with PS scores following a negative linear association. In contrast, hand preference, pregnancy outcome, maternal behavior and parity are associated in a quadratic manner. One interpretation of these results is that left-handedness in high parity, older female offspring may represent a marker of prenatal pathology that is differentiated from left-handedness observed in firstborn offspring. This interpretation is most supported by the findings depicted in Fig. 3. After standardizing the scores within each sample, first-borns have unusually high PS scores and low HI values (which reflect left-handedness). In contrast, later-born subjects have

Fig. 3. The mean z-scores for handedness and PS scores in relation to birth order.

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both low PS and HI scores. Alternatively, it could be argued that PS scores have no relation to handedness and that the observed patterns are simply independent events. However, we have previously reported that low PS scores are associated with left-handedness and therefore this argument is not supported [34]. There are at least two other plausible explanations for the observed pattern of findings between handedness, PS scores and parity. First, it is possible that different mechanisms underlie the expression of left-handedness in relation to parity. Accordingly, the manifestation of left-handedness in first-born offspring may reflect mild brain damage associated with birth trauma or stress rather than prenatal hormonal factors, as suggested by Bakan [3]. In contrast, left-handedness observed in high parity offspring may be a result of low estrogen exposure during the prenatal stages of development that influences the maturational gradients of the left and right cerebral hemispheres. Second, the perineal marker may reflect sensitivity to estrogen rather than the absolute amounts of estrogen circulating in the prenatal environment. In chimpanzees, nulliparous females during their normal follicular phases exhibit an increased sensitivity to swelling with high PS scores at low estrogen levels compared to multiparous females [16]. Moreover, Dahl [13] reports an extended and exaggerated swelling pattern in many low parity pregnancies that may be indicative of the same high level of sensitivity to low estrogen levels. Thus, lower levels of estrogen may account for both the higher incidences of left-handedness in firstand latter-born chimpanzees but the marker differentiates these patterns due to the pregnant females’ sensitivity to the estrogen and progesterone. It is important to recognize that first born and high-parities births were also more likely to be rejected by the mother and raised by humans, a finding consistent with the prediction by Dahl [13]. Notwithstanding, this observation cannot explain the observed relation between handedness and parity because the number of left- and right-handed subjects were comparable in the 8th+ born group, albeit heavily biased toward nursery-reared offspring. We believe that these two alternative hypotheses can potentially be tested in human and nonhuman primate subjects by using measures of developmental instability in conjunction with hand preference assessment. Specifically, a number of authors have speculated that measures of developmental instability (DI) represent markers of either genetic or environmentally induced prenatal perturbations [59]. Of particular interest has been the measurement of dermatoglyphics in relation to hand preference. The most frequent measure has been the counting of dermal ridges on the homologous digits of the left and right hand, although other measures such as ATD patterns have been employed [39,46,59]. Typically, the number of dermal ridges on homologous

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fingers are symmetrical and deviations from symmetry reflect prenatal perturbations. Asymmetries in dermal ridge count have been linked to specific prenatal perturbation such as Down’s syndrome and fetal alcohol syndrome [39,59] and therefore appear to be valid markers of genetically or environmentally induced prenatal pathology. More recently, asymmetries in dermal ridge counts and finger print patterns have been linked to hand preference [8,59]. If our hypothesis that different mechanisms influence the expression of hand preference in chimpanzees, then we would predict that latter-born offspring would have higher dermatoglyphic asymmetries than first- and middle-born offspring. In contrast, if low estrogen, as reflected in low PS scores, is the single factor explaining the higher incidences of left-handedness in first and latter-born subjects then larger asymmetries in dermatoglyphics should be evident in first- and latter-born subjects’ compared to middle-born subjects. Although we have not yet examined the relation between PS scores and measures of DI, we have at least some evidence that non-righthanded male chimpanzees have larger asymmetries in testicle size compared to moderately right-handed individuals [17]. From a comparative perspective, the results of this study clearly challenge the long held belief that different mechanisms influence the expression of human and nonhuman primate hand preference [56]. Based on these findings, parity appears to be at least one factor that accounts for individual variation in hand preference in chimpanzees and humans. These findings, coupled with the recent evidence of heritability of hand preference in chimpanzees [32], strongly suggest potential common biological factors as determinants of both human and chimpanzee hand preference. As some authors have noted [7,32], the ratio of right- to lefthanded individuals is different between humans (roughly 9:1) and chimpanzees (roughly 2:1) and this discrepancy remains to be explained. In conclusion, the results from this study suggest that increasing age and parity influence the expression of hand preference, PS scores and pregnancy outcomes. Parity is most strongly associated with hand preference and PS scores while maternal age is the best predictor of pregnancy outcome. It should be emphasized that socioeconomic or life style variables cannot explain the increased incidences of negative pregnancy outcome and left-handedness and therefore these data strongly suggest that biological factors associated with maternal age and parity are the causes. In light of the association between decreased PS scores, handedness and negative pregnancy outcome, the most obvious area for future studies should be to experimentally test the effect of estrogen suppression on each of these outcome variables. These and other related studies will lead to a better understanding of brain-behavior relationships in

relation to prenatal and postnatal events in primates, including humans.

Acknowledgements This research was supported by NIH grants NINDS29574, NINDS-36605, and RR-00165 to the Yerkes Regional Primate Research Center. The authors are especially thankful for the assistance of Sue Setezkorn in obtaining birth and health records on the chimpanzees. The Yerkes Center is fully accredited by the American Association for Accreditation of Laboratory Animal Care. APA guidelines for the ethical treatment of animals were adhered to during all aspects of this study.

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