Library of Excerpts

Metabolic and Developmental Rates, Heterochrony, and Human Evolution

"Prolongation beyond birth (mainly apes and man) and acceleration (man) of fetal brain growth rate result in a heavier adult brain. This implies that the neonatal brain is a smaller proportion of its final adult weight. In rheses monkeys, chimpanzees and man, these proportions are about two-thirds, one-half and one-quarter (Passingham, 1982; Hofman, 1983). A lower value implies a greater immaturity if many parts of the neonatal brain are still in a vestigal stage of functioning. This would explain why the early motor helplessness increases in the order of rhesus monkey, chimpanzee and man. Is there a connection between the first appearances of behavioral capacities and the percentage of the adult brain weight that has developed?" (Dienske, H. (1986) A comparative approach to the question of why human infants develop so slowly, in Primate Ontogeny, Cognition and Social Behavior. Else JG, Lee PC (eds.) Cambridge Univ. Press: Cambridge p. 150)

"In Fig. 3, another behavior is given that does not correspond with the developmental sequences of motor capacities, off-mother and social play. the play-face (cf. smile) in the rhesus monkey appears at about the same time as social play. It is shown occasionally if a peerless infant plays with the mother. In chimpanzees, however, smiling develops at a much earlier stage, long before playful interactions with other infants are common. Unlike in the rhesus monkey, the chimp smile is first shown during manual and oral interactions with the mother (Plooij, 1979). In man the smile develops at about the same (chronological) age as in chimpanzees, i.e. again at an earlier stage of development. So the slower the development, the earlier the smile appears." (Dienske, H. (1986) A comparative approach to the question of why human infants develop so slowly, in Primate Ontogeny, Cognition and Social Behavior. Else JG, Lee PC (eds.) Cambridge Univ. Press: Cambridge p. 151)

"The present theory lays great store in the malleability or adaptability of organisms, especially the higher vertebrates (birds and mammals--more on this latter point later). The creation of behavioral neophenotypes is necessarily dependent upon the existence of some degree of behavioral plasticity or adaptability. Thus, the determinants of behavioral plasticity are an important consideration. One key limiting component of plasticity is the nervous system, particularly the brain, and the other is the developing organism's early experiences. These two components are in lockstep: larger-brained species can make more of their early experiences and early experiences affect the maturation and size of the brain. Thus, the most conspicuous developmental route to increasing behavioral plasticity and creating behavioral neophenotypes is through early experimental alterations (including nutrition of the brain) that have positive effects on enhancing the maturation of the brain." (Gilbert, G (1992) Individual Development & Evolution. Oxford Univ. Press: New York p. 180-1)

"Consequently, given the relationship between large brains and behavioral plasticity, behavioral neophenogenesis predicts that species with large brain should show evidence of a faster evolutionary pace than species with smaller brains. That prediction accords rather well with the finding of Wyles, Kunkel, and Wilson (1983) of an almost perfect correlation between relative brain size and rate of anatomical evolution for a large number of vertebrate species." (Gilbert, G (1992) Individual Development & Evolution. Oxford Univ. Press: New York p. 192)

"In feeding thyroid hormones to newborn rats, they accelerated maturation at a rate exponentially related to the size of the dose, but did not affect growth except at the highest levels. Scow and Simpson's study represents the intermediate case of thyroid deficiency -- an incomplete juvenilization. More severe deficiency may lead to complete juvenilization, as in neotenic Ambrystoma. (Gould, S.J. (1977) Ontegeny and Phylogeny. Cambridge: Belknap Press. p. 301)

"The existence of mammary ridges on the embryo concording with ancient synapsids suggests that those ancient animals also had nutrient-supplying ridges on their bodies for which there is no paleontological evidence. On the human embryo, the mammary ridges gradually coalesce and finally resolve into discrete nipples on day 58. This event concords almost exactly withthe lowermost Triassic, where the fossils of Cynognathus are found. Discrete mammary glands and a fused secondary palate in the enbryo coincide with a fused secondary palate in the fossil record." (Swan, Lawrence W. (1990) The concordance of ontogeny with phylogeny. Bioscience 40: 380)

"However, this discrepancy became understandable when it was realized that the newborn infant concords very well with 20 million years ago in the Miocene epoch, when our ancestors were apes of some sort. Newborn infants can often grasp and suspend themselves and even swing enough to suggest brachiation. Their hallux or big toe is often highly movable and the rest of their feet (showing a slope of their curled toes that is virtually tranverse) are apelike. In an evolutionary sense, a newborn concords well with some ancestral Miocene ape. However, after nine months of a year, when the curve is found at the time of birth, a child approaches the evolutionary present. It starts to stand erect and practices with its lumbar curve before it walks upright. Its hallux assumes a forward position, and its starts to acquire the normal slope of human toes. The chin acquires a better-defined protuberance that expresses Homo sapiens as a species, and the jabberings of an infant transform into human speech." (Swan, Lawrence W. (1990) The concordance of ontogeny with phylogeny. Bioscience 40: 383)

"Male offspring of rats subjected to stress from days 14 to 21 of pregnancy show a persistence of female behavioral potentials and an inability to exhibit normal male copulatory patterns in adulthood. Thus the processes involved in masculinization and defiminization appear to have been compromised in the male fetuses of stresses mothers. ... On the basis of the above observations, we propose that day 18 of gestation represents a distinct and critical point in the process of sexual differentiation of the fetal rat brain." (Ward IL, Weisz J (1980) Maternal stress alters plasma testosterone in fetal males. Science 207: 328-9)

"The tears did not run over the eyelids and roll down the cheeks of this child, whilst screaming badly, when 122 days old. This first happened 17 days later, at the age of 139 days. A few other children have been observed for me, and the period of free weeping appears to be very variable. In one case, the eyes became slightly suffused at the age of only 20 days; in another, at 62 days. With two other children, the tears did not run down the face at the ages of 84 and 110 days; but in a third child they did run down at the age of 104 days. In one instance, as I was positively assured, tears ran down at the unusually early age of 42 days. It would appear as if the lacrymal glands required some practice in the individual before they are easily exited into action, in somewhat the same manner as various inherited consensual movements and tastes require some exercise before they are fixed and perfected. This is all the more likely with a habit like weeping, which must have been acquired since the period when man branched off from the common progenitor of the genus Homo and of the non-weeping anthropomorphous apes." (Darwin C.(1965 (1872)) The Expression of the Emotions in Man and Animals. John Murray: Londonp. 153)

"If right-sidedness occurs as a function of the normal maturation of the nervous system, it would seem reasonable to assume that any disruption of delay in physical maturation in a sub-group of the population could result in an increased proportion of left-sidedness. Several lines of evidence support this notion. For instance, Porac, Coren, and Duncan (1980b) compared the lateral preferences (hand, foot, eye, and ear) of a group of mentally retarded individuals with a group of individuals of equivalent chronological age (mean age approximately 17 years) and with a group of equivalent mental age (mean age approximately 4 years). The retarded group had significantly more left-sided preferences than their age peers, replicating earlier work by Gordon (1921) and Mintz (1947). To account for this finding, these researchers suggested that, when retardation in not caused by specific injury, cognitive development in the retardate is simply slower or arrested at a level below that achieved normally. If this hypothesized maturational lag affects more than the retardates' mental ability (Achenbach, 1970), then it might extend also to handedness. Thus one can predict that the retardates' pattern of handedness should be similar to that shown by the more immature preschool group who served as their mental-age controls, showing the decreased proportion of right-sidedness commonly associated with the young. This prediction was confirmed by the data. Additional evidence that left-handedness may be associated with maturational lag comes from some other clinical groups. There is evidence that males with 47,XXY Klinefelter's Syndrome have slower than normal maturational growth rates (Stewart et al., 1979, 1982). Netley and Rovet (1984) have also found that the incidence of nonright-handedness was more than twice as large in a sample of 47,XXY males when compared with age-matched controls. Coren et al. (1986) extended these results to demonstrate that sinistrality is associated with maturational delays in nonclinical samples. They tested 713 females and 467 males and assessed their relative rate of physical maturation using the onset of secondary sexual characteristics, age of menarche, and relative body size as their indicators. They were able to demonstrate that delayed rates of maturation were associated with an increased incidence of left-handedness for both the males and females in their samples. Also consistent with the notion that left-handers have delayed maturation is Coren's (1989b) observation that left-handedness is associated with somewhat smaller body size in terms of both height and weight." (Coren, S. & Halpern, D.F. (1991) Left-handedness: A marker for decreased survival fitness. Psychological Bulletin 109: 99)

"For instance, Corballis and his associated (Corballis, 1983; Corballis & Beale, 1983; Corballis & Morgan, 1978; Morgan & Corballis, 1978) have suggested that both cerebral laterality and handedness are under the control of a maturational gradient." (Coren, S. & Halpern, D.F. (1991) Left-handedness: A marker for decreased survival fitness. Psychological Bulletin 109: 99)

“The relationship between current reading ability and the achievement of early language and motor developmental milestones was evaluated in 240 children, aged 7 1/2 years, whose language and motor achievement had been charted at each well baby visit during the first 2 years of life. Those children whose composite reading score was 6 months behind their chronologic age on the Woodcock-Johnson Psychoeducational Battery were classified as having reading delay. Relationships to reading outcome were assessed for individual infant milestones, for critical screening values, and by statistical techniques that characterized the developmental process rather than single milestones. Significant differences (P less than .05) were noted between children with and without reading delays for the following milestones: 4 to 6 words, 7 to 20 words, 50 words, 2-word sentences, and 5 and 8 body parts. The positive predictive value of slower milestone achievement ranged from 0% to 50%. Techniques that focused on the developmental process during the first 2 years (either rate of achievement of neurodevelopmental milestones or order of milestone acquisition) were better able to classify children with reading delay (sensitivity = .73, specificity = .78). Although the language milestone measures did not classify children sufficiently well to be diagnostic, the data served to determine whether a child would be at high risk based on performance rather than historical factors.” (Shapiro BK, Palmer FB, Antell S, Bilker S, Ross A, Capute AJ (1990) Precursors of reading delay: neurodevelopmental milestones. Pediatrics 85 (3 Pt 2): 416)

“...both male and female Indian subjects had lower metabolic rates per unit weight than had Europeans. The differences were not small - about 10%. The data used to establish this racial difference are the results of numerous investigations conducted many years ago. Recent work (Shetty 1984) shows that poor Indian labourers do indeed have a basal metabolism which is 17% less than the FAO/WHO/UNO standards, and other studies (McNeill et al. 1987) suggest a lowering by 12%. Whether the low basal metabolism in Indians is a true racial characteristic, is due to climatic factors or is the result of depression of metabolism by long-term under-nutrition is not known.” (Blaxter K (1989) Energy metabolism in animals and man. Cambridge U. Press, Cambridge p. 144)

"Historically, the first genetic condition to be reported to be associated with autism was phenylketonuria. Phenylketonuria (PKU) is an inborn error of metabolism, inherited as an autosomal recessive disorder (Folling, 1934, and usually, but not universally, associated with mental retardation. Most newborns in the United States are now screened for PKU, and a phenylalaline-free diet is instituted within the first weeks of life. The diet substantially diminishes the cognitive behavioral handicap, although Stevenson and colleagues (Stevenson et al., 1979) found a high rate of behavioral deviance in an unselected school-aged sample with PKU that had been treated from infancy. None were autistic or had other behaviors common to autistic children. ... It is of interest that not all socially unresponsive children with PKU were mentally retarded by IQ testing. (Sutherland et al., 1960; Blainy & Gulliford, 1956; Crowie, 1951; Bjornson, 1964), and reports from the 1950's and 1960's suggest that when dietary treatment was instituted after infancy, IQ showed no improvement, but that autistic symptoms frequently disappeared (Lewis, 1959; Bickel et al., 1954; Berry, Sutherland, Guest, & Umbarger, 1958; Armstrong & Tyler, 1955; Armstrong, Low, & Bosma, 1957; Blainy & Guillford, 1956; Woolf, Griffiths, & Moncrieff, 1955). [note: all citations after Lewis not in bibliography, find in some other way] In his review, Friedman concluded that autism and mental retardation were separate manifestations of PKU, as evidenced by the presence of autistic symptoms in normally intelligent children with PKU and by the improvement of autistic symptoms, but not mental retardation, when a phenylalanine-free diet was begun after infancy." (Folstein SE, Rutter ML (1988) Austism: Familial aggregation and genetic implications. J Autism and Developmental Disorders 18: pp. 14-15)

"Certain consistent and stable patterns of EEG development were evident. In general, there were five dominant growth periods in intrahemispheric corticocortical coupling from birth to adulthood. The first, from birth to 3 years of age, was a topographically scattered developmental change, which primarily, but not exclusively, involved a decrease in coherence and phase (Figs. 2 and 3). Beyond 3 years of age a much more uniform and synchronized pattern of development was observed. The second period, from age 4 to 6, involved a change in the left frontal-occipital coupling, the left frontal-temporal coupling, and a localized right frontal pole pairing (Figs. 1 and 2). The third growth period, from age 8 to 10, involved connections between the right hemisphere temporal-frontal regions. The fourth and fifth growth periods, which occurred during the periods from about age 11 to 14 and from age 15 to adulthood, repectively, but not exclusively, frontal lobe connections. ... The present findings provide evidence of differential rates of human cerebral development, and they provide some answers to the questions initially posed: that relatively specific anatomical connections within the left and right human cerebral hemispheres develop at different rates and at different postnatal onset times. Furthermore, the strength and the specificity of the patterns in the data strongly favor the ontogenetic hypothesis of human cortical development in which there is a genetically programmed unfolding of specific corticocortical connections at relatively specific postnatal ages. " (Thatcher RW, Walker RA, Giudice S (1987) Human cerebral hemispheres develop at different rates and ages. Science 236: 1113)

"Regardless of sex, early maturing adolescents performed better on tests of verbal than spactial abilities, the late maturing one showed the opposite pattern. Those maturing late were more lateralized for speech than those maturing early. Sex differences in mental abilities, it is argued, reflect differences in the oranization of cortical function that are related to differential rates of physical maturation." (Waber, D.P. (1976) Sex differences in cognition: A function of maturation rates. Science 192: pp. 572)

"The striking relation between rate of physical maturation (independent of sex) and spatial ability, verbal-spatial patterns and lateralization has several important implications. First, sex accounted for only a very small proportion of the variance in comparison to maturational rate. Therefore, reported sex differences in these behaviors probably reflect the differential distribution of the sexes along a physiologicall continuum more than a categorical difference between male and female. This concept might also apply to other behaviors not examined in this study. Second, since matuational rate was shown not to be related to verbal ability, the sex differences in verbal and spatial abilities may have very different etiologies and cannot be explained by a common set of causes, whether environmental or constitutional. Finally, rate of maturation (or its implicit physiological correlates) may play an important role in the organization of higher cortical functions." (Waber, D.P. (1976) Sex differences in cognition: A function of maturation rates. Science 192: pp. 573)

"During sleep, metabolic rate falls to about 10% (Blaxter 1989). It also falls in other contexts, such as during starvation. It can differ between human populations by as much as 17% (Blaxter 1989: 144)." (Wrangham RW, Jones JH, Leighton M (1995) response to ...Expensive-tissue hypothesis: the brain and digestive system in human and primate evolution. Current Anthroplogy 36(2): pp. 216)

"Reduced shift implies that twins are slightly less biased toward dextrality than nontwins such that, when the incidence of left-handedness in the general population is 7 or 8%, about 11 or 12% is expected in twins." (Annett, M. (1996) In defence of the right shift theory. Perceptual Motor Skills 82 (1): pp. 119)

"There are sex differences in R-L hand skill such that females are slightly more right shifted than males. Females tend to be more mature at birth than males. This observation, together with the finding of a lesser shift in twins than in nontwins, suggested the important hypothesis that cerebral asymmetry depends on rate of hemispheric maturation in fetal life." (Annett, M. (1996) In defence of the right shift theory. Perceptual Motor Skills 82 (1): pp. 120)

"...cell size is inversely related to metabolic rate" (Riska, B. & Atchley, W.R. (1985) Genetics of growth predict patterns of brain-size evolution. Science 229: pp. 669)

"Because body size can evolve in these different ways, by change in different components of growth, the parallel change induced in brain size may differ. This will depend upon the timing, during growth, of pleiotropic gene effects. For example, if pleiotropic gene effects influencing these two traits occur mostly in the early portions of body growth, body-size evolution occurring by change in later growth will induce little parallel change in brain size. Evolution occurring by change in early growth, however, will induce greater change in brain size for a given amount of body-size evolution." (Riska, B. & Atchley, W.R. (1985) Genetics of growth predict patterns of brain-size evolution. Science 229: pp. 669)

"Mean MR's were different for male and female patients, and these differences were significant only for the cerebellum. Even when differences were not statistically significant, women had higher mean MRs than men in all regions. However, metabolic reference ratios of men and women did not show significant differences, except for the left caudate in patients with late-onset dementia. The lack of significant MR differences between male and female patients with AD may be the result of the small sample sizes and proportionately high variances. Three previous investigations have studied cerebral MR differences between nondemented men and women. Duara and associates reported 37% higher mean MRs for yound women compared with young men, but no differences in their elderly population. In a study of seven men (mean age 30 + - 4.5 (SD) yeears) and seven women (mean age 33.1 years + - 3.5 (SD)), Baxter and associates found whole-brain glucose MRs of women 19% higher than those of men (P=.03). In a middle-aged group of 22 nondemented women (mean age 49 + - 17 (SD)) years) nine men (54 + - 21 (SD) years), Riege et al found no reliable regional MR differences between men and women." (Small GW, Kuhl DE, Riege WH, Densen G, Fujikawa DG, Ashford JW, Metter EJ, Mazziotta JC (1989) Cerebral glucose metabolic patterns in Alzheimer’s disease. Archives Gen Psychiatry 46: 530)

"It is satisfying to consider embryos and adults as merely different parts of the slope of a curve subject to natural selection. If biologists cannot agree to Haeckel's concept, "ontogeny recapitulates phylogeny," there may be room for a less ringing slogan, "ontogeny concords with phylogeny."" (Swan, Lawrence W. (1990) The concordance of ontogeny with phylogeny. Bioscience 40: 384)

[citations removed] "Schacter reported that women exposed in utero to the synthetic estrogen diethylstilbestrol had a handedness distribution on the Edinburgh Handedness Inventory (EHI) that was shifted away from strong right-handedness. Nass et al found that females with congenital adrenal hyperplasia (CAH), a disorder that results in increased androgen production during gestation, displayed a lesser degree of right-hand preference than unaffected sibling controls on the EHI. However, males with CAH displayed a trend in the opposite direction. More recently, Helleday et al. reported that females with CAH did not differ from controls in either degree of right-hand preference or in dichotic listening asymmetry." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 225)

"Right-handers (RH) had higher T concentrations than left-handers (LH). This was also true within each sex independently (see Fig. 1). Although males overall had much higher T concentrations than females, as expected (F(1,76)=366.56, P<0.001), male RH had higher T concentrations than male LH (t (38)=2.15, P=0.038) and female RH had higher T concentrations than female LH(t (38)= 1.99, P=0.054). The magnitude of the left handedness effect approaches 3/4 of a standard deviation in both males and female." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 227)

"To summarize, results indicated that LH of both sexes had significantly lower salivary T concentrations than RH. All means were nevertheless within the normal physiological range. A possible further association between T and language lateralization was suggested by the tendency, among males, for LH who showed a REA on the Fused Dichotic Words Test to have lower salivary T concentrations than LH who showed a LEA." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 229)

"instead, we found a trend for LH males with a REA [right ear advantage] to have lower T concentrations than LH males with a LEA." (Moffat, S.D. & Hampson, E. (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34 (3): pp. 231)

"Of the 39 ELBW [extremely low birth weight] children none had cerebral palsy and their average IQ at 4 years was 93. About half (54%) of the children were left-handed (-4 or -3) while of those with greater birthweights only 8% were left-handed (p=0.001) (table). The frequency of left-handedness did not differ among birthweight groups above 1000 g. Using these same tests on a separate group of 4-year-old kindergarden children of normal birthweight one of us (M. J. O'C.) found 15% left-handedness. One possible explanation for these findings is brain damage after birth. Ultrasound was not available when there children were in intensive care so we do not have direct evidence of brain damage. A 50% prevalence of left-handedness would, under the Satz hypothesis, mean that almost all the ELBW children were brain injured, all handedness being "pathological". If postnatal damage was the principal cause of the left-handedness there should have been a gradation in prevalence of left-handedness from the ELBW to the heavier infants. There was, however, no increase in left-handedness among children with birthweights 1000 and 1240g many of whomalso experienced severe neonatal difficulties. Among the main group of 115 infants a mutivariate logistic regression model showed that though a moderate or high neonatal risk score was indepentently associated with a relative risk of 4.5 for left-handedness (p=0.01), ELBW itself had an independent relative risk for left-handedness of 48 (p+0.0001). An alternative explanation is that premature delivery of ELBW infants (all were born between 26 and 29 weeks' gestation) prevents the development of normal asymmetry of the brain. Chi and co-workers have shown that differences between the temporal lobes appear at about 31 weeks' gestation. This finding, coupled with the suggestion of Geschwind and Galaburda that handedness in symmetrical brains is randomly distributed, could account for the high level of left-handedness amongst these ELBW children." (O’Callaghan EM, Tudehope DI, Dugdale AE, Mohay H, Burns Y, Cook F (1987) Handedness in children with birthweights below 1000 g. Lancet 1: 1155 (letter))

"Titers of testosterone in plasma were determined by radioimmunoassay in male rat fetuses of stressed and control mothers on days 17, 18, 19, 21, and 23 (the day of birth) after conception. In fetuses of stressed mothers, testosterone concentrations were highest on day 17, declined on days 18 and 19, and then remained unchanged. In the control fetuses, testosterone increased from relatively low concentrations on day 17 to the highest amounts on days 18 and 19, and then declined. Thus, the persistence of feminine and impaired masculine sexual behavior in male offspring of stressed mothers could be due to the absence of a surge of circulating testosterone during days 18 and 19 after conception, a period postulated to be critical in the development of the central nervous sy tem in the rat." (Ward IL, Weisz J (1980) Maternal stress alters plasma testosterone in fetal males. Science 207: 328)

"The patients were referred at ages ranging from 1 month to 5 years (Table 1). Males represented 60% of the population. Mean birthweight was 2250 g with only 42% of the infants weighing greater or equal to 2500 g. Mean birthweight of full-term infants was 2808 g. In comparison, 86% of the infants in the general population born at the hospital weighed greater or equal to 2500 g. Mean gestational age (SEM) determined by reports from referring physicians and agencies was 36.4 (0.7) weeks, with 44% representing preterm deliveries. [p.316] ... The head circumference data (Table 2) showed 34% of the subjects had head circumferences below the 5th percentile at the time of referral. Significant developmental delays were noted in all areas tested (Figure). While most of the subjects with language delays had difficulties with expressive skills, more than 11% had severe communicative disorders in which receptive as well as expressive skills were abnormal. .... Characteristic fine motor delays included failure to bring hands to the midline, to engage in midline hand play, or to exchange items from one hand to the next at the age-appropriate time. ... Detectable neurological abnormalities were seen in more than 40% of the children (Table 3)." (Davis E, Fennoy I, Laraque D, Kanem N, Brown G, Mitchell J (1992) Autism and developmental abnormalities in children with perinatal cocaine exposure. J Natl Med Assoc 84(4):315-317)

"It has been proposed that prenatal testosterone (T) may contribute to the development of hand preference and cerebral functional asymmetry in humans. To investigate any persisting association between T and asymmetry in adulthood, left-handed (LH) and right-handed (RH) men and women were administered a hand preference questionnaire and the Fused Dichotic Words Test. Testosterone was measured in samples of saliva. Results showed that LH subjects of both sexes had lower salivary T concentrations than their RH counterparts. Among LH males, subjects with a right-ear advantage in dichotic listening tended to have lower T concentrations than subjects with a left-ear advantage. These results are consistent with the notion that T may be involved in the development of hand preference and cerebral functional asymmetry." (Moffat SD, Hampson E (1996) Salivary testosterone levels in left- and right-handed adults. Neuropsychologia 34(3):225)

[abstract] "Sex-related differences have been reported for some brain neuroanatomical structures and several measures of brain function. We studied the cerebral glucose metabolic rates of normal men (n = 7) and women (n = 7) with positron emission tomography and the fluorodeoxyglucose method. Women were studied between days 5 and 15 of the menstrual cycle. Women had whole brain glucose metabolic rates that were 19% higher than those of men. All neuroanatomical structures surveyed showed significant female greater than male rates, with no particular regions being outstanding. The higher cerebral glucose metabolic rates we observed in women may have been related to the effects of the high estrogen levels that can obtain in the phase of the menstrual cycle during which we tested our female subjects." (Baxter LR Jr, Mazziotta JC, Phelps ME, Selin CE, Guze BH, Fairbanks L (1987) Cerebral glucose metabolic rates in normal human females versus normal males. Psychiatry Res 21(3):237-45)

"Hypertonia was present in 30%. ... Eight (11%) of the children met DSM-III-R criteria for autism. Of these eight children, six were full-term and two were born at 32 to 34 week gestation. The mean age of their mothers at delivery was 23 1/2 years. Three mothers had histories of alcohol use on a regular basis, and one had used phencyclidine. Only one mother reported the use of heroin. ... The data in this study, showing 50% of the children at or below the 15th percentile in height and weight, would suggest that this problem may extend beyond the newborn period. ... Austistic disorder is a rare syndrome previously reported to occur in 2 to 21 per 1000 live births. To our knowledge, autism has not previously been reported in association with in utero drug exposure. [p.318] ... In addition, the drug abuse seen was clearly polydrug abuse, thus confounding the interpretation of cocaine as the responsible agent. [p.319]" (Davis E, Fennoy I, Laraque D, Kanem N, Brown G, Mitchell J (1992) Autism and developmental abnormalities in children with perinatal cocaine exposure. J Natl Med Assoc 84(4):318-19)

"If it is assumed that the last common ancestor of apes and humans had a diet similar to that of a modern ape, and that the earliest members of our species (Homo sapiens sapiens) consumed a diet whose composition fell within the range encompassed by modern hunter-gatherers, then it appears that hominid evolution was characterized by increasing diet quality. The distinctiveness of the human diet relative to other primates is likely associated with important metabolic differences. One possiblity is that the high caloric density of our diet is reflective of elevated resting metabolic requirements." (Leonard, William R. (1994) Evolutionary perspectives on human nutrition: the influence of brain and body size on diet and metabolism. American Journal of Human Biology 6(1): pp. 79)

"Dietary patterns strongly influence metabolic requirements in mammalian species (McNab, 1978, 1986; Kurland and Pearson, 1986; Nagy, 1987). McNab (1986) found that mammals consuming high quality food items, such as, vertebrates, seeds, or nuts, tended to have high resting metabolic rates (RMR), while those consuming poor quality foods, e.g., leaves and woody plants, tended to be hypometabolic. If such a pattern holds for primates, it should be expected tht metabolic rates will vary according to relative diet quality." (Leonard, William R. (1994) Evolutionary perspectives on human nutrition: the influence of brain and body size on diet and metabolism. American Journal of Human Biology 6(1): pp. 80)

"These results imply that changes in diet quality during hominid evolution were linked with the evolution of brain size. The shift to a more calorically dense diet was probably needed in order to substantially increase the amount of metabolic energy being used by the hominid brain. Thus, while nutritional factors alone are not sufficient to explain the evolution of our large brains, it seems clear that certain dietary changes were necessary for substantial brain evolution to take place. ... It is intriguing that the clear departure from the general primate brain-metabolism regression occurs with the emergence of species of our own genus, H. habilis and H. erectus, since this is a time when other important anatomical and behavioral changes appear. Specifically, both archeological and morphological evidence indicate that these early members of the genus Homo incorporated greater amounts of animal material in their diet than the australopithecines (Bunn, 1981; Wolpoff, 1980). With early Homo there is the first clear evidence of home bases, implying that resources were collected and brought back to a central location where they were shared. (Potts, 1988). Hence, it is likely that what supported the rapid expansion of brain size in Homo habilis and Homo erectus were both the higher quality and greater stability of the diet." (Leonard, William R. (1994) Evolutionary perspectives on human nutrition: the influence of brain and body size on diet and metabolism. American Journal of Human Biology 6(1): pp. 83-4)

"Contemporary human foraging groups obtain at least 30% of their dietary energy from animals foods, compared to 5-7% in chimpanzees. Adaptation to this calorically dense, easy to digest diet is evident in our gut morphology, as humans have a relatively reduced digestive tract in comparison to most other primates (Sussman, 1987; Chivers and Hladik, 1980; Milton, 1987). This distinct diet appears to be linked to the high metabolic costs of the human brain. In general, primate brain size varies as a direct (linear) function of body metabolism. This means that the proportion of metabolic energy spent on the brain is relatively constant across primates of all size (about 8-9% of RMR). Species spending a larger proportion of RMR on their brain have a higher quality diet than expected for their body size. Conversely, small brains relative to metabolic turnover are associated with poor quality diets. Humans represent the positive extreme, having both a very high quality diet and a brain that accounts for 20-25% of resting metabolic energy. Other researchers have previously noted the apparent link between metabolic rate and brain size. (Armstrong, 2985; Mink et al., 1981; Martin, 1989, 1990). In particular, Martin (1989) has argued tht this relationship reflects the association between brain growth and maternal metabolism. Theis hypothesis posits that since the majority of brain growth in humans and other primates occurs prenatally and early in the postnatal period, it is maternal metabolic output (through pregnancy and lactation) that largely determines achieved adult brain size. If this hypothesis is correct, the results of the present study would imply that improvement in the stability and quality of maternal nutrition (to support the high metabolic demands of pregnancy and lactation) was a consequence of the selection for larger brain size in hominid evolution." (Leonard, William R. (1994) Evolutionary perspectives on human nutrition: the influence of brain and body size on diet and metabolism. American Journal of Human Biology 6(1): pp. 85)

"Barnes and Richards {12} measured the time it took for newborns to establish normal breathing, and then followed up these Ss to age three when handedness was established. They found that 29 of 30 who became right handed had established breathing in 2 min or less, whereas only 6 of 15 who became either left-handed or ambidextrous had established breating in this time. Hypoxia at birth thus seems to be a good predictor of handedness at age three." (Bakan, P. (1977) Left handedness and birth order revisted. Neuropsychologia 15 (6): 838)

"If it is assumed that the last common ancestor of apes and humans had a diet similar to that of a modern ape, and that the earliest members of our species (Homo sapiens sapiens) consumed a diet whose composition fell within the range encompassed by modern hunter-gatherers, then it appears that hominid evolution was characterized by increasing diet quality. The distinctiveness of the human diet relative to other primates is likely associated with important metabolic differences. One possiblity is that the high caloric density of our diet is reflective of elevated resting metabolic requirements. Indeed, the work of McNab (1986) and Nagy (1987) indicates that greater diet quality is associated with higher resting and total metabolic rates among mammalian species. An alternative hypothesis is that the high metabolic costs of our large brain necessitate an energy-rich diet (Martin, 1989; Leonard and Robertson, 1992). Each of these possibilities is examined subsequently. ... Dietary patterns strongly influence metabolic requirements in mammalian species (McNab, 1978, 1986; Kurland and Pearson, 1986; Nagy, 1987). McNab (1986) found that mammals consuming high quality food items, such as, vertebrates, seeds, or nuts, tended to have high resting metabolic rates (RMR), while those consuming poor quality foods, e.g., leaves and woody plants, tended to be hypometabolic. If such a pattern holds for primates, it should be expected that metabolic rates will vary according to relative diet quality. " (Jolly, Clifford J. (1963) A suggested case of evolution by sexual selection in primates. Man (London) 63: 79-80)

"These results imply that changes in diet quality during hominid evolution were linked with the evolution of brain size. The shift to a more calorically dense diet was probably needed in order to substantially increase the amount of metabolic energy being used by the hominid brain. Thus, while nutritional factors alone are not sufficient to explain the evolution of our large brains, it seems clear that certain dietary changes were necessary for substantial brain evolution to take place. ... It is intriging that the clear departure from the general primate brain-metabolism regression occurs with the emergence of species of our own genus, H. habilis and H. erectus, since this is a time when other important anatomical and behavioral changes appear. Specifically, both the archaelogical and morphological evidence indicate that these early members of the genus Homo incorporated greater amounts of animal material in their diet than the australopithecines (Bunn, 1981; Wolpoff, 1980). With early Homo there is the first clear evidence of home bases, implying that resources were collected and brought back to a central location where they were shared (Potts, 1988). Hence, it is likely that what supported the rapid expansion of brain size in Homo habilis and Homo erectus were both the higher quality and greater stability of the diet. (Jolly, Clifford J. (1963) A suggested case of evolution by sexual selection in primates. Man (London) 63: 83-84)

"Contemporary human foraging groups obtain at least 30% of their dietary energy from animals foods, compared to 5-7% in chimpanzees. Adaptation to this calorically dense, easy to digest diet is evident in our gut morphology, as humans have a relatively reduced digestive tract in comparison to most other primates (Sussman, 1987; Chivers and Hladik, 1980; Milton, 1987). This distinct diet appears to be linked to the high metabolic costs of the human brain. In general, primate brain size varies as a direct (linear) function of body metabolism. This means that the proportion of metabolic energy spent on the brain is relatively constant across primates of all size (about 8-9% of RMR). Species spending a larger proportion of RMR on their brain have a higher quality diet than expected for their body size. Conversely, small brains relative to metabolic turnover are associated with poor quality diets. Humans represent the positive extreme, having both a very high quality diet and a brain that accounts for 20-25% of resting metabolic energy. Other researchers have previously noted the apparent link between metabolic rate and brain size. (Armstrong, 1985; Mink et al., 1981; Martin, 1989, 1990). In particular, Martin (1989) has argued that this relationship reflects the association between brain growth and maternal metabolism. This hypothesis posits that since the majority of brain growth in humans and other primates occurs prenatally and early in the postnatal period, it is maternal metabolic output (through pregnancy and lactation) that largely determines achieved adult brain size. If this hypothesis is correct, the results of the present study would imply that improvement in the stablity and quality of maternal nutrition (to support the high metabolic demands of pregnancy and lactation) was a consequence of the selection for larger brain size in hominid evolution." (Jolly, Clifford J. (1963) A suggested case of evolution by sexual selection in primates. Man (London) 63: 84-5)

"The association between selected demographic variables and birth weight on the one hand and a composite hand preference score based on seven hand tasks (each performed twice) on the other was investigated in a sample of 1387 male and female schoolchildren aged 5 to 10 years old. In multiple regression models left-handedness was significantly more common among boys and among children of better educated mothers and tended to decrease with age. No association was found with respect to urban or rural residence or birth order. Increased birth weight was associated with right-handedness in boys but with left-handedness in girls, and the birth weight by sex interaction term was statistically significant (p = 0.037). The demographic associations in the present study are compatible with those reported previously. The different associations of birth weight with hand preference in boys and girls indicate that the pr natal hormonal factors that affect brain lateralization and handedness are qualitatively or quantitatively different in the two sexes and may be differentially associated with birth weight." (Petridou, E., Flytzani, V., Youroukos, S., Lee, I.M., Yen, Y.Y., Yong, D., Trichopoulos, D. (1994) Birth weight andhandedness in boys and girls. Human Biology 66 (6): 1093-1101)

"During periods of fetal and postnatal growth, the demands of the brain for fats, proteins, and other nutrients are especially high (Morgan and Gibson, this volume). During the first year of human life, 65% of the total metabolic rate is devoted to the brain in contrast to 9% devoted to muscle tissue (Holliday, 1978)." (Gibson, K.R. (1991) Myelination and Behavioral Development: A Comparative Perspective on Questions of Neoteny, Altriciality and Intelligence in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 50)

"Studies from around the world indicate that severe maternal calorie restriction produces infants of lower birth weight, but that calorie supplements during pregnancy can reduce this problem (Habricht et al., 1974; Winick, 1976, 1989)." (Morgan, B. & Gibson, K.R. (1991) Nutritional and Environmental Interactions in Brain Development in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 97)

"A useful paradigmatic case is provided by the emergence of bipedal locomotion, a species typical, centrally organized neuromotor action pattern shown by all normal adults --- indeed by all normal 2 year olds--- in our species. The mean age of attainment of one useful criterion, three steps taken without hands held, hovers around a year of age in many samples, usually falling between 11 and 14 months. Large samples studies is five European cities had means with 6 weeks of each other at the extremes. (Hindley et al., 1966) Precocity for infants in developing countries, especially Africa, has been frequently been claimed (Super, 1981; Werner, 1972, 1979). Some carefully designed and conducted studies, however, fail to show any difference, and one critical review of a large numbe of studies concluded that African infant precocity has not been demonstrated. (Konner, Melvin (1991) Universals of Behavioral Development in Relation to Brain Myelination in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 200)

"Since blind infants develop reliable social smiling only a month or two later than sighted infants (Fraiberg, 1977; Freedman, 1964; see also Thompson, 1941), a crucial role for visual perception in the growth of the behavior can be ruled out." (Konner, Melvin (1991) Universals of Behavioral Development in Relation to Brain Myelination in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 204)

"This model of the development of social behavior in infancy is related to the evolutionary model proposed by MacLean (1973, 1985) and commonly known as "the triune brain." Interesting parallels are drawn between the major events of psychosocial development in infancy and the phylogenetic sequence of MacLean, with the suggestion that ontogeny in this area of development recapitulates, to a limited extent, phyleny. " (Konner, Melvin (1991) Universals of Behavioral Development in Relation to Brain Myelination in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 212)

"In all major theories of development the period around 6 years assumes particular importance (White, 1965, 1970). This age therefore appears to be an attractive candidate for relating changes in brain and behavior. The behavioral evidence is both broad and detailed. Piaget and his associated (e.g., Inhelder and Piaget, 1964), for example, locate the beginnings of rational, operational thought at this time. Similarly, Soviet psychologists emphasize that higher order processes overlay the mechanisms of classical conditioning beginning around 6 years of age. This concept dates back to Pavlov's "second signal system," and both Vygotsky (1962) and Laria (1961) preserve the shift as the central feature of adult cognitive functioning. The American mediation theorists, in their expansion of traditional learning theory, point to a similar process in the sixth year, as language plays as increasing role in conceptual learning (Kendler, 1963). Even Freud, for whom cognition was not a central concern, saw in the resolution of the Oedipal conflict the emergence of inhibitory systems in the superego, and thus a new level of cognitive control. For each theorists, in different languages and from different data, the period around 5 to 7 years is seen as the beginning of a dramatically more mature organization of the mind. More recent theorizing, of less sweeping design than that of earlier generations, preserves the period of about 6 to 7 years as one of particular significance. Watson's (1981) analysis of children's understanding of social roles, for example, finds a full representational system at age 7. Siegler (1981) comments, on the basis of studies of within- and between-concept sequences of development, that children under age 6 may reason about diverse concepts in similar ways, while older children's reasoning becomes increasingly differentiated. Case's (1984) reformulation of Piagetian theory, although differing from some others in the kind of demarcation seen between ages 5 and 7 years, nevertheless emphasizes major developmental changes in this period. Fischer and Silvern (1985) have recently reviewed the concept of developmental stages and the evidence for such structure: they conclude that "there is strong research evidence to indicate a major change in capacity at (age 6 or 7 years) that fits all six empirical criteria" of true developmental stages (Fisher and Silvern, 1985, p. 635) (Super, Charles M. (1991) Developmental Transitions of Cognitive Functioning in Rural Kenya and Metropolitan America in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 225-226)

"Two findings are of particular relevance here, First 5 year olds do not experience verbal transformations when hearing a recorded word repeatedly. The effect begins to appear at age 6 and is reportedly experienced by all children 8 years and older. (The effect declines during middle adulthood and is largely absent in those over 65 years.) Second, not only the rate but also the quality of transformations changes with age..." (Super, Charles M. (1991) Developmental Transitions of Cognitive Functioning in Rural Kenya and Metropolitan America in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 241)

"If the results form these three studies are combined, the overall proportion of left-handers is 13.3 per cent for autistic children and 8.3 per cent for matched controls, not a significant difference. However, if left- and mixed-handers are summed, then the frequency of non-right-handedness among autistic children is considerably higher than that found in age-matched normally developing children although it is similar to that found in other children of the same intellectual ability." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 111)

"Evidence against a genetic predisposition to left-handedness in autism came from studies by Boucher (1977), Tsai (1982) and Fein et al. (1985), all of which found that the overall rate of left-handed relatives in autistic individuals was similar to expected population values, and non-right-handers and right-handers had similar numbers of left-handed relatives." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 111)

"The data reviewed so far point toward an explanation of increased non-right handedness in autism arising as a consequence of generally poor motor functioning which results in a failure to learn the types of motor skills for which hand preference is normally shown. Lack of hand preference rather than stable left-handedness is what differentiates autistic from normal children. Neither pathological left-handedness nor a genetic predisposition towards decreased cerebral lateralization seem able to account for available data." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 113)

"Another possibility is that there may be developmental changes in language processing in autism: in this study, evidence of left hemisphere language functions was strongest in the older subjects." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 115)

"Interest in handedness in Rett syndrome was fuelled by a report by Nomura et al. (1984) who noted that out of 11 girls with the syndrome five were left-handed, one was right-handed and five had never been observed to show a preference. Handedness ceased to be apparent as children grew older and hand function declined so that the child could no longer grasp objects. Olsson and Rett (1986) studied handedness is 33 children with Rett syndrome. A range of toys and foods was presented, with hand preference being coded if one hand was used for grasping at least three times more often than the other. Olsson and Rett reported a striking difference between children aged above and below 7 years. For the younger group, there was a confirmation of the findings of Nomura et al., with nine out of the 14 girls using the left hand more than the right, one using the right more than the left, and the remainder showing no hand preference. However, for those aged above 7 years, only one out of the 12 preferred the left hand, whereas nine out of 12 preferred the right. These older children had evidence of asymmetical pathology affecting the upper limb, with the left side more abnormal than the right." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 116)

"In the early adolescent years, there is thought to be a major transformation in cognitive thought leading to abstract reasoning (Inhelder and Piaget, 1958; Super, this volume). Some researchers even characterize cognitive change at this time as a disruption and/or reorganization of cognition (Carey and Diamond, 1980; Merola and Liederman, 1985). It is important to note, however, that change is not uniformly seen. For example, abstract thoght is not ubiquitous among adolescents, at least as measured by Piagetian tasks (Dulit, 1972). Indeed, data on adults suggest that about half of adults, even in our society, do not manifest abstract thinking on Piagetian tasks (Tomlinson-Keasey, 1972). Whether these results reflect task effects (i.e. inadequate measures) or real deficits in abstract thinking is unclear." (Graber, J.A. & Peterson, A.C. (1991) Cognitive changes in adolescence: biological perspectives in Brain Maturation and Cognitive Development: Comparative and Cross-cultural Perspectives (K.L. Gibson & A.C. Peterson, ed.) DeGruyter, N.Y. pp. 256)

"Primary endocrine control of somatic growth is established by the secretion and circulation of growth hormone (GH), a large polypeptide molecule with multiple effects on cell division and metabolism. GH is synthesized and secreted by the somatotropic cells of the anterior pituitary gland. This secretion is regulated by the interaction of two hypthalamic hormones, growth hormone-releasing factor (GHRF) and growth hormone inhibiting factor (somatostatin), which in turn are regulated by a variety of humoral and central nervous system feedback controls. GH travels form the pituitary to all cells of the body, where it binds to specific growth horone receptors (GHR), which are widely distributed. After GH binds to the receptor on the cell membrane, it circulates with a carrier protein known as high-affinity growth hormone-binding protein (GH-BP), which appears to be the extracellular portion of the GHR dissociated from the cell. Serum levels of high-affinity GH-BP can be assayed, and are thought to provide an indirect measure of the number of GHR present and active (Baumann et al., 1989)." (Shea, B.T. & Bailey, R.C. (1996) Allometry and adaptation of body proportions and stature in African pygmies. American Journal of Physical Anthropology 100(3): pp. 313)

"Whatever the precise hormonal mechanisms ultimately determined to underlie the reduced body size in pygmies, their effects appear to be exhibited throughout the entire span of postnatal growth (Bailey, 1991a) and not simply during or just prior to puberty, as previously claimed by Merimee et al. (1987). This is just what would be expected of an alteration involving IGF-l levels and/or distal subresponsiveness, since the predominant effects of this important mitogen are seen postnatally (e.g. Rechler et al., 1987)." (Shea, B.T. & Bailey, R.C. (1996) Allometry and adaptation of body proportions and stature in African pygmies. American Journal of Physical Anthropology 100(3): pp. 314)

"In the decade since the publication of Ontogeny and Phylogeny (Gould, 1977), there has been considerable advances in our understanding of the controls of growth processes (Bryant and Simpson, 1984). There are many control substances that affect aspects of bodily growth, but the most important immediate influence on general postnatal growth appears to be the hormone insulin-like growth fctor 1 (IFG-1, or somatomedin C). Growth hormone (GH, also known as somatotropin) regulates the local production of IGF-1 and undergo multiplication, thus resulting in growth. In turn, amounts of circulating GH secreted by the pituitary are under neurendocrine control. Any number of recent reviews and texts can be consulted for further information on the hormonal control of growth (e.g., Ludecke and Tolis, 1985; Raiti and Tolman, 1986). (Shea, B.T. (1989) Heterochrony in human evolution: the case for neoteny reconsidered. Yearbook of Physical Anthropology 32: pp. 95)

[from abstract]"Information was obtained on the hand preference of 88 premature and 80 matched full-term children at 7-8 years old. These children were also evaluated for neurologic status, IQ, attention-deficit hyperactivity disorder, and learning disabilities. Although the difference on hand preference was not significant, 12% more of the premature children than the full-term children were left- or mixed-handed. Results showed that, among premature children, there is an association between non-right-handedness and cognitive and behavioral deficits and that left-handed children show relative clumsiness with the non-preferred hand." (Ross G, Lipper E, Auld PA (1992) Hand preference, prematurity and developmental outcome at school age. Neuropsychologia 1992 May;30(5):483-494)

"Liederman further proposed that maturity of the corpus callosum may be a crucial factor affecting hand preference. Until interhemispheric callosal connections are functional, hand movements that cross the body midline are seldom observed. Young infants, like split brain patients, typically use the left hand to reach for locations on the left side and the right hand to rech to the right. Once the corpus callosum is functional, the child is able to use the preferred hand regardless of the location of an action relative to the body. A mature corpus callosum is also probably important for the inhibition of symmtrical bilateral movements ('mirror movements'). Such inhibition seems necessary to enable asymmetical bimanual actions to occur (Fog and Fog 1963). There have been few studies relevant to the issue of neuromotor maturity and handedness, although Cohen (1966) showed that consistent hand preference at 8 months of age was significantly related to advanced developmental status, and the lack of preference to below average develop. Kaufman et al. (1978) and Tan (1985) confirmed that preschool children with 'unestablished' hand preference (assessed on the McCarthy scales) had lower levels of motor skill than those with consistent handedness, and Tierney et al. (1984) found a link with lower overall scores on the General Cognitive Index." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 67)

"In a mata-analysis of published data, Searlman et al. (1989) found that certain indices of birth stress (e.g. low birthweight, rhesus incompatibility, caesarian delivery) were associated with decreased right-handedness, but effects were tiny and only reached significance with the huge samples generated by combining data from many sources. The clearest evidence for a link between left-handedness and perinatal condition comes form studies of infants of extremely low birthweight. O'Callaghan et al. (1987) reported that 21 out of 39 children with birthweight below 1000g were left-handed at 4 years of age, compared with 8 per cent of other infants admitted to intensive care. None of the very low birthweight group had cerebral palsy. Ross it al. (1987) found that while 80 per cent of a full-term control group were right-handed, only 63 per cent of perterm children with very low birthweight were, this being a statistically significant difference. Furthermore, the two groups did not differ in the distributions of parental handedness. Only six children in this sample had asymmetry of body tone, but four of these were left-handed. In addition, within the preterm group, the non-right-handed children had significantly lower IQ's impaired expressive language and a higher frequency of articulation defects relative to right-handed children. Although this study appears to provide strong support for the notion that very preterm children are vulnerable to brain damage affecting handedness, it should be noted that not only was left-handedness more frequent in this sample, but so too was mixed handedness." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 90-1)

"Furthermore, those left-handers with poor non-preferred hand scores had fewer left-handed relatives than other left-handers. In general, children with poor scores of the non-preferred hand were more likely to have had a history of neurological impairment, and obtained lower scores on tests of intellectual function, than did other children." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 98)

"By fitting the model shown in Figure 7.5 to data obtained with this large sample, it was estimated that it follows that around one in 20 of all left-handers are pathological left-handers, and just over one-third of left-handers with very poor non-preferred hand skill are pathological left-handers. This study indicated that it is not implausible to postulate that an increase in left-handedness due to pathological influences may be found even in populations where frank neuromotor abnormality is not evident. ... We need to develop better ways of distingishing pathological from non-patholgical left-handers. Familial sinistrality, the most widely used index, yields such a high rate of misclassification as to make it worthless. Hypotrophy on one limb, strength of hand preference and poor motor skill of one side are all promising indices." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 100)

"Furthermore, where a distinction has been made between mixed- and left-handedness, it is clear that in general it is lack of hand preference rather than left-handedness that is particularly common in mentally handicapped people (Dart 1938, Porac et al. 1980)." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 106)

"However, another source of evidence suggests that ambigous handedness may be indicative of particular type of brain pathology. Lonton (1976) assessed handedness for drawing and writing in 203 children with spina bifida and hydrocephalus. Despite the fact that both tasks involved pencil use, a substantial minority of the spina bifida children used both hands, a behavior that was observed only rarely in the youngest normal control children. Although these 'mixed handers' were significantly lower IQ than other children in the sample, the majority of them (68%) hadIQ's above 70. Anderson and Spain (1977) suggested that while failure to develop hand preference is children with spina bifida might simply be a conseqence of general motor delay, a specific neuroanatomical basis could be the stretching and thinning of the corpus callosum that often occurs in this condition. This interpretation fits well with contemporary views on the role of the corpus callosum in normal development of handedness (see Chapter 4). If the callosal thinning hypothesis is correct we would predict that children with spina bifida who did not develop hand preference should show mirror movements beyond the usual age and should also have difficulty in executing movements that crossed the midline or involved asymmetrical bimanual actions. We need to test these predictions in studies that compare children with spina bifida with younger children matched for level of motor ability." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 107-8)

"The studies on lateralization of motor and language functions in this population caution against equating morphological brain symmetry with lack of language lateralization. Rather, just as with dyslexic children, it seems likely that language-impaired children have verbal functions lateralized to the left hemisphere, but this hemisphere is not sufficiently well-developed to process language adequately." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 136)

"Another group providing relevant data is males with an extra X chromosome (Klinefelter syndrome: 47, XXY). Individuals with this syndrome usually perform quite normally on tests of non-verbal ability, but typically are impaired on language tests (Netley and Rovet 1982a). Netley and Rovet (1982b) reported a rate of 24 per cent left-handedness in 33 individuals with Klinefelter syndrome, which was significantly above the frequency in age-matched controls. Similarly, Thielgaard (1981) reported that XXY males were much more likely than XYY males to be ambidextrous (although the criterion for ambidexterity was not defined). Netley and Rovet (1984) noted that there is evidence for slowed development in XXY males, both fetaly and in early childhood. They interpreted their findings in terms of delayed maturation of the left hemisphere. To this extent, the syndrome is consistent with Geschwind and Galaburda's theory. However, there is one major flaw in the hormonal explanation of these findings: Netley and Rovet (1988) reported that males with Klinefelter syndrome do not have abnormally high levels of testosterone during fetal life --- if anything, their levels are unusually low. Thus, while left-handedness and language delay may be signs of slow maturation in this sydrome, there is no evidence that fetal testosterone plays a causal role. A final piece of evidence linking non-right-handedness with immaturity comes from Coren et al. (1986), who obtained questionnaire data on handedness and retrospective reports of age at puberty form a sample of 1180 university students. There was a significant association between left-handedness and late puberty in both sexes." (Bishop, D.V.M. (1990) Handedness and Developmental Disorder. MacKeith, Manchester pp. 152)

[abstract] Multifactorial inheritance applied to brain development implies a large continuum of normal variation with deviation from the norm at the extremes of maturational rate. The greater population of neurons, greater arborization of neural networks and excessive synaptic density in early maturation imply that adaptability (plasticity) is a main advantage, as opposed to a deficit in adaptability associated with the reduced number of neurons, reduced connectivity and reduced synaptic density in late slow maturation. It is hypothesised that Planum Temporale (PT) asymmetry and hand-preference predict the rate of CNS maturation as does the cognitive profile on the Wechsler Adult Intelligence Scale (WAIS): PT leftward asymmetry, right-handedness and a left-hemisphere cognitive advantage signifies early fast matura tion: PT rightward asymmetry, left-handedness and a right-hemisphere cognitive advantage signify late maturation, while PT symmetry and ambilaterality represent rates of maturation in between. The slower development of males implies a male predominance in disorders affecting late maturers: Developmental Dyslexia (DD) with a predominance of rightward PT asymmetry/symmetry, left-handedness and multiple functional deficits, as well as excessive regressive events confirmed on PT/MRI. Schizophrenia, hypothesised to be a disorder in late maturers, is distinguished by rightward asymmetry/symmetry. Left-handedness and DD are common as is prior delayed development supporting excessive regressive events as do the findings on PT/MRI. To reduce the risk of DD and schizophrenia requires a reduction in late maturation through the enhancement of maturational rate by optimal nutrition before and during pregnancy and later. (Saugstad LF (1998) Cerebral lateralisation and rate of maturation. Int J Psychophysiol 28(1):37-62)

[abstract] The relationship between current reading ability and the achievement of early language and motor developmental milestones was evaluated in 240 children, aged 7 1/2 years, whose language and motor achievement had been charted at each well baby visit during the first 2 years of life. Those children whose composite reading score was 6 months behind their chronologic age on the Woodcock-Johnson Psychoeducational Battery were classified as having reading delay. Relationships to reading outcome were assessed for individual infant milestones, for critical screening values, and by statistical techniques that characterized the developmental process rather than single milestones. Significant differences (P less than .05) were noted between children with and without reading delays for the following milestones: 4 to 6 words, 7 to 20 words, 50 words, 2-word sentences, and 5 and 8 body parts. The positive predictive value of slower milestone achievement ranged from 0% to 50%. Techniques that focused on the developmental process during the first 2 years (either rate of achievement of neurodevelopmental milestones or order of milestone acquisition) were better able to classify children with reading delay (sensitivity = .73, specificity = .78). Although the language milestone measures did not classify children sufficiently well to be diagnostic, the data served to determine whether a child would be at high risk based on performance rather than historical factors. (Shapiro BK, Palmer FB, Antell S, Bilker S, Ross A, Capute AJ (1990) Precursors of reading delay: neurodevelopmental milestones. Pediatrics 85(3 Pt 2):416-420)

[abstract] Schizophrenic symptoms are conceived as arising from inter-individual variability in the distribution of those fibres that connect asymmetrical regions of the hemispheres related to language. Language (a bihemispheric phenomenon) arose as a result of a genetic change that allowed the two hemispheres to develop with a degree of independence. One component, the phonological output sequence, became localised to the dominant hemisphere, interacting through the corpus callosum with other component functions, including the associated meanings, in the non-dominant hemisphere. Nuclear symptoms are a consequence of failure of segregation of these two functions. This failure is associated with abnormal connectivity between the hemispheres and relates particularly to those regions that are late developing and differ between the sexes. (Crow TJ (1998) Schizophrenia as a transcallosal misconnection syndrome. Schizophr Res 1998 Mar 10;30(2):111-114)