Hindawi Publishing Corporation Child Development Research Volume 2013, Article ID 169509, 10 pages http://dx.doi.org/10.1155/2013/169509 Research Article Developmental Risk: Evidence from Large Nonright-Handed Samples Filippos Vlachos,1 Francois Gaillard,2 Kiriazis Vaitsis,1 and Argiris Karapetsas1 1 2 Department of Special Education, University of hessaly, Argonaton & Filellinon, 38221 Volos, Greece Institute of Psychology, University of Lausanne, Géopolis, 1015 Lausanne, Switzerland Correspondence should be addressed to Filippos Vlachos; fvlachos@uth.gr Received 29 March 2013; Revised 4 June 2013; Accepted 19 June 2013 Academic Editor: Ross Flom Copyright © 2013 Filippos Vlachos et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. he aim of the present study is twofold. First, we tested the view that individuals who do not develop a typically strong behavioral laterality are distributed diferentially among the two genders across age. Second, we examined whether let handedness and mixed handedness are associated with an elevated risk of some developmental or cognitive deicits. A special recruitment procedure provided norms of the Rey-Osterrieth Complex Figure (ROCF) copy from large samples of let-handed (� = 420) and mixedhanded (� = 72) compared to right-handed (� = 420) schoolchildren and adults (� = 545). his graphic task was considered as relective of the growth of visual-spatial skills and impairment at copying as a developmental risk. Subjects’ hand preference was assessed by the Edinburgh Handedness Inventory. Data analysis indicated that (1) the trend towards consistent right handedness is sex related. Girls are clearly ahead of boys in this lateralization process, and boys are overrepresented in mixed-handed subjects. he greater prevalence of mixed-handed boys compared to girls decreases with age. (2) Performance on drawing the ROCF varies according to age and handedness groups. Mixed-handed subjects scored worse in all age groups. he results are discussed in relation to the hormonal-developmental, neuropathological, and learning theories of lateralization. 1. Introduction Handedness is a signiicant feature of ontogenetic development. Its consistency and stability provide evidence for brain hemispheric specialization and can be used as an indicator of developmental stages. Lateralization is both cause and consequence of having a brain with two cerebral hemispheres specialized to perform diferent tasks and work together in order to improve many motor and cognitive tasks. At the irst glance, no hand lateralization is observed in young children who have not yet learned to use innate biological asymmetry. However, careful observation of motor behavior in infants already reveals the human speciic trend towards dextrality [1, 2]. he study of handedness has been of interest for many years because subtle cognitive and behavioral diferences have been demonstrated in relation to various handedness measures [3]. Gender diferences in handedness are widely reported. A recent meta-analysis of 144 studies [4] demonstrated that the gender diference in handedness is both signiicant and robust, indicating that the overall best estimate, albeit not universal, for the male to female odds ratio was 1.23. he purpose of this study is to investigate further the efects of handedness, as a proxy for hemispheric laterality, in terms of gender diferences, performance on a cognitive task, and the potential for later cognitive impairment, examining large let-handed and mixed-handed groups of children and adults. Large samples of nonright handers are rare because only 9-10% of the population of schoolchildren is let-handed, and there are even fewer nonlateralized children. In previous studies [5–7], using a special recruitment procedure in order to obtain a large group of let handers (each lethanded child was matched by age and sex to a right-handed child), we have demonstrated diferences between let and right handers on the Rey-Osterrieth Complex Figure (ROCF) test, a popular tool used to test visuospatial-constructional functions [8]. In the present study, we complete this observation by including non-lateralized children. We are also adding 2 a group of adults in order to present the whole cognitive development. A very recent study [9] indicated that there is no single pattern in the development of handedness from 6 to 24 months, and the shit to more robust hand use preferences may be a developmental phenomenon. Inconsistent and unstable handedness has been found in several clinical groups with pathological cognitive development [10, 11]. However, many studies showed no relationship between handedness and cognitive development in samples of normal children [12–16]. hese observations show that factors that disrupt cognitive development can also disrupt the development of consistent manual dominance. We can explain this discrepancy between apparently contradictory results by considering progressive handedness to be merely a sign of brain specialization and not a condition of mental development. However, during the school years, consistent and stable handedness appears as a tool for learning ine motor tasks such as writing and for developing the spatial sense necessary for written language and calculation. Although nonlateralized schoolchildren are not delayed in maturation, they lack the advantage that let and right handers have in their learning. his is why nonlateralized schoolchildren are oten at risk of being considered as slow learners or as learning disabled as far as visual-spatial abilities are concerned. In this sense, they are subjected to a true developmental risk. Progressive hand preference indicates neurophysiological asymmetry which is genetic and biological in origin [17– 20]. However, some handedness conditions are pathological. According to the theoretical account of pathological lethandedness syndrome, a subgroup of let handers sufers from a condition that involves an early injury. his syndrome is believed to be caused by a hemispheric lesion that is predominantly let-sided (or bilateral asymmetric), which onsets before the age of 6 and which encroaches upon the critical speech zones of the frontotemporal/frontoparietal cortex [10]. Indeed, the trend towards functional lateralization reveals itself to be sensitive to any cerebral disturbance. he neuropathological hypothesis of handedness would irstly predict that difused brain injury would result in a lack of hand dominance and, secondly, that lateralized hemispheric damage would produce strong ipsilateral hand dominance. In the irst case, patients present a habitus of mixed handedness characterized by low motor performances on both body sides. Research on prematurity, on risk pregnancy, and on dystocia has shown that very oten these conditions are associated with cognitive deicits and an increased frequency of inconsistent right handedness. hese studies suggest that the brain might be afected as a whole resulting in mixed handedness and bilateral clumsiness [21–24]. Additionally, several studies consider mixed handedness as a pathological condition [13, 25–27]. In the second case, some of the 100% let handers are sufering from right hand handicap corresponding to let brain damage [1, 10, 28]. he non dominant hand of such strongly lateralized persons actually acts as a symptomatic limb. Obstetricians and pediatricians estimate that 1.5–6% of children are likely to sufer from brain damage early in life [29, 30]. hus, it is reasonable to expect to have some of these brain Child Development Research damaged patients in a sample of 912 children. Surprisingly there seems to be no literature on pathological 100% right handedness, which is, of course, the reverse possibility. However, the neuropathological hypothesis only accounts for one explanation of the variation in the relationship between handedness and skills. Table 1 presents ive hypotheses related to this variation. he genetic inluence on laterality has been proved by comparing parental with child handedness both in normal and adoptive families [31–33]. At present, laterality genetics is far from clear. Some claim that there may be a single gene inluencing laterality development with homozygotically and heterozygotically diferent conditions [17]. Others believe that the inheritance process is polygenetic [19], and the recent molecular studies strongly favor a polygenic model. More speciically, a few years ago Francks et al. [40] identiied an imprinted gene, LRRTM1, within the 2p12-q11 region, which is expressed during the development of speciic forebrain structures. he paternal copy of this gene was associated with both let handedness and schizophrenia, and this was the irst potential genetic inluence on human handedness identiied, and the irst putative genetic efect on variability in human brain asymmetry. Other researchers [41] identiied the X-linked androgen receptor as a candidate gene for handedness. In another study of genetic inluences on handedness [42] researchers ater analyzing a large sample of twin and family data for hand preference concluded that the familial aggregation for hand preference was found to be consistent with additive genetic efects, which accounted for about a quarter of the variation in the trait with the remainder accounted for by nonshared environmental inluences. All these indings are consistent with the emerging view that handedness is determined by multiple interacting genetic and environmental factors. A recent study [43] showed that human handedness is afected by early lateralised visual experience, thus leading the researchers to the suggestion that a combined gene-environment model could better explain the development of human handedness. Hormones also inluence brain development, as has been demonstrated by comparing female and male brain lateralization and specialization [44, 45]. Female brains show weaker lateralization, but this sex diference only accounts for 1 or 2% of the variance in laterality [46]. Clinically, women sufer less than men from aphasia following brain damage. hey also seem to recover better than males when similar aphasic states are observed [47]. here is a slight preponderance of nonright-handed males in child clinical samples where girls appear as more lateralized than boys [34, 48–50]. According to Geschwind and Galaburda’s hypothesis [34] there is a fundamental link between abnormal let-hemisphere development, reduced dextrality, various learning disorders, and various immune related and other medical conditions, which is forged by the prenatal inluence of testosterone on the developing nervous system. he authors propose that excessive levels of fetal testosterone inluence the rate of maturation of the cerebral hemispheres which, in turn, may increase the probability of nonright handedness and learning disorders, afecting males more than females due to the higher rates of testosterone [34]. Two decades ago, a review by Child Development Research 3 Table 1: Inluence on the lateralization process: evidence and implication. Type of inluence Efect evidenced Genetic Children with let-handed parents more oten become let handers but not in adopted samples. Hormonal/developmental Greater prevalence of nonright handedness in males. Cerebral lateralization more pronounced in males. Male’s overall maturational gap. Male’s overall boost of right-hemispheric functions [34]. Neuropathological Any brain injury before, during and ater birth contradicts the lateralization process. Results depend on global or focal brain sufering. If global, some ambidextrous subjects sufer bilateral brain damage. If focal, some 100% right-handed and some 100% let-handed sufer hemispheric dysfunction [1, 10, 28]. Neuropsychological Each hand shows an ability advantage corresponding to the specialization of the direct linked hemisphere. he right hand is better at communicating, and the let hand is better at visual-spatial tasks [35–37]. Learning Children take progressively advantage of their lateralization by building body-space relationships and developing constructional abilities. Lateralized children develop a better spatial sense than nonlateralized ones. Risks for academic learning are lower in lateralized than ambidextrous children. Target: arithmetic, eidetic reading, and writing [38, 39]. Bryden et al. [51] questioned the Geschwind and Galaburda’s hypothesis [34] as a cohesive entity. However, this same review did acknowledge an empirical basis for the association of a number of developmental and health problems with hand preference and hormone action. Even though a strong version of the link between handedness with hormone action has been refuted [51], still numerous reports exist to point to some role of hormone action in hand preference. For example, a few years ago [52] pointed out that the length of the index inger relative to that of the ring inger (the 2D : 4D ratio) is a marker of the amount of testosterone that was present in the foetal environment. Recent studies [53, 54] conirmed that the diference between the digit ratios of the right and let hands was a signiicant predictor of handedness. here are two more hypotheses that predict a relation between lateralization and neuropsychological development: neuropsychology and learning. Concerning neuropsychology, brain hemispheric specialization directly inluences hand specialization. Despite the fact that every human being acts in a bihemispheric manner, the right hand is more efectively used for let-hemispheric functions and the let for right-hemispheric functions. his does not mean that the right hand cannot obey the right hemisphere, but experimental studies have shown that the right hand is simply better than the let hand in performing let hemisphere specialized tasks [35–37]. For our purpose this means that we could predict that the let hand is better than the right in copying the ROCF. Of course, we did not ask our right handers to draw with their let hand in order to check this prediction. However, in a recent study aiming to investigate intermanual diferences in copying performance, Yamashita [55] examined the right- and let-hand performance on the ROCF in a nonclinical sample of undergraduates. Yamashita Hypothesis for research Becoming let-handed is as physiological as becoming right-handed. Some people do not inherit the genetic inluence, therefore lateralizing themselves by the other inluences or even by chance. Healthy genetic let-handed develop an original mind in comparison with right-handed individuals [31–33]. found that hand use had a minimal efect on performance in the copy trial. So the hemispheric specialization theory does not imply that let handers will better succeed in copying the ROCF than right handers. Indeed, a dominant hand for speciic tasks is the result of long training which can interfere with hemispheric specialization. his is particularly true for drawing and writing. As far as learning is concerned, lateralization provides a child with a tool for space behavior, since lateral preference strongly helps the child to build his/her body scheme and organize peri corporal behavior. his boosted training results in a certain advantage in developing visual-spatial abilities, reading, and even calculation in lateralized children [38, 39]. he aim of the study reported here is twofold. First, we tested the view that individuals who do not develop a typically strong behavioral laterality are distributed differentially among the two genders across age. Second, we examined whether let handedness and mixed handedness are associated with an elevated risk of some developmental or cognitive deicits. To this end, we used two popular tools, the Edinburgh Handedness Inventory (EHI) [56] and the Rey-Osterrieth Complex Figure (ROCF) test [57–59] in order to assess handedness and cognitive development, respectively. EHI is a reliable and well-validated instrument and, according to the Citation Index, has been the most widely used handedness inventory in the literature. he ROCF is a popular neuropsychological test designed for adults that has been successfully employed with school-aged children. Its utility with this population stems largely from the fact that it provides such a rich data source, allowing for the assessment of multiple cognitive processes (e.g., perceptual, spatial, metacognitive, and memory). he ROCF has proven useful in the study of normal (Karapetsas and Kantas, 1991 [60]; 4 Waber and Holmes, 1985 [61]) and atypical child development (Brandys and Rourke, 1991 [62]). Children’s performance on the ROCF follows a clear developmental trajectory; it is very challenging for early primary school children but becomes more manageable for older children and adults [60, 61]. he ive hypotheses concerning the origin and the consequences of handedness in cognitive development mentioned in Table 1 could explain why experimental results oten contradict each other depending on case selection and on the handedness characteristics considered. he present study deals with three of them: hormonal-developmental, neuropathological, and learning. In line with the delayed development of the let hemisphere in males proposed by Geschwind and Galaburda [34], we expect to ind a preponderance of boys in the nonlateralized group because of their slight delay in brain maturation when compared to girls (Hypothesis 1). According to the neuropathological model [1, 10, 28], it was hypothesized that performance on copying the ROCF would be particularly low in mixedhanded and in extremely lateralized persons (Hypothesis 2). Finally, the learning model of handedness [38, 39] would predict that the worst scores on ROCF would be found in mixed-handed subjects, because non-lateralized children lack laterality support in the development of their skills (Hypothesis 3). 2. Method 2.1. Population . We followed a two-stage process for our case selection. Children were recruited from normal schools using a procedure which aimed at collecting as many let handers as right handers. Teachers were asked to indicate which students wrote with their let hand. Using the Edinburgh Handedness Inventory [56], we subsequently identiied 420 children as let-handed and 72 children as nonlateralized. hen, each lethanded child was matched by age and sex to a right-handed child. By the end of this procedure, we collected observations from a total sample of 912 schoolchildren consisting of 420 let handers, 420 right handers, and 72 mixed handers. All of these children were drawn from regular schools and had no history of major medical illness, psychiatric illness, developmental disorder, or signiicant visual or auditory impairments according to the medical reports of their schools. he 912 children were subdivided into two age groups. he younger age group (5.5 to 9.5 yr.) consisted of 512 subjects, and the older group (aged 9.5 to 12.5 yrs.) consisted of 400 subjects. he adults were 545 students (199 men and 346 women), aged 17.6 to 32 years (� = 19.5, SD = 1.8), all drawn from the Engineering Faculty and the Humanities Faculty of the University of hessaly, Greece. University students in Greece represent 30 percent of the total young adult population, so we selected a subgroup of the total population at the highest academic level. Given the overrepresentation of women in our adult sample and the study’s aim to compare the gender ratio of adults with that of children, we calculated a corrective index (dividing the number of men by that of women), in order to represent men and women equally. he corrective Child Development Research index applied was number of women × 0.575 = corrected number of women compared to men. 2.2. Materials and Procedure 2.2.1. Lateralization Index. In the present study we used a shortened version of the EHI [56] to assess hand preference. Following Bryden and Steenhuis’ recommendation [63] we saved the following items from the original version: writing, drawing, use of scissors, striking a match, and opening a box. he ive items listed are deemed suicient to produce reliable and valid results [64] and allow for safe classiication of the participants into handedness groups [65]. Numerous studies have conirmed the superior rigour and reliability of the EHI compared to other handedness questionnaires [66–69]. Test-Retest reliability of the EHI as measured by the Pearson �, Kendall �, and Spearman �� ranges from 0.95 to 0.98 [68]. he medium to high correlations of the EHI with other behavioral measures of handedness (e.g., the Purdue Pegboard test, a test of manual dexterity) demonstrate the high concurrent validity of the test [70–72]. Procedure. For children aged 5.5 to 7.5, the assessment of hand preference was done through demonstration in order to avoid any interpretational diiculties that could occur with a written questionnaire. For each handedness questionnaire item, children were asked to indicate whether they had used the right hand or the let hand. his type of procedure has been proposed by Coren [65] as the most appropriate means for assessing handedness in younger groups. Further, Steenhuis and Bryden [73] indicated that preference questions are closely related to performance measures concerning similar activities. Scoring. Children aged 7.5 to 12.5, and adults completed the EHI. he score for the EHI is computed as the diference between the total number of right- or let-handed responses divided by the total number of responses, and the result is multiplied by 100 to produce the Laterality Quotient. Subjects who scored between +91 and +100 were labelled consistent right-handers (CRH), those with scores between +30 and +90 inconsistent right-handers (IRH), those with scores between −29 and +29 mixed-handers (MH), those with scores between −30 and −90 inconsistent let-handers (ILH), and those with scores between −91 and −100 consistent let-handers (CLH). 2.2.2. Visual-Spatial Skills . In order to examine visual-spatial skills, we used the Rey-Osterrieth Complex Figure (ROCF), according to the directions provided by the authors [57–59]. Procedure. he igure was displayed on a piece of white paper measuring 30 cm × 21 cm so that the base rectangle measured 8.0 × 5.5 cm. When tested, each participant was provided with a piece of white paper of the same dimensions as the one on which the Rey-Osterrieth igure was presented. Participants were tested in their classroom groups. Ater the igure had been administered, we asked participants Child Development Research to copy it as best they could without neglecting any of its iner details. here were no time restrictions. When a participant stopped, we asked him/her if he/she had inished. If he/she answered airmatively, we removed the copying sheet. All the let handers used their let hand for the drawing task, and all the right handers used their right hand. Mixed-handed people were allowed to draw with either hand. Scoring. To evaluate the data in the manner described by Osterrieth [59], the complex igure was divided into 18 elements, each of which was assigned the same value. hen the number of elements in each igure reproduced by the participants was counted, their positions in relation to the whole igure were noted, and the accuracy of reproduction was noted. he following scoring method was employed. For each element that was correctly placed in its proper position and, moreover, was accurately drawn, a score of 2 was allocated. If the element was correct, but, in the wrong position, a score of 1 was allocated. If the element was distorted or incomplete but recognizable and in the right position a score of 1 was allocated. If the element possessed the same characteristics and was misplaced, a score of 0.5 was allocated. Finally, if an element was not easily recognisable or was absent, the score was zero. he highest possible score for each igure was 36 points. he time required for the completion of the igure was not taken into consideration during scoring, but on average copying took between 3 and 5 minutes. A random sample of 80 igures was scored by two scorers on the basis of the aforementioned criteria, with 94% agreement. his indicated suicient interrater reliability of the scoring method, and thus the remaining igures were scored by one judge only. 3. Results 3.1. Sex Ratio in Lateralized and Nonlateralized Samples. We found unequal numbers of boys and girls among the mixedhanded children: 27 boys and 7 girls in the younger group (a ratio of 3.6 : 1) and 27 boys and 13 girls in the older group (a ratio of 2.1 : 1). Taking into account the corrected number of women, in order to be able to make comparisons with the data of children, we found a sex ratio of 1.4 men for 1 woman in mixed-handed adults. A Kruskall-Wallis test indicated a signiicant relationship between sex ratio and age in mixedhanded people (� = 5.76, �� = 2, and � = .018). Table 2 recapitulates the frequencies and sex ratio according to handedness and age groups. Table 2 shows that mixed handedness exists in all age groups. However, there are three times more mixed-handed boys than girls in the younger group. Maturation and learning change the igures. However, mixed handedness is still more frequent in adult males than females. he right-handedness igures conirm the existence of a relationship between sex and handedness development. Indeed, because let-handers were matched to right-handers for both boys and girls, we would expect to ind equivalent frequencies of inconsistent and consistent right-handers regardless of sex. his was held true for younger children 5 where we observed 57 IRH boys compared to 59 IRH girls and 63 CRH boys compared to 61 CRH girls (�2 = .07, �� = 1, ns). However, a developmental trend seems to be observed regarding sex ratio in right-handers since we found 41 IRH boys compared to 28 IRH girls and 49 CRH boys compared to 62 CRH girls in older children (�2 = 3.97, �� = 1, and � = .046). To examine whether the older right-handed children were making a transition from the inconsistence use of the right hand to the consistence use and the possible efect of sex a Kruskall-Wallis test was performed. he signiicance test between younger and older children revealed a main efect for hand consistency (�2 = 4.16, � = .041) and a main efect for sex ratio (�2 = 18.01, � < .001). hus, even when applying a strict recruitment procedure in order to balance let-handed and right-handed boys and girls, we found a tendency for older right-handed girls to become more strongly lateralized than boys with age, and sex-related developmental trends appeared to exist. To summarize, we observed a sex-related developmental change in handedness distribution. his refers to the hormonal-developmental hypothesis of lateralization. Both the diminishing prevalence of boys in the mixed-handed sample and the stronger lateralization of older right-handed girls compared to boys indicate a relative delay in the lateralization process of boys. 3.2. Age, Sex, and Handedness Diferences in Visual-Spatial Skills (Intelligence). ROCF raw scores show systematic changes across ages (see Table 3). Scores were evaluated using a 5 × 3 × 2 (handedness × age × sex) mixed-efect analysis of variance. here were statistically signiicant main efects for handedness (�4,1427 = 25.26, � < .001) and age (�2,1427 = 182.46, � < .001), which means, respectively, that performance improved with age (as can be seen in Table 3) and that handedness groups difered in their performance. he main efect between males and females was not statistically signiicant (�1,1427 = 3.19, ns). here was also a statistically signiicant age by handedness interaction (�8,1427 = 154.39, � < .001), which indicates that the efect of handedness difered at diferent ages. No other signiicant interaction between the factors was found (handedness × sex �4,1427 = 0.59, ns; age × sex �2,1427 = 1.47, ns; handedness × age × sex �8,1427 = 0.63, ns). In order to identify the diferences in ROCF performance by handedness in the various age groups, we applied oneway analysis of variance followed by Duncan tests for post hoc comparisons between the handedness groups. he results of these analyses revealed statistically signiicant diferences between handedness groups in the younger children (�4,507 = 14.99, � < .001). Duncan tests showed that there were signiicant diferences between the mixed-handed group (MH) and all the other groups. he diference in ROCF mean scores regarding handedness was also statistically signiicant in older children (�4,395 = 20.23, � < .001). he Duncan test showed that the MH group difered signiicantly from all the other groups. As was previously demonstrated, let handers did not perform as well as right handers [5, 6]. his was true for children in both age groups. In adults, the diference 6 Child Development Research Table 2: Sex ratio (males/females) according to handedness and age groups. Handedness groups CRH IRH MH ILH CLH Lateralization index +100 +90 to +30 +20 to −20 −30 to −90 −100 Younger children 1.0 0.9 3.6 1.0 1.0 Older children 0.8 1.5 2.1 0.9 1.1 Adults 0.9 1.1 1.4 0.8 1.0 Note: CRH: consistent right-handers, IRH: inconsistent right-handers, MH: mixed handers, ILH: inconsistent let handers, CLH: consistent let-handers. Table 3: Rey-Osterrieth Complex Figure scores by handedness and age group. Handedness group CRH IRH MH ILH CLH Total M 24.7 24.7 16.1 21.6 18.8 22.3 Younger children SD 8.5 8.8 5.1 7.2 6.7 8.2 Older children M SD 30.3 6.3 31.9 5.0 22.9 5.6 27.7 5.1 27.4 5.4 28.6 6.1 Adults M 30.9 31.5 29.9 31.0 31.0 31.1 Total SD 2.9 2.5 2.9 2.1 2.2 2.7 M 29.2 29.6 21.9 24.9 23.2 27.3 SD 6.2 6.2 7.1 7.0 7.6 7.1 Note: CRH: consistent right handers, IRH: inconsistent right handers, MH: mixed handers, ILH: inconsistent let-handers, CLH: consistent let-handers. 36 32 Mean ROCF scores in ROCF scores between handedness groups was marginally signiicant (�5,540 = 2.38, � = .05) with the Duncan test showing that the MH group difered signiicantly only with the IRH group, which was the handedness subgroup which revealed the higher performance. hese diferences are presented in Figure 1. he limited diferences between handedness groups in adults could be attributed to a ceiling efect as the maximum score was 36, with an average score being 31.1 with much less variability than in the children samples (2.7 versus 6.1 and 8.2). A similar ceiling efect for the copy measure of the ROCF has been previously reported in a study of college students [74]. 28 24 20 16 4. Discussion he present study investigated whether individuals who do not develop a typically strong behavioral laterality are distributed diferentially among the two genders across age and whether let handedness and mixed handedness are associated with an elevated risk of some developmental or cognitive deicits. hanks to the vast amount of data collected from nonright-handed samples, the present study revealed developmental and sex-related lateralization efects on a task of visual-spatial skills and evaluated these efects with regard to the hypotheses based on the hormonal-developmental, the neuropathological, and the learning models of handedness. Firstly, based on the hormonal-developmental hypothesis [34] we predicted sex diferences in the distribution of handedness across age groups. Our results conirm that the trend towards consistent right handedness is sex related. Speciically, girls in our sample were more advanced than boys in this lateralization process. Moreover, right-handed girls in the older group of this study had become more strongly lateralized than boys. On the other hand, boys were over represented in the mixed-handed group. his tendency 12 CRH IRH AM Handedness ILH CLH Age Younger children Older children Adults Figure 1: Rey-Osterrieth Complex Figure scores by handedness in younger children (—), older children (-⋅⋅-), and adults (- - -). appears in our study to continue into adulthood, albeit to a much lesser extent. However, further longitudinal research is needed in order to substantiate this claim. Such longitudinal studies are vital given the discrepancy that exists between neuropsychological studies suggesting that functional brain asymmetry is more characteristic of the right-handed male population and magnetic resonance imaging (MRI) studies [75] pointing to a greater asymmetry in females, at least for motor functions. Child Development Research he inding that men are more prone to mixed handedness compared to women is in accordance with that of a recent meta-analysis [4]. Additionally, the same metaanalysis concluded that the magnitude of the diference between sexes was signiicantly moderated by the way in which handedness was assessed (e.g., by hand writing or by other means). Papadatou-Pastou et al. [4] suggested that, in addition to innate biological diferences between the two sexes, handedness is also modulated by psychological inluences. his suggestion has been conirmed by the recent study of Dirnberger [76], which examined whether the modulating factors of sex and self-perception (measured as hypochondriac traits) interact and afect handedness in a mixed male and female sample. heir indings suggested that handedness data are inluenced by self-perception, attention to action, or inconsistent sensitivity to stimuli from the environment. Nevertheless, the researchers concluded that some modulating psychological or behavioural variables may also underlie genetic inluences, which, in turn, might even be sex speciic. he second hypothesis of the present study emanated from the neuropathological model of handedness [1, 10, 28]. According to this hypothesis the prediction was that performance on copying the ROCF would be particularly low in mixed-handed and in extremely lateralized persons. Our results showed that performance on this visualspatial and graphic task was comparatively low in extremely lateralized persons, who may include symptomatic hemiparesis. he present study complements previous indings [5, 6] concerning the let handers’ disadvantage in ROCF copying: extreme let handers performed at a lower level in copying than inconsistent let-handers in the younger children’s group. Some pathological cases among let-handers might be responsible for this group trend. It could be postulated that pure let handedness emerged precociously in such cases because of an impaired right hand. We know from developmental neuropsychological studies that when the right hemisphere is required to take over language functions in addition to visual-spatial functions, the latter does not develop completely [77]. his might well be the case happening in some of our extreme let-handed youngsters. It is also interesting to note that in the present study extreme lateralization does not correspond to higher cognitive scores than moderate lateralization. Furthermore, the clear disadvantage of extreme let-handedness gradually dissolves with age and completely vanishes in adults. hus, either our sampling strategy has prevented us from choosing neuropathological cases in the student population, or the visual-spatial impairment is compensated for or even cured by adulthood. Our third hypothesis based on the learning model [38, 39] predicted that low scores on ROCF test would be found in mixed-handed subjects, because these persons lack laterality support in the development of their skills. Backwardness in visual-spatial skills as detected by low ROCF scores is conirmed in mixed-handed children from irst to sixth grade. Overall, the results of this study conirm the learning model predictions but are not in agreement with all the 7 predictions of the neuropathological model. Although poor performance among strong dextral has been found for many types of cognitive and educational tests (for a review see [78]), in our study no diferences were found in visual-spatial skills between consistent and inconsistent right handers in this age group. It could be suggested that the appropriate brain mechanisms for successful ROCF copying are established earlier in both right-handed groups. Moreover, another study [79] examined the motor skills of young (approximately seven years old) children and discovered that let- and mixedhanded children were inferior to right-handed children in motor performance. he present data seem to it in with Crow et al.’s indings [25] that the most substantial deicits in ability are close to the point of equal hand skill or hemispheric indecision. Crow and his collaborators [25] claimed that the failure to establish unequivocal hemispheric dominance is indicative of developmental delay. Similar indings are supported by research on gitedness. In children aged 8 to 14, more nongited than gited students are distributed in the let- and mixed-handedness categories [80]. Replication of the Crow et al. study [25] by Mayringer and Wimmer [81] was unsuccessful, probably, in our view, for two reasons: irstly the experimental sample involved was relatively modest and biased since the researchers had deliberately brought reading diiculties to the fore (boys only), and, secondly, because hemispheric indecision was less precisely deined. A more recent study [82] using a multiple regression approach, showed that the Mayringer and Wimmer’s [81] reanalysis sufered from statistical problems and that the lower scores close to the point of equal hand skill reported by Crow et al. [25] are part of a general monotonic relationship of laterality to cognitive ability, which is independent of overall hand skill. Additionally, our indings are in accordance with recent studies [83, 84] which indicated that mixed handedness compared to right handedness was associated with poorer scholastic performance. Overall from the aforementioned studies [25, 82–84] we could conclude that mixed handedness could aid in the recognition of children who are at risk for academic problems. In adults, however, all handedness groups performed equally. Only a marginal diference in copying the ReyOsterrieth Complex Figure was detected between mixedhanded and the inconsistent right-handed university students. Does this mean that such cognitive diiculties in children are only incidental and can be ignored? Indeed, we do not know if time will complete the gap in visual-spatial development, particularly in the most exposed group, that is, the non-lateralized children. Ignoring what appears to be a simple gap and not a permanent handicap would mean paying little attention to the learning disability condition. For example, the fact that dyslexic children can eventually succeed in professional careers should not prevent consideration of their sufering during development. We think that this gap in development is pathological both from the pediatric and the psychological points of view. Yeo et al. [85] have shown that let or nonright handers and extreme right handers are characterized by some degree of developmental instability, that is, minor physiological abnormalities. hey propose that the underpinnings of 8 developmental instability may illuminate the association of handedness with a variety of developmental disorders. Our results show that delayed learning afects boys three times more than girls in the early school years. Whether they are boys or girls, schoolchildren exhibiting developmental and learning gap deserve our attention in order to prevent academic failure. he sex ratio in mixed-handed schoolchildren reminds us of the prevalence of learning disability which touches two to three times more males than females. he present indings it in with the epidemiology of learning disabilities. In sum, even if minority handedness status is not the direct cause of learning disability, as was believed in Orton’s time, for example, it nevertheless provides us with an easy means of detecting developmentally “at risk” children. Neuropathological cases are likely to be found in all handedness groups. Some children with mild neurological syndromes are likely to be present among consistent right handers. However, these pathological cases represent a very small percentage of the consistent right-handed group, a larger proportion of consistent let handers, and a much larger proportion of mixed-handed children. Moreover, recent structural neuroimaging indings [86, 87] have indicated that mixed handedness is associated with neuroanatomical diferences, thus ofering additional support to the view that individuals who do not develop a typically strong behavioral laterality difer signiicantly and are at somewhat higher risk of certain disorders and brain abnormalities from consistently let- and right-handed individuals. More speciically, a recent study [86] showed that mixed handedness was associated with increased hippocampal and amygdalar atrophy in ageing. Another study [87] showed that mixed handedness, but not let handedness per se, was associated with corpus callosum thickness, which is indicative of increased interhemispheric interaction. hese indings provide evidence for a somewhat diferent neurobiological background (of either biological or environmental origin) in mixed handers, which might give rise to a number of risk factors leading to certain developmental disabilities. 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