Right-shift Theory Research Articles

The protocadherin 11X/Y (PCDH11X/Y) gene pair as determinant of cerebral asymmetry in modern Homo sapiens

Annett's right-shift theory proposes that human cerebral dominance (the functional and anatomical asymmetry or torque along the antero-posterior axis) and handedness are determined by a single “right-shift” gene. Familial transmission of handedness and specific deviations of cerebral dominance in sex chromosome aneuploidies implicate a locus within an X–Y homologous region of the sex chromosomes. The Xq21.3/Yp11.2 human-specific region of homology includes the protocadherin 11X/Y (PCDH11X/Y) gene pair, which encode cell adhesion molecules subject to accelerated evolution following the separation of the human and chimpanzee lineages six million years ago. PCDH11X and PCDH11Y, differentially regulated by retinoic acid, are highly expressed in the ventricular zone, subplate, and cortical plate of the developing cerebral cortex. Both proteins interact with β-catenin, a protein that plays a role in determining axis formation and regulating cortical size. In this way, the PCDH11X/Y gene pair determines cerebral asymmetry by initiating the right shift in Homo sapiens.

Dyslexia and hand preference in secondary school students.

results with regard to handedness and dyslexia have been ambiguous. The present study investigated the relationship between handedness and dyslexia in secondary school students based on genetic (Right-Shift) and hormonal- developmental theories of handedness. A total of 135 students (45 dyslexics and 70 age- and sex-matched controls) participated in the study. Handedness was defined according to the Edinburgh Handedness Inventory. We developed several classifications that represented various levels of handedness. Both continuous and dichotomous classifications of handedness revealed a small but reliable increase in the proportion of non-right-handers among dyslexics, likely because of the increased proportion of dyslexics among pure left-handers. Dyslexics did not display precisely the same pattern of right and left responses as controls, with some differences at the extremes of the continuum. The present results provide empirical support for Annett's (1985) Right-Shift theory predictions. Additionally, the present study indicates that using a numerical scoring system or dichotomous classifications with restricted criteria that permit the measurement of several degrees of handedness appears to better determine hand preference than using broad classifications into handedness groups.

Familial handedness and spatial ability: A study with Chinese students aged 14–24

This study tested Annett’s right-shift theory on spatial ability with two samples from China. The Vandenberg Mental Rotation Test (MRT), Edinburgh Handedness Inventory, and Family Handedness Questionnaire were administered to 266 high school students and 297 undergraduates. We found very few r++ or r−− among Chinese students. Most Chinese are either moderately right-handed or ambidextrous. Consistent with Casey’s finding, we found using different methods to classify handedness leads to different conclusions. However, we did not find the effect of familial handedness that Casey found. Visual strategy is related to success on the MRT but handedness is not.

Genetic influence on the expression of hand preferences in chimpanzees (Pan troglodytes): evidence in support of the right-shift theory and developmental instability.

Genetic mechanisms have been proposed to explain the pervasive representation of right-handedness in humans, whereas random, nongenetic factors have been posited to explain the lack of population-level right-handedness in nonhuman primates. We report evidence that hand preferences in chimpanzees are heritable, even among related individuals raised in different environments. Furthermore, we report that the degree of heritability is modified by factors associated with developmental instability, notably, offspring parity. The data are interpreted to reconcile both genetic models for handedness and hypotheses suggesting that developmental instability influences variation in handedness.

The theory of an agnosic right shift gene in schizophrenia and autism

The right shift (RS) theory (Annett, M., 1972. The distribution of manual asymmetry. Br. J. Psychol. 63, 343–358; Annett, M., 1985. Left, Right, Hand and Brain: The Right Shift Theory. Lawrence Erlbaum, London) suggests that the typical pattern of human cerebral and manual asymmetries depends on a single gene (RS+) which impairs speech-related cortex of the right hemisphere. The theory offers solutions to several puzzles, including the distribution of handedness in families (Annett, M., 1978. A Single Gene Explanation of Right and Left Handedness and Brainedness. Lanchester Polytechnic, Coventry; Annett, M., 1996. In defense of the right shift theory. Percept. Motor Skills 82, 115–137), relations between handedness and cerebral speech laterality (Annett, M., 1975. Hand preference and the laterality of cerebral speech. Cortex 11, 305–328; Annett, M., Alexander, M.P., 1996. Atypical cerebral dominance: predictions and tests of the right shift theory. Neuropsychologia 34, 1215–1227) and handedness and dyslexia (Annett, M. et al., 1996. Types of dyslexia and the shift to dextrality. J. Child Psychol. Psychiatry 37, 167–180). If Crow's (Crow, T.J. et al., 1989. Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. Arch. Gen. Psychiatry 46, 1145–1150; Crow, T.J., 1997. Is schizophrenia the price that Homo sapiens pays for language? Schizophr. Res. 28, 127–141) theory that schizophrenia is due to an anomaly of cerebral dominance is correct, and if the RS theory is correct, schizophrenia could be due to an anomaly of the RS+ gene. If the RS+ gene were at risk for a mutation which caused a loss of directional coding, the mutant could be described as ‘agnosic’ for left and right. Such a gene would impair either hemisphere at random. When paired with another RS+ gene, both hemispheres would be impaired in 50% of cases. The other 50% and people in whom the agnosic gene is paired with an RS-allele (neutral for asymmetry and not giving hemisphere impairment) would have one unaffected hemisphere and, thus, normal development. Quantitative predictions based on the RS genetic theory as previously developed, plus an agnosic mutant with frequency required to give schizophrenia in 1% of the population, are consistent with estimates of concordance for schizophrenia in relatives. Homozygotes of the agnosic mutant would occur at about the rate estimated for autism.

Failure to support the right-shift theory's hypothesis of a 'heterozygote advantage' for cognitive abilities.

Annett's (1985) 'right-shift' theory of language dominance and handedness posits three genotypes, rs++, rs(+)- and rs(-)-, and Annett has hypothesized that there are cognitive ability correlates of these genotypes. The rs++ genotype person is held to be 'at risk' for maldevelopment of spatial or other right hemisphere-based cognitive abilities, and the rs(-)- genotype individual is held to be at risk for maldevelopment of phonological abilities. Noting that there must be some adaptive advantage conferred by the heterozygous genotype for it to have survived over a presumably long period of evolution, Annett has hypothesized that heterozygotes are afforded an adaptive advantage over homozygotes because of their freedom from 'risks' to intelligence generally. Annett and colleagues have used two different indices, or markers, from which they have inferred differing concentrations of the three genotypes within groups of participants. One marker, based on responses to hand preference items of the Annett Handedness Inventory, was found by Annett (1992) to support her theory in that the least dextral of right-handed participants did best on spatial tests. The other marker Annett has used is based on the degree of right-hand advantage on a simple peg moving speed task. The present study utilized both methods and studied the performances of 259 dextral college men and women on two tests of mental rotation ability and two tests of verbal abilities. Results were not supportive of the heterozygote advantage hypothesis, and suggested that visuospatial ability was modestly related to greater dextrality of participants.

Testing the hypothesis of the relationships between laterality and ability according to Annett's right-shift theory: findings in an epidemiological sample of young adults.

In a large epidemiological sample of young adults, predictions of the right-shift (RS) theory of Annett that cognitive abilities will vary with right-left hand skill were tested. Presenting a theory of a genetic balanced polymorphism with heterozygote advantage for laterality and ability, Annett & Manning (1989, 1990a) and Annett (1993c) claimed that probands at the right end of the R-L hand skill continuum would show lower general intelligence in IQ testing and that specific verbal abilities and educational success would be lower at both extremes of the R-L distribution, taking the form of an inverted U. Most of these predictions could not be confirmed by our study. In particular, our data contrast with the important and specific prediction of the RS theory that strong dextrals will be the most disfavoured group. In our sample, probands at the left end of the R-L continuum had significantly lower scores in spelling and educational success and showed a tendency to have lower non-verbal IQ scores, while strong dextrals tended to have average or even marginally higher ability scores. The effects, however, are small and decrease when controlling for other variables. Implications of these empirical findings for the right-shift theory are discussed.

Atypical cerebral dominance: Predictions and tests of the right shift theory

Alexander and Annett ( Brain and Language, in press) described new cases of atypical cerebral specialization, and suggested that these observations and others in the literature could be explained by the right shift (RS) theory. The theory generates specific predictions as to the prevalence of different patterns of cerebral dominance and their distribution among right-handers and left-handers. Predictions differ between strict and generous criteria of sinistrality, as between left writers and non-right-handers. Tests of the predictions against reports in the literature reveal good fits for most data. New studies will test the RS theory if their design permits examination of the present predictions

In defence of the right shift theory.

The right shift (RS) theory of a gene for left-cerebral dominance which increases the probability of right-handedness is outlined, together with two proposed alternatives, the 1985a genetic theory of McManus and the 1993 developmental instability theory of Yeo and Gangestad. Similarities and differences among the three theories are reviewed. Both of the genetic theories can predict the distribution of handedness in families and in twins more efficiently than the developmental instability theory, and the RS theory better than the McManus theory.

Handedness and dyslexia: a meta-analysis.

The question whether there is an association between handedness and dyslexia has been investigated in many studies spanning more than 50 years. In 1990, Bishop reviewed studies which met stringent methodological criteria and concluded that there was little support for an association. A reanalysis of the same studies using newer procedures of meta-analysis shows that there is a small but reliable increase in the proportion of nonright-handers among dyslexics as expected by the right-shift theory of handedness of Annett.

Handedness as a continuous variable with dextral shift: sex, generation, and family handedness in subgroups of left- and right-handers.

Percentages of left-handed relatives were compared between subgroups of left-handers and of right-handers to test the prediction that the subgroups are ordered for probability of carrying the rs +/gene (hypothesized by the right-shift theory of handedness). Data included families of undergraduates and Open University students who described their children as well as other relatives. Linear relationships were found between subgroup order and percentage of left-handed relatives. In agreement with previous evidence that some right-writers with weak sinistral preferences (class 2) are in fact more dextral than consistent right-handers (class 1), class 2 tended to have fewer left-handed relatives than class 1 in both samples. Left writers with weak dextral tendencies (class 7) tended to have more left-handed relatives that consistent left-handers (class 8). Comparisons of the distribution of subgroup handedness in undergraduates and their parents revealed strong effects for sex and for generation. In both cases, the main contrasts were not between left-handers and right-handers but between left-handers plus right-handers with weak dextrality and right-handers with strong dextrality. The findings are consistent with the theory that the relevant factor is not handedness as such but, rather, the absence or presence of the rs +/gene.

Rejoinder to ‘Annett's theory’ by McManus, Shergill & Bryden (1993)

Criticisms of the right shift (RS) theory (Annett, 1972, 1985) by McManus, Shergill & Bryden (1993) are shown to be ill‐founded. The hypothesis of a genetic balanced polymorphism with heterozygote advantage (BP + HA) is not based on the misconceptions McManus et al. (1993) suppose, and the evidence for a BP + HA is more robust than they suggest. The RS theory continues to lead to new findings, some directly contrary to assumptions of McManus (1985).

Mathematical ability and the right-shift theory of handedness

A genetic theory of handedness, the right-shift theory, associates differential patterns of cerebral functioning with contrasting handedness groups and suggests that individuals with an rs++ genotype will be disadvantaged in mathematical performance. This hypothesis is investigated with contrasting handedness groups drawn from a national sample of over 11 000 children from the National Child Development Study. Some differentiation in cognitive performance between handedness groups is found in the direction predicted by the right-shift theory but the level of the findings is not statistically significant. The rs++/mathematical deficit hypothesis is not confirmed.

Comments on Tambs, Magnus, and Berg: Twinning and the Right-Shift Theory of Handedness

The evidence of Tambs, et al. (1986) that left-handedness is caused by environmental and not by genetic factors is shown to be consistent with Annett's right-shift theory of handedness. Maternal effects need to be evaluated in the light of possible reporting biases.

Which theory fails? A reply to McManus

The claim that the right shift (RS) theory fails is examined and rejected on several grounds. First, it is uncertain that the symmetric bimodal (SB) theory can generate predictions that are clearly distinct from those of the RS theory. Second, the interpretation of the empirical data depends on an analysis of the skills required for the task and of the samples tested; the latter were not drawn from the general population. Third, the aim of seeking algorithmic solutions is inappropriate as an alternative to the original aim (Annett & Kilshaw, 1983) of testing whether previously successful heuristic solutions could be rejected. Fourth, the common‐sense classification into left‐ and right‐handers, although undoubtedly the starting point of all analyses of laterality, including that of the RS theory, has led to little progress in the search for the causes and consequences of lateral asymmetries. The classification can lead to sterile arguments about the ‘true’ incidence of left‐handedness, of which examples are to be found in McManus's paper. Finally, elaborate statistical techniques may assist but cannot supplant the careful evaluation of evidence. The RS theory is falsifiable, but not on the grounds suggested by McManus.