Laterality and Types of Dyslexia

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MARIAN ANNETT Department of Psychology, Universityof Leicester, Leicester LE1 7RH, UK

A M L a Nt o d N N B E R 2 I E6 i 1U rO s T3 9t yR 0 B 9 T1 O o h a ca s n pse t e t d i a ucru esi gnb i i b sea a z e erey sr n o ger a d hnul dl ha a h a a as f i ni h pw i tai pg e u n o l l rh h m c c ca noh e m T s dr bi a m t i vae pee a f d t r id a a i as c a s o a c po t i f l son t rl nl h ht iy a aat t e r bd o m ci omu h T d o hi i fsa a c b et n a i t r s xt dd n i mhd peoeb a s g i h urxedl+ d ta ltni a w t f o t g r i e f t e p sh o d qr t w e u yh o ul i r o n t h l ps ev e mt ei o p hni nal r h T eg mi se r p ai g buo n s p pg e g apw o oh o h l h ga e ln r tfy e th ed t ma re ey l a a i tb e i r l an il i t A o tp m t d p ed l l vt to h i y e t b cy l h s hoa ( pdo– – a pr t+l mo m hi oeo g a a er f r Tn c q e ow w r t u itat o c i h yp r e d d o o a pte ehsr i g seyi x i a s b p f t rp – a n ao b fo t e r c + T fn s e s i a - e m s lo hao ms h nn s ec p s h w t l as b m s n d ha th c t Ed e f o t t rd o i ved h nx b oih t tir o ut s t l ne h s o c g hs ba f d ao t i o h i np a nr a y i ibo d s o e C ni te e O 1a o l o iad t a p um i E S L l c s i et e v in d H

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THE TYPICAL pattern of cerebral specialization is now fairly well established but there is no agreed theory of exceptions to the general rule. A full understanding of the nature of hemisphere specialization requires a theory of atypical cases. There appears to be a type of “default” assumption that atypical cerebral asymmetries depend on pathologies of development. The most ambitious attempt to explain atypical dominance was that of Geschwind (22,23). Many factors were suggested which might interfere with the normal pattern of cerebral development, with particular emphasis on testosterone and the immune system. There is no unequivocal support for this theory (18). Atypical cerebral specialization is associated statistically with atypical hand preference (31) but the causes of the association are obscure. Orton (27) suggested that children with developmental language disorders of speech and reading are likely to have atypical handedness also. There have been many studies of the handedness of poor readers, but few give clear support for Orton’s thesis. Bishop (16) reviewed the literature on handedness in relation to developmental disorders of many kinds, including reading, and came to the conclusion that the supposed relationship is not worth further attention, in agreement with several previous reviewers (29,30,32).

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The question of the O D relationship U between Chuman hand preference and cerebral speech literality was the starting point and the main focus of my research in this field. The theory I proposed, the right shift (RS) theory (2,6) was not invented or plucked out of the sky. It was discovered in a series of steps over many years of empirical research. I would like to tell you about the most recent findings which explain the puzzling controversies about handedness and dyslexia, but I must first outline some key features of the theory. O

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After I had been researching questions about handedness and cerebral dominance for some 10 years, there were four facts, of which I was quite certain, as follows. (1) The proportions of left, mixed and right handers in humans. When I observed children performing

several actions like drawing, throwing a ball, hammering with a toy hammer and pretending to clean the teeth, or asked students to observe one another in psychology laboratory classes, or to answer questions about these actions by questionnaire, the proportions of people using the left hand for all actions (consistent left handers) were around 3 and the proportions of consistent right handers around 640/.. About 3370 631

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preferred to use the right hand for some actions, and the left hand for others. I called these people mixed handers. They are not ambidextrous, and they are not ambiguous or uncertain which hand to use. They have stable preferences for particular actions, but the preferred hand happens to differ between the actions. I showed a long time ago that the three types of handedness occurred reliably in these proportions (l). I have continued to collect data from students in psychology laboratory practical classes, and the distributions continue to be fully predictable. It astonishes me that the existence of mixed handers is glossed over in the handedness literature. The analysis of mixed handedness is one of the essential foundations of the RS theory. (2) The proportions of lejl, mixed and right pawedness in non-humans. The literature on hand and paw preferences of non-humans (rats, mice, cats, monkeys and chimpanzees) suggested that consistent preferences for the left side occurred in approximately 25~0, consistent right preferences in 25~0 while some 50% of animals were mixed handed in the sense that they changed the hand used between trials, usually when reaching for food. (3) A Gaussiandistributionof differences between the hands in skill. Measurement of the actual skill of each hand was important for a study I was making of hemiplegia (3), and considerable data were collected for a peg-moving task, in schoolchildren and in undergraduates. When several trials were performed by each hand, and the mean difference between the hands was plotted, the distribution clearly approximated a unimodal Gaussian curve. (4) Degrees of hand preference and degrees of hand skill are reliablyrelated. Left, mixed and right handers differ for right minus left (R-L) hand skill for peg moving. Subgroups of mixed handers were distinguished so as to define degrees of hand preference, ordered along the continuum of hand skill (6). Left handers were divided into three groups; some who do all of 12 actions with the left hand, some who do all important (primary) actions with the left hand, and a third group who write with the left hand but perform skilled actions like throwing, cleaning teeth, or hammering with the right hand. Similarly,subgroups of right handers were distinguished whose preferences for the left hand can be described as absent, mild, moderate or strong. The subgroups were defined by coordinating data for hand preference and hand skill. When the same classificationwas made in a second very large sample of Open University students, the match between subgroups and R–L times for peg moving were almost exact for most groups (6). Thus, I was convinced that there are degrees of hand preference which are reliably ordered for degrees of R–L hand skill. How are these four facts related? This question was answered when I plotted the percentages of hand preference under a normal curve as in Fig. 1. Each letter represents IYo under the curve. There are 25, 50 and 25 of the letters L, M and R, to represent the left, mixed and right handers of the non-human distribution. I then plotted the 4, 33 and 63% required for

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the human distribution, and the astonishing finding was that the thresholds separating left handers from mixed handers, and mixed handers from right handers, were the same distance apart in humans and non-humans. The non-human distribution becomes the human distribution, if the whole curve is moved a small distance to the right. This brought together all of the four facts, the human and non-human distributions of preference, the continuum of R–L hand preference and skill, and the Gaussian curve (2). All that is needed is a normal distribution of R–L differences for all species and a small displacement to the right in humans only. Hence the term “Right Shift Theory”. This analysis suggested that there are two characteristicsto be explained, a normal distribution of asymmetries and the shift for humans to the right. The most parsimonious explanation of the Gaussian curve is chance asymmetry. There is strong evidence that paw preferences in rodents are not genetic (19,28) but that they are congenital (20). This suggests that asymmetries of hand and brain arise in each individual in the course of early growth, through random asymmetries which occur as normal accidents of embryonic development. The Gaussian curve is likely to be due to randomly generated asymmetries in the efficiency of the two sides of the brain and body. The human shift to the right must depend on some systematic influence. The obvious hypothesis to consider first is that the relative advantage to the right hand is a by-product of human left hemisphere advantage. A small relative advantage to the left hemisphere could act like a mathematical constant added to a random distribution. It would displace the whole distribution to the right, without affecting its shape or variability. In the absence of left hemisphere dominance (and right shift), the simplest hypothesis is that all other phenomena arise as chance accidents of development. Thus, left handedness and right handedness depend on chance, but the chances of dextrality are increased by the presence of left hemisphere advantage.

LATERALITYAND TYPESOF DYSLEXIA An examination of the dysphasia literature for relations between handedness and brainedness showed that there were no findings which conflicted with this model (4). If right hemisphere speech develops by chance in those who lack the RS factor, then the proportion of dysphasic with right hemisphere lesions provides an important clue as to the proportion of people with absence of RS. It was shown that RS could be due to a single gene (rs+) (5). When the frequency of the rs – gene was estimated from the proportion of right hemisphere dysphasic, the genetic data for handedness in families were accounted for. This supported the assumption that it is a gene for left hemisphere speech that is involved, not a gene for handedness. The rs – allele(s) are hypothesized to be null or indifferent to literality of hand and brain. Because the RS theory is about handedness and because it assumes a genetic influence, it is sometimes misunderstood as a theory which postulates genes for handedness. The rs + gene is for cerebral asymmetry, not handedness. McManus (25) proposed a gene for right handedness and a gene for chance, implying that some people are influenced by chance and some are not. By contrast, the RS theory assumes that chance is the main determinant of asymmetries of the hand and brain in everyone. The gene introduces a small left hemisphere advantage which is sufficient to induce that hemisphere to serve speech. The relative increase in the skill of the right hand is incidental to cerebral asymmetry. The fact that pairs of monozygotic (MZ) twins sometimes differ for handedness (RL pairs) is a problem for theories which propose genes for handedness. It is not a problem for the RS theory because RL pairs of MZ and dizygotic (DZ) twins occur by chance. However, if only chance were involved, there should be 50Y0RL pairs instead of the approximately 20’%. observed. There are more RR pairs in both types of twins than expected by pure chance. Thus, handedness in twins depends on chance plus right shift, just as it does in everyone else. Almost all of the variability is non-genetic, while the genetic effect is virtually constant. The small amount of genetic variability associated with the rs locus does lead to stronger concordance in MZ than DZ pairs for handedness, but the sample size must be enormous to detect this (5). Predictionsfor Cognitive Development

The analysis above began with observed hand preference. It then inferred relationships with cerebral asymmetry, and a genetic foundation. In seeking to test the predictions of the theory for dyslexiawe must work through the levels again from genes, through cerebral asymmetry, and cognitive processes to handedness. The levels are summarized in Fig. 2. At the genetic level are the genotype frequencies, approximately 19, 49, 32 per cent for rs – –, rs +– and rs ++ genotypes, respectively. It must be emphasized that the genotype frequencies were not invented (9,26) but inferred from the proportion of right hemisphere dysphasic, as said above. The most striking thing about the genotype frequencies is that the proportion

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of heterozygotes is about as large as possible for a single genetic locus (maximum 50Yo). The relative proportion can be appreciated from the distributions in Fig. 3, which show 49% rs +– genotypes. The proportions of both homozygotes (rs – – and rs ++) are smaller, but substantial as required to maintain the high proportion of heterozygotes. The proportions suggest that there could be a genetic balanced polymorphism with heterozygote advantage. This means that having one copy of the rs + gene is better than having no copy or two copies. For this reason, the rs – gene must be maintained in the population. Both homozygotes could be at risk for problems, but the types of problem should differ, and there should be a balance in the population as a whole for overall costs and benefits. What could the costs and benefits be? Since 1978, this has been the main research question I have asked. From the beginning, it seemed likely that people who lack a gene for left hemisphere advantage would be at risk for the development of speech and speech based aspects of language function. Left hemisphere advantage is expected to be absent in the rs – – genotype, but present in the rs +- and rs ++ genotypes. The question of the nature of the disadvantages associated with a double dose of right shift was puzzling. The idea that left hemisphere speech and dextrality might have

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costs was an entirely original suggestion of the theory. Annett (5) speculated there may be over-dependence on the left hemisphere, at the expense of right hemisphere functions. A close look at the actual skill of the right and left hands for peg moving showed that consistent right handers tend to have very weak left hands (24). Figure 4 shows the mean right and left hand scores when children were classified for degrees of R–L difference, in four groups along the R–L continuum (14). Group 1 has the least bias to dextrality, and is mainly left handed for . skill, while groups 2, 3 and 4 can be described as mild, moderate and strong dextrals. It is evident that the right hand improves 1 1 1 1 w U E 0 n z $

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slightly between groups 1 and 2, but not much thereafter. The left hand drops steeply and linearly over all groups. These observations for differences between the hands in skill have a marked resemblance to those for asymmetries of the planum temporale as described by Galaburda et al. (7,21). In brains with symmetrical plana, the plana tend to be relatively large, but the typical pattern of asymmetry is associated with a smaller planum on the right side. Thus, it is reasonable to suggest that human cerebral asymmetry is associated with disadvantages for the right hemisphere, loss of substance for the right PT, and loss of skill for the left hand. The cognitive level of analysis summarizes the types of risk expected for each genotype. For speech based processes, there are risks for the rs – – genotype, but not for the rs +– or rs ++. The risks are summarized under the term “phonology”, meaning the types of cognitive processes which depend on the efficient representation of speech sounds. It does not imply that the child has an overt speech problem, although there may be a history of speech delay. It means that the child may be poor at cognitive representations of speech, as in auditory short term memory for digit span, or for phoneme deletion (saying the word “jam” without the “j’’-’’am”) or for reading new words or non-words (“lif”, “caik”, “brane”). The cognitive risks associated with right hemisphere disadvantage are summarized under the term “visuospatial”. Just what this term entails in this context needs to be worked out more fully, but it probably includes visual memory for words, as well as poor maths (12,15), spatial visualization and memory for complex figures (8). Note that risks to visuospatial processes are absent in the rs – – but moderate and strong I in the rs +– and rs ++ genotypes, respectively. The pattern of risks shows a balance between d o a o the i types r vof risks G o date the e rtwo extremes. i h gi nz Heterozygotes s l nc 1 saprobably dhaveio an- overalldo advantage rf 4 in e

LATERALITYAND TYPES OF DYSLEXIA because they enjoy the benefits of left hemisphere speech with minimum cost to the right hemisphere. At the behavioral level, there are identical Gaussian curves for all genotypes, with shifts which are absent, moderate and strong in the three genotypes. The proportions of cases with superior left hand skill for an objective measure like peg moving are 50, 16 and 2!4. (to the left of O,which represents R=L or no difference between the hands in skill). The proportions of left writers are smaller, because people who are evenly balanced between the two sides are likely to follow the majority and write with the right hand. Thus the predictions are 34, 8 and IYo for left writers, when 10% of the total population are left writers. (The percentages always depend on the overall criterion, because the RS theory is a threshold model, not a discrete R versus L model.) Predictionsfor Dyslexics

The surprising idea that strong right handers could be at risk for learning to read was suggested by findings in a dyslexia clinic sample (13). There were more left and mixed handers than in controls, but there were also some very strong dextrals. The reliability of this finding was checked in a school sample, when it was found that mean reading quotients were lower at both ends of the literality distribution (14). There was an inverted U-shape between reading scores and R–L hand skill. The critical question for the RS theory was whether the type of reading problem associated with the two extremes of the literality distribution differed as expected for the rs – – and the rs ++ genotypes. The prediction was that within the general population of schoolchildren, some have particular difficulty in learning to read because they have weak cognitive representations of speech sounds. The dominant theory of dyslexia in the current literature is that dyslexics have weak phonological processing. What the RS theory suggests is that poor readers with poor phonology should be unbiased to either side for hand skill. There should be more left handers, and also more mixed handers, as expected for a random distribution of handedness without any shift to the right. The RS theory also predicts that there should be some poor readers who do not have problems of phonological processing, but other difficulties, probably of visual memory functions as suggested by Boder’s term “dyseidetic” (17). For the present purpose, poor readers are classified into those with and without poor phonology. The prediction was that the latter would be strongly biased to dextrality, as expected for the rs ++ genotype. These predictions have been tested in a representative school sample (11). A whole year cohort was assessed by group tests, and selected children were followed up with individual tests on two further occasions. Poor readers and poor spellers without reading problems included 12.5°%Jleft writers while controls included 1OO/..This difference was in the direction expected, but not statistically significant, as typically found in the literature. Poor readers were then classified for phonology, on the basis of three different tests (short-term memory

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for word order, phoneme segmentation and non-word reading). Children with poor scores on two or three of these tests were classified as having a phonological problem and were called “phenols”. The remaining dyslexics were called “non-phonols”. The proportions of left writers were 29Y0 for phenols and OYOfor nonphenols. The groups differed significantly for hand preference @ = 0.02). Comparisons for subgroup handedness and hand skill were highly significant. In contrast with the literature mentioned above, analyses based on the RS theory found strong and reliable effects. The phenols were always well to the left of non-phenols and controls. The non-phenols were to the right of controls, although not significantly. Further, and particularly important for the genetic model, there were differences between the relatives of phenols and the relatives of controls for subgroup handedness. These contrasts between poor readers for types of cognitivedeficitsand associatedtypes of handedness are not restricted to poor readers. Samples of undergraduates and school children have been examined for the presence of cases with specific weakness of auditory memory for words, in comparison with specific weaknesses for visual memory for words. The former were less biased to dextrality than controls, and the latter more biased to dextrality than controls, as predicted for the above model (10). A quantity of evidence, from several samples, supports the idea of a dissociation between specific risks to speech based versus non-speech based cognitive processing, and absence versus strong presence of the bias to dextrality. The implications of this model for the understanding of hemisphere asymmetries are profound. Individual differences in hemisphere specialization must be envisaged as occurring in at least three groups, “typical”, “atypical”, and a third strongly asymmetrical type which may be termed “over-typical”. The pattern of risks to cognitive processes implies that studies based on university students or staff, and other professionals are not likely to be representative of the general population, because they include more of the advantaged heterozygotes. Neuroscientist have hardly begun to explore the variability of hemisphere specialization that probably exists. The prevalence of the typical pattern has probably been greatly overestimated. I suspect that atypical findings are often put aside as due to unfortunate methodological errors. It will be necessary to take the variability of human cerebral asymmetries more seriously. The fundamental point is that there are individual differences in patterns of cerebral specialization that occur as normal variants at the rs genetic locus, which have consequences for education, learning and cognition. A

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I am grateful to John Ashworth for drawing the figures. Elizabeth Eglinton and Pamela Smythe assisted in the collection, analysis and presentation of the dyslexia data. The work described was supported by project grants from the Medical Research Council, UK and the Wellcome Trust.

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