Language lateralization correlates with verbal memory performance in children with focal epilepsy

PURPOSE: Assessment of language dominance with functional magnetic resonance imaging (fMRI) and neuropsychological evaluation is often used prior to epilepsy surgery. This study explores whether language lateralization and cognitive performance are systematically related in young patients with focal epilepsy. METHODS: Language fMRI and neuropsychological data (language, visuospatial functions, and memory) of 40 patients (7-18 years of age) with unilateral, refractory focal epilepsy in temporal and/or frontal areas of the left (n = 23) or right hemisphere (n = 17) were analyzed. fMRI data of 18 healthy controls (7-18 years) served as a normative sample. A laterality index was computed to determine the lateralization of activation in three regions of interest (frontal, parietal, and temporal). RESULTS: Atypical language lateralization was demonstrated in 12 (30%) of 40 patients. A correlation between language lateralization and verbal memory performance occurred in patients with left-sided epilepsy over all three regions of interest, with bilateral or right-sided language lateralization being correlated with better verbal memory performance (Word Pairs Recall: frontal r = -0.4, p = 0.016; parietal r = -0.4, p = 0.043; temporal r = -0.4, p = 0.041). Verbal memory performance made the largest contribution to language lateralization, whereas handedness and side of seizures did not contribute to the variance in language lateralization. DISCUSSION: This finding reflects the association between neocortical language and hippocampal memory regions in patients with left-sided epilepsy. Atypical language lateralization is advantageous for verbal memory performance, presumably a result of transfer of verbal memory function. In children with focal epilepsy, verbal memory performance provides a better idea of language lateralization than handedness and side of epilepsy and lesion.

Further Evidence for Hemisity Sorting During Career Specialization

Hemisity refers to binary thinking and behavioral style differences between right and left brain-oriented individuals. The inevitability of hemisity became clear when it was discovered by magnetic resonance imaging (MRI) that an anatomical element of the executive system was unilaterally embedded in either the right or the left side of the ventral gyrus of the anterior cingulate cortex in an idiosyncratic manner that was congruent with an individual's inherent hemisity subtype. Based upon the MRI-calibrated hemisity of many individuals, a set of earlier biophysical and questionnaire hemisity assays was calibrated for accuracy and found appropriate for use in the investigation of the hemisity of individuals and groups. It had been reported that a partial sorting of individuals into hemisity right and left brain-oriented subgroups occurred during the process of higher education and professional development. Here, these results were extended by comparison of the hemisity of a putative unsorted population of 1,049 high school upper classmen, with that of 228 university freshmen. These hemisity outcomes were further compared with that of 15 university librarians, here found to be predominantly left brain-oriented, and 91 academically trained musicians, including 47 professional pianists, here found to be mostly right brainers. The results further supported the existence of substantial hemisity selection occurring during the process of higher education and in professional development.

Age, sex, and performance influence the visuospatial working memory network in childhood

This study describes the influence of age, sex, and working memory (WM) performance on the visuospatial WM network. Thirty-nine healthy children (7-12 years) completed a dot location functional magnetic resonance imaging (fMRI) task. Percent signal change measured the intensity and laterality indices measured the asymmetry of activation in frontal and parietal brain regions. Old children showed greater intensity of activation in parietal regions than young children but no differences in lateralization were observed. Intensity of activation was similar across sex and WM performance groups. Girls and high WM performers showed more right-sided lateralization of parietal regions than boys and low WM performers.

Differential effect of side of temporal lobe epilepsy on lateralization of hippocampal, temporolateral, and inferior frontal activation patterns during a verbal episodic memory task

The encoding of verbal stimuli elicits left-lateralized activation patterns within the medial temporal lobes in healthy adults. In our study, patients with left- and right-sided temporal lobe epilepsy (LTLE, RTLE) were investigated during the encoding and retrieval of word-pair associates using functional magnetic resonance imaging. Functional asymmetry of activation patterns in hippocampal, inferior frontal, and temporolateral neocortical areas associated with language functions was analyzed. Hippocampal activation patterns in patients with LTLE were more right-lateralized than those in patients with RTLE (P<0.05). There were no group differences with respect to lateralization in frontal or temporolateral regions of interest (ROIs). For both groups, frontal cortical activation patterns were significantly more left-lateralized than hippocampal patterns (P<0.05). For patients with LTLE, there was a strong trend toward a difference in functional asymmetry between the temporolateral and hippocampal ROIs (P=0.059). A graded effect of epileptic activity on laterality of the different regional activation patterns is discussed.

Verb generation in children with spina bifida.

We investigated verb generation in children with spina bifida meningomyelocele (SBM; n = 55) and in typically developing controls (n = 32). Participants completed 6 blocks (40 trials each) of a task requiring them to produce a semantically related verb in response to a target noun and an additional 40 trials on which they were simply required to read target nouns aloud. After controlling for reading response time, groups did not differ significantly in verb generation response time or learning. Children with SBM produced more non-verb errors than controls and tended to repeat their mistakes over blocks. Verb generation performance was associated with brain volume measures in participants with SBM. Congenital cerebellar dysmorphology is associated with impaired performance in verb generation accuracy, although not with increased response times to produce verbs

Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography.

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6-68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients.

Peripheral responses to attended and unattended angry prosody: a dichotic listening paradigm.

We investigated the effects of angry prosody, varying focus of attention, and laterality of presentation of angry prosody on peripheral nervous system activity. Participants paid attention to either their left or their right ear while performing a sex discrimination task on dichotically presented pseudo-words. These pseudo-words were characterized by either angry or neutral prosody and presented stereophonically (anger/neutral, neutral/anger, or neutral/neutral, for the left/right ear, respectively). Reaction times and physiological responses (heart period, skin conductance, finger and forehead temperature) in this study were differentially sensitive to the effects of anger versus neutral prosody, varying focus of attention, and laterality of presentation of angry prosody.

Primary lung cancer after breast cancer: The role of radiation therapy and cigarette smoking

The magnitude of the interaction between cigarette smoking, radiation therapy, and primary lung cancer after breast cancer remains unresolved. This case control study further examines the main and joint effects of cigarette smoking and radiation therapy (XRT) among breast cancer patients who subsequently developed primary lung cancer, at The University of Texas M. D. Anderson Cancer Center (MDACC) in Houston, Texas. Cases (n = 280) were women diagnosed with primary lung cancer between 1955 and 1970, between 30–89 years of age, who had a prior history of breast cancer, and were U.S. residents. Controls (n = 300) were randomly selected from 37,000 breast cancer patients at MDACC and frequency matched to cases on age at diagnosis (in 5-year strata), ethnicity, year of breast cancer diagnosis (in 5-year strata), and had survived at least as long as the time interval for lung cancer diagnosis in the cases. Stratified analysis and unconditional logistic regression modeling were used to calculate the main and joint effects of cigarette smoking and radiation treatment on lung cancer risk. Medical record review yielded smoking information on 93% of cases and 84% of controls, and among cases 45% received XRT versus 44% of controls. Smoking increased the odds of lung cancer in women who did not receive XRT (OR = 6.0, 95%CI, 3.5–10.1) whereas XRT was not associated with increased odds (OR = 0.5, 95%CI, 0.2–1.1) in women who did not smoke. Overall the odds ratio for both XRT and smoking together compared with neither exposure was 9.00 (9 5% CI, 5.1–15.9). Similarly, when stratifying on laterality of the lung cancer in relation to the breast cancer, and when the time interval between breast and lung cancers was >10 years, there was an increased odds for both smoking and XRT together for lung cancers on the same side as the breast cancer (ipsilateral) (OR = 11.5, 95% CI, 4.9–27.8) and lung cancers on the opposite side of the breast cancer (contralateral) (OR= 9.6, 95% CI, 2.9–0.9). After 20 years the odds for the ipsilateral lung were even more pronounced (OR = 19.2, 95% CI, 4.2–88.4) compared to the contralateral lung (OR = 2.6, 95% CI, 0.2–2.1). In conclusion, smoking was a significant independent risk factor for lung cancer after breast cancer. Moreover, a greater than multiplicative effect was observed with smoking and XRT combined being especially evident after 10 years for both the ipsilateral and contralateral lung and after 20 years for the ipsilateral lung. ^

Influencia de la información termográfica infrarroja en el protocolo de prevención de lesiones de un equipo de fútbol profesional español

El fútbol es un deporte en cuya práctica existe una alta incidencia de lesión. Además, en el ámbito profesional las lesiones suponen un duro proceso de recuperación para el futbolista, una reducción del rendimiento deportivo para éste y para el equipo, y unos grandes costes económicos para el club. Dentro de esta problemática, la bibliografía consultada concluye que en las pretemporadas se produce una mayor incidencia de lesión por sobrecarga, es decir, sin contacto; un tipo de lesiones que está a nuestro alcance poder prevenir. Por ello, consideramos importante el conocer y desarrollar métodos, herramientas y principios para obtener programas preventivos efectivos, que reduzcan las elevadas cifras de incidencia de lesión mostradas por la literatura. El presente estudio observa y registra las lesiones, a través del cuestionario F-MARC, de un equipo profesional de fútbol de la Liga Española durante las pretemporadas 2008 (n=24) y 2009 (n=24). Además, durante la pretemporada 2009 se aplicó la termografía infrarroja para adquirir información sobre la asimilación de la carga de entrenamiento por parte de los jugadores, y dicha información se utilizarón para mejorar las tomas de decisiones de protocolos post-ejercicio específicos en prevención de lesiones, los cuales fueron los mismos que se utilizaron previamente en la pretemporada 2008. El estudio tiene un diseño con características pre-post sin grupo de control. Es un estudio longitudinal donde, tras un registro inicial de lesiones en la pretemporada 2008, los sujetos fueron expuestos a la variable independiente, utilización de la termografía infrarroja, en el protocolo de prevención de lesiones durante la pretemporada 2009. Los resultados de este trabajo muestran una reducción significativa de hasta el 60% en la frecuencia de lesión durante la pretemporada 2009, y un descenso de la incidencia de lesión total que pasa de 8,3 lesiones por cada 1000 horas de exposición en 2008 a 3,4 en 2009. Con ello, la probabilidad de lesión se redujo considerablemente pasando de un 85% de los jugadores lesionados en 2008 a un 26% en 2009; además, las lesiones de carácter muscular descendieron en 2009 un 70% con respecto al 2008, y los días de baja que causaron todas las lesiones pasó a reducirse un 91,8% en la pretemporada 2009. Por otro lado, el perfil térmico de los jugadores en función de su lateralidad y dominancia, guarda una gran similitud en sus temperaturas, tanto medias como máximas, con temperaturas más elevadas en la zona corporal lumbar y poplítea, y con temperaturas más bajas en tobillos y rodillas. Todas las zonas corporales estudiadas, exceptuando el tobillo (p<0,05), no presentan diferencias significativas entre ambos hemicuerpos, estableciendo un promedio de diferencia entre ambos lados de 0,06±0,16 ºC. Teniendo en cuenta estos resultados, consideramos el límite superior de normalidad de asimetría térmica bilateral en 0,3ºC para todas las zonas corporales estudiadas del miembro inferior exceptuando los tobillos. El parámetro ambiental que más relación tiene con la temperatura registrada por la cámara termográfica es la temperatura de la sala con un coeficiente de correlación cercano a r=1,00, seguido de la presión atmosférica con un coeficiente de correlación cercano r=0,50, y, por último, la humedad que no guarda ningún tipo de relación con la temperatura registrada en cada zona corporal en el rango de valores considerados en el estudio. Por otro lado, los resultados del ANOVA de un factor nos indican que existen diferencias de medias entre los tres grupos formados de temperatura ambiente de sala (1º=18º-21ºC, 2º=22º-24ºC y 3º=25º-31ºC). Además, los resultados de la prueba HSD de Tukey nos indican que existen diferencias entre cada uno de los grupos en todas las zonas corporales estudiadas exceptuando los tobillos. Por último, se propone la ecuación; TC-estándar = TC-real – [0,184 * (TS – 21ºC)] para predecir la influencia de la temperatura ambiente sobre la temperatura registrada por la cámara termográfica. Para concluir, tras los resultados obtenidos, podemos afirmar que la aplicación de un protocolo post-ejercicio de prevención de lesiones basado en la información adquirida a través de valoraciones con termografía infrarroja reduce la incidencia de lesión en el grupo de futbolistas profesionales estudiado. Tenemos que ser conscientes que nos encontramos ante un estudio de campo, donde existen muchos factores que han podido influenciar en los resultados y que son difíciles de controlar. Por lo tanto, debemos ser cautos y concluir que la información adquirida de las evaluaciones termográficas ha sido uno de los aspectos que ayudó a la reducción significativa de la incidencia de lesión en la pretemporada 2009 en el equipo de fútbol profesional español de este estudio, pero que seguramente hayan podido existir otros factores que también hayan favorecido este hecho. ABSTRACT Soccer is a sport with a high incidence of injury. Moreover, in professional soccer injuries lead to a tough recovery process for the players, a reduction athletic performance for them and for their teams, and large economic costs for the club. In this issue, the literature concludes that in the preseason a greater incidence of overuse injury occurs (ie, without contact), and this is a type of injury that we can prevent. Therefore, we consider that it is important to know and develop methods, tools and principles to obtain effective preventive programs that reduce the high injury incidence figures shown in the literature. This study observed and recorded injuries, through the questionnaire F-MARC, from a professional soccer team in the Spanish league during the preseason 2008 (n = 24) and 2009 (n = 24). Moreover, during the 2009 preseason infrared thermography was applied to acquire information about the assimilation of the training load by the players, and this information was used to improve the decision making in the specific post-exercise injury prevention protocols, which were the same used in the previous season 2008. The study had a pre-post design without control group. Is a longitudinal study where, after an initial registration of injuries in the 2008 preseason, subjects were exposed to the independent variable, using infrared thermography, included in the protocol for injury prevention during the 2009 preseason. The results of this study show a significant reduction of up to 60% in the frequency of injury during the 2009 preseason, and a decrease in total injury incidence passing from 8.3 injuries per 1000 hours of exposure in 2008 to 3.4 in 2008. With this, the likelihood of injury decreased significantly from 85% of the players injuried in 2008 to 26% in 2009, also muscle injuries in 2009 fell 70% compared to 2008, and sick leave days that caused by all the injuries happened were reduced a 91.8% in the 2009 preseason. On the other hand, the thermal profile of the players according to their laterality and dominance, is quiet similar in their temperatures, both average and maximum values, with an estimated average of the highest temperatures in the lower back and popliteal areas in the back areas, and lower temperatures in the ankles and knees. All body areas studied, except for the ankle (p <0.05), had no significant differences between both sides of the body, establishing an average difference between both sides of 0.06 ± 0.16 °C. Given these results, we consider the upper limit of normal bilateral thermal asymmetry 0.3 °C for all body areas studied in the lower limb except for ankles. The environmental parameter higher related with temperature recorded by the camera is the temperature of the room with a correlation coefficient close to r = 1.00, followed by atmospheric pressure with a correlation coefficient near r = 0.50, and finally, the humidity that, in the range of values considered in the study, it is not related with temperature in each body area. On the other hand, the results of one-way ANOVA indicate that there are differences between the three temperature of the room groups (1 ° = 18-21 °C, 2 º = 22-24 ºC and 3 º = 25-31 ºC). Moreover, the results of the Tukey HSD test indicate that there are differences between each of the groups for all body areas studied except the ankles. Finally, we propose the equation TC-standard = TC-real – [0,184 * (TS – 21ºC)] to predict the influence of temperature on the temperature recorded by the thermographic camera. In conclusion, we can say from our results that the implementation of a post-exercise injury prevention protocol based on information from assessments with infrared thermography reduces the incidence of injury in professional soccer players. We must be aware that we are facing a field study, where there are many factors that could influence the results and they are difficult to control. Therefore, we must be cautious and conclude that the information acquired from the thermographic evaluation has been one of the aspects that helped to significantly reduce the incidence of injury in the preseason 2009 in the Spanish professional football team, but probably they could exist other factors with a positive effect on the reduction of the injury rates.

A large-capacity memory system that recognizes the calls and songs of individual birds.

Auditory responses in the caudomedial neostriatum (NCM) of the zebra finch (Taeniopygia guttata) forebrain habituate to repeated presentations of a novel conspecific song. This habituation is long lasting and specific to individual stimuli. We here test the acoustic and ethological basis of this stimulus-specific habituation by recording extracellular multiunit activity in the NCM of awake male and female zebra finches presented with a variety of conspecific and heterospecific vocalizations, white noise, and tones. Initial responses to conspecific song and calls and to human speech were higher than responses to the other stimuli. Immediate habituation rates were high for all novel stimuli except tones, which habituated at a lower rate. Habituation to conspecific calls and songs outlasted habituation to other stimuli. The extent of immediate habituation induced by a particular novel song was not diminished when other conspecific songs were presented in alternation. In addition, the persistence of habituation was not diminished by exposure to other songs before testing, nor was it influenced by gender or laterality. Our results suggest that the NCM is specialized for remembering the calls and songs of many individual conspecifics.

Avaliação de linguagem por ressonância magnética funcional em pacientes com epilepsia associada à esclerose mesial temporal unilateral: correlação com avaliação clínica de linguagem

Introdução: A esclerose mesial temporal (EMT) é a principal causa de epilepsia resistente ao tratamento medicamentoso. Pacientes com EMT apresentam dificuldades no processamento semântico e fonológico de linguagem e maior incidência de reorganização cerebral da linguagem (bilateral ou à direita) em relação à população geral. A ressonância magnética funcional (RMf) permite avaliar a reorganização cerebral das redes de linguagem, comparando padrões de ativação cerebral entre diversas regiões cerebrais. Objetivo: Investigar o desempenho linguístico de pacientes com EMT unilateral esquerda e direita e a ocorrência de reorganização das redes de linguagem com RMf para avaliar se a reorganização foi benéfica para a linguagem nestes pacientes. Métodos: Utilizamos provas clínicas de linguagem e paradigmas de nomeação visual e responsiva para RMf, desenvolvidos para este estudo. Foram avaliados 24 pacientes com EMTe, 22 pacientes com EMTd e 24 controles saudáveis, submetidos a provas de linguagem (fluência semântica e fonológica, nomeação de objetos, verbos, nomes próprios e responsiva, e compreensão de palavras) e a três paradigmas de linguagem por RMf [nomeação por confrontação visual (NCV), nomeação responsiva à leitura (NRL) e geração de palavras (GP)]. Seis regiões cerebrais de interesse (ROI) foram selecionadas (giro frontal inferior, giro frontal médio, giro frontal superior, giro temporal inferior, giro temporal médio e giro temporal superior). Índices de Lateralidade (ILs) foram calculados com dois métodos: bootstrap, do programa LI-Toolbox, independe de limiar, e PSC, que indica a intensidade da ativação cerebral de cada voxel. Cada grupo de pacientes (EMTe e EMTd) foi dividido em dois subgrupos, de acordo com o desempenho em relação aos controles na avaliação clinica de linguagem. O <= -1,5 foi utilizado como nota de corte para dividir os grupos em pacientes com bom e com mau desempenho de linguagem. Em seguida, comparou-se o desempenho linguístico dos subgrupos ao índices IL-boot. Resultados: Pacientes com EMT esquerda e direita mostraram pior desempenho que controles nas provas clínicas de nomeação de verbos, nomeação de nomes próprios, nomeação responsiva e fluência verbal. Os mapas de ativação cerebral por RMf mostraram efeito BOLD em regiões frontais e temporoparietais de linguagem. Os mapas de comparação de ativação cerebral entre os grupos revelaram que pacientes com EMT esquerda e direita apresentam maior ativação em regiões homólogas do hemisfério direito em relação aos controles. Os ILs corroboraram estes resultados, mostrando valores médios menores para os pacientes em relação aos controles e, portanto, maior simetria na representação da linguagem. A comparação entre o IL-boot e o desempenho nas provas clínicas de linguagem indicou que, no paradigma de nomeação responsiva à leitura, a reorganização funcional no giro temporal médio, e possivelmente, nos giros temporal inferior e superior associou-se a desempenho preservado em provas de nomeação. Conclusão: Pacientes com EMT direita e esquerda apresentam comprometimento de nomeação e fluência verbal e reorganização da rede cerebral de linguagem. A reorganização funcional de linguagem em regiões temporais, especialmente o giro temporal médio associou-se a desempenho preservado em provas de nomeação em pacientes com EMT esquerda no paradigma de RMf de nomeação responsiva à leitura

Experimental hand pain delays recognition of the contralateral hand: Evidence that acute and chronic pain have opposite effects on information processing?

Recognising the laterality of a pictured hand involves making an initial decision and confirming that choice by mentally moving one's own hand to match the picture. This depends on an intact body schema. Because patients with complex regional pain syndrome type 1 (CRPS1) take longer to recognise a hand's laterality when it corresponds to their affected hand, it has been proposed that nociceptive input disrupts the body schema. However, chronic pain is associated with physiological and psychosocial complexities that may also explain the results. In three studies, we investigated whether the effect is simply due to nociceptive input. Study one evaluated the temporal and perceptual characteristics of acute hand pain elicited by intramuscular injection of hypertonic saline into the thenar eminence. In studies two and three, subjects performed a hand laterality recognition task before, during, and after acute experimental hand pain, and experimental elbow pain, respectively. During hand pain and during elbow pain, when the laterality of the pictured hand corresponded to the painful side, there was no effect on response time (RT). That suggests that nociceptive input alone is not sufficient to disrupt the working body schema. Conversely to patients with CRPS1, when the laterality of the pictured hand corresponded to the non-painful hand, RT increased similar to 380 ms (95% confidence interval 190 ms-590 ms). The results highlight the differences between acute and chronic pain and may reflect a bias in information processing in acute pain toward the affected part.

Opposite effects of androgen receptor CAG repeat length on increased risk of left-handedness in males and females

Prenatal exposure to testosterone has been hypothesised to effect lateralization by influencing cell death in the foetal brain. Testosterone binds to the X chromosome linked androgen receptor, which contains a polymorphic polyglutamine CAG repeat, the length of which is positively correlated with testosterone levels in males, and negatively correlated in females. To determine whether the length of the androgen receptor mediates the effects of testosterone on laterality, we examined the association between the number of CAG repeats in the androgen receptor gene and handedness for writing. Association was tested by adding regression terms for the length of the androgen receptor alleles to a multi-factorial-threshold model of liability to left-handedness. In females we found the risk of left-handedness was greater in those with a greater number of repeats (p=0.04), this finding was replicated in a second independent sample of female twins (p=0.014). The length of the androgen receptor explained 6% of the total variance and 24% of the genetic variance in females. In males the risk of left-handedness was greater in those with fewer repeats (p=0.02), with variation in receptor length explaining 10% of the total variance and 24% of the genetic variance. Thus, consistent with Witelson's theory of testosterone action, in all three samples the likelihood of left handedness increased in those individuals with variants of the androgen receptor associated with lower testosterone levels.

Genetic and environmental influences on dentofacial structures and oral health: studies of Australian twins and their families

Our studies of the teeth and faces of Australian twins commenced at the School of Dentistry, The University of Adelaide in the early 1980s. There are now over 900 pairs of twins enrolled in our continuing investigations, together with 1200 relatives. There are 3 main cohorts of participants. The first cohort comprises around 300 pairs of teenage twins for whom various records have been collected, including dental casts, facial photographs, finger and palm prints and information on laterality, including handedness. The second cohort comprises around 300 pairs of twins who have been examined at 3 stages of dental development from approximately 4 years of age to about 14 years: at primary, mixed, and permanent dentition (excluding 3rd molars) stages. The most recent study of tooth emergence and oral health, for which we are currently recruiting twins, will provide a third cohort of around 500 twin pairs aged from around birth to 3 to 4 years of age. Our broad aim in these studies has been to improve our understanding of how genetic and environmental factors contribute to variation in dental and facial features, and to oral health. We have also used our data to investigate aspects of the determination of laterality, particularly the fascinating phenomenon of mirror imaging. We plan to maximize the use of the longitudinal data and DNA we have collected, and continue to collect, by performing genome-wide scans for putative genetic linkage peaks for a range of dental features, and then to test for association between a series of likely candidate genes and our phenotypes.

PCSK6 is associated with handedness in individuals with dyslexia

Approximately 90% of humans are right-handed. Handedness is a heritable trait, yet the genetic basis is not well understood. Here we report a genome-wide association study for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)]. The most highly associated marker, rs11855415 (P = 4.7 × 10-7), is located within PCSK6. Two independent cohorts with RD show the same trend, with the minor allele conferring greater relative right-hand skill. Meta-analysis of all three RD samples is genome-wide significant (n = 744, P = 2.0 × 10-8). Conversely, in the general population (n = 2666), we observe a trend towards reduced laterality of hand skill for the minor allele (P = 0.0020). These results provide molecular evidence that cerebral asymmetry and dyslexia are linked. Furthermore, PCSK6 is a protease that cleaves the left–right axis determining protein NODAL. Functional studies of PCSK6 promise insights into mechanisms underlying cerebral lateralization and dyslexia.