On the other hand: including left-handers in cognitive neuroscience and neurogenetics

Journal name:
Nature Reviews Neuroscience
Volume:
15,
Pages:
193–201
Year published:
DOI:
doi:10.1038/nrn3679
Published online

Abstract

Left-handers are often excluded from study cohorts in neuroscience and neurogenetics in order to reduce variance in the data. However, recent investigations have shown that the inclusion or targeted recruitment of left-handers can be informative in studies on a range of topics, such as cerebral lateralization and the genetic underpinning of asymmetrical brain development. Left-handed individuals represent a substantial portion of the human population and therefore left-handedness falls within the normal range of human diversity; thus, it is important to account for this variation in our understanding of brain functioning. We call for neuroscientists and neurogeneticists to recognize the potential of studying this often-discarded group of research subjects.

At a glance

Figures

  1. Hemispheric activation differences in left- and right-handers during action verb reading.
    Figure 1: Hemispheric activation differences in left- and right-handers during action verb reading.

    Participants were asked to read action verbs involving hand actions (for example, 'to throw') or non-hand actions (for example, 'to laugh'). The graph shows the differences in activation in the premotor cortex (Brodmann area 6) between the two conditions. In right-handed participants, the difference in activation between hand-related and non-hand-related action conditions was most pronounced in the left hemisphere, which conforms to their hand preference (that is, right-handers preferentially use their right hand for performing manual actions, and motor control of the right hand is mainly governed by the left motor cortex). In left-handers, the pattern was reversed. Error bars represent SEM. There was a statistically significant three-way interaction effect between hemisphere (left versus right), group (left-handers versus right-handers) and action verb (manual versus non-manual). Figure is reproduced, with permission, from Ref. 55 © (2010) SAGE Publications.

  2. Language and visuospatial activations in left-handers with typical and atypical language lateralization.
    Figure 2: Language and visuospatial activations in left-handers with typical and atypical language lateralization.

    Activation in the language network during a word-generation task is shown in blue. Left-handed individuals with typical language lateralization (panel a) show more activation in left-hemispheric language regions than in right-hemispheric regions, whereas the reverse is true for left-handed individuals with atypical, right-lateralized language function (panel b). A set of regions activated during a visuospatial attention task (shown in green) was also differentially lateralized in these two groups. In left-handed individuals in whom language is left-lateralized (typical), activation was most pronounced in the right hemisphere (panel a), whereas in left-handed individuals in whom language was right-lateralized (atypical), activation was most pronounced in the left hemisphere (panel b). This study was conducted in left-handers because of the greater variability in language lateralization in left-handers. By actively looking for atypically lateralized individuals within the left-handed population, the issue of co-lateralization of linguistic and visuospatial functions could be addressed. Figure is reproduced from Ref. 82.

  3. Left- and right-handers show differences in lateralization during face perception.
    Figure 3: Left- and right-handers show differences in lateralization during face perception.

    Parts of the extrastriate cortex are selectively sensitive to the perception of faces or bodies, and these areas are sometimes dubbed the fusiform face area (FFA), and the extrastriate body area (EBA) and fusiform body area (FBA), respectively. The FFA in particular is thought to be right-lateralized, and the figure shows that this may in fact not be the case for left-handers. Left- and right-handed participants were asked to view pictures of faces, bodies and chairs (control stimuli), and the extent of activation was quantified. The graphs show the extent of activation (in number of voxels on the y axis) in four extrastriate visual areas when participants viewed faces or bodies compared with the extent of activation during the viewing of chairs. a | The typical right-lateralization of the FFA in right-handers is absent in left-handers. b | Right-handers show a similar right-lateralization in the EBA, and left-handers again show no statistically significant lateralization in this area. c | There is no statistically significant lateralization in the FBA in either left-handers or right-handers. d | The human motion area MT (hMT), which is a visual area that is sensitive to motion, also did not show any lateralization effect of handedness. These findings indicate that right-lateralization does not occur in all functional areas in the visual system but is specific for the FFA and EBA in right-handers. Statistically significant differences between activity in the left versus right hemisphere are indicated by an asterisk. Figure is reproduced, with permission, from Ref. 99 © (2010) Oxford University Press.

References

  1. McManus, I. C. Right Hand, Left Hand (Phoenix, 2002).
  2. Smits, R. The Puzzle of Left-Handedness (Reaktion Books, 2011).
  3. Blau, A. Don't let your child be a lefty! Tri-City Herald (Washington) 38 (1961).
  4. Oldfield, R. C. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97113 (1971).
  5. Büsch, D., Hagemann, N. & Bender, N. The dimensionality of the Edinburgh Handedness Inventory: an analysis with models of the item response theory. Laterality 15, 610628 (2010).
  6. Dragovic, M. Towards an improved measure of the Edinburgh Handedness Inventory: a one-factor congeneric measurement model using confirmatory factor analysis. Laterality 9, 411419 (2004).
  7. Annett, M. Left, Right, Hand and Brain: The Right Shift Theory (Laurence Erlbaum, 1985).
  8. Annett, M. Patterns of hand preference for pairs of actions and the classification of handedness. Br. J. Psychol. 100, 491500 (2009).
  9. Nicholls, M. E. R., Chapman, H. L., Loetscher, T. & Grimshaw, G. M. The relationship between hand preference, hand performance, and general cognitive ability. J. Int. Neuropsychol. Soc. 16, 585592 (2010).
  10. Triggs, W. J., Calvanio, R., Levine, M., Heaton, R. K. & Heilman, K. M. Predicting hand preference with performance on motor tasks. Cortex 36, 679689 (2000).
  11. Björk, T., Brus, O., Osika, W. & Montgomery, S. Laterality, hand control and scholastic performance: a British birth cohort study. BMJ Open 2, e000314 (2012).
  12. Badzakova-Trajkov, G., Häberling, I. S. & Corballis, M. C. Magical ideation, creativity, handedness, and cerebral asymmetries: a combined behavioural and fMRI study. Neuropsychologia 49, 28962903 (2011).
  13. Somers, M., Sommer, I. E., Boks, M. P. & Kahn, R. S. Hand-preference and population schizotypy: a meta-analysis. Schizophr. Res. 108, 2532 (2009).
  14. Eckert, M. A. et al. Manual and automated measures of superior temporal gyrus asymmetry: concordant structural predictors of verbal ability in children. Neuroimage 41, 813822 (2008).
  15. Groen, M. A., Whitehouse, A. J. O., Badcock, N. A. & Bishop, D. V. M. Does cerebral lateralization develop? A study using functional transcranial Doppler ultrasound assessing lateralization for language production and visuospatial memory. Brain Behav. 2, 256269 (2012).
  16. Bryden, M. P., Roy, E. A., McManus, I. C. & Bulman-Fleming, M. B. On the genetics and measurement of human handedness. Laterality 2, 317336 (1997).
  17. Reiss, M., Tymnik, G., Kögler, P., Kögler, W. & Reiss, G. Laterality of hand, foot, eye, and ear in twins. Laterality 4, 287297 (1999).
  18. Elias, L. J. & Bryden, M. P. Footedness is a better predictor of language lateralisation than handedness. Laterality 3, 4151 (1998).
  19. Mcmanus, I. C. in Language Lateralization and Psychosis (eds Sommer, I. E. C. & Kahn, R. S.) 3757 (Cambridge Univ. Press, 2009).
  20. Faurie, C. & Raymond, M. Handedness frequency over more than ten thousand years. Proc. R. Soc. Lond. B 271, S43S45 (2004).
  21. Perelle, I. B. & Ehrman, L. An international study of human handedness: the data. Behav. Genet. 24, 217227 (1994).
  22. Hepper, P. G., McCartney, G. R. & Shannon, E. A. Lateralised behaviour in first trimester human foetuses. Neuropsychologia 36, 531534 (1998).
  23. Hepper, P. G. The developmental origins of laterality: fetal handedness. Dev. Psychobiol. 55, 588595 (2013).
  24. Hugdahl, K. & Davidson, R. J. The Asymmetrical Brain (MIT Press, 2004).
  25. Hering-Hanit, R., Achiron, R., Lipitz, S. & Achiron, A. Asymmetry of fetal cerebral hemispheres: in utero ultrasound study. Arch. Dis. Child. Fetal Neonatal Ed. 85, F194F196 (2001).
  26. Rogers, L. J. & Andrew, R. (eds) Comparative Vertebrate Lateralization (Cambridge Univ. Press, 2002).
  27. Hopkins, W. D. et al. Hand preferences for coordinated bimanual actions in 777 great apes: implications for the evolution of handedness in hominins. J. Hum. Evol. 60, 605611 (2011).
  28. Gannon, P. J., Holloway, R. L., Broadfield, D. C. & Braun, A. R. Asymmetry of chimpanzee planum temporale: humanlike pattern of Wernicke's brain language area homolog. Science 279, 220222 (1998).
  29. Hopkins, W. D. et al. Gray matter asymmetries in chimpanzees as revealed by voxel-based morphometry. Neuroimage 42, 491497 (2008).
  30. Lyn, H. et al. Planum temporale grey matter asymmetries in chimpanzees (Pan troglodytes), vervet (Chlorocebus aethiops sabaeus), rhesus (Macaca mulatta) and bonnet (Macaca radiata) monkeys. Neuropsychologia 49, 20042012 (2011).
  31. Corballis, M. C. From mouth to hand: gesture, speech, and the evolution of right-handedness. Behav. Brain Sci. 26, 199208 (2003).
  32. Corballis, M. C., Badzakova-Trajkov, G. & Häberling, I. S. Right hand, left brain: genetic and evolutionary bases of cerebral asymmetries for language and manual action. Cogn. Sci. 3, 117 (2012).
  33. Pinel, P. et al. Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions. J. Neurosci. 32, 817825 (2012).
  34. Kos, M. et al. CNTNAP2 and language processing in healthy individuals as measured with ERPs. PLoS ONE 7, e46995 (2012).
  35. Kim, B. et al. The effects of the catechol-O-methyltransferase val158met polymorphism on white matter connectivity in patients with panic disorder. J. Affect. Disord. 147, 6471 (2013).
  36. Rose, E. J. et al. The effect of the neurogranin schizophrenia risk variant rs12807809 on brain structure and function. Twin Res. Hum. Genet. 15, 296303 (2012).
  37. Hibar, D. P. et al. Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins. Twin Res. Hum. Genet. 15, 286295 (2012).
  38. Chen, J. et al. A combined study of genetic association and brain imaging on the DAOA gene in schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet. 162, 191200 (2013).
  39. Sprooten, E. et al. An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain. Magn. Reson. Imag. 30, 13731380 (2012).
  40. Yang, X. et al. Impact of brain-derived neurotrophic factor Val66Met polymorphism on cortical thickness and voxel-based morphometry in healthy Chinese young adults. PLoS ONE 7, e37777 (2012).
  41. Li, Y. et al. Less efficient information transfer in Cys-allele carriers of DISC1: a brain network study based on diffusion MRI. Cereb. Cortex 23, 17151723 (2013).
  42. Paulus, F. M. et al. Association of rs1006737 in CACNA1C with alterations in prefrontal activation and fronto-hippocampal connectivity. Hum. Brain Mapp. http://dx.doi.org/10.1002/hbm.22244 (2013).
  43. van der Heijden, C. D. C. C. et al. Genetic variation in ataxia gene ATXN7 influences cerebellar grey matter volume in healthy adults. Cerebellum 12, 390395 (2013).
  44. Nieto-Castañón, A. & Fedorenko, E. Subject-specific functional localizers increase sensitivity and functional resolution of multi-subject analyses. Neuroimage 63, 16461669 (2012).
  45. Hancock, R. & Bever, T. G. Genetic factors and normal variation in the organization of language. Biolinguistics 7, 075095 (2013).
  46. Townsend, D. J., Carrithers, C. & Bever, T. G. Familial handedness and access to words, meaning, and syntax during sentence comprehension. Brain Lang. 78, 308331 (2001).
  47. Tzourio-Mazoyer, N. et al. Left hemisphere lateralization for language in right-handers is controlled in part by familial sinistrality, manual preference strength, and head size. J. Neurosci. 30, 1331413318 (2010).
  48. Tzourio-Mazoyer, N. et al. Effect of familial sinistrality on planum temporale surface and brain tissue asymmetries. Cereb. Cortex 20, 14761485 (2010).
  49. Willems, R. M. & Casasanto, D. Flexibility in embodied language understanding. Front. Psychol. 2, 116 (2011).
  50. Mahon, B. Z. & Caramazza, A. A critical look at the embodied cognition hypothesis and a new proposal for grounding conceptual content. J. Physiol. Paris 102, 5970 (2008).
  51. Willems, R. M. & Francken, J. C. Embodied cognition: taking the next step. Front. Cogn. Sci. 3, 582 (2012).
  52. Willems, R. M. & Hagoort, P. Neural evidence for the interplay between language, gesture, and action: a review. Brain Lang. 101, 278289 (2007).
  53. Aziz-Zadeh, L., Wilson, S. M., Rizzolatti, G. & Iacoboni, M. Congruent embodied representations for visually presented actions and linguistic phrases describing actions. Curr. Biol. 16, 18181823 (2006).
  54. Hauk, O., Johnsrude, I. & Pulvermuller, F. Somatotopic representation of action words in human motor and premotor cortex. Neuron 41, 301307 (2004).
  55. Willems, R. M., Hagoort, P. & Casasanto, D. Body-specific representations of action verbs: neural evidence from right- and left-handers. Psychol. Sci. 21, 6774 (2010).
  56. Willems, R. M., Toni, I., Hagoort, P. & Casasanto, D. Body-specific motor imagery of hand actions: neural evidence from right- and left-handers. Front. Hum. Neurosci. 3, 39 (2009).
  57. Hauk, O. & Pulvermüller, F. The lateralization of motor cortex activation to action-words. Front. Hum. Neurosci. 5, 149 (2011).
  58. Lewis, J. W., Phinney, R. E., Brefczynski-Lewis, J. A. & DeYoe, E. A. Lefties get it 'right' when hearing tool sounds. J. Cogn. Neurosci. 18, 13141330 (2006).
  59. Longcamp, M., Anton, J. L., Roth, M. & Velay, J. L. Visual presentation of single letters activates a premotor area involved in writing. Neuroimage 19, 14921500 (2003).
  60. Longcamp, M., Anton, J. L., Roth, M. & Velay, J. L. Premotor activations in response to visually presented single letters depend on the hand used to write: a study on left-handers. Neuropsychologia 43, 18011809 (2005).
  61. Longcamp, M., Tanskanen, T. & Hari, R. The imprint of action: motor cortex involvement in visual perception of handwritten letters. Neuroimage 33, 681688 (2006).
  62. Willems, R. M. & Hagoort, P. Hand preference influences neural correlates of action observation. Brain Res. 1269, 90104 (2009).
  63. Hari, R. et al. Activation of human primary motor cortex during action observation: a neuromagnetic study. Proc. Natl Acad. Sci. USA 95, 1506115065 (1998).
  64. Casasanto, D. Embodiment of abstract concepts: good and bad in right- and left-handers. J. Exp. Psychol. Gen. 138, 351367 (2009).
  65. Casasanto, D. Different bodies, different minds the body specificity of language and thought. Curr. Dir. Psychol. Sci. 20, 378383 (2011).
  66. De Nooijer, J. A., van Gog, T., Paas, F. & Zwaan, R. A. When left is not right: handedness effects on learning object-manipulation words using pictures with left- or right-handed first-person perspectives. Psychol. Sci. 24, 25152521 (2013).
  67. Eling, P. Broca on the relation between handedness and cerebral speech dominance. Brain Lang. 22, 158159 (1984).
  68. Ettlinger, G., Jackson, C. V. & Zangwill, O. L. Cerebral dominance in sinistrals. Brain 79, 569588 (1956).
  69. Goodglass, H. & Quadfasel, F. A. Language laterality in left-handed aphasics. Brain 77, 521548 (1954).
  70. Hécaen, H., De Agostini, M. & Monzon-Montes, A. Cerebral organization in left-handers. Brain Lang. 12, 261284 (1981).
  71. Knecht, S. et al. Handedness and hemispheric language dominance in healthy humans. Brain 123, 25122518 (2000).
  72. Szaflarski, J. P. et al. Language lateralization in left-handed and ambidextrous people: fMRI data. Neurology 59, 238244 (2002).
  73. Steinmetz, H., Volkmann, J., Jäncke, L. & Freund, H. J. Anatomical left–right asymmetry of language-related temporal cortex is different in left- and right-handers. Ann. Neurol. 29, 315319 (1991).
  74. Sommer, I. E. C., Ramsey, N. F., Mandl, R. C. W. & Kahn, R. S. Language lateralization in monozygotic twin pairs concordant and discordant for handedness. Brain 125, 27102718 (2002).
  75. Bookheimer, S. Functional MRI of language: new approaches to understanding the cortical organization of semantic processing. Annu. Rev. Neurosci. 25, 151188 (2002).
  76. Price, C. J. The anatomy of language: a review of 100 fMRI studies published in 2009. Ann. NY Acad. Sci. 1191, 6288 (2010).
  77. Hagoort, P., Baggio, G. & Willems, R. M. in The Cognitive Neurosciences 4th edn (ed. Gazzaniga, M. S.) 819836 (MIT Press, 2009).
  78. Sperry, R. Some effects of disconnecting the cerebral hemispheres. Science 217, 12231226 (1982).
  79. Van der Haegen, L., Cai, Q. & Brysbaert, M. Colateralization of Broca's area and the visual word form area in left-handers: fMRI evidence. Brain Lang. 122, 171178 (2012).
  80. Seghier, M. L., Kherif, F., Josse, G. & Price, C. J. Regional and hemispheric determinants of language laterality: implications for preoperative fMRI. Hum. Brain Mapp. 32, 16021614 (2011).
  81. Tzourio-Mazoyer, N., Josse, G., Crivello, F. & Mazoyer, B. Interindividual variability in the hemispheric organization for speech. Neuroimage 21, 422435 (2004).
  82. Cai, Q., Van der Haegen, L. & Brysbaert, M. Complementary hemispheric specialization for language production and visuospatial attention. Proc. Natl Acad. Sci. USA 110, E322E330 (2013).
  83. Whitehouse, A. J. O. & Bishop, D. V. M. Hemispheric division of function is the result of independent probabilistic biases. Neuropsychologia 47, 19381943 (2009).
  84. Bryden, M. P., Hécaen, H. & DeAgostini, M. Patterns of cerebral organization. Brain Lang. 20, 249262 (1983).
  85. Badzakova-Trajkov, G., Häberling, I. S., Roberts, R. P. & Corballis, M. C. Cerebral asymmetries: complementary and independent processes. PLoS ONE 5, e9682 (2010).
  86. Króliczak, G., Piper, B. J. & Frey, S. H. Atypical lateralization of language predicts cerebral asymmetries in parietal gesture representations. Neuropsychologia 49, 16981702 (2011).
  87. Raymer, A. M. et al. Crossed apraxia: implications for handedness. Cortex 35, 183199 (1999).
  88. Goldenberg, G. Apraxia — the cognitive side of motor control. Cortex http://dx.doi.org/10.1016/j.cortex.2013.07.016 (2013).
  89. Vingerhoets, G. et al. Praxis and language are linked: evidence from co-lateralization in individuals with atypical language dominance. Cortex 49, 172183 (2013).
  90. Van den Berg, F. E., Swinnen, S. P. & Wenderoth, N. Involvement of the primary motor cortex in controlling movements executed with the ipsilateral hand differs between left- and right-handers. J. Cogn. Neurosci. 23, 34563469 (2011).
  91. Kloppel, S. et al. The effect of handedness on cortical motor activation during simple bilateral movements. Neuroimage 34, 274280 (2007).
  92. Solodkin, A., Hlustik, P., Noll, D. C. & Small, S. L. Lateralization of motor circuits and handedness during finger movements. Eur. J. Neurol. 8, 425434 (2001).
  93. Dassonville, P., Zhu, X. H., Uurbil, K., Kim, S. G. & Ashe, J. Functional activation in motor cortex reflects the direction and the degree of handedness. Proc. Natl Acad. Sci. USA 94, 1401514018 (1997).
  94. Verstynen, T., Diedrichsen, J., Albert, N., Aparicio, P. & Ivry, R. B. Ipsilateral motor cortex activity during unimanual hand movements relates to task complexity. J. Neurophysiol. 93, 12091222 (2005).
  95. Corballis, M. C. The Lopsided Ape: Evolution of the Generative Mind (Oxford Univ. Press, 1991).
  96. Polk, T. A., Park, J., Smith, M. R. & Park, D. C. Nature versus nurture in ventral visual cortex: a functional magnetic resonance imaging study of twins. J. Neurosci. 27, 1392113925 (2007).
  97. Yovel, G., Tambini, A. & Brandman, T. The asymmetry of the fusiform face area is a stable individual characteristic that underlies the left-visual-field superiority for faces. Neuropsychologia 46, 30613068 (2008).
  98. Hamilton, C. R. & Vermeire, B. A. Complementary hemispheric specialization in monkeys. Science 242, 16911694 (1988).
  99. Willems, R. M., Peelen, M. V. & Hagoort, P. Cerebral lateralization of face-selective and body-selective visual areas depends on handedness. Cereb. Cortex 20, 17191725 (2010).
  100. Sun, T. et al. Early asymmetry of gene transcription in embryonic human left and right cerebral cortex. Science 308, 17941798 (2005).
  101. Ocklenburg, S., Beste, C. & Güntürkün, O. Handedness: a neurogenetic shift of perspective. Neurosci. Biobehav. Rev. 37, 27882793 (2013).
  102. Medland, S. E. et al. Genetic influences on handedness: data from 25,732 Australian and Dutch twin families. Neuropsychologia 47, 330337 (2009).
  103. Medland, S. E. et al. Meta-analysis of GWAS for handedness: results from the ENGAGE consortium. Am. Soc. Hum. Genet. Abstr. [online], (2009).
  104. Armour, J. A. L., Davison, A. & McManus, I. C. Genome-wide association study of handedness excludes simple genetic models. Heredity http://dx.doi.org/10.1038/hdy.2013.93 (2013).
  105. Singleton, A. B., Hardy, J., Traynor, B. J. & Houlden, H. Towards a complete resolution of the genetic architecture of disease. Trends Genet. 26, 438442 (2010).
  106. Francks, C. et al. LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. Mol. Psychiatry 12, 11291139 (2007).
  107. Francks, C. Leucine-rich repeat genes and the fine-tuning of synapses. Biol. Psychiatry 69, 820821 (2011).
  108. Ko, J., Fuccillo, M. V., Malenka, R. C. & Südhof, T. C. LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation. Neuron 64, 791798 (2009).
  109. Linhoff, M. W. et al. An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers. Neuron 61, 734749 (2009).
  110. Siddiqui, T. J., Pancaroglu, R., Kang, Y., Rooyakkers, A. & Craig, A. M. LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development. J. Neurosci. 30, 74957506 (2010).
  111. De Wit, J. et al. LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation. Neuron 64, 799806 (2009).
  112. Südhof, T. C. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455, 903911 (2008).
  113. DeLisi, L. E. et al. Hand preference and hand skill in families with schizophrenia. Laterality 7, 321332 (2002).
  114. Orr, K. G., Cannon, M., Gilvarry, C. M., Jones, P. B. & Murray, R. M. Schizophrenic patients and their first-degree relatives show an excess of mixed-handedness. Schizophr. Res. 39, 167176 (1999).
  115. Csernansky, J. G. et al. Abnormalities of thalamic volume and shape in schizophrenia. Am. J. Psychiatry 161, 896902 (2004).
  116. DeLisi, L. E. et al. Anomalous cerebral asymmetry and language processing in schizophrenia. Schizophr. Bull. 23, 255271 (1997).
  117. Kawasaki, Y. et al. Anomalous cerebral asymmetry in patients with schizophrenia demonstrated by voxel-based morphometry. Biol. Psychiatry 63, 793800 (2008).
  118. Oertel-Knöchel, V., Knöchel, C., Stäblein, M. & Linden, D. E. J. Abnormal functional and structural asymmetry as biomarker for schizophrenia. Curr. Top. Med. Chem. 12, 24342451 (2012).
  119. Shenton, M. E., Dickey, C. C., Frumin, M. & McCarley, R. W. A review of MRI findings in schizophrenia. Schizophr. Res. 49, 152 (2001).
  120. Sommer, I., Ramsey, N., Kahn, R., Aleman, A. & Bouma, A. Handedness, language lateralisation and anatomical asymmetry in schizophrenia: meta-analysis. Br. J. Psychiatry J. Ment. Sci. 178, 344351 (2001).
  121. Bailey, A. et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol. Med. 25, 6377 (1995).
  122. Boles, D. B., Barth, J. M. & Merrill, E. C. Asymmetry and performance: toward a neurodevelopmental theory. Brain Cogn. 66, 124139 (2008).
  123. De Fossé, L. et al. Language-association cortex asymmetry in autism and specific language impairment. Ann. Neurol. 56, 757766 (2004).
  124. Herbert, M. R. et al. Abnormal asymmetry in language association cortex in autism. Ann. Neurol. 52, 588596 (2002).
  125. Herbert, M. R. et al. Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. Brain J. Neurol. 128, 213226 (2005).
  126. Deep-Soboslay, A. et al. Handedness, heritability, neurocognition and brain asymmetry in schizophrenia. Brain J. Neurol. 133, 31133122 (2010).
  127. Scerri, T. S. et al. PCSK6 is associated with handedness in individuals with dyslexia. Hum. Mol. Genet. 20, 608614 (2011).
  128. Arning, L. et al. PCSK6 VNTR polymorphism is associated with degree of handedness but not direction of handedness. PLoS ONE 8, e67251 (2013).
  129. Brandler, W. M. et al. Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. PLoS Genet. 9, e1003751 (2013).
  130. McManus, I. C., Martin, N., Stubbings, G. F., Chung, E. M. K. & Mitchison, H. M. Handedness and situs inversus in primary ciliary dyskinesia. Proc. Biol. Sci. 271, 25792582 (2004).
  131. Tanaka, S., Kanzaki, R., Yoshibayashi, M., Kamiya, T. & Sugishita, M. Dichotic listening in patients with situs inversus: brain asymmetry and situs asymmetry. Neuropsychologia 37, 869874 (1999).
  132. Geschwind, N. & Galaburda, A. M. Cerebral Lateralization (MIT Press, 1987).
  133. Lust, J. M. et al. Differential effects of prenatal testosterone on lateralization of handedness and language. Neuropsychology 25, 581589 (2011).
  134. Stein, J. L. et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genet. 44, 552561 (2012).
  135. Guadalupe, T. et al. Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets. Hum. Brain Mapp. http://dx.doi.org/10.1002/hbm.22401 (2013).
  136. Button, K. S. et al. Power failure: why small sample size undermines the reliability of neuroscience. Nature Rev. Neurosci. 14, 365376 (2013).

Download references

Author information

Affiliations

  1. Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525 EN Nijmegen, The Netherlands.
    Max Planck Institute for Psycholinguistics, 6525 XD Nijmegen, The Netherlands.

    • Roel M. Willems,
    • Simon E. Fisher &
    • Clyde Francks
  2. Department of Experimental Psychology, Ghent University, Ghent, 9000, Belgium.

    • Lise Van der Haegen

Competing interests statement

The authors declare no competing interests.

Corresponding authors

Correspondence to:

Author details

  • Roel M. Willems

    Roel M. Willems is a senior researcher at the Donders Institute for Brain, Cognition and Behaviour and at the Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands. He obtained his Ph.D. from Radboud University Nijmegen, on the neural integration of information from speech and gestures. He previously held positions at the Radboud University Nijmegen and the University of California, Berkeley, USA, during which he investigated the role of the motor cortex in language understanding. He investigates the neural basis of our language capacities, and his current main interest is the role of mental simulation in the comprehension of literature. Roel M. Willems's homepage.

  • Lise Van der Haegen

    Lise Van der Haegen is a postdoctoral researcher at the Department of Experimental Psychology at Ghent University, Belgium. She is a member of the Center for Reading Research group and is supported by a grant from the Research Council of Ghent University. For her Ph.D. degree she investigated the need for interhemispheric communication in visual word reading by comparing left- and right-handed subjects with a clear typical or atypical language organization. Current research focuses on the relationship between the hemispheric specialization of language sub-processes and non-language-related cognitive functions. Lise Van der Haegen's homepage.

  • Simon E. Fisher

    Simon E. Fisher is Director of the Max Planck Institute for Psycholinguistics Nijmegen, the Netherlands, and a professor of language and genetics at the Donders Institute for Brain, Cognition and Behaviour in Nijmegen. Before this, he was a Royal Society research fellow, leading a group at the Wellcome Trust Centre for Human Genetics at the University of Oxford, UK. As a neurogeneticist investigating human cognitive traits, he was co-discoverer of FOXP2, the first gene to be implicated in a speech and language disorder. His subsequent research has used language-related genes as molecular windows into critical neural pathways. He received several awards in recognition of this work, including the Francis Crick Lecture and the Eric Kandel Young Neuroscientists Prize. Simon E. Fisher'shomepage.

  • Clyde Francks

    Clyde Francks completed his D.Phil. (2002) and postdoctoral studies in the human neurogenetics laboratory of Anthony Monaco at the University of Oxford, UK, on the genetics of dyslexia and handedness. He then worked as a manager in the pharmaceuticals industry (GlaxoSmithKline), leading collaborations with academic institutes on genetic studies of schizophrenia and smoking. In 2010, he moved back to full-time academic research to start a group investigating the genetics of human brain lateralization and its links to cognitive variation at the Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands (an institute of the Max Planck Society), where he is a W2 (German academic scale) senior investigator. He is also a research fellow at the Donders Institute for Brain, Cognition and Behaviour in Nijmegen. Please see the Genetics of Handedness project website.

Additional data