This article is a commentary on:
Differences in cerebral cortical anatomy of left- and right-handers
Sebastian Ocklenburg
Alexis Garland
Felix Ströckens
Anelisie Uber Reinert- Institute of Cognitive Neuroscience, Department of Biopsychology, Ruhr University Bochum, Bochum, Germany
A commentary on
Differences in cerebral cortical anatomy of left- and right-handers
by Guadalupe, T., Willems, R. M., Zwiers, M. P., Arias Vasquez, A., Hoogman, M., Hagoort, P., et al. (2014). Front. Psychol. 5:261. doi: 10.3389/fpsyg.2014.00261
When we look at our hands, outwardly they look remarkably similar to each other—and the bones, muscles and nerves within the two hands are equally symmetric. Way before the advent of modern neuroimaging, this fact led researchers to the conclusion that the striking preference most people show in using one hand over the other to conduct fine motor tasks must originate somewhere in the cerebral cortex and not in the peripheral nervous system (McManus, 1996). However, the question of where exactly has been proven surprisingly hard to answer, even with advanced neuroimaging methods. Functionally, the cortical correlates of handedness have been investigated by different authors using fMRI (functional magnetic resonance imaging), for example by measuring brain activity in motor areas of left- and right-handers during unilateral or bilateral finger or hand movements (e.g., Gut et al., 2007; Klöppel et al., 2007; Grabowska et al., 2012). In addition, several studies were aimed at identifying the macrostructural correlates of left-and right-handedness in the cerebral cortex (e.g., regarding the volume of different gray matter brain areas), with mixed results. While some authors found significant structural differences between left and right-handers, e.g., in the precentral gyrus and sulcus (Amunts et al., 1996; Foundas et al., 1998), the planum temporale (Hervé et al., 2006) and Broca's area (Powell et al., 2012a), others could not identify any macrostructural correlates of handedness (e.g., Good et al., 2001). These somewhat ambiguous results might in part be due to sample characteristics, since especially in studies with a small number of left-handers, individual anatomical properties in this group might have had a disproportionally large impact on the overall effect.
In the paper by Guadalupe et al. (2014), the authors avoided this issue by investigating an impressively large sample of 1960 right-handed and 106 left-handed participants, the largest cohort that has so far been investigated in relation to this question. In order to identify structural differences in the cortices of left- and right-handers, MRI-scans of the subjects were analyzed using an automated parcellation technique, which allowed for analysis of the cortical surface area of 74 different brain parcellations in each hemisphere. The authors then compared left- and right-handers regarding the cortical surface area of 10 different candidate regions related to language, motor control and visual processing which were obtained from previous studies investigating the structural correlates of handedness in the brain. While the authors found a nominally significant association between handedness and the surface area of the left precentral sulcus, not a single effect survived statistical correction for multiple testing. These striking results yield a very important insight into the structural correlates of handedness by showing that macrostructural properties of gray matter brain areas might not represent the major cortical correlate (or even “cause”) of handedness. Thus, the findings by Guadalupe et al. (2014) implicate that future research on structure-function relationship in regard to handedness should focus on other structural properties of the motor and related systems, e.g. the microstructure of gray matter areas (Chance, 2014) or micro- and macrostructural properties of white matter pathways (Powell et al., 2012b). Gaining a better understanding of the anatomical base of handedness is also of particular importance for several related areas within the broader scope of research, such as the ontogenesis and clinical significance of hemispheric asymmetries. For example, studies identifying structural markers for left- or right-handedness may provide endophenotypes that aid the ongoing quest to identify the genetic, epigenetic and environmental influences that determine handedness (e.g., Francks et al., 2007; Arning et al., 2013; Ocklenburg et al., 2013a). This in turn might benefit research investigating the ontogenesis of neuropsychiatric or developmental disorders related to a reduced frequency of right-handedness, such as schizophrenia (Hirnstein and Hugdahl, 2014), autism (Lindell and Hudry, 2013), and dyslexia (Brandler and Paracchini, 2014).
Aside from meta-analyses, single large-scale studies are one of the most important tools neuroscientists have for a comprehensive examination of structure-function relationships in the human brain (Hirnstein et al., 2014). Importantly, they avoid one of the biggest issues of meta-analyses: Due to the so-called file-drawer problem, e.g. the bias to only submit significant results to scientific journals, meta-analyses are strongly affected by publication biases (Rosenberg, 2005). By both avoiding this issue and the statistical power problems often associated with smaller studies, studies such as the work by Guadalupe et al. (2014) allow for comprehensive answers with regard to the association of structural properties of different brain regions and behavior. Hence, this type of study is exactly what is needed in order to advance our understanding of which properties of the brain are related to handedness and which are not. In this sense, a non-significant result in a large-scale study such as the one by Guadalupe et al. (2014) can be more meaningful than several contradicting significant findings in smaller, possibly underpowered, studies. In our opinion, this principle is not limited to handedness research but applies to any field of neuroscience and clinical research that heavily relies on groups comparisons between two or more groups showing high intra-group heterogeneity. For example, the field of cognitive sex differences (Hirnstein et al., 2013) or any type of patient-control comparison (Peterburs et al., 2012) e.g., between schizophrenic (Ocklenburg et al., 2013b) or autistic patients (Chmielewski and Beste, 2015) comes to mind.
We hope that the work by Guadalupe et al. (2014) encourages other researchers in cognitive neuroscience not only to conduct more studies with larger samples, but also to publish their findings even if they are non-significant.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Amunts, K., Schlaug, G., Schleicher, A., Steinmetz, H., Dabringhaus, A., Roland, P. E., et al. (1996). Asymmetry in the human motor cortex and handedness. Neuroimage 4, 216–222. doi: 10.1006/nimg.1996.0073
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Arning, L., Ocklenburg, S., Schulz, S., Ness, V., Gerding, W. M., Hengstler, J. G., et al. (2013). PCSK6 VNTR Polymorphism is associated with degree of handedness but not direction of handedness. PLoS ONE 8:e67251. doi: 10.1371/journal.pone.0067251
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Brandler, W. M., and Paracchini, S. (2014). The genetic relationship between handedness and neurodevelopmental disorders. Trends Mol. Med. 20, 83–90. doi: 10.1016/j.molmed.2013.10.008
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Chance, S. A. (2014). The cortical microstructural basis of lateralized cognition: a review. Front. Psychol. 5:820. doi: 10.3389/fpsyg.2014.00820
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Chmielewski, W. X., and Beste, C. (2015). Action control processes in autism spectrum disorder - insights from a neurobiological and neuroanatomical perspective. Prog. Neurobiol. 124C, 49–83. doi: 10.1016/j.pneurobio.2014.11.002
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Foundas, A. L., Hong, K., Leonard, C. M., and Heilman, K. M. (1998). Hand preference and magnetic resonance imaging asymmetries of the central sulcus. Neuropsychiatry Neuropsychol. Behav. Neurol. 11, 65–71.
Francks, C., Maegawa, S., Laurén, J., Abrahams, B. S., Velayos-Baeza, A., Medland, S. E., et al. (2007). LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. Mol. Psychiatry 12, 1129–1139. doi: 10.1038/sj.mp.4002053
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Good, C. D., Johnsrude, I., Ashburner, J., Henson, R. N., Friston, K. J., and Frackowiak, R. S. (2001). Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 14, 685–700. doi: 10.1006/nimg.2001.0857
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Grabowska, A., Gut, M., Binder, M., Forsberg, L., Rymarczyk, K., and Urbanik, A. (2012). Switching handedness: fMRI study of hand motor control in right-handers, left-handers and converted left-handers. Acta Neurobiol. Exp. 72, 439–451.
Guadalupe, T., Willems, R. M., Zwiers, M. P., Arias Vasquez, A., Hoogman, M., Hagoort, P., et al. (2014). Differences in cerebral cortical anatomy of left- and right-handers. Front. Psychol. 5:261. doi: 10.3389/fpsyg.2014.00261
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Gut, M., Urbanik, A., Forsberg, L., Binder, M., Rymarczyk, K., Sobiecka, B., et al. (2007). Brain correlates of right-handedness. Acta Neurobiol. Exp. 67, 43–51.
Hervé, P. Y., Crivello, F., Perchey, G., Mazoyer, B., and Tzourio-Mazoyer, N. (2006). Handedness and cerebral anatomical asymmetries in young adult males. Neuroimage 29, 1066–1079. doi: 10.1016/j.neuroimage.2005.08.031
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Hirnstein, M., and Hugdahl, K. (2014). Excess of non-right-handedness in schizophrenia: meta-analysis of gender effects and potential biases in handedness assessment. Br. J. Psychiatry 205, 260–267. doi: 10.1192/bjp.bp.113.137349
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Hirnstein, M., Hugdahl, K., and Hausmann, M. (2014). How brain asymmetry relates to performance—a large-scale dichotic listening study. Front. Psychol. 4:997. doi: 10.3389/fpsyg.2013.00997
Hirnstein, M., Westerhausen, R., Korsnes, M. S., and Hugdahl, K. (2013). Sex differences in language asymmetry are age-dependent and small: a large-scale, consonant-vowel dichotic listening study with behavioral and fMRI data. Cortex 49, 1910–1921. doi: 10.1016/j.cortex.2012.08.002
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Klöppel, S., van Eimeren, T., Glauche, V., Vongerichten, A., Münchau, A., Frackowiak, R. S., et al. (2007). The effect of handedness on cortical motor activation during simple bilateral movements. Neuroimage 34, 274–280. doi: 10.1016/j.neuroimage.2006.08.038
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Lindell, A. K., and Hudry, K. (2013). Atypicalities in cortical structure, handedness, and functional lateralization for language in autism spectrum disorders. Neuropsychol. Rev. 23, 257–270. doi: 10.1007/s11065-013-9234-5
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
McManus, I. C. (1996). “Handedness,” in The Blackwell Dictionary of Neuropsychology, eds J. G. Beaumont, P. M. Kenealy, and M. J. C. Rogers (Oxford: Blackwell), 367–376.
Ocklenburg, S., Beste, C., and Güntürkün, O. (2013a). Handedness: a neurogenetic shift of perspective. Neurosci. Biobehav. Rev. 37, 2788–2793. doi: 10.1016/j.neubiorev.2013.09.014
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Ocklenburg, S., Westerhausen, R., Hirnstein, M., and Hugdahl, K. (2013b). Auditory hallucinations and reduced language lateralization in schizophrenia: a meta-analysis of dichotic listening studies. J. Int. Neuropsychol. Soc. 19, 410–418. doi: 10.1017/S1355617712001476
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Peterburs, J., Gajda, K., Koch, B., Schwarz, M., Hoffmann, K. P., Daum, I., et al. (2012). Cerebellar lesions alter performance monitoring on the antisaccade task—an event-related potentials study. Neuropsychologia 50, 379–889. doi: 10.1016/j.neuropsychologia.2011.12.009
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Powell, J. L., Kemp, G. J., Roberts, N., and García-Finaña, M. (2012a). Sulcal morphology and volume of Broca's area linked to handedness and sex. Brain Lang. 121, 206–218. doi: 10.1016/j.bandl.2012.03.003
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Powell, J. L., Parkes, L., Kemp, G. J., Sluming, V., Barrick, T. R., and García-Fiñana, M. (2012b). The effect of sex and handedness on white matter anisotropy: a diffusion tensor magnetic resonance imaging study. Neuroscience 207, 227–242. doi: 10.1016/j.neuroscience.2012.01.016
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Rosenberg, M. S. (2005). The file-drawer problem revisited: a general weighted method for calculating fail-safe numbers in meta-analysis. Evolution 59, 464–468. doi: 10.1111/j.0014-3820.2005.tb01004.x
Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar
Keywords: handedness, genetics, cortex, ontogenesis, endophenotype, motor cortex, MRI imaging
Citation: Ocklenburg S, Garland A, Ströckens F and Uber Reinert A (2015) Investigating the neural architecture of handedness. Front. Psychol. 6:148. doi: 10.3389/fpsyg.2015.00148
Received: 04 December 2014; Accepted: 28 January 2015;
Published online: 11 February 2015.
Edited by:
Bernhard Hommel, Leiden University, NetherlandsReviewed by:
Jacqueline Angelique de Nooijer, Erasmus University Rotterdam, NetherlandsCopyright © 2015 Ocklenburg, Garland, Ströckens and Uber Reinert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: sebastian.ocklenburg@rub.de