Research articleVoxel-wise grey matter asymmetry analysis in left- and right-handers
Introduction
When conducting fine motor activities such as writing, a large majority of humans consistently prefer one hand over the other [1]. On average, roughly 10% of the population prefers to use the left hand, while the remaining 90% prefers to use the right hand [2]. Since there are no obvious muscular, osseous or peripheral nervous system differences between the left and right hands of left- and right-handers, it has been suggested that handedness originates in the central nervous system [3], [4]. One idea put forward by several authors is that structural asymmetries in grey matter areas might underlie handedness, but empirical results have been surprisingly incoherent. Areas for which associations with handedness have been reported include the left precentral sulcus [5], left central sulcus [6], planum temporale [7] and Boca’s area [8]. However, other studies have failed to find any associations between structural asymmetries in these areas and handedness [9]. The largest study so far has been conducted by Guadalupe et al. [10]. They analyzed cortical surface area differences between 106 left-handed and 1960 right-handed subjects, reporting that no cortical region showed any association with left-handedness that survived statistical correction for multiple testing.
A common technique to assess grey matter asymmetries is voxel based morphometry (VBM). VBM allows for a voxel-wise comparison of local grey matter concentration between two groups of subjects, e.g. left- and right-handers or patients and controls. It involves spatial normalization of structural MRI scans from all participants into the same stereotactic space, followed by segmentation into grey and white matter, and smoothing of grey matter segments. Using these smoothed grey-matter images, voxel-wise statistical tests are then used to compare the two groups [11], [12].
VBM is a workhorse tool in neuroimaging that has been used in hundreds of published studies. However, it has recently been pointed out that the standard VBM protocol might not be ideally suited to specifically assess group differences in structural grey matter asymmetries, as it involves accurate voxel-wise correspondence across individuals but not necessarily across both hemispheres [13]. This methodological issue might have lead to biased results in previous asymmetry studies, potentially omitting existing asymmetries or causing false positive results. Recently, Kurth et al. [13] published a novel 12-step protocol for specifically analyzing voxel-wise grey matter asymmetries. This protocol solves the problems standard VBM encounters in asymmetry analyses by ensuring accurate voxel-wise correspondence across individuals and hemispheres by means of spatial normalization into a symmetric space using DARTEL (Diffeomorphic Anatomical Registration using Exponentiated Lie algebra) [14]. Additionally, the protocol avoids blurring of information across hemispheres and controls the possible impact of noise in the data by applying an explicit brain mask and a spatial smoothing procedure. The protocol has recently been successfully used in a study investigating differences in gray matter asymmetry between long-term meditators and non-meditating controls [15], but has not yet been used in the context of handedness.
Here, we used the protocol by Kurth et al. [13], [15] to re-investigate structural grey matter asymmetries in left-and right-handers. Using the advanced statistical analysis features of the toolbox, we not only compared left- and right-handers on the group level, but also linked grey matter asymmetries to inter-individual quantitative measures of hand preference and hand skill, an aspect not investigated in previous studies.
Section snippets
Participants and handedness assessment
Overall, 60 volunteers participated in the present study (30 males; 30 females). Mean age was 23.33 years, with a range of 18 to 33 years. None of the participants had any history of psychiatric or neurological disorders.
Participants’ hand preference was assessed with the Edinburgh Handedness Inventory [16]. This ten-item questionnaire yields a so-called lateralization quotient (LQ) ranging from −100 (consistent left-handedness) to +100 (consistent right-handedness). There were two groups of
Structural grey matter asymmetries in the overall sample
First we set up two statistical models to check for clusters with AIs significantly different from zero using a one-sample t-test (cluster extent threshold = 20, FWE-corrected, p < 0.05). One was for positive AIs and the other for negative AIs. Overall, 11 clusters reached significance for positive AIs, indicating larger right-hemispheric volume (see Table 1 and Fig. 1). The three largest clusters were located in middle temporal gyrus, precuneus, and superior frontal gyrus. Additional clusters were
Discussion
Preferences to use one forelimb over the other when performing fine motor tasks have been observed in dozens of animal species and represent an important functional principle in mammalian motor system organization [22]. Despite continuous research efforts, the structural correlates of human handedness in the brain are still not well understood. One idea is that structural grey matter asymmetries influence handedness, but the literature is very incoherent with regard to the question, which areas
Conclusion
The present findings imply that macroscopic structural grey matter asymmetries as assessed with VBM are not a major determinant of handedness. Recently, it has been suggested that functional lateralization can only be understood by taking into account callosal interactions, gray matter asymmetries and asymmetrical interhemispheric pathways (the triadic model [29]). The present results suggest that researchers looking for the structural determinants of handedness may want to focus more on the
References (31)
- et al.
Cognitive benefits of right-handedness: a meta-analysis
Neurosci. Biobehav. Rev.
(2015) - et al.
Handedness: a neurogenetic shift of perspective
Neurosci. Biobehav. Rev.
(2013) - et al.
Asymmetry in the human motor cortex and handedness
Neuroimage
(1996) - et al.
Interhemispheric asymmetry of the human motor cortex related to handedness and gender
Neuropsychologia
(2000) - et al.
Sulcal morphology and volume of Broca’s area linked to handedness and sex
Brain Lang.
(2012) - et al.
Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains
Neuroimage
(2001) - et al.
Voxel-based morphometry: the methods
Neuroimage
(2000) - et al.
Why voxel-based morphometry should be used
Neuroimage
(2001) A fast diffeomorphic image registration algorithm
Neuroimage
(2007)The assessment and analysis of handedness: the Edinburgh inventory
Neuropsychologia
(1971)