Traditionally research on structural asymmetries has focussed on grey matter (GM) volume using region-of-interest measurements of the cerebral cortex (e.g. Amunts et al., 2003; Keller et al., 2007) or voxel-based statistics on large data sets (e.g. Good et al., 2001a,b; Watkins et al., 2001). Cortical regions in isolation cannot, however, perform all language processing. Rather, it is the active network of regions, connected by white matter (WM) fibre bundles, that is required (Frederici, 2009). Given the structural asymmetries and functional lateralities reported in language-associated cortical regions,
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similar asymmetries in WM structure particularly language-associated cortical fibres are thought to exist. Voxel based morphometry (VBM) studies performed on GM and WM densities have shown differences between the two hemispheres (e.g. Barrick et al., 2005; Good et al., 2001a, Luders et al., 2004; Watkins et al., 2001). These studies however, found no significant effect for handedness. Hervé et al (2006) examined cerebral anatomical asymmetry in 56 right- and 56 left-handed males using VBM and observed leftward WM asymmetry in both groups. Their study found that only two small WM asymmetry clusters differed between the left- and right-handed groups (P<0.001) in the cerebellum and middle frontal gyrus, however results were uncorrected for multiple comparisons. Whilst studies using VBM on structural MR images have found no clear effect of handedness on GM or WM asymmetries Watkins et al (2001) in a sample of 142 subjects, found variations in T-statistics for WM volume (with greater T-statistics in males and right-handers for leftward WM volume asymmetry) when processing, separately, groups of either men or right-handed subjects. The suggestion here is that a significant effect for sex and/or handedness may be detected in a larger sample of subjects balanced for sex and handedness.
Recent years have seen a growth in voxel-based studies exploring diffusion anisotropy (Barnea-Goraly et al., 2003; Büchel et al., 2004; Burns et al., 2003; Eriksson et al., 2001; Foong et al., 2002; Park et al., 2004; Rugg-Gunn et al., 2001). Using a voxel- based approach Büchel et al (2004) found leftward fractional anisotropy (FA) asymmetry in a C-shaped structure connecting temporal and frontal cortex. This C- shaped structure was thought to represent the arcuate fasciculus (AF), the main WM pathway connecting frontal (Broca’s area) and parieto-temporal language areas and is thought to play a major role in language functioning (e.g. Catani et al., 2007; Friederici, 2009; Glasser and Rilling, 2008). An image of the AF can be seen in Figure 2.2. Takao et al (2010) explored FA asymmetry by performing VBM on asymmetric FA images in a sample comprising only right-handed subjects. Results revealed a significant leftward FA asymmetry in the AF, cingulate fasciculus and cortico-spinal tract. Additionally cognitive abilities have been correlated with measures of WM such as FA to explain some of the variance in performance within samples of healthy subjects and clinical populations, such as schizophrenic patients (e.g. Karlsgodt et al., 2008).
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Findings using FA maps obtained from DTI show asymmetries in similar anatomical regions to those observed when exploring WM volume asymmetries using WM segments from T1-weighted images (e.g. Good et al., 2001a; Paus et al., 1999; Pujol et al., 2002). Good et al (2001a) for instance, observed WM asymmetry in occipital, frontal, and temporal lobes, including Heschl's gyrus, planum temporale (PT) and the hippocampal formation and there was no significant effect for handedness. Additionally diffusion tensor (DT) tractography studies provide supporting evidence for a structural asymmetry of the AF (Catani et al., 2007; Glasser and Rilling, 2008; Hagmann et al., 2006; Nucifora et al., 2005; Parker et al., 2005; Powell et al., 2006) and suggest that language networks represent a more likely anatomical substrate for lateralization of language function than cortical areas alone. It should be noted however, that there are discrepant findings in the literature regarding the existence of the AF in the right hemisphere. While Catani et al (2007) report a right hemispheric AF representation in around 40% of their right-handed subjects Gharabarghi et al (2009) using a similar identification approach to that of Catani et al (2005, 2007), were able to identify both direct and indirect language pathways in the right hemisphere in all 12 of their right- handed subjects. Vernooij et al (2007) were able to identify a right hemisphere AF in their 20 subjects and additionally report leftward asymmetry of the AF in 80% of individuals. Moreover subjects comprised 13 left- and 7 right-handers.
What is evident from the literature is leftward laterality of WM language tracts whether this is assessed using volumetric measures such as VBM on WM images, voxel-wise statistical analysis of FA maps or asymmetry calculations of WM fibres as obtained using DT-tractography. What is unclear from the literature is whether differences in WM anisotropy asymmetry or WM volume asymmetry between left- and right-handed groups exist. To date the research provides no compelling evidence to suggest any significant effect of handedness on WM language tracts.
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Figure 2.2. Broca’s area, Wernicke’s area and the arcuate fasciculus (AF). Broca’s area and Wernicke’s can be seen in the top image, these regions are located in the frontal and temporal lobe respectively. The AF can be seen in the bottom image extending from Broca’s area to Wernicke’s area. The long segment connects these regions directly. However another pathway connecting these regions is thought to exist. This pathway is broken and is composed of two pathways: an anterior and a posterior pathway which goes through Geschwind’s territory. The top image was created from the T1-weighted MR image of a subject used in this thesis and the bottom image is taken directly from Catani et al (2005).
Most diffusion asymmetry studies have focused exclusively on right-handers (Barrick et al., 2007; Catani et al., 2005, 2007; Gharabaghi et al., 2009; Glasser and Rilling, 2008; Nucifora et al., 2005; Powell et al., 2006; Xiang et al., 2009; Yu et al., 2008) and the
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few studies that have considered left-handers (Büchel et al., 2004; Hagmann et al., 2006; Saur et al., 2008; Vernooij et al., 2007) have examined only small numbers (i.e. between 9-16 left-handed subjects). Hagmann et al (2006) also studied the interaction between sex and handedness on fibre tract connectivity and observed left hemisphere fibre tract differences between right and left-handers in men to a much greater extent than in women. Takao et al (2011) showed in a sample of 109 right-handers aged 21-29 years GM and WM asymmetries using voxel-based analysis of FA maps derived from DTI. Leftward WM anisotropy asymmetries were observed in the AF, cingulum and corticospinal tract. However, no effect of sex on GM or WM asymmetry was observed. No study to my knowledge, has examined differences in WM integrity across the whole brain between left and right-handers.