Structural and functional asymmetries are ubiquitous in the human brain, where developmental, hereditary, and pathological factors may influence the magnitude and direction of asymmetries [4
]. We report significant leftward cortical thickness asymmetries in motor, perisylvian, lateral temporal, and parahippocampal regions that are largely consistent with earlier findings, at least for the lateral aspects of the brain [1
]. Leftward asymmetries, however, appeared less pronounced in nondextral participants, where localized leftward asymmetry patterns in dextral participants were more spatially diffuse in those who were nondextral (). Furthermore, rightward asymmetries shown in parietal association regions in dextral groups were observed in the opposite direction in nondextral groups. Thus, our findings support that dextrality relates to both the pattern and direction of regional cortical thickness asymmetries. Trends in our results may also indicate that disease processes in schizophrenia mediate rightward asymmetry patterns in the dorsomedial prefrontal cortices of both dextral and nondextral participants, though effects did not survive FDR correction.
Nondextral participants exhibited leftward asymmetries in posterior association cortices including the angular and bordering supramarginal gyrus, regions that showed rightward asymmetries in dextral participants. These supra-modal and heteromodal cortical association regions serve several brain functions including aspects of language and somatosensory processing, with localized lesions to these areas resulting in the disruption of lateralized functions [20
]. Thus, the presence of handedness-related cortical thickness asymmetries within these areas is not surprising, although the functional significance of increases versus decreases in hemispheric cortical thickness patterns in relation to dextrality is less obvious. As there is an established left-hemisphere bias for language processing and hand preference, and parietal association regions play a role in integrating language information, these regional asymmetries and their differences across handedness may relate to language dominance. Notably, recently identified fiber density asymmetries in the arcuate fasciculus, which connects parietal and other language-related regions, are suggested to relate to functional asymmetries in language [21
]. Although a greater percentage of left handers than right handers, however, are right-lateralized for language, 70% of left handers remain left-lateralized [4
]. Dextrality effects for parietal lobule cortical thickness asymmetries may thus also relate to somatosensory functions through lateralized inputs from the left and right hands [6
]. Finally, given that nondextral participants exhibit less localized thickness asymmetries than dextral participants (), our results suggest that cortical thickness asymmetries are less structurally organized in those with nondextral hand preference and, consequently, that those who are nondextral are less lateralized than those who were dextral.
Sex and disease status had little measurable effect on cortical thickness asymmetries. We observed some regional thickness asymmetry increases in men compared with women that are consistent with our earlier studies showing similar sex-related thickness asymmetry trends [1
], with reports of increased structural asymmetries in men [4
], but findings did not survive FDR correction. As earlier research indicates that schizophrenia is a lateralized disease [22
] with disturbances in both functional laterality as well as increases in left, mixed, and ambiguous handedness [3
], we sought to clarify how schizophrenia and handedness interact with regard to cortical thickness asymmetries. Although we found that diagnosis alone had little effect on cortical thickness asymmetry patterns, uncorrected results showed some indication that schizophrenia affects cortical thickness asymmetries differentially in dextral and nondextral, which implies more complex relationships between handedness and disease processes. Our findings do not preclude the existence of disturbances in other structural asymmetries in schizophrenia, but suggest that cortical thickness abnormalities reported in the disorder are similar across hemispheres. This is consistent with earlier reports of bilateral effects in schizophrenia, albeit that asymmetry effects were not tested explicitly [24
Although our overall sample size was large (N=157), the number of nondextral participants in our study was relatively modest (N=26). Thus, statistical power issues may have influenced our results in which cortical asymmetry patterns examined within nondextral participants included fewer subjects. These issues also rendered it impractical to investigate the presence of more complex interactions among sex, diagnosis, and dextrality. The methods used for defining handedness may also have impacted results. Future studies relating functional and structural asymmetries could help to elucidate the underlying mechanisms responsible for handedness and specifically to determine how the direction of cortical thickness asymmetries relate to hand preference or other behavioral asymmetries.