Originating from a series of morphometric studies conducted in the 1980s, it appears a widely held belief in cognitive neuroscience that the corpus callosum is larger in left or mixed handers than in right handers (RH). However, a recent meta-analysis challenges this belief by not finding significant differences in corpus callosum size between handedness groups. Yet, relying on the available published data, the meta-analysis was not able to account for a series of factors potential influencing its outcome, such as confounding effects of brain size differences and a restricted spatial resolution of previous callosal segmentation strategies. To address these remaining questions, we here analysed N = 1057 participants' midsagittal corpus callosum of from the Human Connectome Project (HCP 1200 Young Adults) to compare handedness groups based on consistency (e.g., consistent RH vs. mixed handers, MH) and direction of hand preference (e.g., dominant RH vs. dominant left handers). A possible relevance of brain-size differences was addressed by analysing callosal variability by both using forebrain volume (FBV) as covariate and utilising relative area (callosal area/thickness divided by FBV) as a dependent variable. Callosal thickness was analysed at 100 measuring points along the structure to achieve high spatial resolution to detect subregional effects. However, neither of the conducted analyses was able to find significant handedness-related differences in the corpus callosum and the respective effect-sizes estimates were small. For example, comparing MH and consistent RH, the effect sizes for difference in callosal area were below a Cohen's d = 0.1 (irrespective of how FBV was included), and narrow confidence intervals allowed to exclude effects above |d| = 0.2. Analysing thickness, effect sizes were below d = 0.2 with confidence intervals not extending above |d| = 0.3. In this, the possible range of population effect sizes of hand preference on callosal morphology appears well below the effects commonly reported for factors like age, sex, or brain size. Effects on cognition or behaviour accordingly can be considered small, questioning the common practise to attribute performance differences between handedness groups to differences in callosal architecture.
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