Language Dominance in Left-Handers: Unveiling Left Hemisphere Global Dominance With Specific Right Hemisphere Regional Dominance.

Introduction The degree to which each human brain hemisphere governs specific cognitive processes, such as language and handedness (the preference or dominance of one hand over the other), varies across individuals. Research has explored the nature of language laterality in left-handed (LH) individuals, indicating that left-hemisphere dominance for language is commonly observed across both left- and right-handed populations. Advanced imaging techniques, including functional transcranial Doppler sonography and fMRI, have revealed subtle differences in language lateralization between LH and right-handed (RH) individuals, particularly in semantic processing tasks. These findings underscore the complex relationship between handedness and language lateralization. This study investigates the spatial patterns of language lateralization in LH and RH individuals using high-resolution fMRI data and the Human Connectome Project (HCP) multimodal parcellation (MMP).  Method We utilized pre-processed MRI scans from the HCP database, comprising 140 healthy young adults, with 70 individuals in each of the RH and LH groups. The language task includes two contrasts: the STORY contrast, where participants listened to brief auditory stories compared to a baseline, and the STORY-MATH contrast, where participants listened to stories versus solving addition and subtraction problems. Data processing involved the HCP Pipelines and the MMP atlas was applied for analysis. The Edinburgh Handedness Inventory categorized participants as either LH or RH. For analysis, we focused on the number of brain surface elements (3D surface vertices) with positive elements (PEs) within each brain region, indicating blood-oxygen-level-dependent (BOLD) activity. The study's methodology aimed to quantify and compare PEs across the hemispheres (paired sample) and handedness groups (independent sample), providing insights into language lateralization. Statistical analysis involved Mann-Whitney U tests for differences across gender and handedness groups and robust t-tests for hemispheric dominance. Results were visualized by projecting mean and effect size values onto a 3D brain surface. Results The analysis of hemispheric mean differences in PEs revealed robust left hemisphere dominance in both the STORY and STORY-MATH contrasts among the RH group, while the LH group exhibited more balanced activity. Significant variations in PEs were observed across numerous MMP regions, with LH individuals showing pronounced asymmetry in 67 and 76 MMP regions (out of 180 regions) in the STORY and STORY-MATH contrasts, respectively, compared to 83 and 99 regions in RH individuals. Additionally, when comparing LH and RH groups, significant differences in PEs were identified within 14 MMP regions (out of 360 regions), all demonstrating significant asymmetry in LH individuals and primarily located in the right hemisphere (12 regions), notably in the inferior parietal lobule (Brodmann 39 and 40). No differences were found in the STORY-MATH contrast. Conclusion We identified hemispheric left-lateralization dominance in brain areas associated with language processing, irrespective of handedness. However, employing multimodal brain parcellation with fMRI language tasks unveiled notable differences in specific regions. Particularly striking was the heightened activity observed in certain right hemisphere regions among LH individuals.