Intrinsic activity identifies lateralized brain regions. (A) Functional laterality was computed using intrinsic (spontaneous) activity by examining relative correlation strengths between seed and target regions in the 2 hemispheres. LL is the strength of correlation between the left hemisphere target region and the left hemisphere seed; LR represents the strength of correlation between the left seed and the right target; and RR and RL represent the contralateral homologues. The intrinsic laterality index (iLI), defined in Eq. 1 (see Materials and Methods), represents the relative correlation strength difference between the left and right hemispheres. (B) Using resting-state fMRI data from 100 right-handed subjects, the iLI of 39,800 pairwise correlations were computed and ranked. The 37 most left-lateralized regions (iLI > 0.3, top row) and 47 most right-lateralized regions (iLI < −0.3, bottom row) are projected onto a surface representation of the brain. (C) The laterality distribution for left-lateralized regions is displayed for an independent sample of 200 right-handed subjects and fit by a Gaussian. The iLI was defined as the mean laterality index of the 37 left-lateralized regions shown in (B). Positive iLI reflects left dominance. (D) The laterality distribution based on the 47 right-lateralized regions is displayed.

Cerebral lateralization is controlled by multiple, distinct mechanisms. Factor analysis derived from the lateralized regions of Fig. 1 reveals 4 factors that are replicable across independent data samples (color intensity represents loading value of the factor, blue and yellow color schemes reflect the different hemispheres). Factors tended to center around individual regions and involve their correlated partner regions. Each sample consists of 50 men and 50 women. The top 3 factors each account for >5% of the between-subject variance (explained variance is shown next to each plot). A factor that included putative language regions (ranked 5th) is also shown. Results were replicated in terms of the cortical topography, ranking, and explained variance associated with each factor. The presence of distinct factors suggests that cerebral lateralization in humans arises from multiple genetic or environmental mechanisms.

Sex differences are present but small. Sex differences of the laterality index distribution for left-lateralized regions (blue regions in Fig. 1) are shown. The distribution for left-lateralized regions is displayed split by men (blue bars) and women (red bars). Overlap is shown in dark blue. The distributions are fit by Gaussian curves revealing that women show more symmetric functional organization than men (Kolmogorov-Smirnov test, P < 0.01). A similar effect is present for the right-lateralized regions.

Handedness differentially affects asymmetry across distinct brain systems. Mean laterality estimates for each of the 4 factors in Fig. 3 are plotted for independent data samples of right-handed (n = 38) and left-handed (n = 38) individuals. (A) A significant interaction between hand dominance and factor is observed (P < 0.005) with an effect of handedness observed for factor 3 (***, P < 0.001). Bars represent standard error of the mean. (B) The laterality index distribution for factor 2 is plotted split by handedness. Though the distributions overlap, there are 2 left-handed individuals with complete reversal of asymmetry. (C) The distributions for factor 3 show a marked effect of handedness with right-handed individuals demonstrating greater asymmetry.