Regional variation in interhemispheric coordination of intrinsic hemodynamic fluctuations

Abstract

Electrophysiological studies have long demonstrated a high degree of correlated activity between the left and right hemispheres, however little is known about regional variation in this interhemispheric coordination. Whereas cognitive models and neuroanatomical evidence suggest differences in coordination across primary sensory-motor cortices versus higher-order association areas, these have not been characterized. Here, we used resting-state functional magnetic resonance imaging data acquired from 62 healthy volunteers to examine interregional correlation in spontaneous low-frequency hemodynamic fluctuations. Using a probabilistic atlas, we correlated probability-weighted time series from 112 regions comprising the entire cerebrum. We then examined regional variation in correlated activity between homotopic regions, contrasting primary sensory-motor cortices, unimodal association areas, and heteromodal association areas. Consistent with previous studies, robustly correlated spontaneous activity was noted between all homotopic regions, which was significantly higher than that between nonhomotopic (heterotopic and intrahemispheric) regions. We further demonstrated substantial regional variation in homotopic interhemispheric correlations that was highly consistent across subjects. Specifically, there was a gradient of interhemispheric correlation, with highest correlations across primary sensory-motor cortices (0.758, SD=0.152), significantly lower correlations across unimodal association areas (0.597, SD=0.230) and still lower correlations across heteromodal association areas (0.517, SD=0.226). These results demonstrate functional differences in interhemispheric coordination related to the brain's hierarchical subdivisions. Synchrony across primary cortices may reflect networks engaged in bilateral sensory integration and motor coordination, whereas lower coordination across heteromodal association areas is consistent with functional lateralization of these regions. This novel method of examining interhemispheric coordination may yield insights regarding diverse disease processes as well as healthy development.

Figure 1.

Regional masks. A total of 112 regional masks (56 in each hemisphere) comprising the entire cerebrum were generated from the Harvard–Oxford Structural Atlas, a validated probabilistic atlas that divides each hemisphere into regions corresponding to portions of cortical gyri and subcortical gray matter nuclei. Atlas-derived values corresponding to each voxel's probability of inclusion in a given region were used to derive probability-weighted time series for all 112 regions (see Materials and Methods for details). For visualization, all three-dimensional reconstructions are thresholded to include voxels with >25% probability of inclusion in a given region. Occluded perisylvian regions are depicted in cut-away views. The lower bank is viewed from a top-down perspective; the upper bank is viewed from a bottom-up perspective.

Figure 2.

Homotopic versus nonhomotopic correlations. Correlations between homotopic regions were significantly higher than correlations between heterotopic regions and between intrahemispheric regions. Data points are shown for each region, averaged across subjects. Black lines indicate mean with SEM.

Figure 3.

Homotopic interhemispheric correlations. A, B, Tukey box-and-whiskers plots showing the distribution of (A) interhemispheric correlations and (B) ranked interhemispheric correlations for all 56 homotopic regions across subjects (vertical line, median; box, interquartile range; whiskers, 1.5 times the interquartile range; closed circles, individual values lying outside 1.5 times the interquartile range).

Figure 4.

Homotopic interhemispheric correlations. A, Regional masks are labeled according to their functional classification, as described by Mesulam (2000). These classifications were used to model interhemispheric correlation as a function of hierarchical subdivision. B, Mean interhemispheric correlation strengths indicated for all cortical regions. Primary sensory-motor cortices exhibit significantly stronger correlations than unimodal association areas, which exhibit significantly stronger correlations than heteromodal association areas.

Figure 5.

Interhemispheric correlation as a function of hierarchical subdivision. Scatterplots of interhemispheric correlation, organized by hierarchical subdivision and plotted to demonstrate: A, all data points (each data point represents homotopic interhemispheric correlation for one region in one subject); B, subject distribution (each data point represents one subject's mean interhemispheric correlation averaged across primary, unimodal, or heteromodal regions, respectively); and C, region distribution (each data point represents one region's mean interhemispheric correlation averaged across all subjects). Primary sensory-motor cortices demonstrated a significantly higher degree of interhemispheric correlation than either unimodal association areas or heteromodal association areas. Unimodal association areas showed significantly higher interhemispheric correlations than heteromodal association areas. D, Within each sensory-motor modality, primary cortices exhibited a high degree of correlated activity across hemispheres, with decreased interhemispheric correlations in unimodal association areas. This decrease was significant in somatosensory, visual, and motor modalities but did not reach significance in the auditory system when corrected for multiple comparisons.

Figure 6.

Interhemispheric correlation as a function of regional volume and interregional distance. A, No relationship was observed between a region's total volume (left plus right) and interhemispheric correlation. B, Consistent with previous studies, the distance between left and right homotopic regions was inversely related to interhemispheric correlation. This relationship was independent of the relationship observed between hierarchical subdivision and interhemispheric correlation.