Aberrant functional network recruitment of posterior parietal cortex in Turner syndrome

Abstract

Turner syndrome is a genetic disorder caused by the complete or partial absence of an X chromosome in affected women. Individuals with TS show characteristic difficulties with executive functions, visual-spatial and mathematical cognition, with relatively intact verbal skills, and congruent abnormalities in structural development of the posterior parietal cortex (PPC). The functionally heterogeneous PPC has recently been investigated using connectivity-based clustering methods, which sub-divide a given region into clusters of voxels showing similar structural or functional connectivity to other brain regions. In the present study, we extended this method to compare connectivity-based clustering between groups and investigate whether functional networks differentially recruit the PPC in TS. To this end, we parcellated the PPC into sub-regions based on temporal correlations with other regions of the brain. fMRI data were collected from 15 girls with TS and 14 typically developing (TD) girls, aged 7-14, while they performed a visual-spatial task. Temporal correlations between voxels in the PPC and a set of seed regions were calculated, and the PPC divided into clusters of voxels showing similar connectivity. It was found that in general the PPC parcellates similarly in TS and TD girls, but that regions in bilateral inferior parietal lobules, and posterior right superior parietal lobule, were reliably recruited by different networks in TS relative to TD participants. These regions showed weaker correlation in TS with a set of regions involved in visual processing. These results suggest that abnormal development of visuospatial functional networks in TS may relate to the well documented cognitive difficulties in this disorder.

Keywords: Turner syndrome; functional connectivity; posterior parietal.

Figure 1

Judgment of line orientation task. (a) Easy version of the task (low cognitive load). Participants press a button if the yellow lines at the bottom of the screen are in the same positions as the lines highlighted in yellow in the protractor at the top of the screen. (b) Difficult version of the task (high cognitive load). The task here is the same as the easy version, but there are 11 lines in the protractor and line segments on the bottom are shortened. (c) Control task in which participants are asked to press the button if the colors of the lines on the bottom match the lines on top. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Connectivity‐based clustering of PPC voxels. PPC voxels were divided into N separate clusters in each participant. At the group level, clusters are defined as the set of voxels which belong to a given cluster for ≥60% of participants. Cluster sizes and centers of mass are listed in Table 2. (a) TD and (b) TS groups with PPC voxels divided into three clusters. Color‐coding relative to Table 2: orange = 1, blue = 2, green = 3. (c) Voxels showing significant group differences in cluster membership for the 3‐cluster case (P < 0.05 uncorrected) are shown in red. (d) TD and (e) TS groups with PPC voxels divided into five clusters. Color‐coding relative to Table 2: orange = 1, blue = 2, green = 3, magenta = 4, yellow = 5. (f) Voxels showing significant differences in cluster membership for the 5‐cluster case (P < 0.05 uncorrected) are shown in red. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Voxels showing group differences in clustering across multiple analyses. Maps of voxels showing significant differences in cluster membership for analyses dividing PPC voxels into 3, 4, 5, and 6 clusters were binarized and summed. From darker to lighter, colors indicate that a voxel clustered significantly different between groups across 1–4 separate analyses (i.e., division of PPC voxels into 3, 4, 5, or 6 clusters). Contiguous voxels in bilateral inferior parietal lobule ([−41, −35, 40] and [41, −35, 40]), and right superior parietal lobule [43, −56, 50] showed significant differences in all four cases (shown in white). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Whole brain correlation maps for PPC clusters. (a) Clusters were defined across the entire group (TD+TS) as the set of voxels which belong to a given cluster in ≥60% of participants. (b) Representative time courses were extracted from each of the five clusters shown in (a) and entered into a whole‐brain SPM analysis. The resulting contrast maps were entered into an F‐contrast at the group‐level and thresholded at P < 0.05 FWE‐corrected over the whole brain. Voxels that significantly correlated with time courses from each of the five clusters shown in (a) are plotted in (b) using the same color coding. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 5

Differences in whole brain correlation for voxels that cluster differently between groups. Time courses from voxels showing significant group differences in cluster membership for division into 3, 4, 5, and 6 clusters (shown in Fig. 3) were entered into whole‐brain regression analyses and compared between groups. Results are shown at an exploratory threshold of P < 0.001 uncorrected: red = TD > TS, blue = TS > TD. (a) Group differences in correlation with right posterior parietal lobule [42, −56, 50]. (b) Group differences in correlation with right [40, −36, 40] (top) and left [−38, −36, 40] (bottom) inferior parietal lobule. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]