Abnormalities of intrinsic functional connectivity in autism spectrum disorders

Abstract

Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.

Figure 1

Functional connectivity within specific regions of the default network for the ASD (left) and control (right) groups separately. All other regions of the default network also showed significant connectivity. Statistics are provided in Table 2. Figure 1A shows superior frontal gyrus activation in the ASD group, xyz coordinates 26 42 40. Figure 1B depicts temporal lobe activation in the ASD group xyz coordinates, 56 −22 −2. Figure 1C illustrates parahippocampal gyrus activation in the ASD group, xyz coordinates, 18 −32 −8. Figure 1D shows superior frontal gyrus activation in the control group, xyz coordinates 24 38 44. Figure 1E illustrates temporal lobe activation in the control group, xyz coordinates, 54 −36 −4. Finally, figure 1F shows parahippocampal gyrus activation in the control group, xyz coordinates, 24 −20 −16. The threshold was set at p < .05 FWE. For this and subsequent figures, the brain images are presented in neurological space.

Figure 2

The control group relative to the ASD group showed stronger positive functional connectivity in the right superior frontal gyrus, t(22) = 3.36 p = .001, xyz 26 42 46. For the illustration, the threshold was set at p = .01 with a minimum cluster size of 50 voxels. The figure depicts voxels showing significant correlation with the seed and the voxels showing a significant difference in correlation between subject groups.

Figure 3

The ASD relative to the control group showed stronger functional connectivity in the right temporal lobe, t(22) = 3.56 p = .001, xyz 54 −20 −2 (A) and the right parahippocampal gyrus, t(22) = 3.66 p = .001, xyz 18 −28 −12 (B). For the illustration, the threshold was set at p = .01 with a minimum cluster size of 50 voxels. The figure depicts voxels showing significant correlation with the seed and the voxels showing a significant difference in correlation between subject groups.

Figure 4

Within the ASD group, social functioning based on the ADI-R measure of total reciprocal social interaction (current), was negatively correlated with functional connectivity with two areas of the superior frontal gyrus, t(10)=3.02, p = .006, xyz coordinates 14 26 48 (A) and t(10)=3.37, p = .004, xyz coordinates 26 54 −2 (C). A higher score in the ADI-R measure indicates worse social function. For Figure 4A and 4C, the threshold was set at p = .05 with a minimum cluster size of 50 voxels. To illustrate this association, contrast values were extracted from a 4 mm sphere around the peak activation and plotted with the ADI-R measure of social function, Pearson r = −.66, P = .019 for xyz coordinates 14 26 48 (B) and Pearson r= −.707 P = .008 and for xyz coordinates 26 54 −2 (D). Although other areas correlated with social function, analyses focused on areas of the default network where group differences were found.

Figure 5

For subjects with ASD, severity of restricted and repetitive behaviors based on the ADI-R measure of total restricted, repetitive and stereotyped patterns of behavior positively correlated with functional connectivity in the right parahippocampal gyrus, t(10)=3.92, p = .001, xyz coordinates 26 54 −2 (A). A higher score in the ADI-R measure indicates worse restricted and repetitive behaviors. For Figure 5A, the threshold was set at p = .05 and a minimum cluster size of 20 voxels. To illustrate this association, contrast values were extracted from a 4 mm sphere around the peak activation and plotted with the ADI-R measure of restricted and repetitive behaviors, Pearson r = .67, P = .016 for xyz coordinates 26 54 −2 (B). As in Figure 4, analyses focused on areas of the default network where group differences were found.