Connectome-wide Functional Connectivity Abnormalities in Youth With Obsessive-Compulsive Symptoms

Abstract

Background: Obsessive-compulsive symptomatology (OCS) is common in adolescence but usually does not meet the diagnostic threshold for obsessive-compulsive disorder. Nevertheless, both obsessive-compulsive disorder and subthreshold OCS are associated with increased likelihood of experiencing other serious psychiatric conditions, including depression and suicidal ideation. Unfortunately, there is limited information on the neurobiology of OCS.

Methods: Here, we undertook one of the first brain imaging studies of OCS in a large adolescent sample (analyzed n = 832) from the Philadelphia Neurodevelopmental Cohort. We investigated resting-state functional magnetic resonance imaging functional connectivity using complementary analytic approaches that focus on different neuroanatomical scales, from known functional systems to connectome-wide tests.

Results: We found a robust pattern of connectome-wide, OCS-related differences, as well as evidence of specific abnormalities involving known functional systems, including dorsal and ventral attention, frontoparietal, and default mode systems. Analysis of cerebral perfusion imaging and high-resolution structural imaging did not show OCS-related differences, consistent with domain specificity to functional connectivity.

Conclusions: The brain connectomic associations with OCS reported here, together with early studies of its clinical relevance, support the potential for OCS as an early marker of psychiatric risk that may enhance our understanding of mechanisms underlying the onset of adolescent psychopathology.

Keywords: Developmental neuroimaging; Functional connectivity; Imaging statistics; Networks; Obsessive-compulsive symptoms; fMRI.

Figure 1.

Illustration of network-based statistic (NBS) results showing functional connectivity that is higher in OCS. Results are visualized at the t-statistic threshold of 3.2 (see Table 3 for summary results across thresholds). In the connectogram, the arc widths represent the number of supra-threshold connections which go between individual brain sub-networks. The number of nodes is annotated on the perimeter of the circle. Arcs representing fewer than 3 total edges have been removed for clarity. Arcs colored red represent connections between canonical functional systems of brain regions, which survive FDR correction as summarized in Table 4, and the regions are colored according to this seven set parcellation by Yeo et al (2011). Anatomical plot with ggseg in R (76). Note Figure 2 shows a similar plot but for the test of lower functional connectivity.

Figure 2.

Illustration of network-based statistic (NBS) results showing functional connectivity that is lower in OCS. Results are visualized at the t-statistic threshold of 3.2 (see Table 3 for summary results across thresholds). In the connectogram, the arc widths represent the number of supra-threshold connections which go between (or within) individual brain systems. The number of nodes is annotated on the perimeter of the circle. Arcs representing fewer than 3 total edges have been removed for clarity. Arcs colored red represent connections between canonical functional systems of brain regions, which survive FDR correction as summarized in Table 4, and the regions are colored according to this seven system parcellation by Yeo et al (2011). Note Figure 1 shows a similar plot for the test of higher functional connectivity.

Figure 3.

Anatomical plot showing hubs of the network-based statistic (NBS) network components in OCS youths compared to controls. For clarity, nodes are shown only if they have at least 10 suprathreshold connections on average across t-statistic thresholds from 2.5–3.4. A) Number of suprathreshold connections (averaged across 2.5–3.4). B) Average effect size of suprathreshold connections. C) Proportion of suprathreshold connections that are increased versus decreased in OCS. See Supplemental Figure 4 for an equivalent plot for all nodes (including nodes with fewer than 10 connections on average).