Hyperconnectivity of the ventromedial prefrontal cortex in obsessive-compulsive disorder

Abstract

Neuroimaging research has highlighted maladaptive thalamo-cortico-striatal interactions in obsessive-compulsive disorder as well as a more general deficit in prefrontal functioning linked with compromised executive functioning. More specifically, dysfunction in the ventromedial prefrontal cortex, a central hub in coordinating flexible behaviour, is thought to be central to obsessive-compulsive disorder symptomatology. We sought to determine the intrinsic alterations of the ventromedial prefrontal cortex in obsessive-compulsive disorder employing resting-state functional connectivity magnetic resonance imaging analyses with a ventromedial prefrontal cortex seed region of interest. A total of 38 obsessive-compulsive disorder patients and 33 matched controls were included in our analyses. We found widespread ventromedial prefrontal cortex hyperconnectivity during rest in patients with obsessive-compulsive disorder, displaying increased connectivity with its own surrounding region in addition to hyperconnectivity with several areas along the thalamo-cortico-striatal loop: thalamus, caudate and frontal gyrus. Obsessive-compulsive disorder patients also exhibited increased functional connectivity from the ventromedial prefrontal cortex to temporal and occipital lobes, cerebellum and the motor cortex, reflecting ventromedial prefrontal cortex hyperconnectivity in large-scale brain networks. Furthermore, hyperconnectivity of the ventromedial prefrontal cortex and caudate correlated with obsessive-compulsive disorder symptomatology. Additionally, we used three key thalamo-cortico-striatal regions that were hyperconnected with our ventromedial prefrontal cortex seed as supplementary seed regions, revealing hypoconnectivity along the orbito- and lateral prefrontal cortex-striatal pathway. Taken together, these results confirm a central role of a hyperconnected ventromedial prefrontal cortex in obsessive-compulsive disorder, with a special role for maladaptive crosstalk with the caudate, and indications for hypoconnectivity along the lateral and orbito pathways.

Keywords: Ventromedial prefrontal cortex; functional magnetic resonance imaging; neuroimaging; obsessive-compulsive disorder; prefrontal cortex; resting state.

Figure 1.

Increased vmPFC autoconnectivity in OCD patients correlates with neutralising scores. (a) Bar plot showing relative increases in autoconnectivity between the vmPFC seed (−2, 26, −2) and the surrounding vmPFC ROI region in OCD (N = 38) in relation to controls (N = 33). OCD patients showed increased connectivity between the vmPFC seed region and the eigenvariates extracted from the surrounding region compared to controls. (b) In OCD patients (N = 38), eigenvariates at the smallest 5-mm vmPFC ROI correlated significantly with neutralising scores (R² = 0.2405, p = 0.0034), remaining significant when correcting for six multiple comparisons (six OCD dimensions) at alpha level = 0.005.

Figure 2.

VmPFC-caudate hyperconnectivity in OCD correlates with Y-BOCS scores: (a) axial, sagittal and coronal views (OCD > Control) of vmPFC connectivity with the right caudate (whole-brain differences p = 0.001 uncorrected, cluster threshold = 10 voxels). The Control > OCD contrast showed no significant differences. (b) First, eigenvariates were extracted for these caudate coordinates (10, 12, 10 MNI), which showed a significant (t₆₉ = 4.022, p = 0.00012) increase in connectivity in OCD. Error bars denote standard error of the mean. (c) A linear regression analysis depicting a significant (R² = 0.1240, p = 0.0301) correlation between the caudate eigenvariates (20 mm) of OCD patients and their respective Y-BOCS scores.

Figure 3.

Schematic map of altered functional connectivity in OCD. Corresponding MNI coordinates and BA can be found in Tables 2 and 3.