Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited

Abstract

Obsessive-compulsive disorder (OCD) is a common, heritable and disabling neuropsychiatric disorder. Theoretical models suggest that OCD is underpinned by functional and structural abnormalities in orbitofronto-striatal circuits. Evidence from cognitive and neuroimaging studies (functional and structural magnetic resonance imaging (MRI) and positron emission tomography (PET)) have generally been taken to be supportive of these theoretical models; however, results from these studies have not been entirely congruent with each other. With the advent of whole brain-based structural imaging techniques, such as voxel-based morphometry and multivoxel analyses, we consider it timely to assess neuroimaging findings to date, and to examine their compatibility with cognitive studies and orbitofronto-striatal models. As part of this assessment, we performed a quantitative, voxel-level meta-analysis of functional MRI findings, which revealed consistent abnormalities in orbitofronto-striatal and other additional areas in OCD. This review also considers the evidence for involvement of other brain areas outside orbitofronto-striatal regions in OCD, the limitations of current imaging techniques, and how future developments in imaging may aid our understanding of OCD.

Fig. 1

Diagram of the affective orbitofronto-striatal circuit. Dysfunction in this circuit is proposed to underlie OCD. After Lawrence et al. (1998).

Fig. 2

Results from a quantitative voxel-level meta-analysis of fMRI studies reporting case-control differences for OCD across a range of paradigms: (a) areas where activation was greater in OCD patients than healthy controls (p<0.05) and (b) areas where activation was greater in healthy controls than OCD patients (p<0.05). R and L markers denote side of brain, numbers denote z dimension of each slice in MNI space. See Table 2 for full details of anatomical coordinates.

Fig. 3

Summary of significant structural abnormalities identified by case-control, region-of-interest MRI studies of OCD patients compared with healthy controls. Positive z-scores represent increased region volume in OCD patients compared with healthy controls, negative z-scores represent decreased region volume in OCD. Each bar represents the z-score for a significant case-control difference identified from a previous study.

Fig. 4

Summary of significant structural abnormalities identified by case-control, voxel-based morphometry studies of OCD. Peak MNI coordinates of decreased and increased grey matter from whole brain VBM studies are shown on axial brain images. The plotted coordinates indicate some agreement with traditional orbitofronto-striatal models of OCD but also a rationale to explore other theoretically unpredicted regions such as parietal areas: (A) areas of increased grey matter and (B) areas of decreased grey matter. R and L markers denote side of brain, numbers denote z dimension of each slice in MNI space.

Fig. 5

Simplified diagram summarising putative regions and circuits which may be affected in OCD. Yellow boxes indicate regions comprising the traditionally implicated orbitofronto-striatal loop. Blue boxes indicate regions comprising the dorsolateral prefronto-striatal loop. White boxes indicate additional brain regions putatively involved in OCD. Red arrows indicate connections proposed as components of fronto-striatal loops by Alexander et al. (1986). Green arrows indicate connections incorporated into fronto-striatal loops by Lawrence et al. (1998). Blue arrows indicate connections with supportive anatomical evidence as denoted by number: (1) Cavada and Goldman-Rakic (1989), (2) Takahashi et al. (2007), (3) Aron et al. (2007) and (4) Mink (1996).