Reduced fronto-callosal fiber integrity in unmedicated OCD patients: a diffusion tractography study

It is widely accepted that abnormalities in the frontal area of the brain underpin the pathophysiology of obsessive-compulsive disorder (OCD). Fundamental to this investigation is the delineation of frontal white matter tracts including dorsal and ventral frontal projections of interhemispheric connections. While previous investigations of OCD have examined the dorsal and ventral frontal regions, the corresponding callosal connections have not been investigated, despite their importance. We recruited twenty patients with OCD (15 drug-naïve and 5 currently unmedicated) and demographically similar healthy controls, and conducted fiber tractography and post hoc quantitative analysis using diffusion tensor imaging. We extracted fractional anisotropy (FA) of the fronto-callosal fibers along the entire length of the tract. Function-specific [by the Brodmann area region-of-interest (ROI) approach] and region-specific (by the length-parameterization approach) tracts were defined. In addition, we devised a new index of dorsal-ventral imbalance (DVII) of fiber integrity. Significant FA decreases were observed in orbitofrontal and dorsolateral prefrontal projections of the corpus callosum (P < 0.05, false discovery rate-corrected) with higher function/region sensitivity than voxel-based or ROI-based approaches. Importantly, OCD patients also exhibited significantly higher ventral-greater-than-dorsal asymmetry of FA values than normal controls (P < 0.05, FDR-corrected). This study is the first to investigate fiber integrity in the dorsal/ventral frontal parts of the callosal tractography in unmedicated OCD patients. Using a more quantitative method in terms of functional and regional specificity than previous studies, we report abnormalities in interhemispheric connectivity of both dorsal and ventral networks in the pathophysiology of OCD.