Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder.

The basal ganglia represents a key component of the pathophysiological model for obsessive-compulsive disorder (OCD). This brain region is part of several neural circuits, including the orbitofronto-striatal circuit and dorsolateral prefronto-striatal circuit. There are, however, no published studies investigating those circuits at a network level in non-medicated patients with OCD. Resting state functional magnetic resonance imaging scans were obtained from 20 non-medicated patients with OCD and 23 matched healthy volunteers. Voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) with remaining brain regions were calculated and compared between groups. We performed additional correlation analyses between strength of connectivity and the severity scores for obsessive-compulsive symptoms, depression, and anxiety in the OCD group. Positive functional connectivity with the ventral striatum was significantly increased (P(corrected) < .05) in the orbitofrontal cortex, ventral medial prefrontal cortex and dorsal lateral prefrontal cortex of subjects with OCD. There was no significant correlation between measures of symptom severity and the strength of connectivity (P(uncorrected) < .001). This is the first study to investigate the corticostriatal connectivity in non-medicated patients with OCD. These findings provide the first direct evidence supporting a pathophysiological model involving basal ganglia circuitry in OCD.

Chondroitinase ABC promotes corticospinal axon growth in organotypic cocultures.

STUDY DESIGN: Organotypic coculture model using brain cortex and spinal cord of neonatal rats was used to test the effect of chondroitinase ABC (ChABC) on corticospinal axon growth. OBJECTIVE: Chondroitin sulfate proteoglycan (CSPG) is neurite outgrowth inhibitory factor that combines with reactive astrocyte at the lesion site to form a dense scar that acts as a barrier to regenerating axons. ChABC is a bacteria enzyme that digests the glycosaminoglycan side chain of CSPG. We investigated the effect of ChABC on corticospinal axon growth quantitatively using the organotypic cocultures of brain cortex and spinal cord. SETTING: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University. METHOD: We used organotypic cocultures with neonatal brain cortex and spinal cord as an in vitro assay system for assessing axon growth. After administering ChABC, we counted the number of axons passing through a reference line running parallel to the junction between the brain cortex and spinal cord 500 and 1000 microm from the junction. The immunoreactivity of CSPG was assessed. RESULT: The average number of axons after ChABC administration was significantly greater than in the control group. Administration of ChABC decreased CSPG expression in this coculture system. CONCLUSION: ChABC induces axonal regeneration by degrading CSPG after central nerve system injury. ChABC has great potential for future therapeutic use in spinal cord-injured patients.