Rules ventral prefrontal cortical axons use to reach their targets: implications for diffusion tensor imaging tractography and deep brain stimulation for psychiatric illness.

The ventral prefrontal cortex (vPFC) is involved in reinforcement-based learning and is associated with depression, obsessive-compulsive disorder, and addiction. Neuroimaging is increasingly used to develop models of vPFC connections, to examine white matter (WM) integrity, and to target surgical interventions, including deep brain stimulation. We used primate (Macaca nemestrina/Macaca fascicularis) tracing studies and 3D reconstructions of WM tracts to delineate the rules vPFC projections follow to reach their targets. vPFC efferent axons travel through the uncinate fasciculus, connecting different vPFC regions and linking different functional regions. The uncinate fasciculus also is a conduit for vPFC fibers to reach other cortical bundles. Fibers in the internal capsule are organized according to destination. Thalamic fibers from each vPFC region travel dorsal to their brainstem fibers. The results show regional differences in the trajectories of fibers from different vPFC areas. Overall, the medial/lateral vPFC position dictates the route that fibers take to enter major WM tracts, as well as the position within specific tracts: axons from medial vPFC regions travel ventral to those from more lateral areas. This arrangement, coupled with dorsal/ventral organization of thalamic/brainstem fibers through the internal capsule, results in a complex mingling of thalamic and brainstem axons from different vPFC areas. Together, these data provide the foundation for dividing vPFC WM bundles into functional components and for predicting what is likely to be carried at different points through each bundle. These results also help determine the specific connections that are likely to be captured at different neurosurgical targets.

The Brown Longitudinal Obsessive Compulsive Study: clinical features and symptoms of the sample at intake.

OBJECTIVE: This article describes the method and intake findings of the Brown Longitudinal Obsessive Compulsive Study, the first comprehensive prospective investigation of the naturalistic course of obsessive-compulsive disorder (OCD) in a large clinical sample using longitudinal research methodology. METHOD: Intake data, collected between June 2001 and October 2004, are presented for 293 adult participants in a prospective, naturalistic study of OCD. Participants had a primary diagnosis of DSM-IV OCD and had sought treatment for the disorder. RESULTS: Our findings indicate that OCD typically has a gradual onset and a continuous course regardless of age at onset. There is a substantial lag between the onset of the disorder and initiation of treatment. OCD, which almost always coexists with other psychiatric symptoms, leads to serious social and occupational impairment. Compared with participants with late-onset OCD, early-onset participants had higher rates of lifetime panic disorder, eating disorders, and obsessive-compulsive personality disorder. The groups also differed on the types of obsessive-compulsive symptoms that were first noticed, as well as on rates of current obsessions and compulsions. CONCLUSION: The demographics, clinical characteristics, comorbidity rates, and symptom presentation of the sample are consistent with those reported for cross-sectional studies of OCD, including the DSM-IV Field Trial. The current sample has a number of advantages over previously collected prospective samples of OCD in that it is large, diagnostically well characterized, recruited from multiple settings, and treatment seeking. This unique data set will contribute to the identification of meaningful phenotypes in OCD based on stability of symptom dimensions, prospective course patterns, and treatment response.