Huntington's disease (HD) is a neurological illness with prominent psychiatric comorbidity. Obsessions and compulsion appear to be highly represented in HD, but have not been studied. There is compelling evidence that obsessive-compulsive disorder (OCD) is related to dysfunctional cortico-striatal networks. Because it is a neurological disorder with well-characterized striatal pathology, and accurate genetic testing, HD provides a unique opportunity for study of these symptoms In this Mentored Clinical Scientist Development Award proposal, a program is outlined that will prepare the candidate to become an independent investigator. The candidate will learn how to evaluate obsessive and compulsive symptoms in HI) patients. HD patients' data will be compared with data from primary OCD patients to examine how obsessions and ompulsions may differ in a neurological illness that primarily affects the striatum. Clinical and neuropsychological correlate of OCD in HD will be explored. Cognitive activation paradigms will be used with neuro-imaging studies to engage network implicated in primary OCD. First, task-related cerebral activation changes particular to HD itself will be studied, and these networks will be related to presence or absence of obsessive and compulsive symptoms. Supervision of the candidate during this award will be provided by these mentors: Drs. Yaakov Stern (training coordination, neuropsychology supervision), Karen Marder (neurological expertise, evaluation of HD), Michael Liebowit training in evaluation of obsessive and compulsive symptoms), and Dr. James Haxby (neuro-imaging). Advanced instruction n the neuroanatomy of frontal-striatal circuitry, including hand-on correlation of brain slices with Magnetic Resonanc mages, is included. The goals of this award are to promote the candidate's training, study psychiatric symptoms in HD, and Ldd to current understanding of neural circuitry implicated in HD. The ultimate goal is to provide the candidate with the skill and knowledge base to become an independent, multidisciplinary investigator of neuropsychiatric illness.
| Mars, Rogier B; Coles, Michael G H; Grol, Meike J et al. (2005) Neural dynamics of error processing in medial frontal cortex. Neuroimage 28:1007-13 |
