This is an application for an NIMH Scientist Development Award for New Minority Faculty (K01 special use) titled, """"""""fMRI Cingulate Dissection in Cingulotomy Patients & ADHD"""""""". The candidate is primarily interested in elucidating the functions of anterior cingulate (AC) subregions and examining their potential role(s) in the pathobiology of psychiatric disorders, especially Attention-Deficit Hyperactivity Disorder (ADHD). Convergent evidence supports AC subregion delineation into a dorsal cognitive/motor division (AC-CMD), and a rostral affective division (AC-AD). A battery of cognitive-motor and emotional tasks will be refined and used off-line and during fMRI to study these AC subregions.
Aim I concentrates on refining the battery of tasks and establishing test-retest reliability. The task battery will be used to resolve questions about AC-CMD mechanisms (i.e., to discern if AC-CMD acts by influencing stimulus selection and/or response selection), and with high-resolution cortical flat mapping to resolve AC topography.
Aim II takes advantage of a unique opportunity to study subjects pre- and post-cingulotomy (which specifically targets AC-CMD) with tasks designed to contrast AC-CMD/AC-AD functions.
In Aim III, AC-CMD function in ADHD is tested in two ways: a) ADHD patients are compared to matched controls (in an attempt to confirm the hypothesis implicating AC-CMD dysfunction in ADHD pathophysiology), and b) within ADHD patients pre- and post-methylphenidate, to see if AC-CMD response normalizes with treatment. By this proposal, the candidate seeks training in: 1) the basic neurobiology of AC subregions, 2) cognitive neuroscience and cognitive psychology methodology, 3) advanced fMRI physics and techniques (i.e., cortical flat mapping, single-trial format, and high field MRI), and 4) specialized statistics relevant to functional neuroimaging. The rigorous training plan, integrating strong didactics and multidisciplinary expertise, will teach the candidate how to synthesize information from diverse fields in studying normal AC function and psychiatric disease. This integrated program of training and research will advance our knowledge of AC functions, generate new data on ADHD pathobiology, yield new tools for studying AC in health and psychiatric disease, and give the candidate the skills needed to achieve independence in a highly complex field.
| Bush, George (2011) Cingulate, frontal, and parietal cortical dysfunction in attention-deficit/hyperactivity disorder. Biol Psychiatry 69:1160-7 |
| Seidman, Larry J; Valera, Eve M; Bush, George (2004) Brain function and structure in adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 27:323-47 |
| Bush, George; Vogt, Brent A; Holmes, Jennifer et al. (2002) Dorsal anterior cingulate cortex: a role in reward-based decision making. Proc Natl Acad Sci U S A 99:523-8 |
| Shin, L M; Whalen, P J; Pitman, R K et al. (2001) An fMRI study of anterior cingulate function in posttraumatic stress disorder. Biol Psychiatry 50:932-42 |
| Lazar, S W; Bush, G; Gollub, R L et al. (2000) Functional brain mapping of the relaxation response and meditation. Neuroreport 11:1581-5 |
| Bush, G; Frazier, J A; Rauch, S L et al. (1999) Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop. Biol Psychiatry 45:1542-52 |
