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Functional MRI of neural activation

Institution: University of California, Los Angeles
Investigator(s): Shantanu Sinha, Ph.D.
Award Cycle: 1997 (Cycle 6) Grant #: 6IT-0255 Award: $48,447
Subject Area: Nicotine Dependence
Award Type: Inno Dev & Exp Awards (IDEAS)

Initial Award Abstract
Cigarette smoking is estimated to cause 85% of the nearly 60,000 deaths attributable to chronic obstructive lung disease (COPD). Many of these deaths are preceded by prolonged respiratory disability. The effects of nicotine addiction on the subjective, behavioral, and heart functions are well documented. It is important therefore to determine the extent to which prolonged exposure to tobacco affects the functional state of those parts of the brain that are the primary control centers for our body's breathing and cognitive functions. It is also important to gain some understanding of the brain regions that are possibly affected by nicotine addiction or even responsible for deciding whether an individual gets addicted to nicotine or not.

This project aims to develop a novel approach to the detection and diagnosis of the biological health consequences of using tobacco. We aim to use the recently developed non-invasive technique of functional magnetic resonance imaging (fMRI) to detect changes in the important areas of the brain that may be involved and affected by smoking, thereby examining the problem simultaneously from the clinical, biological and neuroscientific perspective. Specifically, we seek to examine and compare these brain regions in patients with COPD, with those of healthy subjects, The insights expected as an outcome of this study might very well explain why one person gets addicted to smoking and another does not, why one is able to go "cold turkey" and another is not.

In our study design, we have made a significant attempt to address the influence of tobacco products on disease progression and a novel method of disease detection. In this effort, we will be utilizing our extensive experience in functional MRI when breathing is made difficult for the subject. Inparticular, we will investigate the use of this nova non-invasive, non-ionizing modality to detect, localize and quantify the activation of brain control centers and their difference between smokers and non-smokers.

Numerous studies in animals have shown convincingly that exposure to nicotine, particularly during early development, produces profound effects on the brain. However, it has been very difficult to translate the results of these studies to humans because the brain, for obvious reasons, is not easily accessible for study in humans while they are alive. Recent developments in imaging technology might lessen this limitation. Proton magnetic resonance spectroscopy ('H MRS) is a technology which is similar to a regular MRI procedure except that more details about tissue chemistry can be obtained. The proposed study in animals will determine if, indeed, we can assess the detrimental effects of nicotine exposure on the brain with this technology. Results of the study will the groundwork for implementing subsequent studies in humans of a comparable nature.