Cigarette smoking causes significant morbidity and mortality in the United States. Smoking cessation is difficult, with the average smoker attempting to quit five times before permanent success. Moreover, the majority of smoking quit attempts result in relapse. Brain stimulation for smoke cessation is an exciting new area that builds on advancing neuroscience knowledge concerning the functional neurocircuitry of addiction. Cortical stimulation can now be performed non-invasively by transcranial magnetic stimulation (TMS). Several studies have shown that TMS can reduce cue-elicited craving in smokers. Previous research by our group has shown that a single session of 15 minutes high frequency (10 Hz) repetitive TMS (rTMS) at 100% motor threshold over the left dorsal lateral prefrontal cortex (DLPFC) can reduce cue-induced craving compared to sham TMS. However, the mechanism by which craving is reduced by rTMS is poorly understood both at behavioral and neural levels. Neuroimaging studies in nicotine dependence have revealed cue-related responses in numerous brain areas, including frontal, parietal cortices and subcortical areas. Recently functional magnetic resonance imaging (fMRI) studies by our group have shown that cue-induced craving induced brain activation in ventral medial prefrontal cortex (VMPFC), including medial frontal, orbital frontal and anterior cingulate. This Chair Research Development Fund (CRDF) pilot proposal will integrate two new techniques- TMS and fMRI to investigate DLPFC-VMPFC pathway in smokers. Using double-masked methods we hypothesize that cue-induced exposure will induce brain activity in VMPFC, and 15 minutes rTMS over DLPFC will reduce cue-induced craving through modulating DLPFC-VMPFC pathway (increased activity DLPFC and decreased activity VMPFC). In the one year of project, we plan to recruit 10 non-treatment-seeking nicotine-dependent cigarette smokers and 20 non-smoking participants, both males and females of all ethnic and racial groups between the ages of 18 and 60 to participate in the study. The participants will randomly receive two different types of brain stimulation: active rTMS or sham rTMS over the left DLPFC with a 1 week interval between treatments. MRI scans will be completed pre and post rTMS. The data from this pilot will provide the information needed for submitting a larger-scale investigation (R01) to investigate cue craving neutral pathway and develop a potential clinical applications of TMS in smoke cessation.
Cigarette smoking is the leading preventable cause of death and disability in the U.S. and individuals with elevated depression symptoms or clinically diagnosed major depressive disorder (MDD) smoke at significantly higher rates than non-depressed individuals. Elevated negative affect and affective dysregulated emotional control may contribute to greater smoking among individuals with MDD. The proposed research will shed new light on the neural mechanisms that govern associations between depression and smoking. Despite known and costly associations between these factors, little is known regarding their co-occurrence and such information will provide a foundation for the development of novel and more effective interventions. We are recruiting adult smokers and nonsmokers, and individuals with or without depression, ages 18 and older to participate.
This research is being conducted to investigate the association of personal, environmental, and occupational risk factors and ALS. A web-based survey that includes questions about demographics, medical history, family history of neurological disorders, hobbies, military history, smoking, physical activity, residential history, and occupational history, etc. will be completed by ALS patients as well as controls without ALS to compare differences among the two groups.