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Nicotine withdrawal, smoking & attention: an fMRI study

Institution: University of California, Los Angeles
Investigator(s): Edythe London, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10RT-0091H Award: $515,303
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Nicotine dependence is a psychiatric disorder characterized by the regular use of nicotine, usually by smoking. When regular smokers abruptly stop smoking or reduce their use of nicotine, they show withdrawal signs. Many of those who smoke continue to do so to avoid nicotine withdrawal, which includes changes in mood and in the ability to focus attention. Most smokers (80%) express a desire to quit, and 35 percent attempt to do so, but very few are successful, even when they receive treatment in the form of nicotine replacement (e.g., patch or gum) or other pharmacological therapy (bupropion, Zyban®). Laboratory studies of abstinent smokers have shown that the act of smoking or receiving nicotine itself improves performance, especially on tests of focused attention. In some cases, smoking even a single cigarette produced improvement for a person in withdrawal. Such enhancing effects of nicotine (or other components of smoking) may be a reason why individuals continue to smoke. This research aims to provide a better understanding of how abstaining from smoking may affect brain function in dependent smokers, how smoking can influence brain function, and to what extent nicotine itself (compared with other components of smoking) may produce positive effects.

In order to help explain how nicotine withdrawal and smoking affect different parts and circuits of the brain, we will use a brain imaging method called functional magnetic resonance imaging (fMRI). This method maps the activity of the brain “at work”. It visualizes activity throughout the brain when a person performs a task that requires a certain type of function, such as focused attention. We will use fMRI to test how nicotine dependence and smoking influence the pattern of brain activity when a person performs mental tests that require focused attention. We will compare brain activity of smokers while they are deprived of cigarettes (16 hours) or after they have smoked to satiety. Brain scans (fMRI) will identify activated areas while the participants perform tests of focused attention. One is the Stroop Color-Word Interference Task, which requires participants to ignore the meaning (a color) of a written word that is presented while naming the color in which it is actually presented. In a special version of the task, the “Smoking Stroop”, smokers are asked to name the colors of words that are related to smoking and are more distracting to them. These tasks activate specific regions in the prefrontal cortex of the brain, especially the anterior cingulate gyrus. This gyrus is thought to play an important part in a person’s ability to ignore distracting stimuli while focusing attention.

Based on prior work, we predict that abstinent smokers will show different patterns (and intensities) of brain activation when they perform tasks that require focused attention, compared to the pattern after they have smoked as much as they like. Other prior work suggests that smokers will have a slower reaction when they perform the two tasks during smoking abstinence than during satiety. We predict that the Smoking Stroop task will create more interference and cigarette craving than the Classic Stroop and will produce greater differences between abstinence and satiety states in brain activity as well. We expect that cigarette smoking will reverse some of the differences in brain activation and in performance of the tasks during abstinence so that these measures will be closer to those from the same research participants when they are in a state of satiety. We also anticipate that smoking cigarettes that contain nicotine will have a larger effect than smoking cigarettes that do not contain nicotine; that is, we expect that the combination of nicotine and smoking will be more effective than the act of smoking alone in reversing some of the withdrawal-related deficits.

This research aims to identify brain regions and circuits important to the effects of smoking and nicotine withdrawal on the ability to focus attention. The results will help explain: (1) how effects of nicotine on focused attention might contribute to dependence, and (2) whether smoking is sustained to avoid cognitive deficits during abstinence. There is a pressing need for improved therapies for nicotine dependence. Although the proposed research cannot identify treatments directly, it will provide a better understanding of the biological basis of nicotine dependence and nicotine withdrawal, and thereby may help in the rational design of new treatments.
Publications

Differences between smokers and non-smokers in regional gray matter volumes and densities.
Periodical: Biological Psychiatry Index Medicus:
Authors: Brody AL, Mandelkern MA, Jarvik ME, Lee GS, Smith EC, Huang JC, Bota RG, London ED, et al ART
Yr: 2004 Vol: 55 Nbr: Abs: Pg: 77-84

Difference between smokers and nonsmokers in tests of selective attention and working membory: effects of abstinence and cigarette smoking.
Periodical: TRDRP Annual Report to the State of California Legislature Index Medicus:
Authors: London ED, Simon SL, Mendrek A, Learn J, Cohen MS, Brody AL, Olmstead RO, Ernst M, Jarvik ABS
Yr: 2002 Vol: Nbr: Abs: Pg:

Brain responses to naturalistic tobacco smoking.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Bramen JE, Bilusic Z, Madsen DC, Olmstead RE, London ED, Jarvik ME, Cohen MS ABS
Yr: 2003 Vol: Nbr: Abs: 559.1 Pg:

Regional brain activation during performance of a working memory task by cigarette smokers and nonsmokers.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: London ED, Zu J, Mendrek A, Cohen MS, Jarvik M, Simon SL, Brody AL, Olmstead R, et al ABS
Yr: 2003 Vol: Nbr: Abs: 559.2 Pg:

More task-related cortical activity in cigarette smokers than in nonsmokers performing a working memory task.
Periodical: American College of Neuropsychopharmacology: Scientific Abstracts Index Medicus:
Authors: London ED, Xu J, Rodriquez PF, Mendrek A, Cohen MS, Simon SL, Brody AL, Olmstead R, et al. ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Smoking-induced ventral striatal dopamine release.
Periodical: American College of Neuropsychopharmacology: Scientific Abstracts Index Medicus:
Authors: Brody A, Olmstead RE, Mandelkern MA, Lee GS, Huang J, Hahn E, London ED ABS
Yr: 2003 Vol: 161 Nbr: Abs: Pg: 1211 -1218

Greater cortical activation during performance of a working memory task by smokers than nonsmokers.
Periodical: Society for Research on Nicotine and Tobacco Conference Index Medicus:
Authors: London ED, Xu J, Rodriquez P, Mendrek A, Cohen M, Simon S, Brody A, Olmstead R, et al. ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

More task-related cortical activity in cigarette smokers than in nonsmokers performing a working memory task.
Periodical: College on Problems of Drug Dependence Index Medicus:
Authors: London ED, Xu J, Rodriquez PF, Mendrek A, Cohen MS, Simon SL, Brody AL, Jarvik ME ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Working memory impairments are associated with chronic smoking and withdrawal.
Periodical: College on Problems of Drug Dependence Index Medicus:
Authors: Mendrek A, Monterosso J, Jarvik M, Brody A, Cohen MS, Olmstead R, London ED, et al. ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Cortical activation and deactivation when healthy nonsmokers perform a working memory task.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Xu J, Monterosso J, Mendrek A, Rodriquez PF, Brody AL, Cohen MS, Simon SL, Olmstead R, Jar ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Smoking and task-related brain activity after overnight vs. brief abstinence in smokers.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: London ED, Xu J, Rodriquez RF, Mendrek A, Cohen MS, MOnterosso J, Simon SL, et al. ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Smoking-induced ventral striatal dopamine release.
Periodical: American Journal of Psychiatry Index Medicus:
Authors: Brody AL, Olmstead RE, London ED, Farahi J, Meyer JH, Grossman P, Lee GS, Huang J, et al. ART
Yr: 0 Vol: Nbr: Abs: Pg:

Attenuated cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers.
Periodical: Psychiatry Research Neuroimaging Index Medicus:
Authors: Brody AL, Mandelkern MA< Lee G, Smith E, Sadeghi M, Saxena S, Jarvik M, London ED ART
Yr: 2004 Vol: 130 Nbr: Abs: Pg: 269 - 281

Brain activity in cigarette smokers performing a working memory task: Effects of smoking.
Periodical: Biological Psychiatry Index Medicus:
Authors: Xu J, Mendrek A, Cohen MS, Monterosso J, Rodriquez P, Simon SL, Brody A, et al ART
Yr: 0 Vol: 58 Nbr: Abs: Pg: 143 - 150

Working memory in cigarette smokers: Comparision to non-smokers and effects of abstinence.
Periodical: Addictive Behaviors Index Medicus:
Authors: Mendrek A, Monterosso J, Simon SL, Jarvik M, Brody A, Olmstead R, Domier CP, et al ART
Yr: 0 Vol: Nbr: Abs: Pg: