Neuroimaging Attentional Impairment During Abstinence

The broad objective of this proposal is to identify functional neuroanatomical correlates of impairments in sustained attention during smoking abstinence. We will measure changes in performance and regional blood oxygenation levels using fMRI while smokers and non-smokers complete a task designed to assess sustained attention-or the continuous monitoring of stimuli.

Our primary hypothesis is that smoking abstinence will result in impaired sustained attention accompanied by decreases in blood-oxygenation-level-dependent (BOLD) fMRI signal in regions associated with sustained attention including right fronto-parietal cortex, thalamus and reticular activation system. Abstinence may also result in performance-related increases in activation in brain regions associated with effortful processing including the anterior cingulate cortex. We also hypothesize that smokers during the satiated state will exhibit brain activity more similar to that of non-smokers.

In addition to task related brain responses, we will also measure changes in absolute regional cerebral blood flow (rCBF) and hypothesize that abstinence will result in significant decreases in regions associated with arousal (e.g., reticular activation system); information processing (e.g., thalamus); and emotional regulation (e.g., anterior cingulate cortex, prefrontal cortex).

Following an extended training period in which performance will become stable, smokers will be tested in the 4 Tesla MRI scanner (GE LX NVi system) 24 hours after quitting smoking, and tested satiated, while non-smokers will be tested in the scanner once under normal conditions. This design will provide an assessment of how tobacco abstinence alters information processing.

Included smoker participants will smoke at least 10 cigarettes per day of a brand delivering at least 0.5 mg nicotine (by FTC method) for at least two years and have afternoon end tidal carbon monoxide (CO) concentrations of at least 10 ppm (confirming they are inhalers). Inclusion criteria for non-smoker participants is that they should have smoked less than 50 cigarettes in their lifetime, have not smoked or used any nicotine products during the last 6 months, and have afternoon end tidal CO of less than or equal to 5 ppm. In order to reduce variability and ensure comparable stimulus exposure, participants will be required to be right-handed, and have at least 20-30 corrected vision.

During a screening session, all aspects of the study will be described to subjects and informed consent will be acquired. Breath and saliva samples will be collected in order to verify smoking status; and paper-and-pencil measures of smoking history, nicotine dependence, and mood will be collected. Each subject will also complete a Brain Imaging and Analysis Center (BIAC) approved fMRI subject screening form. For females of child bearing potential, a blood sample will be taken for pregnancy testing. For all participants, a urine sample will be taken for illicit drug testing. Finally, each subject will be escorted to the hospital where they will view and be placed in a mock fMRI scanner for a short time in order to increase familiarity with study procedures. Subjects who meet all selection criteria will be scheduled for the remainder of sessions.

Participants will learn and practice a sustained attention task. The planned sustained attention task, called the rapid visual information processing task (RVIP) requires participants to identify series of three odd or three even numbers among a series of numbers presented one at a time on a computer monitor. A control task in which participants press a button when they see a '0' will also be practiced. Total task time is 15 minutes (practice version) and each participant will be required to complete as many as 8 practice versions or until 50% accuracy is achieved on two consecutive attempts. Training may require 2-8 visits but will not exceed 2 hours and 40 minutes in total duration. One practice version of the task will be conducted in the mock fMRI scanner.

Following the training period, smoker participants will complete two fMRI scans and non-smokers will complete one fMRI scan in which they will complete 1) undergo a five minute resting state BOLD scan, 2) two 12.5 minute versions of the RVIP and 3) a 12.5-minute 'cue-viewing' task in which they view pictures of people smoking. For the 'satiated' sessions, smoker participants will be instructed to smoke as usual before and after the session. For the 'abstinent' session, smoker participants will be required to quit smoking for 24 hours prior to the scan and 24 hours following the scan. Quitting will be verified using CO and salivary cotinine and nicotine levels collected at the time of the scan and a short session 24 hours after the scan. All smoker participants will be given information about quitting smoking for 48 hours and we will answer questions about quitting smoking. The order of the sessions-satiated first vs. abstinent first-will be randomly assigned.

One week after their second scan, participants will attend a 30-minute office visit in which they will complete questionnaires and the RVIP task.

Eligibility Criteria:
Inclusion Criteria:

1. smoked an average of 10 cigarettes per day for two years
2. a brand that delivers (by Federal Trade Commission rated yields) at least 0.5 mg nicotine
3. have an expired air carbon monoxide reading of at least 10 ppm.
4. be in general good health
5. Participants with controlled medical conditions (e.g., hypertension) will be considered if treatment is not thought to interfere with fMRI measures or potentially ameliorate smoking withdrawal symptoms

Exclusion Criteria:

1. Individuals with a major medical condition that would make participation unsafe (e.g., have pacemaker or other metallic implant),
2. uncomfortable (e.g., chronic pain),
3. confound results (e.g., psychiatric condition)
4. suffering from claustrophobia; abnormally afraid of closed-in places will be excluded from participation,
5. Current alcohol or drug abuse,
6. smokeless tobacco use, or use of nicotine replacement therapy or other smoking cessation treatment will also be a basis for exclusion and evaluated via a urine test.