Neuroimaging Attentional Impairment During Abstinence
Condition: Smoking
Study type: Interventional

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Smoking Abstinence
Intervention type(s): Behavioral
Intervention description(s): Smokers were scanned after having quitting smoking for 24 hours, and scanned after smoking as usual.
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science