Effects of Nicotine on Cognitive Task Performance and Brain Activity as Measured by fMRI
| Status: | Completed |
|---|---|
| Conditions: | Smoking Cessation, Psychiatric, Tobacco Consumers |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 4/17/2018 |
| Start Date: | September 17, 2002 |
| End Date: | November 26, 2012 |
Background:
- Many cigarette smokers claim that smoking improves their ability to think and concentrate,
and have reported problems in thinking and concentration after quitting smoking. Some
research has indicated that nicotine can enhance certain aspects of attention and memory in
humans. However, more research is needed to determine how nicotine affects different elements
of the brain s ability to think, pay attention, respond to rewards, and make decisions.
Researchers are interested in using functional magnetic resonance imaging (fMRI) to study the
effects of nicotine on brain function and activity.
Objectives:
- To determine the effects of nicotine on attentional and other thinking processes, including
reward-seeking behavior.
Eligibility:
- Individuals between 18 and 50 years of age who are either current smokers (10 or more
cigarettes per day for at least 1 year) or nonsmokers.
Design:
- The study has four experiments. Each experiment requires two MRI scanning sessions and a
training session. Participant can do one or all of the experiments.
- Participants will receive training on the types of computerized tests that will be given
during the active portion of the study. Participants will also fill out questionnaires
on nicotine use and other alcohol and drug use, and provide breath and urine samples.
- During the test sessions, participants will have fMRI scanning while performing up to
four different sets of tasks that test attention, memory, concentration, reward-seeking
behavior, and decision making. Smokers will wear a nicotine patch or placebo patch
during the test sessions, but will not be told which patch they are receiving. The order
of these sessions will be different for individual participants.
- Participants will provide blood and urine samples throughout the research study for
evaluation purposes.
- Many cigarette smokers claim that smoking improves their ability to think and concentrate,
and have reported problems in thinking and concentration after quitting smoking. Some
research has indicated that nicotine can enhance certain aspects of attention and memory in
humans. However, more research is needed to determine how nicotine affects different elements
of the brain s ability to think, pay attention, respond to rewards, and make decisions.
Researchers are interested in using functional magnetic resonance imaging (fMRI) to study the
effects of nicotine on brain function and activity.
Objectives:
- To determine the effects of nicotine on attentional and other thinking processes, including
reward-seeking behavior.
Eligibility:
- Individuals between 18 and 50 years of age who are either current smokers (10 or more
cigarettes per day for at least 1 year) or nonsmokers.
Design:
- The study has four experiments. Each experiment requires two MRI scanning sessions and a
training session. Participant can do one or all of the experiments.
- Participants will receive training on the types of computerized tests that will be given
during the active portion of the study. Participants will also fill out questionnaires
on nicotine use and other alcohol and drug use, and provide breath and urine samples.
- During the test sessions, participants will have fMRI scanning while performing up to
four different sets of tasks that test attention, memory, concentration, reward-seeking
behavior, and decision making. Smokers will wear a nicotine patch or placebo patch
during the test sessions, but will not be told which patch they are receiving. The order
of these sessions will be different for individual participants.
- Participants will provide blood and urine samples throughout the research study for
evaluation purposes.
Objective:
Experiments in this protocol employ fMRI to address the interactions of nicotine with such
cognitive processes as working memory, attention, and the executive functions of inhibitory
control, conceptual reasoning and attention switching, in addition to reward and temporal
error reward processing. The effects of nicotine on these cognitive processes will also be
assessed outside the MRI scanner. Assessments of genetic variants will be done with the
hypothesis that these will account for some inter-individual differences in the brain imaging
data.
Study Population:
The study population will consist of adult (18-50 y.o.) non-treatment seeking smokers and age
and gender matched non-smoking control subjects. The control subjects will provide normative
data on cognitive task performance and corresponding neural activation, as well as providing
control for any time effects (e.g. practice effect on repeated cognitive task performance).
Smokers will smoke at least 10 cigarettes per day for a period of 1 year. Both smokers and
controls will be suitable for fMRI scanning. Subjects may not be dependent on any other drug
except nicotine or caffeine.
Design:
In a within subjects design, experienced smokers will perform cognitive tasks involving
memory encoding and consolidation, selective/divided and sustained attention, as well as
reward and temporal error reward processing two hours following single blind application of a
nicotine patch (21 mg/24 hr) and during a separate session on a different day, following
application of a placebo patch. The tasks will be performed during fMRI scanning. Not all of
the tasks will be done at the same time, rather, groups of tasks are run in series as task
sets: Task set A: Selective/divided attention task and Intention/ attention task; Task set B:
The SARAT (Spatial Attentional Resource Allocation task) which is designed to enable
dissociation of top-down and stimulus driven processes of visuospatial selective attention as
well as the CEFER task which is a measure of central executive function task which isolates
the allocation of attentional resources within working memory; Task set C: Monetary Incentive
Delay and Temporal Delay Error processing tasks; Task set D: Affective Forecasting and Loss
Aversion task. Control subjects will do the tasks during scanning without a patch. Blood will
be drawn from all participants for analysis of genetic variants and for smokers, plasma
nicotine and cotinine will be measured.
Outcome:
We will determine the acute effects of nicotine on attentional and other cognitive mechanisms
and how emotional processes such as the anticipation and receipt of reward affects the
neuronal activation properties of acute nicotine administration in experienced smokers. In
addition, we will determine whether genetic polymorphisms predict BOLD response during
cognitive tasks pertinent to nicotine addiction. Plasma nicotine and cotinine will be
included as a factor in analyses of nicotine-induced effects on fMRI signal to take account
of potentially large inter-individual variability in circulating nicotine concentrations.
Experiments in this protocol employ fMRI to address the interactions of nicotine with such
cognitive processes as working memory, attention, and the executive functions of inhibitory
control, conceptual reasoning and attention switching, in addition to reward and temporal
error reward processing. The effects of nicotine on these cognitive processes will also be
assessed outside the MRI scanner. Assessments of genetic variants will be done with the
hypothesis that these will account for some inter-individual differences in the brain imaging
data.
Study Population:
The study population will consist of adult (18-50 y.o.) non-treatment seeking smokers and age
and gender matched non-smoking control subjects. The control subjects will provide normative
data on cognitive task performance and corresponding neural activation, as well as providing
control for any time effects (e.g. practice effect on repeated cognitive task performance).
Smokers will smoke at least 10 cigarettes per day for a period of 1 year. Both smokers and
controls will be suitable for fMRI scanning. Subjects may not be dependent on any other drug
except nicotine or caffeine.
Design:
In a within subjects design, experienced smokers will perform cognitive tasks involving
memory encoding and consolidation, selective/divided and sustained attention, as well as
reward and temporal error reward processing two hours following single blind application of a
nicotine patch (21 mg/24 hr) and during a separate session on a different day, following
application of a placebo patch. The tasks will be performed during fMRI scanning. Not all of
the tasks will be done at the same time, rather, groups of tasks are run in series as task
sets: Task set A: Selective/divided attention task and Intention/ attention task; Task set B:
The SARAT (Spatial Attentional Resource Allocation task) which is designed to enable
dissociation of top-down and stimulus driven processes of visuospatial selective attention as
well as the CEFER task which is a measure of central executive function task which isolates
the allocation of attentional resources within working memory; Task set C: Monetary Incentive
Delay and Temporal Delay Error processing tasks; Task set D: Affective Forecasting and Loss
Aversion task. Control subjects will do the tasks during scanning without a patch. Blood will
be drawn from all participants for analysis of genetic variants and for smokers, plasma
nicotine and cotinine will be measured.
Outcome:
We will determine the acute effects of nicotine on attentional and other cognitive mechanisms
and how emotional processes such as the anticipation and receipt of reward affects the
neuronal activation properties of acute nicotine administration in experienced smokers. In
addition, we will determine whether genetic polymorphisms predict BOLD response during
cognitive tasks pertinent to nicotine addiction. Plasma nicotine and cotinine will be
included as a factor in analyses of nicotine-induced effects on fMRI signal to take account
of potentially large inter-individual variability in circulating nicotine concentrations.
- INCLUSION CRITERIA:
1. Subjects must be between the ages of 18-50.
2. Subject must be in good health based on history and physical exams.
3. Subjects must be right-handed.
4. Smoking subjects must demonstrate that they are experienced users based upon
urine cotinine levels of at least 100ng/ml, and must smoke a minimum of 10
cigarettes/day with duration of use of at least 1 year.
5. Subjects may be users of alcohol and/or marijuana but may not meet criteria for
dependence on either substance.
EXCLUSION CRITERIA:
1. Are pregnant or breast feeding. Urine pregnancy tests will be performed on all female
volunteers of child-bearing potential before each experimental session.
2. Have implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial
joints, metal pins, surgical clips or other implanted metal parts) or claustrophobia
rendering them unable to undergo fMRI scanning.
3. Have major medical illnesses to include, but not limited to, hypertension,
cardiovascular disease, asthma, diabetes, peripheral vascular diseases,
coagulopathies, syncope, history of superficial or deep vein thrombosis, HIV, or other
clinically significant infectious diseases.
4. Have current major psychiatric disorders to include, but not limited to, mood,
anxiety, psychotic disorders, or substance-induced psychiatric disorders.
5. Have neurological illnesses to including, but not limited to, seizure disorders,
migraine, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS
tumor.
6. Have significant alcohol or other drug use, other than nicotine dependence.
7. Have gros structural abnormalities onT1 weighted images.
8. Have cognitive impairment as assessed by screening WASI vocabulary subtest below 48,
corresponding to full IQ of 85 (in that case on screening, a full WASI will be done to
verify IQ of 85 or above). Justification: Cognitive impairment and learning
disabilities are associated with alterations in brain regions used to accomplish
tasks, and, therefore, may introduce significant variably into the data.
9. Are engaged in or actively seeking smoking cessation treatment.
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