Nicotinic Modulation of the Default Network
| Status: | Completed |
|---|---|
| Conditions: | Cognitive Studies, Smoking Cessation |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 21 - 50 |
| Updated: | 1/27/2018 |
| Start Date: | October 2010 |
| End Date: | September 2013 |
Nicotinic Modulation of the Default Network of Resting Brain Function
Many disorders where attentional problems are a hallmark, such as Alzheimer's disease and
schizophrenia, display abnormal regulation of the so-called default network of resting brain
function that maintains internally directed thought when the mind is free to wander. There is
indication that nicotine may improve attention by aiding the deactivation of the default
network, and this mechanism may be of therapeutic benefit for the above disease states. The
current project aims at providing a proof of concept by demonstrating that nicotinic drugs
modulate default network function. The nicotinic agonist nicotine is hypothesized to improve
attention by facilitating the down-regulation of default network activity, and the nicotinic
antagonist mecamylamine is hypothesized to impair attention by impeding the down-regulation
of default network activity during attentional task performance.
schizophrenia, display abnormal regulation of the so-called default network of resting brain
function that maintains internally directed thought when the mind is free to wander. There is
indication that nicotine may improve attention by aiding the deactivation of the default
network, and this mechanism may be of therapeutic benefit for the above disease states. The
current project aims at providing a proof of concept by demonstrating that nicotinic drugs
modulate default network function. The nicotinic agonist nicotine is hypothesized to improve
attention by facilitating the down-regulation of default network activity, and the nicotinic
antagonist mecamylamine is hypothesized to impair attention by impeding the down-regulation
of default network activity during attentional task performance.
This study only enrolls healthy non-smokers. Participants perform attention tasks while
undergoing functional Magnetic Resonance Imaging on three separate days. Across the three
days, three difference conditions are tested in a double-blind manner, in randomized order.
In all test sessions, participants receive a skin patch and swallow a capsule. In one
session, both are a placebo. In another, the patch is a low-dose nicotine patch, and the
capsule is a placebo. In another session, the patch is a placebo and the capsule contains a
low dose of mecamylamine.
undergoing functional Magnetic Resonance Imaging on three separate days. Across the three
days, three difference conditions are tested in a double-blind manner, in randomized order.
In all test sessions, participants receive a skin patch and swallow a capsule. In one
session, both are a placebo. In another, the patch is a low-dose nicotine patch, and the
capsule is a placebo. In another session, the patch is a placebo and the capsule contains a
low dose of mecamylamine.
Inclusion Criteria:
- Age 21 through 50.
- Did not consume cigarettes, cigarillos, cigars, or other tobacco or
nicotine-containing products more than 20 times in lifetime, and did not use any
nicotine-containing product at all within the last two years.
- Normal or corrected to normal vision (at least 20/80).
Exclusion Criteria:
- Presence of metal objects in the body, implanted electronic devices, or any other
counter indication for MRI.
- Claustrophobia.
- Major psychiatric disorders including mood, anxiety or psychotic disorders.
- Cardiovascular or cerebrovascular disease, such as history of myocardial infarction,
heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities.
- Kidney or liver disease.
- Hypertension (resting systolic BP above 140 or diastolic above 85 mm Hg).
- Hypotension (resting systolic BP below 95 or diastolic below 60).
- Use of any prescription or over-the-counter drug other than supplements and birth
control.
- History of or current neurological illnesses, such as stroke, seizures, dementia or
organic brain syndrome.
- Learning disability, attention deficit disorder, or any other condition that impedes
memory and attention.
- Glaucoma, organic pyloric stenosis, uremia or renal insufficiency.
- Prostatic hypertrophy, bladder neck obstruction or urethral stricture.
- Left-handed or ambidextrous.
- Pregnant as determined by urine test, or breast-feeding.
- History or current diagnosis of drug or alcohol abuse or dependence.
- IQ < 85 as estimated by the WASI vocabulary subtest.
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