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.

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.

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.

21 healthy non-smokers were randomized.

1 day (on each of separate 3 test days)

Only the statistician performing the randomization and the pharmacist dispensing the drugs were aware which drug was given on which day.