Nicotinic Modulation of the Default Network of Resting Brain Function

Background:

- A brain circuit called the default network is the brain circuit that is active when the brain is at rest; that is, when individuals are not concentrating on specific tasks. Previous research has shown that the default network functions differently in people with schizophrenia and Alzheimer s disease, and may contribute to the problems with memory and concentration that can affect people who have these conditions. Studies have also shown that nicotine affects the default network, but more research is needed on the ways in which nicotinic receptors may change activity in these regions and thereby affect individuals ability to concentrate on specific tasks.

Objectives:

- To determine whether and how nicotine and mecamylamine, a drug that blocks nicotinic receptors, affect the default network in nonsmokers in ways that improve thinking and concentration.

Eligibility:

• Healthy, right-handed volunteers between 21 and 50 years of age.
• Volunteers must not have used any kind of tobacco product in the past 2 years.

Design:

• This study involves an initial screening visit, a training visit, and three testing visits.
• Participants will be screened with a medical history and physical examination, as well as blood and urine samples and questions about smoking history.
• Participants will have an initial training session to practice the tasks that will be done during magnetic resonance imaging scans at the testing visits. These tasks will test participants concentration and memory.
• Participants will have three test sessions with the following combinations of study drugs: (1) a nicotine patch and a placebo capsule, (2) a placebo patch and a capsule of mecamylamine, or (3) a placebo patch and capsule. Different combinations will be given at each visit, and participants will not know which one they receive.
• Participants will perform the same concentration and memory tasks at each testing visit, and will provide a blood sample after each visit to determine levels of nicotine and mecamylamine.