Aging
Conditions
Keywords
nicotine, acetylcholine, functional magnetic resonance imaging
Brief summary
Nicotine enhances auditory-cognitive function because it mimics the brain's system for paying attention to important sounds amid distractions (for example, understanding speech in a noisy environment). In part, nicotine does this by activating inhibitory neurons in the auditory cortex. Since age-related hearing deficits result, in part, from the loss of inhibitory neurons in auditory cortex, this project will determine whether nicotine's effects can compensate for reduced inhibition in the aging auditory cortex and thereby restore auditory function. The investigators will use functional magnetic resonance imaging (fMRI) to measure the selectivity of responses in auditory cortex to tones of various frequencies. The investigators will measure the effects of nicotine (administered as chewing gum) and aging on these fMRI response properties. The investigators hypothesize that frequency selectivity will decrease with aging and increase following nicotine administration.
Interventions
DRUGNicotine gum
The effects of over-the-counter nicotine gum will be compared to a placebo gum
OTHERPlacebo gum
The effects of over-the-counter nicotine gum will be compared to a placebo gum
Sponsors
National Institute on Aging (NIA)
University of California, Berkeley
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Nicotine (6 mg, polacrilex gum) and placebo will be administered to each participant in separate sessions in a within-subject double-blind randomized crossover design. Subjects will be in either a young (18-28 years) or old (60-85 years) group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* non-smokers with a score of 0-2 out of 10 maximum on the Fagerström index of smoking dependency
Exclusion criteria
* deafness or excessive hearing loss * smokers with a score between 3 and 10 on the Fagerström index of smoking dependency * history of psychiatric illness, neurological disorders, diabetes mellitus, renal failure, or cardiovascular disease * regular use of prescription medications (excluding oral contraceptives) * drug dependency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| frequency tuning of excitatory auditory fMRI cortical responses | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | Functional magnetic resonance imaging (fMRI) responses to pure tone stimuli ranging from 88-8000 Hz will be recorded. For each voxel in objectively identified auditory cortical area, a tuning curve model will be fit to the data. One of the parameters of this model is the width of frequency tuning of excitatory responses, and this is the primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| frequency tuning of inhibitory auditory fMRI cortical responses | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | Functional magnetic resonance imaging (fMRI) responses to pure tone stimuli ranging from 88-8000 Hz will be recorded. For each voxel in objectively identified auditory cortical area, a tuning curve model will be fit to the data. One of the parameters of this model is the width of frequency tuning of inhibitory responses, and this is Outcome 2. |
| amplitude of excitatory auditory fMRI cortical responses | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | Functional magnetic resonance imaging (fMRI) responses to pure tone stimuli ranging from 88-8000 Hz will be recorded. For each voxel in objectively identified auditory cortical area, a tuning curve model will be fit to the data. One of the parameters of this model is the amplitude of excitatory responses, and this is Outcome 3. |
| amplitude of inhibitory auditory fMRI cortical responses | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | Functional magnetic resonance imaging (fMRI) responses to pure tone stimuli ranging from 88-8000 Hz will be recorded. For each voxel in objectively identified auditory cortical area, a tuning curve model will be fit to the data. One of the parameters of this model is the amplitude of inhibitory responses, and this is Outcome 4. |
Countries
United States
Contacts
Primary ContactMichael A Silver, PhD
Outcome results
None listed