Effects of Nicotine and Attention on Frequency Tuning in Auditory Cortex

Study Overview
=================
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.

Official Title
-----------------
Effects of Nicotine and Attention on Frequency Tuning in Auditory Cortex

Conditions
-----------------
Aging

Intervention / Treatment
-----------------
* Drug: Nicotine gum
* Other: Placebo gum


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Young (18-28 years) participants - nicotine gum<br>6 mg nicotine gum, one time before fMRI measurements | Drug: Nicotine gum<br>* The effects of over-the-counter nicotine gum will be compared to a placebo gum<br>* Other names: polacrilex;|
| Experimental: Old (60-85 years) participants - nicotine gum<br>6 mg nicotine gum, one time before fMRI measurements | Drug: Nicotine gum<br>* The effects of over-the-counter nicotine gum will be compared to a placebo gum<br>* Other names: polacrilex;|
| Placebo Comparator: Young (18-28 years) participants - placebo gum<br>placebo gum, one time before fMRI measurements | Other: Placebo gum<br>* The effects of over-the-counter nicotine gum will be compared to a placebo gum<br>|
| Placebo Comparator: Old (60-85 years) participants - placebo gum<br>placebo gum, one time before fMRI measurements | Other: Placebo gum<br>* The effects of over-the-counter nicotine gum will be compared to a placebo gum<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency tuning of excitatory auditory fMRI cortical responses | 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. | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency tuning of inhibitory auditory fMRI cortical responses | 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. | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | 
| amplitude of excitatory auditory fMRI cortical responses | 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. | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | 
| amplitude of inhibitory auditory fMRI cortical responses | 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. | Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nicotine, acetylcholine, functional magnetic resonance imaging