Effects of Nicotine and Attention on Frequency Tuning in Auditory Cortex

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.

Study Overview

• Status: Recruiting
• Conditions: Aging
• Intervention / Treatment: Drug: Nicotine gum; Other: Placebo gum

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Michael A Silver, PhD; Phone Number: 5106423130; Email: masilver@berkeley.edu

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94720
      • Recruiting
      • University of California, Berkeley
      • Contact: Michael A Silver, PhD; Phone Number: 510-642-3130; Email: masilver@berkeley.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

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.

Collaborators and Investigators

• Sponsor: University of California, Berkeley
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Michael A Silver, PhD, University of California, Berkeley

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: functional magnetic resonance imaging; nicotine; acetylcholine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 2018-12-11682; R01AG067073-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No