The purpose of this study is to use an experimental inflammatory challenge to examine whether older adults with symptoms of anxiety experience loss of pleasure or loss of motivation when they are exposed to inflammation. Loss of pleasure or loss of motivation will be evaluated using self-report questionnaires, computer tasks, and during a brain scan.
Participants will undergo phone screening, two in-person visits, and telephone follow-up. The first visit will last 4 hours and the second visit will last 10.5 hours. Phone screening and follow-up will take no longer than 30 minutes. Phone Screening and Visit #1: Following phone screening to determine potential eligibility, participants will have an in-person evaluation. Following informed consent in the first session, participants will undergo semi-structured clinical interviews and complete questionnaires to assess medical- and medication histories; current- and past history of psychiatric disorders, and evaluation of behavioral symptoms of anxiety and depression. They will also complete computer tasks that assess motivation and sensitivity to reward. As part of one of these tasks, they will be asked to provide a picture of a loved one, which they will later view during a fMRI scan. Visit #2 and telephone follow-up: The second session will be about two weeks later. It will begin at 7:30AM and will involve placement of two intravenous catheters (one in each arm), evaluation of heart rate and blood pressure, administration of endotoxin vs. placebo, repeated blood sampling along with questionnaires about mood and symptoms for approximately 10.5 hours. Two hours post-injection participants will complete a 1-hour brain scan that includes tasks to assess motivation and sensitivity to reward. Study staff will escort the participant to a nearby facility to complete the brain scan. 24 hrs and 2-weeks following this session, study staff will call the subject and ask about physical and mood symptoms, using the same set of items used during the experimental protocol.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Norman Cousins Center for Psychoneuroimmunology, University of California, Los Angeles
Los Angeles, California, United States
Neural Indices of Reward Motivation - Anticipatory Reward Response
Task-based functional magnetic resonance imaging (fMRI) will be used to assess reward motivation, as operationalized by ventral striatum (VS) activity during anticipation of monetary reward cue trials vs no-reward cue trials during the Monetary Incentive Delay Task.
Time frame: approximately 2 hours post-injection for 7 minutes
Neural Indices of Reward Motivation - Effort-Based Decision Making
Task-based functional magnetic resonance imaging (fMRI) will be used to assess effort-based motivational processing, as assessed by VS, ventromedial prefrontal cortex (vmPFC), and pre-supplementary motor area (pre-SMA) activity with choice phase as event onset during an adapted version of the Effort Expenditure for Rewards Task (EEfRT).
Time frame: approximately 2 hours post-injection for 14 minutes
Neural Indices of Monetary Reward Sensitivity during Effort-Based Decision Making
Task-based functional magnetic resonance imaging (fMRI) will be used to assess sensitivity for monetary reward, as operationalized by VS and VMPFC activity during receipt of monetary reward (vs. fixation) and during choice of low vs. high reward trials during the EEfRT.
Time frame: approximately 2 hours post-injection for 14 minutes
Neural Indices of Reward Sensitivity for Non-Monetary Reward
Sensitivity for non-monetary reward as assessed by VS and VMPFC activity when viewing positive non-social vs neutral images, and when viewing positive social vs. neutral images, in a positive picture viewing task.
Time frame: approximately 2 hours post-injection for 10 minutes
Resting state functional connectivity
Resting-state functional connectivity will be assessed over a 7-minute period, focusing on functional connectivity between the ventromedial prefrontal cortex and ventral striatum.
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Enrollment
40
Time frame: 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Social Reward Motivation
Task-based functional magnetic resonance imaging (fMRI) will be used to assess social reward motivation, as operationalized by ventral striatum (VS) activity during anticipation of social reward cue trials vs no-reward cue trials on the Social Incentive Delay Task.
Time frame: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Reward Motivation for Close Social Reward
Motivational processing for a close other social reward will be assessed with the Social Incentive Delay Task as VS activity during anticipation of viewing images of a close other (vs no-reward cue).
Time frame: approximately 2 hours post-injection for 7 minutes
Behavioral Indices of Reward motivation - close other social reward
Motivational processing for a close other social reward will be assessed as self-reported desire to be around the close other on a scale of 1 (not at all) to 7 (a lot).
Time frame: 2 hours post-injection
Monetary Incentive Delay Task -Neural Indices of Monetary Reward Sensitivity
Sensitivity for monetary reward as assessed by VS and VMPFC activity during outcome (reward vs. no-reward) and anticipation (low vs. high reward cues) on the Monetary Incentive Delay task.
Time frame: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Social Reward Sensitivity
Sensitivity for social reward as assessed by VS and VMPFC activity during outcomes (reward vs. no-reward) on the Social Incentive Delay Task.
Time frame: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Reward Sensitivity for Close Social Reward
Reward sensitivity for a close other will be assessed as VS and VMPFC activity during the outcome phase (close other reward vs no-reward outcomes) and anticipation phase (general social reward vs. close other social reward cue anticipation) on the Social Incentive Delay Task.
Time frame: approximately 2 hours post-injection for 7 minutes
Behavioral Indices of Reward Motivation - Effort-Based Decision Making
Motivation for monetary reward is assessed with an Effort Expenditure for Rewards Task (EEfRT); willingness to exert physical effort for monetary reward (i.e., selection of hard vs easy tasks) is the outcome measure with higher willingness indicative of higher motivation.
Time frame: Pre-injection and approximately 2 hours post-injection
Behavioral Indices of Reward Sensitivity and Learning - Probabilistic Reward Task
Implicit reward learning and sensitivity to monetary reward is assessed with the probabilistic reward task (PRT); change in the magnitude of response bias from baseline to post-injection is the outcome measure. Higher response bias indicates higher reward sensitivity/learning.
Time frame: Pre-injection and approximately 2 hours post-injection
Depressed Mood Subscale of the Profile of Mood States (POMS)
The Depressed Mood Subscale of the POMS is a self-reported assessment of depressed mood in which subjects rate severity of depressed mood using a visual analog scale from 1 to 10 (10 being most severe). Each timepoint is scored and analyses examine the temporal profile of change with assessment every hour
Time frame: 10 hours
Motivation for social and non-social reward (interest in activities scale).
This task will evaluate motivation for reward by subjective reports of interest in engaging in a variety of social and non-social activities on a 1 to 5 Likert scale on an hourly basis, with higher score indicating more interest. Each timepoint is scored and analyses examine the temporal profile of change with assessment at baseline and at 1 hour intervals post-injection.
Time frame: 10 hours