Aging and Reward System Response to Inflammation and Anxiety Study

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.

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).

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.

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.

Resting-state functional connectivity will be assessed over a 7-minute period, focusing on functional connectivity between the ventromedial prefrontal cortex and ventral striatum.

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.

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).

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).

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.

Sensitivity for social reward as assessed by VS and VMPFC activity during outcomes (reward vs. no-reward) on the Social Incentive Delay Task.

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.

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.

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.

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

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.

Behavioral performance on the Monetary and Social Incentive Delay Tasks is tested as reaction time for reward vs no- reward cue trials (an index of motivation) and reaction time for low vs. high reward trials (an index of sensitivity to changes in reward magnitude).

Sensitivity for non-monetary reward assessed by self-report affect when viewing positive non-social vs neutral images, and when viewing positive social vs. neutral images, on a 1(extremely negative affect) to 4(extremely positive affect) scale.

Sensitivity for monetary reward assessed by the degree to which higher potential winnings predict hard task choice.

This is a short computer-based task used to test emotion detection with a face morphing task. Faces morph from neutral to expressions of emotions (happy, sad, angry, or fearful) and participants indicate when and what emotion is presented; the dependent variables are reaction time and accuracy.

This is a short computer-based task used to test attentional bias towards positive and negative valenced facial expressions (low arousal happy, high arousal happy, sad, angry) relative to neutral faces. Higher attentional bias scores indicate greater bias towards emotion.

Systemic inflammation as measured by circulating levels of interleukin-6 in plasma in pg/ml. Each timepoint is assayed and analyses examine the temporal profile of change with assessment every hour

Transcriptional profile of inflammation as measured by Conserved Translational Response to Adversity in circulating peripheral blood mononuclear cells

The Antisaccade task is used to assess Inhibition. Participants are tasked with inhibiting a reflexive response towards a visual cue in order to correctly identify a target stimulus presented elsewhere. For each of 72 trials, participants view a centrally positioned fixation point (the letter X) on the computer screen for a variable amount of time (1500-3500ms). A visual cue (a black circle) is then presented on one side of the computer screen for 225ms. The target stimulus (a number from 1 to 9) is presented on the opposite side of the screen for 250, 233, or 200ms before being masked by gray cross-hatching. The participant verbally reports the target number to a trained research assistant or recording device or uses the keyboard to indicate the number. The participant does not receive feedback regarding accuracy, and there is no time limit for participant response for each trial.

The Spatial 2-Back task is used to assess Updating, the ability to monitor and replace information in working memory. For each of 120 trials, participants view an array of boxes, 11 white and 1 black. The location of the black box varies across trials. Participants are tasked with using one of two keys to indicate whether the black box is presented in the same location as it was two trials back. Participants do not receive feedback regarding accuracy, and trials proceed automatically if a response is not made within 2000ms. The task includes 20 practice trials

The Color-Shape task is used to assess Shifting, or the ability to switch between mental sets. For each of 104 trials, participants are presented with a circle or square that is of blue or red color. Participants are asked to use 1 of 2 keys to indicate whether the figure is red or blue (52 color trials) or square or triangle (52 shape trials). One key is paired with a color and a shape (e.g., red and square) and one key is paired with the other color and shape (e.g., blue and circle). For each trial, the letter C or S is presented above the figure to indicate color versus shape trials. The order of C/S trials is randomized, and there is no time limit for participant response for each trial. A quiet "ding" occurs following incorrect trials. The task includes 52 practice trials: 26 color followed by 26 shape trials.

Depressed mood and depressive symptom severity by self-reported assessment using the Montgomery Asberg Depression Rating scale with a range from 0 to 54 with a higher score indicating more severe depressive symptoms. Each timepoint is scored and analyses examine the temporal profile of change with assessment at baseline and at 2 hour intervals post-injection.