Thirty right-handed participants (21 females) between the ages of 20 and 67 years (mean age = 47.1, ± 4.9) with an average education of 14.0 years (± 0.8) were consented under an Institutional Review Board approved protocol at the University of Arkansas for Medical Sciences. Participants indicating substance abuse/dependence (other than cigarettes) or significant psychiatric disorder were excluded from participation. Subjects completed delay-discounting conditions including real money gains (RMG), hypothetical money gains (HMG), and hypothetical money losses (HML) in a behavioral session prior to scanning with an average time between behavioral session and scanning session of 38 days (± 10.5). Two previous studies have exhibited stability in the discounting of rewards over 2 and 3 month spans respectively (Takahashi et al., 2007
; Ohmura et al., 2006
) but to our knowledge the stability of the discounting of losses has not been reported.
Behavioral discounting conditions were counterbalanced across participants and presented on computer using a decreasing amount algorithm (Du et al., 2002
). Trials were presented on a computer monitor with the immediate alternative above a horizontal line bisecting approximately the middle of the screen, and the delayed alternative beneath. Participants were instructed to respond to their preferred alternative with a hand held response pad similar to the one that would be subsequently used within the scanner. Seven indifference points (at delays of 1, 7, 30, 180, 365, 1825, 9125 days) were determined in the HMG and HML conditions. Four indifference points (at delays of 1, 7, 30, 180 days) were determined in the RMG condition due to pragmatic issues regarding delivery of extremely delayed rewards. In this condition, one of the choices that the participant made was selected at random and the participant was paid the outcome of that choice (1 reinforcer for 24 choices).
Three delay discounting conditions, designed to represent the three outcomes of interest obtained in the behavioral session, were administered to each participant during the scanning session: RMG, HMG, and HML. Each of the three conditions included two types of trials: 1) discounting trials, where participants indicated their preference between immediate and delayed outcomes (e.g., “Receive $99.85 now”, “Receive $100.00 in 1 week”) and 2) control trials, where the participants responded to their preference between outcomes without a temporal component (e.g., “Receive $99.85”, “Receive $100.00”). In all discounting trials, the delayed outcome was fixed at $100 with delays of 1 week, 1 month and 6 months, while the immediate outcome was varied systematically. (See supplemental material
for additional information and full listing of stimuli (Table S1
) available at www.jneurosci.org
). Control trial stimuli were created to include common task-related physiological requirements (e.g., visual perception, premotor, motor) in order to better identify brain regions associated with the deliberative process by contrasting choices made in the discounting trials to those made in the control trials. These control stimuli were based upon the choices appearing in the discounting trials however, one half of the delayed amounts ($100) were substituted with an amount equal to 150% of the smaller alternative (e.g., “Receive $99.85”, “Receive $149.78”) in order to ensure that a judgment was being made with respect to the amount of the outcome and not a simple response to the location of the $100 amount.
In all, there were 56 unique trials per condition (28 discounting trials and 28 control trials). Each trial was visually presented with one choice appearing above a horizontal line bisecting approximately the center of the screen, and the second choice appearing below. For discounting trials, immediate and delayed outcomes were counterbalanced with respect to their position on the screen (top/bottom), as were the larger and smaller amounts contained within the control trials. Participants were informed prior to scanning that they would be awarded the outcome chosen in one randomly selected discounting trial of the RMG condition, and that choices that appeared without an explicit temporal component were experimental controls and would not be considered for selection (1 reinforcer for 36 choices). The HMG condition was identical to the RMG condition in every facet except for the awarding of a randomly selected trial choice. HMG and HML conditions differed only in that the word “Receive” was replaced by the word “Lose” in both discounting and control trials. Prior to the first trial in each of the three conditions, an instruction screen was presented that notified the participant of which task was about to be administered and required the participant to push a response pad button in order to proceed.
The stimuli were visually presented to participants in the scanner using IFIS-SA. Participants were instructed to respond to their preferred alternative via button push of an MRI compatible response pad: right index finger for choice appearing above the horizontal line and right thumb for choice appearing below the horizontal line. Stimulus blocks were comprised of 3–4 trials of a trial-type (i.e., discounting, control) with each block of trials alternating. Trials within each block terminated at button-push (or at a maximum of 6000 ms) at which time a fixation point would appear for a varied duration (3000–5000 ms) in order to jitter stimulus onset within each block. Each block was followed by a 12 second rest period (fixation point). See Figure S8 in supplemental material
for schematic diagram of experimental design. Each functional scan (per condition) consisted of acquiring 190 volumes (including 2 dummy scans preceding stimulus onset of the first trial to allow the magnet to reach a steady state and subsequently removed prior to pre-processing and analysis of the data). If the participant completed all 56 trials prior to acquiring 190 volumes, the sequence of trials would repeat without interruption or notification. The average number of trials completed in the RMG condition was 70.6 ±1.7, with HMG, 70.5 ±1.6 and HML, 69.3 ±1.5. Order of presentation of conditions was balanced over participants to control for novelty.
Imaging data were acquired on a Siemens 3T Trio using a standard head coil. T1-weighted high resolution anatomical images were acquired using a magnetization-prepared rapid gradient-echo sequence (MPRAGE). Whole brain, blood oxygen level dependent (BOLD)-weighted images were acquired as participants responded to choices in three discounting conditions using an echo-planar imaging (EPI) sequence (TR = 2940 ms, TE = 30 ms, flip angle = 90°, 36 slices acquired at a thickness of 4 mm with a 1 mm gap, field of view = 22 cm, 64 × 64 acquisition matrix, 3.44 mm × 3.44 mm in plane resolution).
Imaging data were adjusted for slice acquisition time, corrected for motion by realigning volumes from the first condition acquired (per subject) to the third EPI volume (given that the first two dummy scans were excluded from the pre-processing) and creating a mean motion corrected volume which was then subsequently used as a reference in realigning volumes from the two remaining conditions. The motion corrected volumes were then normalized to Montreal Neurological Institute (MNI) coordinates, resampled at 3 mm3
resolution, and spatially smoothed with an 8 mm full-width half maximum Gaussian kernel using SPM2. Signal changes were modeled as delta functions temporally synchronized with the onset of each trial and convolved with a canonical hemodynamic response function. Two regressors were established for each condition’s general linear model to represent discounting trials and control trials, and subsequently used to detect differences in responses between the two. We excluded events from the analysis where the participant failed to respond within 6 seconds of stimulus onset. The resulting individual t
-maps were then entered into a second level, random effects analysis to establish significant patterns of activation at the group level and controlled for multiple comparisons using a False Discovery Rate (FDR) of p
<.05. We subsequently used the random effects results in a repeated measures analysis of variance (ANOVA) to detect main effect statistical differences between the three conditions, as well as paired t
tests, and in a correlation analysis using pre-scan discounting parameters as predictors. Non-linear transformations of Montreal Neurologic Institute (MNI) coordinates to Talairach coordinates were conducted using a Matlab function (mni2tal (http://imaging.mrc-cbu.cam.ac.uk/imaging/MniTalairach
)). Transformed coordinates for cluster maximum voxels were subsequently entered into the Talairach daemon database (http://www.talairach.org
) to establish Talairach and Brodmann area labels.