www.sciencemag.org/cgi/content/full/318/5854/1305/DC1

Supporting Online Material for

Social Comparison Affects Reward-Related Brain Activity in the Human Ventral Striatum

K. Fliessbach, B. Weber, P. Trautner, T. Dohmen, U. Sunde, C. E. Elger, A. Falk*

*To whom correspondence should be addressed. E-mail: armin.falk@uni-bonn.de

Published 23 November 2007, Science 318, 1305 (2007)

DOI: 10.1126/science.1145876

This PDF file includes: Materials and Methods

SOM Text

Figs. S1 to S3

Tables S1 to S5

References

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Supporting Online Material Material and methods Scanning procedure: Scanning was performed on a 1.5 Tesla (T) Avanto Scanner and a 3 T Trio Scanner (Siemens, Erlangen, Germany) using standard 8 channel head coils. Slices were in axial orientation and covered all of the brain including the midbrain but not the entire cerebellum. Scan parameters for the 1.5 T scanner were: Slice thickness: 3 mm; interslice gap 0.3 mm; matrix size: 64x64; field of view: 192 x 192 mm; echo time (TE): 50 ms; repetition time (TR): 2.91 s. Scan parameters for the 3 T scanner were: Slice thickness: 2 mm; interslice gap 1 mm; matrix size: 128x128; field of view: 230 x 230 mm; echo time (TE): 33 ms; repetition time (TR): 2.5 s. Subjects: Thirty-eight male subjects (19 subject pairs) without any history of neurological or psychiatric disease were included. Five subjects had to be excluded from the analysis due to scanner dysfunction (two subjects), excessive head movement (two subjects) or inappropriate use of the response grips (one subject), so that data from 18 subjects from the 3 T scanner and 15 from the 1.5 T scanner was finally analyzed. The 33 subjects who were analyzed were on average 27.4 years of age (SD 4.8), range 21 - 39 years). We chose to include only male subjects to control for gender specific differences in reward processing. All subjects were right-handed according to the Edinburgh Handedness Scale. All subjects gave written informed consent and the study was approved by the Ethics committee of the University of Bonn. Experimental setting and task: Two subjects were simultaneously placed in the two MR scanners (see above) which are situated at opposite sides of the same control room in our institution. The two subjects saw each other when being led to the scanners, but did not have the opportunity to talk to each other or to familiarize before the experiment began. The task was presented via video goggles (Nordic NeuroLab, Bergen, Norway) using Presentation© software (NeuroBehavioural Systems Inc.). During scanning, both subjects performed 300 trials of the following task (see Figure 1): they saw a screen with a varying number (4 to 55) of blue dots for 1.5 s. The time of the appearance of this screen defined the task onset. Immediately thereafter, a number was presented that differed by 20 percent from the number of dots previously shown. Subjects had to decide whether they had seen less or more dots before. They indicated their answers with the help of response grips (NordicNeuroLab, Bergen) within a time-limit of 1.5 s. Later responses were counted as incorrect. A response terminated the screen and the selected option was highlighted for 250 ms as a response-feedback. These parameters were derived from pretests showing that on average ~ 80 % of trials were solved correctly at this difficulty level, a sufficient number of events for each experimental condition. The presentation stopped when both subjects had responded, introducing a variable delay of at most 1500 ms for the faster responding subject. Once both responses were available and after a ~ 200 ms delay for the exchange of response information between the two presentation computers a feedback screen was displayed for 4 s. This screen revealed to both players whether they were correct (indicated by a green tick) or not (indicated by a red cross), as well as the amount of money they earned in this trial. The next trial started after a time interval of 4.5-7 s. Payoff conditions were as follows: When both subjects were incorrect, both received nothing. When only one of the subjects was correct this subject received either ~ 30 € (low level) or ~ 60 € (high level) while the other subject was not rewarded. When both players were correct, one of six

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possible conditions was randomly selected; generated by a 2x3 factorial design that varied the absolute amount (factor 1) and the relative amount of money (factor 2) (see Table 1). In order to prevent boredom resulting from repeatedly seeing the same monetary amounts, we varied the rewards in each condition within a 10 percent interval from the mean (i.e., 27 to 33 € in a 30 € trial). At the end of the experiment one trial was randomly selected and paid according to the respective outcomes in this trial. In order to determine the paid trial, both subjects had to write down a number between 0 and 100. The experimenters also determined a random number between 1 and 100. These three numbers were added up. The sum was between 1 and 300 and determined the trial that was paid. This procedure was explained in the instructions. On average, subjects earned 43 € during the experiment. In addition, each subject received a show-up fee of 15 € for participation. FMRI data analysis: FMRI data analysis was performed using Statistical Parametric Mapping 2 (SPM2, www.fil.ion.ucl.ac.uk/spm/). For preprocessing, functional images were realigned to the first image of each time series and again realigned to the mean image after first realignment. Images were then slice-timed using a sync interpolation, normalized to the canonical EPI template used in SPM2 and smoothed with an 8mm Gaussian Kernel. After normalization images were re-sampled to a voxel size of 3x3x3mm for both scanners, allowing for a combined analysis of data from both scanners. For modeling the BOLD response, eleven types of events were defined according to the payoff conditions. These event types were: both subjects incorrect (C1) (0/0), only subject A correct (C2 (60/0), C3 (30/0)), only subject B correct (C4 (0/60), C5 (0/30), both subjects correct (C6-C11) (60/120, 30/60, 60/60, 30/30, 120/60, 60/30). The onset times of the feedback screen informing the subjects about the outcome was convolved with the canonical hemodynamic response function (HRF) used in SPM2 and its temporal derivative. Additionally, a regressor for the onset times of the task was included into the model. Parameter images for the contrasts for each single condition were generated for each subject and were then subjected to a second-level random effects analysis using a one-way within subject ANOVA specification. Note that 300 trials have been observed in each subject. In our analysis we analyzed parameter estimates for each subject for the eleven conditions. These parameter estimates represent effect strengths of the condition’s influence on the BOLD response. Because of the low signal-to-noise ratio it is not possible to analyze brain responses to single events, which makes it necessary to repeat the same event type several times. In order to identify regions potentially associated with reward processing, we defined a contrast between the conditions in which a subject received a reward and the other did not (C2, C3) and conditions in which a subject did not receive a reward at all (C1, C4, C5). The T-image for this contrast was determined with threshold at P < 0.05 using the Family Wise Error (FWE) correction for multiple comparisons implemented in SPM2 and an extent threshold of 10 adjacent voxels. To test for regions showing stronger responses for trials without reward (C1, C4, C5) than win-alone-trials (C2, C3) the opposite contrast was analyzed with a threshold of P<0.005 (uncorrected) with an extent threshold of ten adjacent voxels. Note that this threshold is by far less strict than the Family Wise Error (FWE)-corrected 5%-threshold used for the ROI-definition. At this threshold, there were two clusters of activation in the right (TAL-coordinates of peak activation: X=42, Y= 11, Z=-8, 65 voxels) and in the left insula (TAL-cordinates: X=-36, Y=16, Z=7, 15 voxels). Using the FWE-correction for this contrast yielded no supra-threshold brain

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regions. This means that in general hemodynamic responses were stronger in trials where subjects earned money, compared to trials where they did not earn anything. Similar findings have often been reported in reward-studies. The supra-threshold clusters from the contrast C2, C3 > C1, C4, C5 were used to define regions of interest for further analysis independently from the contrasts of interest (C6-C11). These regions of interest included regions a priori known to be involved in the processing of reward (1). The mean contrast values for the contrasts of interest were derived from these regions and then analyzed by a within-subject ANOVA. We set up a 2x3 factor model with the absolute (low vs. high) and the relative amount (1:2, 1:1, 2:1) of money as within subject factors. In regions showing bilateral activations, the side (left vs. right) of the activation was considered as an additional factor. To control for differences between the two scanners, scanner type was included as a between subject factor. Additional analyses using data from both scanners separately yielded the same results. Time-courses for each subject were extracted for the regions of interest using the Marsbar extension of SPM (www.marsbar.sourceforge.net/), and event-locked peristimulus time histograms were constructed for the onsets of the task (Fig. S1) and the reward feedback screen (Fig. 3c), respectively. These histograms show an estimate of the BOLD response following the presentation of the respective screens. The time-scale was homogenized with Time = 0 when the respective screen appeared. Anatomical cluster labeling was done using the Anatomical Automated Labeling Tool for SPM (www.cyceron.fr/freeware). To test for regions sensitive to relative reward outside our regions of interest, we conducted a whole brain analysis using the 2x3 repeated measurements ANOVA described above as a model (for this analysis Statistical Parametrical Mapping 5 (SPM5, www.fil.ion.ucl.ac.uk/spm/) was used). We identified regions showing a significant main effect of relative reward using a threshold of p < 0.001 (uncorrected) with an extent threshold of ten adjacent voxels. This threshold is commonly used in heuristic whole brain analyses.

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In the following we present an English translation of the German instructions.

Instructions You are now taking part in an economic experiment. Please read the following instructions carefully. You will learn everything you need to know in order to participate in this experiment. Don’t hesitate to ask, if there is anything you don’t understand. At the beginning of the experiment all participants receive a show up fee of 15 Euro. During the experiment you and another participant can earn additional money. The amount of money, which you will actually receive, depends on your decisions. The amount of money, which will be received by the other participant, depends on his decisions. The experiment has several rounds. In each round you will have to take a decision, which you enter by pressing a button with your left or right thumb. In total there are 300 rounds. The experiment in the scanner will last about one hour. At the end of the experiment you will be paid in cash the amount of money that you earned in the experiment plus the show-up fee of 15 Euro.

Description of the Experiment

In each round of the experiment you will see a first screen with a number of blue dots on a black background. You will see this screen for 1.5 seconds. Then there appears a second screen. On this screen you see under the heading „Number of dots“ a number, e.g., 18, 37, or 50 etc. You must now decide whether you have seen more or less dots on the first screen than indicated on the second screen. For example: On the first screen there are actually 27 dots. On the second screen it says that the number of dots is 31. In this case the correct answer is “less”. If on the first screen there are, e.g., 21 dots and on the second screen it says 19 (below the heading „Number of dots“), the correct answer is „more“. On the second screen you can click on „less“ or „more“ with the help of a button. The left button means „less“, the right one means „more“. For your answer you have only 1.5 seconds. Please note: If you don’t give an answer within 1.5 seconds, your answer will automatically counted as incorrect! Since you see the first screen only for a short period of time, you will typically not be able to count the dots. Thus you will have to estimate whether there are more or less dots. On the third screen you are informed, whether your estimate was correct or incorrect. In addition you will be informed about the amount of money that you earn in this period. You will also learn, whether the other participant, who has dealt with the exact same problem, has solved the problem

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correctly or incorrectly, and what his income in this period is. On the third screen you will see two lines:

• In the first line you see „He“. Right next to this there is either a green tick if the estimate of the other participant was correct, or a red cross, in case the answer was incorrect. Next to this you see the amount of money in Euro, which the other participant earns in this period.

• In the second row you see „You“. Right next to this you see, whether your answer was correct (green tick) or incorrect (red cross). Next to this you see the amount of money in Euro, which you earn in this period.

Please note:

• In each period of the experiment, you work on exactly the same problem as the other participant.

• The level of income can change in each period. However, you will always earn more if you solve the problem correctly than if your answer is incorrect. If your answer is incorrect, you will always earn zero in this period. Thus it pays off to estimate as well as possible.

• For your and the other participant’s income it is only relevant, whether, within the 1.5 seconds, you have estimated your income correctly or incorrectly. For the level of payments, it plays no role, who clicked faster within the 1.5 seconds.

In total there are 300 periods. At the end of the experiment one period will be randomly chosen. Both participants receive the amount of money cash in Euro, which they have earned in this respective period. The amount can be zero Euro for a participant, if his estimate was incorrect in this period. In addition both participants receive their show up fee. Do you have any question?

PLEASE NOTE!!! The buttons are quite free-moving. It happens that participants press buttons accidentally and – without noticing – keep a button pressed for a longer period of time. Often we cannot scientifically use these periods. Therefore, please, let go of the button, after you have pressed it. Please also try to move your head as little as possible.

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Supporting Text Whole brain analysis: Regions showing a significant main effect of the relative reward level are shown in Figure S2 and Table S4. The activation clusters in the basal ganglia of both sides overlap with the ventral striatal regions of interest. On the left side, the activation extends to the amygdala and putamen. In both the right and the left cluster there was a systematic increase of the BOLD signal with increasing relative reward, i.e., responses are lowest when a subject receives less than the other subject (1:2) and highest when a subject receives more (2:1). Besides this, in addition significant activations were found in several bilateral parietal and occipital regions and in the right dorsolateral prefrontal cortex. In all regions outside the basal ganglia the activation does not show a systematic increase with relative reward level: responses were highest for the high payment condition in the 1:2 and the 2:1 condition, i.e., in situations when high amounts of money were unequally paid regardless of the fact which of the subjects received more Questionnaire results: Right after the experiment we elicited measures on reciprocal inclination, personality, subjective well-being and locus of control. We used six questions concerning reciprocity (three questions about positive and negative reciprocity, respectively). These questions have been used in the Socio-Economic Panel, a large representative panel in Germany and have been analyzed in great detail (2). The questions read as follows: i) If someone does me a favor, I am prepared to return it; ii) I go out of my way to help somebody who has been kind to me before; iii) I am ready to undergo personal costs to help somebody who helped me before; iv) If I suffer a serious wrong, I will take revenge as soon as possible, no matter what the cost; v) If somebody puts me in a difficult position, I will do the same to him/her; vi) If somebody insults me, I will insult him/her back. Answers were given on 7-point scales, where 1 means: “does not apply to me at all”; 7 means: “applies to me perfectly”. We constructed our reciprocity variable by adding the responses to all six questions and dividing the sum by 6. Larger scores indicate a greater willingness to reciprocate. As personality measures we used the “Big Five” concept. The Big-Five approach originates in the psycho-lexical and differential-clinical tradition of personality research and uses respondents' self-assessment in terms of agreement to certain adjectives to describe their personality (3). The 2005 wave of the Socio-Economic Panel (SOEP) contains a short version of this personality test (on the implementation and reliability of this measure see: 4, 5). Based on this test, a respondent’s personality can be described in terms of five traits: conscientiousness, extraversion, agreeableness, openness to new experiences, and neuroticism. We use standardized sums of the respective questions. The concept of locus of control was originally formulated by Rotter (6). A scale in the German language was developed by Krampen (7). We use a measure of locus of control that was also used in the Socio-Economic Panel (SOEP). The measure consists of 10 items (8). We use principal component analysis to obtain variables that measure the extent to which subjects have an external or internal locus of control. People who have an external locus of control believe that the course of their life is strongly influenced by external circumstances, while those with an internal locus of control believe that they are in command of their lives and attribute success or failure in life to their own control. Subjective well-being was elicited on an eleven-point scale, using a standard question that asks about how satisfied people are with their life in general (0 = not at all satisfied, 10 = very satisfied).

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Supporting Figures

Figure S1: Event-related signal changes in the left and right ventral striatum show a strong positive hemodynamic response after the onset of the task at time 0s.

Figure S2: Parameter estimates for the conditions of interest for all ROI. Colors indicate relative reward level (blue = 1:2, red = 1:1, green = 2:1), hue indicates absolute reward level (dark= high, light = low).

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Figure S3: Left: Glassbrain projection of regions showing a main effect of relative reward in the whole brain analysis (p<0.001 (uncorrected), extent threshold 10 voxels). Right: Projection of the striatal clusters from this analysis (blue) and the previously defined ventral striatal regions of interest used for the main analysis (yellow) on a single subject brain (focusing on TAL-coordinates X=-12, Y=8, Z=-8). Supporting Tables Table S1: Brain regions showing a significant BOLD-response for win vs. non-win-Trials (P (FWE-corrected) < 0.05, extent threshold 10 voxels). These regions are being use as regions of interest for the main analysis. N=number of supra-threshold voxels, z=Z-score for the peak activation voxel.

Brain region (peak activation) TAL-coordinates N z Pcor

X Y Z L. middle occipital gyrus -15 -96 -5 329 Inf <0.001 L. Putamen -12 8 -8 155 Inf <0.001 R. caudate nucleus 9 11 -6 136 7.82 <0.001 R. middle occipital gyrus 30 -90 13 481 7.47 <0.001 L. middle cingulate cortex 0 -45 35 285 6.83 <0.001 R. angular gyrus 53 -57 28 70 6.03 <0.001 L. medial orbitofrontal gyrus -3 52 -8 20 5.63 0.001 L. medial orbitofrontal gyrus 0 37 -14 20 5.35 0.002 L. angular gyrus -42 -66 28 22 5.27 0.003

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Table S2: Mean parameter estimates and standard error (SE) of the mean in the ventral striatum across conditions. Condition Payoffs in Euro

(subject A – subject B) Mean SE

C1 0 – 0 -0.67 0.19 C2 60 – 0 0.79 0.19 C3 30 – 0 0.54 0.23 C4 0 – 60 -0.67 0.21 C5 0 – 30 -0.73 0.17 C6 60 – 120 -0.06 0.18 C7 30 – 60 -0.12 0.18 C8 60 – 60 0.14 0.16 C9 30 – 30 0.14 0.20

C10 120 – 60 0.36 0.18 C11 60 – 30 0.21 0.17

Note: It is possible to conduct four pair wise comparisons of conditions where the own absolute income is held constant (C7-C9, C6-C8, C6-C11 and C8-C11). The first three are significant at least at the 10%-level irrespective of whether we use parametric or non-parametric-tests. The comparison between C8 and C11 yields the expected sign but is not significant at conventional levels. Note that the signs of the coefficient estimates have no direct interpretation because they are conventionally scaled to add up to zero. Table S3: Results of the repeated-measurements ANOVA assessing the effects of relative and absolute payment variations in the regions of interest.

Brain region Main effect of relative reward level

Main effect of absolute reward level

Interaction relative x absolute reward level

F2,32 P F1,31 P F3,30 P Left and right angular gyrus

3.7 0.030** 6.7 0.014** 1.2 0.299

Left and right occipital lobe

6.4 0.003*** 9.4 0.004** 2.6 0.084

Left and right ventral striatum

8.0 <0.001*** 0.9 0.356 0.3 0.744

Precuneus/Cingulate 3.8 0.029** 5.2 0.029** 1.5 0.232 Orbitofrontal (post.) 0.9 0.422 4.3 0.47** 5.2 0.011** Orbitofrontal (ant.) 1.3 0.279 4.8 0.035** 2.0 0.148 Note: ** indicates significance at 5%; *** at 1%.

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Table S4: Brain regions showing a significant main effect of relative reward in the whole brain analysis (P<0.001 (uncorrected), extent threshold 10 voxels). N=number of supra-threshold voxels, z=Z-score for the peak activation voxel.

Brain region (peak activation) TAL-coordinates N z

X Y Z L. Putamen -24 17 -6 65 4.34 R. caudate nucleus 9 6 -5 25 4.14 R. Precuneus (BA7) 6 -56 46 23 4.11 L. sup. occipital lobe -24 -65 33 13 3.82 R. sup. parietal lobe 27 -70 50 47 3.81 R. middle frontal gyrus (BA9) 45 28 40 15 3.63 R. supramarginal gyrus (BA40) 65 -22 20 11 3.60 R. Precuneus 9 -70 56 10 3.53 R. sup. occipital lobe 27 -67 39 10 3.33 Table S5: Sensitivity and reciprocal inclination Explanatory variables Beta-values Standard error Reciprocity 0.822** 0.392 Std. Conscientiousness 0.245 0.325 Std. Extraversion 0.475* 0.275 Std. Agreeableness 0.462 0.319 Std. Openness to experience 0.012 0.27 Std. Neuroticism -0.175 0.268 Locus_internal 0.064 0.127 Locus_external 0.092 0.08 Subjective well-being 0.148 0.156 Constant -2.326 2.039

Observations 31 R-squared 0.32

Note: OLS regression with standard errors. * indicates significance at 10 %, ** indicates significance at 5%, *** at 1%. Observations of two subjects could not be used due to item non-response in the survey. Dependent variable is variability of ventral striatal activation due to different relative reward levels and measured as follows: we first determined the mean activation level for each subject for conditions that involved payments of 60 Euro (conditions C6, C8 and C11). Then we added up all absolute differences of mean activation of these conditions and the mean for each subject, i.e., abs(C6 – mean) + abs(C8 – mean) + abs(C11 – mean). If only the absolute amount of money matters for reward-related brain activity, this sum should be small; the larger the sum, the higher is the sensitivity of ventral striatal response with respect to different relative payments. Note that this measure is non-directional, i.e., high values do not necessarily imply increases of activation with increasing relative reward level. The percentage of deviations above the mean was 24% in C6, 51% in C8 and 55% in C11, respectively.

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Supporting References 1. J. P. O’Doherty, Curr. Opin. Neurobiol. 14:769 (2004). 2. T. Dohmen, A. Falk, D. Huffman, U. Sunde, Econ. Inquiry, forthcoming. 3. L. R. Goldberg, Psychol. Assess. 4:26 (1992). 4. F. Lang, DIW Research Notes, 9 (2005). 5. J.-Y. Gerlitz, J. Schupp, DIW Research Notes, 4 (2005): 6. J. B. Rotter, Psychological Monographs 80:1 (1966). 7. G. Krampen, IPC-Fragebogen zu Kontrollueberzeugungen (“Locus of Control”), (Goettingen, Toronto, Zurich: Verlag für Psychologie Hogrefe (1981). 8. H. Nolte, C. Weischer, U. Wilkesmann, J. Maetzel, H.-G. Tegethoff, Discussion paper, 97-06, Ruhr-Universität Bochum (1997).