We sought to identify brain regions that represent reward (win/loss) with changes in distributed patterns of activity that do not necessarily entail a change in their overall activity levels, to test the possibility that representations of reinforcement and punishment signals are not adequately exposed by conventional analyses that contrast BOLD response magnitudes between two different outcomes. We conducted a set of multivoxel pattern analyses

(MVPA; Hanke et al., 2009 and Kahnt et al., 2010), considering trial-by-trial voxel values within a given anatomical region of interest (ROI) as a pattern (Experimental Procedures). For Experiment 1, we trained linear support vector machine classifiers to recognize wins and losses during matching pennies, and evaluated

how well they transfer in classifying untrained samples in a leave-one-run-out cross-validation procedure. Above-chance performance for a given INK 128 chemical structure ROI across the sample implies the presence of information about rewarding outcomes, even in the absence of significant differences in mean activation. MVPA can be susceptible to imbalance in the numbers of samples across different classes within a training set. To avoid such undesirable effects, we separately balanced training sets for each fold, and the transfer set as a whole, to have equal numbers of trials in each class of interest by discarding trials before analysis R428 cell line (see Experimental Procedures). In Experiment 1, strict balancing constraints resulted in an average of 189 training trials and 230 total transfer trials. For our first analysis of reward signals (win versus loss classification) in matching pennies (Experiment 1), we tested 43 bilateral

anatomical ROIs defined using automated cortical and subcortical parcellation routines (Desikan et al., 2006 and Fischl et al., 2004). Reward was reliably decoded in 37 of these 43 regions (p < 0.0012, one-tailed test for above-chance performance; all p < 0.05 with a conservative Bonferroni correction for multiple comparisons; see Figure 2A and Table S1). Of the six remaining regions, postcentral, parahippocampal, and entorhinal regions were marginally significant (all p < 0.0018), while Ketanserin temporal pole, transverse temporal, and frontal pole regions did not reach significance after correction for multiple comparisons (p < 0.05; temporal and frontal pole were notable as regions with high signal dropout due to our sequence parameters). By contrast, a conventional general linear model (GLM) analysis based on differences in average BOLD response magnitude between wins and losses revealed reward signals in substantially more limited areas. Two models (an FIR model and an HRF model; Experimental Procedures) produced significant (p < 0.05, corrected) results in only 9 (FIR) and 7 (HRF) of 43 regions. Even at an uncorrected threshold, only 20 (FIR) and 25 (HRF) regions showed significant reward-related changes (compared with 43 of 43 for MVPA; Figure 2A).