The relationship between increases in VMPFC activation and subsequent inference performance was present even when equating for differences in memory for directly learned associations (partial r = 0.53, p = 0.007; p < 0.05 Bonferroni corrected). The relationship between hippocampal activation decreases and inference performance was only significant in right hippocampus when accounting for performance on directly learned associations (bilateral hippocampus partial r = 0.22, p = 0.29; right hippocampus partial r = 0.39, p = 0.05). No other brain region demonstrated a significant

relationship between changes in activation (increases or decreases) across AB repetitions when controlling for performance on directly learned associations, though Z-VAD-FMK supplier a statistical trend was observed in inferior frontal gyrus pars orbitalis (r = 0.38, p = 0.06). These findings indicate that the relationship between right hippocampal and VMPFC encoding activation and subsequent inference goes above and beyond learning of directly experienced associations, suggesting

that these regions mediate binding click here of current experiences to reactivated memories. In line with recent rodent research (Iordanova et al., 2007 and Iordanova et al., 2011; Tse et al., 2007 and Tse et al., 2011), the present findings indicate that hippocampus and VMPFC are both engaged in support of retrieval-mediated learning. To further test for learning-related changes in hippocampal-VMPFC coupling, we performed

a functional connectivity analysis using bilateral hippocampus as the seed region to determine whether the pattern of connectivity between hippocampus and VMPFC changed across repeated presentations of overlapping associations. Within each individual functional run, we constructed separate regressors corresponding to the first, second, and third repetitions of individual associations for each participant. A repeated-measures ANOVA revealed that hippocampal-VMPFC connectivity increased across repetitions of overlapping associations irrespective of the functional run (repetition linear trend F(1,21) = 9.78, p = 0.005). Importantly, hippocampal-VMPFC connectivity did not change over the course of the experiment (run linear trend F < 1); rather, increases in hippocampal-VMPFC connectivity were specific to repetitions of Chlormezanone overlapping events within each run (repetition x run interaction F(1,21) = 1.74, p = 0.20; Figure 6), suggesting increased functional connectivity between hippocampus and VMPFC during the online formation of integrated memory representations. Three additional regions—frontal pole, precuneus, and superior parietal cortex—showed increased connectivity with hippocampus across repetitions of overlapping associations (Figure S4); however, unlike VMPFC, encoding activation in these regions was not related to inference performance (all r < 0.14, p > 0.5).