Figure 6.
Inferred Outcomes Are Represented in mPFC and Midbrain
(A–D) In humans (A and B) and mice (C and D) hippocampal activity patterns during auditory cues Xn in the inference test were compared with activity patterns during outcome Zn in conditioning using RSA. In mice, time bins with SWRs were excluded. Activity patterns during Xn in the inference test, but not Zn in conditioning, were filtered by the “decision point” on each trial, such that representations of Zn were spatially decoupled from representations of Yn. Hippocampal activity in humans and mice did not significantly predict activity associated with the relevant outcome Zn ([average within association XnZn correlations, RSM main diagonal] – [average between association XnZm correlations, RSM off-diagonals]; correct and incorrect inference; humans, conditional on intermediary cues: Z21 = −0.06, p = 0.526, and Z21 = −0.75, p = 0.772; mice: Z17 = −0.87, p = 0.808; and Z17 = 0.44, p = 0.331; mean ± SEM), including when comparing the group mean against a null distribution generated by permuting the identity labels for cues Xn (correct and incorrect inference; humans: p = 0.464, and p = 0.868; mice: p = 0.829 and p = 0.176). See Figure S6C for results in humans unconditional on intermediary cues. By contrast, robust dCA1 representation of Zn was observed in mice during experience of outcome Zn in conditioning trials (Figure 3).
(E–J) In humans, searchlight RSA with multiple regression (Figures S6D and S6E) was used to identify regions showing representational similarity between auditory cues Xn in the inference test and outcomes Zn in conditioning. During correctly inferred cues Xn, both the mPFC (F) and putative dopaminergic midbrain (G) regions showed significant representation of the associated Zn, conditional on sensory cues that predicted the outcome as shown in the model RSM in (E) (F, mPFC: t21 = 5.09, p = 0.003; G, midbrain: t21 = 5.56, p < 0.001; thresholded at p < 0.01 uncorrected for visualization purposes only). This result held for cues in set 2 as shown in the model RSM in (H) (I: mPFC: t21 = 4.60, p = 0.006; J, midbrain: t21 = 3.37, p = 0.027; peak-level FWE corrected using small-volume correction; Figures S6F and S6G; thresholded at p < 0.01 uncorrected for visualization purposes only).