We then estimated Granger causalities for each direction of influence (OFC-to-amygdala and amygdala-to-OFC)
in the frequency domain (Geweke, 1982) from the AR parameters (Brovelli et al., 2004). We examined the evolution of Granger mTOR inhibitor causality by analyzing brief segments of LFP signal starting 0.5 s before CS onset until US onset (200 ms window, stepped by 50 ms, yielding 43 steps). The short window ensured that the LFPs within it could be considered stationary. For each step, the 200 ms LFP segments from trials of the same type (positive or negative) were concatenated separately and the parameters of the AR model for the resulting time series were estimated using the Nutall-Strand method (Schlögl, 2006). We fixed the AR model order to 50, and assessed model fit by testing for lack of residual correlations (Li and Mcleod, 1981). We determined the statistical significance INCB018424 price for Granger causality at each time-frequency bin using the frequency-domain test described by Breitung and Candelon (2006). To average Granger causality
values, we first normalized these values for each pair to the value estimated for the first time window (−0.5 to −0.3 s relative to CS onset). This was performed separately for each frequency bin between 0 and 100 Hz. For each pair and trial type, we only averaged data from pairs that yielded Granger causality values with four consecutive significant time bins (p < 0.01, spanning 350 ms). To compare the Granger causality in the two different directions of influence (Figure 9A), all trials of the reversal block were combined as described above. At each time bin, the Granger causality values for all frequencies from 5 to 100 Hz were averaged together. We determined the statistical significance of the difference between the two directions (OFC-to-amygdala and amygdala-to-OFC) using a permutation test (10,000 shuffles). To assess the effect of learning on the influence between the amygdala and OFC (Figures 9B and 9C), only the six first trials of each type (12 total) after reversal
and the last six next trials of each type in the experiment were used. Granger causality was computed for these two sets of trials, and we compared its relative magnitude in both directions during and after reversal learning. For each set of trials, the Granger causality values were averaged across pairs and trial types as described above. The difference between the mean Granger causality in the two directions was then compared for the during-learning and postlearning sets in the time domain (Figure 9B) by averaging across frequencies from 5 to 100 Hz; Figure 9C does this in the frequency domain by averaging across times from CS onset until the end of the trace interval. The significance of the difference between during-learning and postlearning was assessed by permutation test (10,000 shuffles).