Fig. 3: Effect of TI stimulation on hippocampal episodic memory activity.

a, Whole-brain group z-score change in BOLD signal during encode and recall stages of the task for TI 1:1 and TI 1:3 stimulation conditions. Note the increase in BOLD signal in the left hippocampus during encode for the TI 1:1 condition, similar to the pattern observed for sham (Fig. 2e), but not for the TI 1:3 condition. b, Comparison of group median change in BOLD signal between stimulation conditions, in the left (stimulated) hippocampus during encoding and recall stages. Showing an effect of stimulation and reduction in the evoked BOLD signal in the left hippocampus during encoding stage by TI 1:3 stimulation (LMM, effect of stimulation F_(2,95) = 3.2, P = 0.0443; task stage F_(1,95) = 44.84, P = 1.49 × 10⁻⁹; interaction F_(2,95) = 2.96, P = 0.056; post hoc comparisons using the Tukey honestly significant difference test, two-sided, Encode: Sham–TI 1:1, P = 0.953; Sham–TI 1:3, P = 0.006; TI 1:1–TI 1:3, P = 0.015); for full statistics, see Supplementary Table 8. c, Comparison of group median change in BOLD signal between stimulation conditions, in the Ant, Mid and Post regions of the left hippocampus during the encoding stage; for ROIs schematic, see Fig. 2b. There is a significant main effect of stimulation in the evoked BOLD signal during the TI 1:3 stimulation; for full statistics, see Supplementary Table 9. d, Voxelwise group-level contrasts comparing stimulation conditions in the left hippocampus, confirming higher BOLD signal for the sham and TI 1:1 conditions compared to TI 1:3. No significant voxels for the comparison between sham and TI 1:1, confirming the results observed in the hippocampal ROIs. e, Group median change in BOLD signal in the left hippocampus for memory associations encoded correctly (green) and incorrectly (gray). Showing significantly higher BOLD signal for correct compared to incorrect associations in the left hippocampus during sham (LMM, effect of response type (correct, incorrect) F_(1,95) = 11.09, P = 0.001), and TI 1:3, (LMM, effect of response type, F_(1,95) = 6.6, P = 0.0117); for full statistics, see Supplementary Fig. 4 and Supplementary Table 10. f, Voxelwise group-level contrasts comparing correctly and incorrectly encoded associations in the left hippocampus, showing that BOLD signal during the formation of correct associations is predominantly modulated in a cluster located in the anterior portion of the hippocampus for sham and TI 1:3 conditions, while no significant voxels were observed for the TI 1:1 condition. g, Same as b but for the right hippocampus, where there is no effect of stimulation; for full statistics, see Supplementary Table 8. h, Comparison of group median percentage change in BOLD signal between stimulation conditions, in the anterior (Ant), Middle (Mid) and posterior (Post) regions of the overlying cortex; for ROIs schematic, see Fig. 1d; for full statistics, see Supplementary Table 12. No difference in the BOLD signal change between stimulation conditions. Similar results were obtained for the brain regions underneath the stimulation electrodes in the right hemisphere; for full statistics, see Supplementary Fig. 5 and Supplementary Table 13. Asterisks identify significant differences, P < 0.05. Bar plots show mean and SE, and black dots show individual participant data. Images in a were thresholded at Z > 3.1, with a cluster significance level of P < 0.05, and are displayed in x = −21 plane of the MNI template. Images in d and f were thresholded at significance level of P < 0.05, TFCE FWE corrected, voxelwise permutation-based t-tests on the ROI. n = 20 throughout except for h where n = 16.