Memory minus perception (the colormap represents the difference in PAC strength between memory and perception trial—note that the contrast is not significant) for the co-modulogram in SEEG contacts that had previously shown an increase in theta and gamma power identified in Fig 1F, retention period).

Memory minus perception (the colormap represents the difference in PAC strength between memory and perception trial—note that the contrast is not significant) for the co-modulogram in SEEG contacts that had previously shown an increase in theta and gamma power identified in Fig 1F, retention period).</p

Theta-gamma PAC in the hippocampus and ventral auditory stream correlates with behavior.

(A) Left panel: SEEG contacts showing a positive correlational relationship between theta-gamma PAC and performance (negative correlation with IES). Results are displayed on the single subject T1 in the MNI space provided by SPM12. Right panel: Scatter plot of IES (note that the scale is inverted for clarity: 5 corresponding to poor performance and 0 corresponding to good performance) against theta-gamma PAC strength for each significant SEEG contact. Each color depicts a different participant (N = 6). Source data can be found at https://osf.io/m7dta/. (B) Left panel: SEEG contacts showing a negative correlational relationship between theta-gamma PAC and performance (positive correlation with IES). Results are displayed on the single subject T1 in the MNI space provided by SPM12. Right panel: Scatter plot of IES (note that the scale is inverted for clarity: 5 corresponding to poor performance and 0 corresponding to good performance) against theta-gamma PAC strength for each significant SEEG contact. Colors show the different participant (N = 4). Source data can be found at https://osf.io/m7dta/. IES, inverse efficiency score; PAC, phase amplitude coupling.</p

Theta gamma PAC is consistent across trials and participants.

(A) SEEG contacts identified in Fig 4A and grouped as a function of their location according to the AAL Atlas: green, left STS; red, left hippocampus; blue, right ITG; yellow, left IFG/insula. Regions are displayed on the single subject T1 in the MNI space provided by SPM12. Source data can be found at https://osf.io/m7dta/. (B) PAC intertrial phase consistency computed for each region. Bar plot shows intertrial phase locking values across participants and SEEG contacts for memory trials (correct responses, colored as a function of the regions) and perception trials in the same region. Error bars indicate SEM. Asterisk indicates significance. Source data can be found at https://osf.io/m7dta/. (C) Preferred coupling phase: gamma power presented as a function of theta phase bins for each region. Shading represents the standard deviation across trials and participants. Asterisks (*** p p S7–S10 Tables. Source data can be found at https://osf.io/m7dta/. IFG, inferior frontal gyrus; ITG, inferior temporal gyrus; PAC, phase amplitude coupling; STS, superior temporal sulcus.</p

Post hoc tests of Fig 5C: Left IFG.

It has been suggested that cross-frequency coupling in cortico-hippocampal networks enables the maintenance of multiple visuo-spatial items in working memory. However, whether this mechanism acts as a global neural code for memory retention across sensory modalities remains to be demonstrated. Intracranial EEG data were recorded while drug-resistant patients with epilepsy performed a delayed matched-to-sample task with tone sequences. We manipulated task difficulty by varying the memory load and the duration of the silent retention period between the to-be-compared sequences. We show that the strength of theta-gamma phase amplitude coupling in the superior temporal sulcus, the inferior frontal gyrus, the inferior temporal gyrus, and the hippocampus (i) supports the short-term retention of auditory sequences; (ii) decodes correct and incorrect memory trials as revealed by machine learning analysis; and (iii) is positively correlated with individual short-term memory performance. Specifically, we show that successful task performance is associated with consistent phase coupling in these regions across participants, with gamma bursts restricted to specific theta phase ranges corresponding to higher levels of neural excitability. These findings highlight the role of cortico-hippocampal activity in auditory short-term memory and expand our knowledge about the role of cross-frequency coupling as a global biological mechanism for information processing, integration, and memory in the human brain.</div

Paradigm, behavioral performance, and brain oscillations.

(A) Auditory tasks (here with 6-tone sequences, 2 s retention): “Same” trials: After a delay, the first melody was repeated. “Different” trials: One tone was changed in the second melody of the pair in comparison to the first melody (red rectangle). Memory load (3 or 6 tones) and duration of the retention period (2, 4, 8 s) varied in separate blocks. Source data can be found at https://osf.io/m7dta/. (B) Accuracy in terms of d prime presented as a function of the duration of the retention period (left panel; N = 6) and memory load (right panel; N = 6). Colored circles depict participants (one color per participant). Asterisks indicate significance (p https://osf.io/m7dta/. (C) Response time (s) presented as a function of the duration of the retention period (left panel; N = 6) and memory load (right panel; N = 6). Colored circles depict participants (one color per participant; same color coding as in Fig 1B). NS, nonsignificant. Source data can be found at https://osf.io/m7dta/. (D) Left panel: T-values in the time-frequency domain (t test relative to baseline −1,000 to 0 before stimulus onset, FDR corrected in time and frequency domains) of SEEG contacts located in the right and left Heschl’s gyrus (displayed on the single subject T1 in the MNI space provided by SPM12) for a trial time window (−1,000 to 6,000 ms) for the condition 6-tone memory load, 2 s retention period (n = 5). Right panel shows the PSD, power spectrum density (zscore) average over a trial time window (0 to 5,000 ms) that was used to define frequency for phase and frequency for amplitude for the PAC analysis. Shaded error bars indicate SEM. Source data can be found at https://osf.io/m7dta/. (E) Left panel: T-values in the time-frequency domain (t test relative to baseline −1,000 to 0 before stimulus onset, FDR corrected in time and frequency domains) of SEEG contacts located in the right and left hippocampus (displayed on the single subject T1 in the MNI space provided by SPM12) for a trial time window (−1,000 to 6,000 ms) for the condition 6-tone memory load, 2 s retention period (n = 14). Right panel shows the PSD, power spectrum density (zscore) average over a trial time window (0 to 5,000 ms) that was used to define frequency for phase for the PAC analysis. Shaded error bars indicate SEM. Source data can be found at https://osf.io/m7dta/. (F) SEEG contacts modelled with 4 mm radius spheres (see Methods) in the MRI volume showing a significant increase in oscillatory power (FDR corrected) relative to baseline in theta (4 Hz) and gamma (30–90 Hz) ranges (Hilbert transform averaged over time) during encoding, retention, and retrieval in all memory conditions in all participants (n = 16). All results are displayed on the single subject T1 in the MNI space provided by SPM12. Source data can be found at https://osf.io/m7dta/.</p