Extended Data Fig. 8: Cross-regional SFC for pre-SMA, dACC, and vmPFC, as well as for fast- and broad-spiking PAC neurons from the hippocampus.

Related to Fig. 5. (a) Cross-regional SFC between hippocampal PAC neurons and LFPs recorded in pre-SMA (left) or dACC (right) did not reveal any difference between the two WM load conditions in any of the frequencies. (b) To test whether the load modulation of theta-band cross-regional SFC between hippocampal PAC neurons and vmPFC LFPs persisted on the patient level, we averaged theta SFC across all PAC neuron to channel pairs within each patient and then compared the within-patient averages between the two load conditions. At the patient-level, theta cross-regional SFC was significantly higher for load 3 than load 1 trials, suggesting that the effect was not driven by a few channels or patients (n = 20; t(19) = −2.8297, p = 0.0071). (c) Comparison of cross-regional hippocampal-vmPFC SFC between PAC and category neurons revealed the load modulation of cross-regional theta SFC between hippocampal neurons and vmPFC LFPs was significantly stronger for PAC than for category neurons (PAC: n = 175, Cat: n = 215; t(376.07) = 3.3942, p = 0.0001; unpaired two-sided permutation t-test). Each dot is a neuron-channel combination. (d) Earlier work has suggested that cognitive control might especially be governed through long-range connections between frontal and sensory regions that target inhibitory interneurons to (dis-)inhibit local circuitries^41,53,85. We thus asked if we observe a differential effect for the hippocampal PAC neuron connections after separating them into narrow- and broad-spiking neurons based off their waveform shapes, which has been suggested to categorize neurons into inhibitory and excitatory neurons, respectively^86,87. For analysis of connections involving narrow- and broad-spiking PAC neurons separately, we observed a significant difference in theta SFC between load 3 and load 1 only for the narrow-spiking PAC neurons (trough-to-peak time <0.5 ms; n = 91 connections; cluster-p = 0.0001, left). No effect was found for broad-spiking PAC neurons (n = 84) (e) Similarly, theta SFC for fast RT was significantly stronger than for slow RT only for narrow-spiking (t(90) = 3.02, p = 0.003, n = 91, left), not for broad-spiking PAC neuron connections between hippocampus and vmPFC (t(75) = −0.66, p = 0.52, n = 76, right; spikes were median split into fast and slow RT trials per load condition and then averaged across loads to avoid potential confounds). (f,g) We did not find significant differences between the load conditions for (f) within-region SFC or (g) cross-regional SFC to hippocampal LFPs across all neurons from the vmPFC. (h) We further tested whether there were any non-specific global state changes between correct and incorrect trials in any of the three frontal regions. FRs for all neurons recorded in the three frontal areas were not significantly different between correct and incorrect trials during the delay period (pre-SMA: n = 201; dACC: n = 180; vmPFC: n = 201). In (a,d,f,g) we performed two-sided cluster-based permutation t-tests, centre values denote mean, coloured areas s.e.m. In (b,c,e,h), we performed two-sided permutation t-tests and centre values denote mean ± s.e.m. *** p < 0.001; ** p < 0.01; ns = not significant.