# Human hippocampal theta–gamma coupling coordinates sequential planning during navigation

## TL;DR

This study shows that human hippocampal theta-gamma brain activity helps coordinate sequential planning during navigation, similar to mechanisms seen in rodents.

## Contribution

The study demonstrates that theta-gamma phase-amplitude coupling supports sequential planning in human navigation.

## Key findings

- Hippocampal theta power decreases as proximity to a goal increases during accurate navigation.
- Theta-gamma phase-amplitude coupling increases with goal proximity, suggesting sequential planning via gamma bursts at theta phases.
- Entorhinal high gamma and hippocampal low gamma activity differ for novel and experienced paths, aligning with rodent findings.

## Abstract

Human behavior often relies on executing specific sequences of actions to achieve desired outcomes—like planning the series of locations one needs to pass through to reach a given destination. However, the neural mechanisms underlying sequential planning are currently unclear. Here, we show that neural activity during navigation is consistent with sequences of upcoming locations being coded within bursts of high frequency gamma activity occurring at successive phases of a lower frequency theta oscillation. This coding scheme has previously been proposed to support short-term memory function and is observed in the rodent brain during active navigation. Hence, our results suggest that this “phase–amplitude coupling” may be a general mechanism for encoding sequential information across cognitive domains and mammalian species.

Human behavior often relies on executing a specific sequence of actions to achieve a desired outcome. However, the neural mechanisms underlying the dynamic construction and maintenance of such sequences during goal-directed behavior are not yet clear. Empirical and theoretical studies of working memory function suggest that sequential information may be encoded in neural circuits by bursts of gamma activity occurring at consecutive theta phases. Here, we asked whether a similar coding scheme might support sequential planning during goal-directed navigation. Using noninvasive magnetoencephalography and an abstract navigation task, we found that hippocampal theta power during both planning and subsequent navigation decreased with proximity to the current goal, only during accurate navigation. At the same time, theta–gamma phase–amplitude coupling (PAC) increased with goal proximity, consistent with sequences of upcoming locations being represented by gamma bursts occurring at successive theta phases. Importantly, entorhinal high gamma and hippocampal low gamma dominated while traversing novel and previously experienced paths, respectively, consistent with previous rodent studies. These findings suggest that hippocampal theta–gamma PAC flexibly and dynamically coordinates sequences of actions during goal-directed behavior across mammalian species, using different gamma bands for mnemonic and prospective planning.