# Directed cortico-limbic dialogue in the human brain

**Authors:** Ellen van Maren, Camille G. Mignardot, Roland Widmer, Cecilia Friedrichs-Maeder, Juan Ansó, Päivi Nevalainen, Markus Fuchs, Claudio Pollo, Athina Tzovara, Timothée Proix, Kaspar A. Schindler, Maxime O. Baud

PMC · DOI: 10.1038/s41467-026-68701-z · 2026-02-02

## TL;DR

This study maps signal flow in the human brain during wakefulness and sleep, revealing that limbic structures send more signals than they receive, challenging previous assumptions.

## Contribution

The study introduces a novel method for causally estimating signal flow in the human brain using repeated electrical probing over days.

## Key findings

- Limbic structures send twice as many signals as they receive in both wakefulness and sleep.
- Signal flow remains directional and does not reverse during sleep, contradicting prior hypotheses.
- The dataset provides a framework for understanding brain network dynamics and potential therapeutic strategies.

## Abstract

How can one trace the brain’s orderly directed signals amid a tangle of nerve fibers? Because direct access to actual brain signaling is rare in humans, the precise wiring diagrams for cortico-limbic communication during sleep and wake remain essentially unmapped, hampering progress in neuroscience. Now, a unique neurosurgical window on the human brain allows for electrically mapping cortical connections at the hospital, but studies so far have relied on average signals, masking the dynamic nature of signal flow across brain regions and vigilance states. To causally estimate signal flow, we repeatedly probed cortico-limbic networks with short-lived electrical pulses over days and assessed the variable fate of each transmitted signal on a single-trial basis. In the resulting openly available dataset, we characterized signaling probabilities and directionality across thousands of local and long-range cortico-limbic connections over days. Challenging established views, we found that limbic structures send twice as many signals as they receive, in both wakefulness and sleep. Our findings provide a fundamental framework for causally interpreting signal flow in the brain and formulating therapeutic strategies for brain network disorders.

Here, the authors mapped signal flow over days from intracranial brain recordings in humans. Across vigilance stages, limbic structures sent twice as many signals as they received from the neocortex, challenging the long-standing hypothesis of flow reversal in sleep.

## Full-text entities

- **Diseases:** brain network disorders (MESH:D001927)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12966484/full.md

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Source: https://tomesphere.com/paper/PMC12966484