Theta-phase locking of single neurons during human spatial memory

Tim A. Guth (), Armin Brandt, Peter C. Reinacher, Andreas Schulze-Bonhage, Joshua Jacobs and Lukas Kunz ()
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Tim A. Guth: University Hospital Bonn
Armin Brandt: University of Freiburg
Peter C. Reinacher: University of Freiburg
Andreas Schulze-Bonhage: University of Freiburg
Joshua Jacobs: Columbia University
Lukas Kunz: University Hospital Bonn

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Memory processes may rely on complex interactions between single-neuron activity and local field potentials. To better understand such spike–field relationships in humans, we examined human theta-phase locking—neuronal firing at similar theta phases over time—using single-neuron recordings in epilepsy patients performing a spatial memory task. Applying frequency-adaptive theta-phase estimation in a broad 1–10 Hz frequency range, we found that theta-phase locking was widespread in the human medial temporal lobe during memory encoding and retrieval. Time-resolved spectral parameterization and cycle-by-cycle analysis demonstrated stronger theta-phase locking during steep aperiodic slopes and prominent theta oscillations. Phase-locking strength was similar across successful and unsuccessful memory trials, with most neurons spiking at similar theta phases during encoding and retrieval. Some neurons shifted their preferred phase, supporting theories that encoding and retrieval are separated within the theta cycle. These results show how local field potential properties and memory states influence human theta-phase locking.

Date: 2025
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DOI: 10.1038/s41467-025-62553-9

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