Single neurons throughout human memory regions phase-lock to hippocampal theta

Abstract Functional interactions between the hippocampus and cortex are critical for episodic memory. Neural oscillations are believed to coordinate these interactions, and in rodents, prefrontal neurons phase-lock to hippocampal theta oscillations during memory-guided behavior. We assessed inter-regional phase-locking to hippocampal oscillations in humans by recording 1,233 cortical and amygdala neurons and simultaneous hippocampal local field potentials in 18 neurosurgical patients. We identified 362 neurons (29.4%) from multiple regions that phase-locked to rhythmic hippocampal activity, predominantly at theta (2-8Hz) frequencies. Compared to baseline spiking, strong theta phase-locking coincided with regionally-specific increases in hippocampal theta power, local and hippocampal high frequency activity, and cross-frequency power correlations between the hippocampus and a phase-locked neuron’s local region. These results reveal that spike-time synchrony with hippocampal theta is a defining feature of cortico-hippocampal functional connections in humans. We propose that theta phase-locking could mediate flexible inter-regional communication to shape the content and quality of episodic memories.