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

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 neurons 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.