Slow-Theta-to-Gamma Phase–Amplitude Coupling in Human Hippocampus Supports the Formation of New Episodic Memories

Abstract

Phase-amplitude coupling (PAC) has been proposed as a neural mechanism for coordinating information processing across brain regions. Here we sought to characterize PAC in the human hippocampus, and in temporal and frontal cortices, during the formation of new episodic memories. Intracranial recordings taken as 56 neurosurgical patients studied and recalled lists of words revealed significant hippocampal PAC, with slow-theta activity (2.5-5 Hz) modulating gamma band activity (34-130 Hz). Furthermore, a significant number of hippocampal electrodes exhibited greater PAC during successful than unsuccessful encoding, with the gamma activity at these sites coupled to the trough of the slow-theta oscillation. These same conditions facilitate LTP in animal models, providing a possible mechanism of action for this effect in human memory. Uniquely in the hippocampus, phase preference during item encoding exhibited a biphasic pattern. Overall, our findings help translate between the patterns identified during basic memory tasks in animals and those present during complex human memory encoding. We discuss the unique properties of human hippocampal PAC and how our findings relate to influential theories of information processing based on theta-gamma interactions.

Slow-theta power decreases during item-place encoding predict spatial accuracy of subsequent context recall

“…Despite this interpretation, our results may seem contradictory to those generated by a recent analysis of slow theta to gamma phase amplitude coupling (PAC) in human hippocampus (Lega et al, 2016). Lega and colleagues found a positive relationship between slow theta SMEs and PAC during the encoding of words.…”

“…On the contrary, hippocampal PAC − electrodes (associated with negative SMEs) exhibited theta gamma coupling at phases more likely to induce long term depres sion (LTD). As discussed in Lega et al, 2016, slow theta power decreases might reflect the disengagement of hippocampus from the global slow activity; because only a small subset of locations would show the opposite pattern, power decreases are more likely to be non invasively detected. An exciting alternative is that slow theta negative SMEs found in our study reflect spatial learning facilitated by LTD.…”

Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples

“…Given the role of SWR-associated slow gamma activity in coordinating sequential replay in the hippocampus, the age-dependent SWR-associated slow gamma deficit in apoE4-KI mice is likely to contribute to their learning and memory impairments. Although it has not been assessed specifically during SWRs, hippocampal gamma activity has been linked to memory processing in humans (Lega et al, 2016; Sederberg et al, 2007), supporting the idea that apoE4-induced slow gamma disruption might contribute to learning and memory impairments in AD patients. Consistent with previous studies (Andrews-Zwilling et al, 2010; Knoferle et al, 2014; Leung et al, 2012), our findings implicate hilar GABAergic interneurons as a key target for therapeutic intervention in AD and promote the strengthening of hippocampal slow gamma coordination during SWRs as a candidate mechanism for cognitive protection.…”

Frequency-specific electrophysiologic correlates of resting state fMRI networks

“…This association was first studied in rodents but has since been amply documented in humans with implanted hippocampal microelectrodes (Kahana et al, 1999; Lega et al, 2016; Sederberg et al, 2003) as well as in humans with ECoG electrodes over retrosplenial cortex (Foster et al, 2013). Hippocampus and retrosplenial cortex unambiguously are part of the intrinsic system (Kahn et al, 2008).…”