Phase precession in the human hippocampus and entorhinal cortex

Abstract

Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta (~5-10~Hz) oscillations. Phase precession may be a general neural pattern for representing sequential events for learning and memory. However, phase precession has never been observed in humans. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal-states. Our findings thus extend theta phase precession to humans and suggest that this phenomenon has a broad functional role for the neural representation of both spatial and non-spatial information.

Hippocampal Sequencing Mechanisms Are Disrupted in a Maternal Immune Activation Model of Schizophrenia Risk

“…Phase precession describes the phenomenon whereby the firing of a hippocampal 'place cell' precesses systematically from later to earlier phases of the underlying local field potential (LFP) theta oscillation as the animal advances across the cell's 'place field' (Huxter et al, 2003; (O'Keefe & Recce, 1993;Skaggs et al, 1996). Phase precession has also recently been confirmed in humans (Qasim et al, 2020).…”

“…In rodents, theta sequences are necessary for maintaining internally generated place fields when external cues are held constant (Wang et al, 2015), and for non-spatial event sequencing (Terada et al, 2017), suggesting that they may play a larger role in sequential processing beyond spatial cognition. Theta sequences have also been associated with goal planning and prediction (Gupta et al, 2012;Wikenheiser & Redish, 2015) and phase precession has been associated with non-spatial forms of sequential processing in both rodents (Pastalkova et al, 2008;Royer et al, 2012) and humans (Heusser et al, 2016;Qasim et al, 2020). In humans the hippocampus is involved in both episodic memory processes and thinking about the future (Schacter et al, 2007), and theta sequences may therefore have a fundamental role in these processes Jaramillo & Kempter, 2017;Terada et al, 2017;Wang et al, 2015).…”

Disorganization of Oscillatory Activity in Animal Models of Schizophrenia

“…Recent findings in animal models have also demonstrated that the precise temporal spiking of single cells in relation to background local field potential (LFP) oscillations is likely to be functionally important for both low-level plasticityrelated processes and for high-level cognition that depends on sequential processing mechanisms (Buzsáki, 2015;Buzsáki and Tingley, 2018;Drieu and Zugaro, 2019). While these synchronizing phenomena appear to occur in humans (Liu et al, 2019;Qasim et al, 2020) they cannot readily be investigated with non-invasive techniques. Thus, although MEG and EEG studies provide important correlational evidence that disturbed network synchrony is likely associated with poor performance across a range of cognitive domains, direct evidence that these phenomena are causally linked is difficult to obtain with these techniques alone.…”

Spatial modulation of hippocampal activity in freely moving macaques

“…To analyze LFP phase precession, LFP phase in the theta bands was unwrapped such that the resulting phase is monotonic instead of cyclic (Mizuseki et al, 2009; Qasim et al, 2020). For each spike, we assigned the corresponding unwrapped LFP phase via nearest neighbor interpolation.…”

“…The precise relationship between theta phase and neuronal firing reflects a temporal code that may support communication across regions and organize ensemble activity into sequences (Mizuseki et al, 2009; O’Keefe and Recce, 1993; Skaggs et al, 1996). In contrast to rodents, primate studies have consistently found a lack of continuous theta oscillations either during virtual navigation or real world locomotion (Ekstrom et al, 2005; Talakoub et al, 2019), but spike-LFP phase coding appears to be conserved to some extent, at least in humans (Jacobs et al, 2007; Qasim et al, 2020).…”