Dissecting the Function of Hippocampal Oscillations in a Human Anxiety Model

Abstract

Neural oscillations in hippocampus and medial prefrontal cortex (mPFC) are a hallmark of rodent anxiety models that build on conflict between approach and avoidance. Yet, the function of these oscillations, and their expression in humans, remain elusive. Here, we used magnetoencephalography (MEG) to investigate neural oscillations in a task that simulated approach–avoidance conflict, wherein 23 male and female human participants collected monetary tokens under a threat of virtual predation. Probability of threat was signaled by color and learned beforehand by direct experience. Magnitude of threat corresponded to a possible monetary loss, signaled as a quantity. We focused our analyses on an a priori defined region-of-interest, the bilateral hippocampus. Oscillatory power under conflict was linearly predicted by threat probability in a location consistent with right mid-hippocampus. This pattern was specific to the hippocampus, most pronounced in the gamma band, and not explained by spatial movement or anxiety-like behavior. Gamma power was modulated by slower theta rhythms, and this theta modulation increased with threat probability. Furthermore, theta oscillations in the same location showed greater synchrony with mPFC theta with increased threat probability. Strikingly, these findings were not seen in relation to an increase in threat magnitude, which was explicitly signaled as a quantity and induced similar behavioral responses as learned threat probability. Thus, our findings suggest that the expression of hippocampal and mPFC oscillatory activity in the context of anxiety is specifically linked to threat memory. These findings resonate with neurocomputational accounts of the role played by hippocampal oscillations in memory.SIGNIFICANCE STATEMENT We use a biologically relevant approach–avoidance conflict test in humans while recording neural oscillations with magnetoencephalography to investigate the expression and function of hippocampal oscillations in human anxiety. Extending nonhuman studies, we can assign a possible function to hippocampal oscillations in this task, namely threat memory communication. This blends into recent attempts to elucidate the role of brain synchronization in defensive responses to threat.

Characterizing hippocampal dynamics with MEG: A systematic review and evidence‐based guidelines

“…In addition, a resting state study of depression included in this review used SAM beamforming source analysis and the ICA method to describe resting state networks in individuals with MDD and found reduced correlations in networks linked to the hippocampus (Nugent, Robinson, Coppola, Furey, & Zarate, 2015). We also found one study examining the role of the hippocampus in healthy individuals performing a task designed to induce anxiety: oscillatory power, particularly in gamma band, was linked to threat probability (Khemka, Barnes, Dolan, & Bach, 2017).…”

Pragmatic spatial sampling for wearable MEG arrays

“…As such, defining spatial discrimination is arguably a statistical problem. The proposed framework has also been used extensively to model laminar sources (Bonaiuto et al, 2017(Bonaiuto et al, , 2018Troebinger et al, 2014) in MEG as well as make probabilistic statements about deep structure activity (Khemka, Barnes, Dolan, & Bach, 2017;Meyer et al, 2017b) where spatial precision is paramount.…”

Impaired processing of response conflicts in mesial temporal lobe epilepsy

“…In later fMRI and magnetoencephalographic studies, the hippocampal role in approach‐avoidance conflicts was confirmed and elucidated in more detail (Khemka, Barnes, Dolan, & Bach, ; Loh et al , ; O'Neil et al , ).…”