Functionally distinct high and low theta oscillations in the human hippocampus

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4–10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta’s function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior–posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.


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Joshua Jacobs 03-16-2020 iEEG data from subjects were obtained via the clinical or research recording system of the hospital at which the patient was being treated (Nihon Kohden; XLTEK; Neuralynx; Blackrock) All data analysis was done in MATLAB 2017b.
The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request. The source data underlying Figures 3B and 5D are provided as a Source Data file.

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October 2018

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Magnetic resonance imaging Experimental design
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Behavioral performance measures Our data consisted of 14 subjects, in whose hippocampi a total of 90 electrodes were implanted. No sample size calculations were performed. This sample size was sufficient to provide adequate statistical power to all analyses within our manuscript.
If two or more neighboring electrodes in one subject were located in nearby slices (less than 10% of the hippocampal A-P axis distance away from each other), and exhibited a similar oscillation frequency (within 2 Hz) during movement, all but one of these electrodes were dropped for all analyses.
All findings reported in this study were obtained using deterministic algorithms, and will thus produce the same result each time they are run.
We conducted our analyses in both electrode-wise and subject-wise manners. Electrodes were allocated into anterior and posterior hippocampi regions, to low-and high-theta oscillation bands, and to single and dual oscillator categories. In subject-wise analyses, each subject's electrodes were allocated into low-anterior, low-posterior, high-anterior, and high-posterior categories. Randomization is not relevant, as all subjects/electrodes were placed into groups based on their biologic characteristics, and were not allocated through some subjective or random means.
Blinding was not relevant to our study, as the outcomes of the study will not directly impact the patients from whom the data was acquired.
8 males and 6 females, ages 23-49, all with diagnoses of medication-intractable epilepsy These were patients who were undergoing seizure monitoring for their medication-intractable epilepsy. All subjects were adequately consented. Systematic bias of epileptic patients possessing epileptiform discharges was controlled for by searching for and excluding these discharges from all analyzed electrodes. Thus, results are likely not impacted by subject recruitment. Subjects had a wide age range and were from both genders, so demographic bias does not exist.