Modulators of 8 Hz theta rhythm recorded in the human hippocampus

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Theta rhythm is an 8 Hz neural oscillatory pattern in electroencephalography (EEG) signals that is associated with function of the hippocampus, a brain region that is crucial for episodic memory and spatial memory. One purported function of theta rhythm is to synchronize activity of neurons in the hippocampus as a mechanism for coding novel memories. Theta rhythm has been associated with spatial memory, motor behaviour, speed of walking, and arousal. Removing low-frequency oscillations (LFO) in the theta band in rodents resulted in impaired spatial learning and memory. In 2017, we published in a Nature Group Journal, Nature Communications, the first clear evidence of 8 Hz theta rhythm from intra-hippocampal depth electrodes in humans. Objectives: The overarching goal of my research program is to assess factors that modulate theta rhythm in order to further characterize this oscillatory pattern associated with learning and memory in humans. Specifically, we will assess the impact of speed of walking, navigation strategies, cognitive training, and sleep on human theta rhythm.Hypotheses: 1) Speed of walking: The rodent literature shows that speed of walking is an important modulator of hippocampus theta rhythm because walking speed will have an impact on the distance travelled in space. We hypothesize that speed of walking will have a significant impact on theta rhythm in humans. 2) Navigation strategies: The literature shows that different navigation strategies rely on separate memory systems, namely the hippocampus and the caudate nucleus. We hypothesize that individuals who navigate primarily using hippocampus-dependent navigation strategies will show significantly stronger theta rhythm. 3) Spatial memory training: Research in both humans and rodents shows that spatial memory training can increase grey matter in the hippocampus. As such, we hypothesize that spatial memory training will increase theta rhythm over a period of two weeks. 4) Sleep: Research in rodents has shown an important role for sleep in the replay of ensembles of neuronal firing. We hypothesize that significantly stronger theta will be observed during sleep for individuals who use hippocampus-dependent navigation strategies compared to those who use caudate nucleus-dependent strategies. We also hypothesize that sleep-related theta rhythm will be greater following the two weeks of spatial memory training. The studies proposed in this grant will be fundamental to help bridge the rodent and human literatures on the role of theta rhythm in learning and memory. In addition, we have a unique opportunity to further explore human theta activity and the factors that modulate it in order to gain a better understand on factors that promote navigation skills and wayfinding abilities in humans.