Abstracts

Rationale: Intracranial electrophysiology of memory has been primarily studied in rodents using spatial navigation paradigms, leading to the momentous discoveries of place and grid cells. Rodent studies at the local field potential level have also found that theta oscillations in the hippocampus are important for encoding spatial memory. However, these discoveries have proven difficult to reproduce in humans.In humans, electrocorticography-based (ECoG-based) studies are typically conducted in a perioperative setting, where the subject is implanted with electrodes through a craniotomy to localize seizures prior to resection surgery. During this period, alterations of subjects’ medication regimens and the side effects of acute implantation injury confound studies of brain activity. Because the electrode wires tether patients to their hospital beds, human spatial navigation studies are typically conducted using video games to simulate real world navigation. During human virtual navigation, theta activity has only been inconsistently observed, possibly due the lack of proprioceptive and vestibular inputs that are present in real world locomotion. Methods: In this study, we recruited four subjects with a chronically implanted neurostimulator (RNS®, NeuroPace Inc.) to perform a real world spatial navigation task. Subjects alternated between navigating through the Dartmouth-Hitchcock Epilepsy Clinic and standing still while we recorded ECoG. Because subjects are not in a perioperative setting, we were able to remove many confounding factors that are present in studies using traditional ECoG methods. However, because the RNS® was originally designed for seizure detection and stimulation, accessories needed to be developed to allow for synchronization of computer assisted tasks with ECoG recordings from the implant as well as externally triggered stimulation. We developed hardware and software tools to allow for interaction with an external task. Results: We found a significant decrease in theta power while subjects were walking compared to standing still in some subjects, but a significant increase in theta power during walking in other subjects (p < 0.05, n>106 for each subject). Furthermore, we demonstrate the use of the RNS® system for scientific electrophysiology studies. Conclusions: This study demonstrates that the role of theta power in human navigation is likely different than in rodents. Further study is necessary to determine the exact role of low frequency hippocampal oscillations during human navigation. Funding: This work was supported by the National Institutes of Health (R01-NS074450) and by the Defense Advanced Research Projects Agency (DARPA) Restoring Active Memory (RAM) program (Cooperative Agreement N66001-14-2-4032).