PROJECT SUMMARY/ABSTRACT Spatial navigation is a fundamental human behavior, and deficits in navigational functions are among the hallmark symptoms of severe neurological disorders such as Alzheimer’s disease. Understanding how the human brain processes and encodes spatial information is thus of critical importance for the development of therapies for affected patients. Previous studies have shown that the brain forms neural representations of spatial information, via spatially-tuned activity of single neurons (e.g., place cells, grid cells, or head direction cells), and by the coordinated oscillatory activity of cell populations. The vast majority of these studies have focused on the encoding of self-related spatial information, such as one’s own location, orientation, and movements. However, everyday tasks in social settings require the encoding of spatial information not only for oneself, but also for other people in the environment. At present, it is largely unknown how the human brain accomplishes this important function, and how aspects of human cognition may affect these spatial encoding mechanisms. This project therefore aims to elucidate the neural mechanisms that underlie the encoding of spatial information and awareness of others. Specifically, the proposed research plan will determine how human deep brain oscillations and single-neuron activity allow us to keep track of other individuals as they move through our environment. Next, the project will determine whether these spatial encoding mechanisms are specific to the encoding of another person, or whether they can be used more flexibly to support the encoding of moving inanimate objects and even more abstract cognitive functions such as imagined navigation. Finally, the project will determine how spatial information is encoded in more complex real-world scenarios, when multiple information sources (e.g., multiple people) are present. To address these questions, intracranial medial temporal lobe activity will be recorded from two rare participant groups: (1) Participants with permanently implanted depth electrodes for the treatment of focal epilepsy through responsive neurostimulation (RNS), who provide a unique opportunity to record deep brain oscillations during free movement and naturalistic behavior; and (2) hospitalized epilepsy patients with temporarily implanted intracranial electrodes in the epilepsy monitoring unit (EMU), from whom joint oscillatory and single-neuron activity can be recorded. In addition, this award will allow me to complete a multifaceted career development plan: Since my current experience with electrophysiological recordings is limited to oscillatory activity from RNS participants, I will learn to record and analyze human single-neuron activity from EMU patients in a clinical setting. My training will be guided by pioneers in this research area, and will take place at UCLA, one of the world’s leading institutions in the clinical and research work with these patient populations. I will further attend seminars, coursework, and conferences, to develop not only as an experimentalist, but also as an independent leader and science communicator. Together, this will provide me with the necessary set of skills for my transition to independence.

PROJECT NARRATIVE Fundamental abilities, such as keeping track of where we are, or forming episodic memories during social experiences, critically depend on the continuous processing and encoding of spatial information about the self, others, and the environment. Impairments in these abilities are among the hallmark symptoms of Alzheimer’s and other neurological diseases. The proposed research therefore aims to enhance our understanding of the neural mechanisms that underlie the encoding of spatial information and awareness of others, which will ultimately help elucidate the neurophysiological origins of malfunctions in these systems.