DESCRIPTION (provided by applicant): Episodic memory is the conscious memory for previously experienced events. The ability to recollect past events and personal experiences is a fundamental faculty for adaptive behavior. Functional brain imaging studies have shown that, in addition to previously identified structures in the medial temporal lobe, a consistent set of distributed cortical regions are also engaged during episodic memory retrieval. Most prominent among this network has been the lateral and medial parietal cortex. However, despite strong evidence of parietal engagement during episodic retrieval, it is not clear what computations parietal subregions perform in the service of retrieval or what mechanisms mediate this contribution. The current application takes a multimodal approach to studying the spatial and temporal patterns of neural activity in the human lateral and medial parietal cortex during episodic retrieval. We will combine neuroimaging (functional magnetic resonance imaging: fMRI), electrophysiology (electrocorticography: ECoG) and stimulation (electrical brain stimulation: EBS) techniques within the same subjects, and will submit the resulting data to advanced multivariate analyses. Specifically, we will localize functional-anatomic parietal subregions with fMRI, and in the same subjects, quantify the temporal dynamics within and between these parietal subregions using ECoG. Finally, we will use targeted EBS to causally interrogate the contributions of these regions to memory behavior. This multimodal strategy provides an optimal approach for functionally dissociating parietal subregions and subsequently revealing the precise temporal sequence of neural events underlying retrieval-based activation patterns in human parietal cortex. To achieve these research aims, the candidate will pursue a series of training aims under the mentorship of Dr. Anthony Wagner (Stanford University), specifically focused on the use of fMRI to study the neural mechanisms of memory retrieval. Training will focus on developing expertise in experimental paradigms for probing episodic memory with fMRI, and in the advanced analysis of fMRI data with multivariate techniques. Combining these skills with the candidate's previous work on the cognitive electrophysiology (ECoG) of medial parietal cortex, along with ongoing mentoring from the candidate's current advisor Dr. Josef Parvizi (co-mentor; Stanford University), will provide a strong methodological and analytical basis for developing an independent research program focused on studying the neurocognitive networks of episodic memory. The multimodal approach of this application will provide important new leverage on the parietal circuits involved in episodic retrieval. Such circuits lie at the core of many mental health disorders, where excessive and vivid rumination of past events or the distorted recollection of past events contributes to psychological distress, such as post-traumatic stress disorder, major depression, generalized anxiety disorder or schizophrenia, respectively.

PUBLIC HEALTH RELEVANCE: This application will quantify the activity of human parietal cortex during episodic memory retrieval. By combining different types of brain activity measurements, allowing high spatiotemporal precision, we will characterize how spatially segregated parietal subregions rapidly interact to influence memory behavior. These findings will improve our understanding of how parietal lobe circuits may contribute to the excessive and vivid rumination of past events and the distorted recollection of past events common to conditions such as post-traumatic stress disorder, major depression, generalized anxiety disorder and schizophrenia.