Posterior Cingulate Cortex and Executive Control of Episodic Memory

Overview

This project will use intracranial recordings and stimulation of the human brain to understand the unique contributions of the posterior cingulate cortex (PCC) to episodic memory behavior. The goal is to test how distinct subregions of the PCC differentially contribute to memory-based decisions (e.g., have I seen this picture before?). The ability to perform invasive studies of the human brain is through routine clinical monitoring of brain activity which occurs during the neurosurgical treatment of epilepsy. However, this project only focuses on the basic science of PCC and memory behavior. Specifically, the investigators will use single-0cell and population measures of brain activity to test a new theory of PCC function which focuses on the executive processes needed to support memory retrieval and memory-based decisions. By studying the PCC, a convergence zone of memory and executive brain systems, progress can be made in elucidating how the failure to successfully leverage past experiences in daily behavior can occur as a common symptom of both neurodegenerative disease (e.g., Alzheimer's disease) and multiple psychiatric conditions (e.g., schizophrenia) implicating PCC dysfunction.

This project reflects a basic experimental study involving human participants (BESH), which focuses on the neuroscience of episodic memory. Episodic memory involves the encoding and retrieval of past experiences to support learned behavior. Aside from these mnemonic processes, it also requires the ability to regulate memory (i.e. executive processes). For example, many real-world decisions will engage episodic retrieval, for which executive processes must help to integrate and evaluate the quality of remembered information (mnemonic evidence) and guide behavior to either decision, action, or continued memory search. While the neural basis of episodic memory encoding and retrieval have been a major focus of research, far less is known about its executive aspects. Executive mnemonic functions likely involve an anatomical substrate that is (i) multisensory/associative, (ii) engaged by memory/executive processing, and (iii) strongly interconnected with both mnemonic regions in the medial temporal lobe (MTL) and executive prefrontal (PFC) regions. Prior non-human primate studies, as well as human electrophysiology and neuroimaging data, suggest that posterior cingulate cortex (PCC) fulfills these criteria. The central hypothesis of this work is that the PCC plays a critical and unique role in executive control of episodic memory retrieval. The investigators further hypothesize that it comprises three subregions regions: dorsal PCC, ventral PCC and retrosplenial cortex (RSC). These subregions are proposed to play complementary roles, corresponding to retrieval regulation, retrieval integration, and scene perception and transformation, respectively. In this account, PCC is a convergence zone of memory and executive systems, whose specific functional organization accounts for prior discrepancies between studies and species. The investigators will utilize human intracranial recordings, including single-cell data and stimulation within PCC, to better resolve the functional organization of this region. The investigators will employ an array of cognitive experiments to delineate three PCC subregions supporting the encoding, retrieval and executive control of memory processing (Aim 1). In delineating these subregions, the investigators will also seek to differentiate PCC responses from those occurring in memory and executive functional networks (Aim 2). Finally, based on these observations, the investigators will demonstrate the causal role of PCC subregions on behavior and local/network activity (Aim 3). By studying PCC, a convergence zone of memory and executive systems, progress can be made in elucidating how the failure to successfully leverage past experiences in daily behavior can occur as a common symptom of both neurodegenerative disease (e.g. Alzheimer's disease) and multiple psychiatric conditions (e.g. schizophrenia) implicating PCC dysfunction.