Posterior Cingulate Cortex and Executive Control of Episodic Memory

September 5, 2025 updated by: University of Pennsylvania
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
130

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All participants are patients undergoing invasive brain monitoring for epilepsy and will be asked to consent to participation in this basic science protocol (which is focused on the patient group but is not focused on the study of epilepsy).

Exclusion Criteria:

  • Individuals not undergoing invasive brain monitoring for epilepsy.
  • Individuals outside of the age range (18-50 yrs).
  • Individuals with cognitive impairment or intellectual difficulty.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experiment 1 - episodic / executive switch
All enrolled participants will be asked to perform experiment 1, which is a cognitive task involving the switch between performing episodic memory decisions (e.g., "did you eat fruit yesterday?") and executive decisions (e.g. "...does 5+3+8 = 17?"). Participants will perform this computer-based task while electrical brain activity is recorded from the posterior cingulate cortex, hippocampus and prefrontal cortex. This task takes 18 minutes to complete.
Behavioral: Cognitive testing
Cognitive tasks testing executive and episodic based decisions, and the switching between these processes.
Experimental: Experiment 2 - executive decision task
All enrolled participants will be asked to perform experiment 2, which is a cognitive task involving reward-based decisions between two options. For each decision, the two options will differ in their risk and reward (e.g., 100% chance of 10 points vs. 30% chance of 50 points). Participants will perform this computer-based task while electrical brain activity is recorded from the posterior cingulate cortex, hippocampus and prefrontal cortex. This task takes 15 minutes to complete.
Behavioral: Cognitive testing
Cognitive tasks testing executive and episodic based decisions, and the switching between these processes.
Experimental: Experiment 3 - episodic decision task
All enrolled participants will be asked to perform experiment 3, which is a cognitive task involving memory-based decisions between two options (pictures of people). For each decision, the two pictures will differ in memory strength and reward (e.g., familiar picture for 10 points vs. unfamiliar picture 50 points). Memory strength for each picture will be defined by how many times the picture was previously shown (e.g., 2 vs. 10 presentations) prior to performing the memory decision task. Participants will perform this computer-based task while electrical brain activity is recorded from the posterior cingulate cortex, hippocampus and prefrontal cortex. This task takes 15 minutes to complete.
Behavioral: Cognitive testing
Cognitive tasks testing executive and episodic based decisions, and the switching between these processes.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Episodic/Executive behavioral task performance accuracy
Time Frame: Outcome assessed 10 minutes after intervention
Participants will perform three tasks each testing the accuracy of executive (reward) or episodic (memory strength) based decisions. Outcome measures will be decision accuracy (% correct).
Outcome assessed 10 minutes after intervention
Episodic/Executive behavioral task performance speed
Time Frame: Outcome assessed 10 minutes after intervention
Participants will perform three tasks each testing the speed of executive (reward) or episodic (memory strength) based decisions. Outcome measures will be response/decision reaction time (milliseconds).
Outcome assessed 10 minutes after intervention
Changes in high-frequency electrophysiological brain response
Time Frame: Outcome assessed 1 hour after intervention
During behavioral task performance, electrophysiological signals recorded from the brain will be quantified for changes in the mean high-frequency activity (70-150 Hz) amplitude during correct and incorrect episodic/executive decisions. The goal is to track this electrophysiological activity to quantify if and when brain activity in the posterior cingulate cortex occurs during memory and non-memory based decisions.
Outcome assessed 1 hour after intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 18, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 2, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 16, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 12, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R01MH129439 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared through the National Institute of Mental Health Data Archive (NIMH NDA).

IPD Sharing Supporting Information Type

  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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