Human Learning of New Structured Information Across Time and Sleep

July 29, 2025 updated by: University of Pennsylvania

Learning Novel Structure Across Time and Sleep

Acting adaptively requires quickly picking up on structure in the environment and storing the acquired knowledge for effective future use. Dominant theories of the hippocampus have focused on its ability to encode individual snapshots of experience, but the investigators and others have found evidence that it is also crucial for finding structure across experiences. The mechanisms of this essential form of learning have not been established. The investigators have developed a neural network model of the hippocampus instantiating the theory that one of its subfields can quickly encode structure using distributed representations, a powerful form of representation in which populations of neurons become responsive to multiple related features of the environment.

The first aim of this project is to test predictions of this model using high resolution functional magnetic resonance imaging (fMRI) in paradigms requiring integration of information across experiences. The results will clarify fundamental mechanisms of how humans learn novel structure, adjudicating between existing models of this process, and informing further model development. There are also competing theories as to the eventual fate of new hippocampal representations. One view posits that during sleep, the hippocampus replays recent information to build longer-term distributed representations in neocortex. Another view claims that memories are directly and independently formed and consolidated within the hippocampus and neocortex.

The second aim of this project is to test between these theories. The investigators will assess changes in hippocampal and cortical representations over time by re-scanning participants and tracking changes in memory at a one-week delay. Any observed changes in the brain and behavior across time, however, may be due to generic effects of time or to active processing during sleep.

The third aim is thus to assess the specific causal contributions of sleep to the consolidation of structured information. The investigators will use real-time sleep electroencephalography to play sound cues to bias memory reactivation. The investigators expect that this work will clarify the anatomical substrates and, critically, the nature of the representations that support encoding and consolidation of novel structure in the environment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

105

Phase

  • 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 Backup

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
        • Contact:
          • Rishi Krishnamurthy, BA

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

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Between 18 and 35 years of age (all aims)
  • Not a member of a vulnerable population (all aims)
  • Normal or corrected-to-normal vision (all aims)
  • Normal hearing (all aims)
  • Able to speak English fluently (all aims)
  • No prior history of major psychiatric or neurological disorders (Aims 1 and 2; MRI-specific)
  • Not currently taking any antidepressants or sedatives (Aims 1 and 2; MRI-specific)
  • No known neurological disorders (Aim 3; EEG-specific)

Exclusion Criteria:

  • The investigators will exclude individuals with MR contraindications such as non-removable biomedical devices or metal in or on the body (Aims 1 and 2; MRI-specific)
  • Claustrophobia (Aims 1 and 2; MRI-specific)
  • Pregnant women will also be excluded from neuroimaging, as the effects of MR on pregnancy are not fully understood (Aims 1 and 2; MRI-specific)

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: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Learning and consolidation in Associative Inference
The proposed functional magnetic resonance imaging study assesses the neural representations contributing to humans' ability to associate objects in the support of simple inferences and generalization. All participants will undergo the same procedure. Participants will learn about pairs of objects and then be asked to make judgments and inferences about the relationships between the objects. The order of presentation of the objects will be manipulated within subjects, as different learning theories make different predictions about how learning will unfold under different orderings. Participants will be brought back one week later for a second scan, to evaluate how the neural substrates of these processes change with consolidation.
Behavioral: Associative inference
Participants will engage in an associative inference paradigm. Memory will be assessed behaviorally and neural representations will be assessed using functional magnetic resonance imaging.
Experimental: Learning and consolidation in category learning
The proposed functional magnetic resonance imaging study assesses the neural representations contributing to humans' ability to learn new categories of objects. All participants will undergo the same procedure. Participants will learn about novel objects, each with several colored parts. Some parts are unique to individual objects and others are shared among the members of the category. The investigators will assess how different regions of the brain contribute to learning and remembering these different kinds of parts, and how the resulting representations support category understanding. Participants will be brought back one week later for a second scan, to evaluate how the neural substrates of these processes change with consolidation.
Behavioral: Category learning
Participants will engage in a category learning paradigm. Memory will be assessed behaviorally (Arms 2 and 3), and neural representations will be assessed using functional magnetic resonance imaging (Arm 2).
Experimental: Manipulating replay during sleep using real-time EEG
In the proposed electroencephalography (EEG) study, all participants will undergo the same procedure. Participants will learn the visual features and spoken names associated with three categories of novel objects. Participants' memory for these objects and the objects' parts will be tested before and after a nap. The investigators will monitor brain activity during the nap in real time and, at optimal moments, quietly play the spoken names of the objects to encourage reactivation of particular objects in particular orders. The investigators will assess how this manipulation impacts memory for these objects.
Behavioral: Category learning
Participants will engage in a category learning paradigm. Memory will be assessed behaviorally (Arms 2 and 3), and neural representations will be assessed using functional magnetic resonance imaging (Arm 2).
Behavioral: Sleep
Participants will sleep after engaging in a category learning paradigm while electroencephalography data are collected, and memory will be assessed behaviorally after sleep.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in multivariate representations
Time Frame: Within first session (spanning 2-3 hrs.) and at approximately one week delay in second session (spanning 1-2 hrs.)
Changes in spatial correlations between the MRI BOLD pattern associated with related objects over the course of learning and across the one-week delay.
Within first session (spanning 2-3 hrs.) and at approximately one week delay in second session (spanning 1-2 hrs.)
Brain-behavior correlations
Time Frame: Within first session (spanning 2-3 hrs.) and at approximately one week delay in second session (spanning 1-2 hrs.)
Correlations between BOLD signal in the brain and participant behavior during judgments about objects.
Within first session (spanning 2-3 hrs.) and at approximately one week delay in second session (spanning 1-2 hrs.)
Correlations between activity across brain regions
Time Frame: Within first session (spanning 2-3 hrs.) and at approximately one week delay in second session (spanning 1-2 hrs.)
Relationships between BOLD activity across different regions of the brain as a function of trial type and delay.
Within first session (spanning 2-3 hrs.) and at approximately one week delay in second session (spanning 1-2 hrs.)
Memory accuracy
Time Frame: Within single study session (spanning 4-5 hrs.)
Change in generalization ability from before to after the nap as a function of the different conditions of object cueing during sleep.
Within single study session (spanning 4-5 hrs.)

Collaborators and Investigators

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

Sponsor

University of Pennsylvania

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Anna C Schapiro, PhD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

June 5, 2023

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

May 10, 2023

First Submitted That Met QC Criteria

June 12, 2023

First Posted (Actual)

June 20, 2023

Study Record Updates

Last Update Posted (Actual)

August 1, 2025

Last Update Submitted That Met QC Criteria

July 29, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 833228B
  • R01MH129436 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlie results in a publication.

IPD Sharing Time Frame

IPD will be available at the time of study publication.

IPD Sharing Access Criteria

IPD will be publicly available without restriction.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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