Wayfinding Intervention and Long-Term Memory (Quest-Tablet)

Virtual Reality Interventions to Stimulate Capabilities for Learning and Retrieval of High-Fidelity Memory

Therapeutic treatment is yet available for declining memory, which is an impairment affecting the quality of life for many older adults and patients with cognitive impairment. Cognitive training with an immersive video game promises to drive hippocampal-cortical plasticity and associated gains that can restore memory capability or provide therapeutic treatment for memory deficits.

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment; Long-Term Memory Decline
• Intervention / Treatment: Behavioral: LabyrinthVR software; Behavioral: Placebo Games software; Behavioral: Labyrinth Tablet software; Behavioral: Labyrinth VR wireless

Detailed Description

A hallmark of higher cognition is the capability for flexible association of diverse bits of information stored in memory, such that experiences can be remembered in detailed and distinct terms (i.e., high-fidelity long-term memory). Interventions capable of sustaining improved learning and flexible association of new information into long-term memory (LTM) have shown promising pilot results, and further development is expected to find treatments to attenuate the decline of high-fidelity LTM in normal aging or provide therapeutic treatment for patients with cognitive impairment without dementia (i.e., MCI).

This project applies a translational neuroscience approach in further development of a cognitive training intervention that targets sustained improvement in capabilities for long-term memory (LTM) and cognitive control. Treatments use commercially available head-mounted display Virtual Reality (VR) technology and tablet computers to present a deeply immersive spatial wayfinding video game.

Based on preliminary results, the hypothesis is that immersion in a game to navigate errands through unfamiliar, visually complex neighborhoods (i.e., wayfinding) will be an effective means to environmental enrichment, which refers to a process whereby new and complex experiences bring change to brain and behavior. Research in humans shows that learning a new, enriched environment spurs the healthy function of the hippocampus and supports lifelong neurogenesis. Adult-borne hippocampal neurogenesis has been linked as the neurobiological basis for the formation of new, high-fidelity memories.

The significance of this project includes functionality for remote training procedures (i.e., at home). The availability for participants to complete some of the experiment procedures at home will expand enrollment opportunities and prove the practicality of the intervention outside of a clinical setting.

The Labyrinth spatial wayfinding game uses 3D and 2.5D computer graphics tools to present dozens of levels of adaptive challenge and deliver a dynamic, engaging experience for participants throughout the training regimen. In this project, participants will effect game movement using hand controllers while playing the game in a seated position.

For each participant, pre- and post-training assessments will occur promptly before and after their 15 to 20-hour training regimen. Cognitive outcome measures will assess capabilities for high-fidelity LTM retrieval and control of sustained visual attention, and some measures will include collection of associated functional MRI (fMRI) and structural MRI data.

Effectiveness of the wayfinding game intervention will be evidenced by post-training improvements in retrieval of high-fidelity LTM and cognitive control capabilities. FMRI results associated with the measured cognitive improvements will localize changes in functional brain networks that support gains in memory capabilities. Structural MRI measures will assess morphometric and volumetric changes from pre- to post-training assessments.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Melissa Arioli; Phone Number: 415-502-7321; Email: melissa.arioli@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Mission Bay
      • Contact: Melissa Arioli; Phone Number: 415-502-7321; Email: melissa.arioli@ucsf.edu
      • Principal Investigator: Peter E Wais, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• fluent speakers of English
• completed 12 or more years of education
• normal or corrected-to-normal vision
• dexterity to comfortably operate the scanner-compatible response box
• freedom from physical and neurological conditions contra-indicated for fMRI
• must confirm physical stamina and comfort for semi-weekly brisk 30-minute walks on level ground

Exclusion Criteria:

• use of psychotropic medications
• history of concussions or dizziness, vestibular or balance problems
• significant discomfort with virtual reality experiences

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Controls; Multi-session cognitive intervention with handheld tablet or wireless virtual reality headset presentation of commercially available, narrative computer games.	Behavioral: Placebo Games software; Commercially-available, narrative computer games marketed as cognitively enriching. Can be tablet-based or wireless VR headset-based.
Experimental: Labyrinth Tablet; Multi-session cognitive intervention with tablet computer, displaying 2.5D version of Labyrinth game in an adaptive spatial wayfinding challenge. Game movement via on-screen control buttons.	Behavioral: Labyrinth Tablet software; Tablet computer playing Labyrinth spatial wayfinding game in 2.5D
Experimental: LabyrinthVR Scoot; Multi-session cognitive intervention with VIVE high-resolution head-mounted display virtual reality computer game that presents an adaptive spatial wayfinding challenge. Game movement via handheld controllers.	Behavioral: LabyrinthVR software; Head-mounted display virtual reality game designed to induce environmental enrichment in an adaptive, highly engaging regimen of wayfinding in novel urban and village neighborhoods.
Experimental: Labyrinth VR wireless; Multi-session cognitive intervention with QUEST head-mounted display virtual reality computer game using wireless technology to present an adaptive spatial wayfinding challenge. Game movement via handheld controllers.	Behavioral: Labyrinth VR wireless; Wireless head-mounted display virtual reality game designed to induce environmental enrichment in an adaptive, engaging regimen of wayfinding in novel urban and village neighborhoods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDT change in mnemonic discrimination	Training-related change in Mnemonic Discrimination Task (MDT) score. MDT tests recognition memory for pairs of common objects (i.e., targets and lures), measuring the variable of the number of images identified as old (studied) or new (novel), and reports a composite index score (0.00 to 1.00) for accuracy post-training (T2) versus baseline (T1)	baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2) providing for a composite score T2-T1
TOUR change in recall	Training-related change in recall of number of details in autobiographical memory from a narrated urban tour, such that a composite parametric score shows how many specific details were recalled post-training (T2) versus baseline (T1)	baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2) providing for a composite score T2-T1
Volumetric-based brain morphometry for gray and white matter	Structural MRI T1 data will be analyzed in terms of volumetric-based morphometry, measuring the variables of cortical area.	collected in association with Outcome 1, at baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2)
Task-based cortical functional connectivity associated with mnemonic discrimination capability and in control of sustained visual attention	functional MRI data will be analyzed in terms of beta-series correlations between co-active cortical regions of interest, measuring the variable of correlation of inter-trial variability across brain regions	collected in association with Outcome 1, at baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remote Cognitive Module (RCM)	A tablet application using a speech-text interface to administer neuropsychological tests comparable to CVLT-II verbal memory, verbal fluency, digit span and Trail Making Test-B. Measured variables are target words remembered	baseline immediately before training regimen begins

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Peter E Wais, PhD, Neuroscape, Department of Neurology

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 23, 2022

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: cognitive training; cognitive aging; amnestic MCI without dementia
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 19-27586-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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