Labyrinth Intervention in High-Fidelity Long-Term Memory

  • End date
    Jun 30, 2022
  • participants needed
  • sponsor
    University of California, San Francisco
Updated on 4 March 2021
cognitive training
memory impairment


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, virtual reality video game promises to drive hippocampal-cortical plasticity and associated gains that can restore memory capability or provide therapeutic treatment for memory deficits.


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 LTM). Interventions capable of sustaining improved learning and flexible association of new information into LTM remain elusive. Interventions have yet to be developed 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 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 for deeply immersive presentation of a spatial wayfinding video game. 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.

The significance of this platform is in value to both gains from cognitive training that can generalize to improvements in untrained capability for high-fidelity LTM and clinical assessments for patients with memory deficits. Research in rodents and humans shows that healthy function of the hippocampus supports lifelong neurogenesis, which has been linked as the neurobiological basis to formation of new, high-fidelity memories.

The VR spatial wayfinding game was developed in-house to incorporate full scientific rigor, as with procedures in any properly controlled behavioral experiment. The game uses both VR computer graphics tools and numerous levels of adaptive challenge to deliver a dynamic, engaging experience for participants throughout the training regimen. A participant's preand post-training assessments will occur promptly before and after their 15-hour training regimen, including collection of functional MRI (fMRI) data and blood-drawn biospecimens. Cognitive outcome measures will assess capabilities for high-fidelity LTM retrieval.

Effectiveness of the VR wayfinding game intervention will be evidenced by post-training improvements in retrieval of high-fidelity LTM and associated cognitive control capabilities. FMRI results associated with the measured cognitive improvements will localize changes in functional brain networks that support gains in memory capabilities. Neuronal-derived exosome factors will provide confirmatory evidence of a hippocampal-dependent mechanism of action stimulated by the training regimen.

Condition Mild Cognitive Impairment, Mild Neurocognitive Disorder, Long-Term Memory Decline, Long-Term Memory Decline, Long-Term Memory Decline, Long-Term Memory Decline
Treatment LabyrinthVR, Placebo Games, Coherence
Clinical Study IdentifierNCT04253587
SponsorUniversity of California, San Francisco
Last Modified on4 March 2021


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Inclusion Criteria

Is your age between 62 yrs and 85 yrs?
Gender: Male or Female
Do you have any of these conditions: Long-Term Memory Decline or Mild Cognitive Impairment?
Do you have any of these conditions: Mild Neurocognitive Disorder or Mild Cognitive Impairment or Long-Term Memory Decline?
Do you have any of these conditions: Mild Neurocognitive Disorder or Mild Cognitive Impairment or Long-Term Memory Decline?
Do you have any of these conditions: Mild Cognitive Impairment or Long-Term Memory Decline or Mild Neurocognitive Disorder?
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 45-minute, brisk walks on level ground

Exclusion Criteria

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