Wayfinding Intervention in High-Fidelity Long-Term Memory (LABYR)

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.

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 (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 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. The significance of this platform is from the effects in brain and behavior arising from cognitive training, which can generalize to improvements in untrained capability for high-fidelity LTM. Research in rodents and 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 Labyrinth spatial wayfinding game was developed in-house to incorporate full scientific rigor, as with procedures in any properly controlled behavioral experiment. The game uses 3D and 2.5D computer graphics tools, as well as numerous levels of adaptive challenge, to deliver a dynamic, engaging experience for participants throughout the training regimen. Training can be administered with and without participant ambulation in movement through wayfinding runs. A participant's pre- and post-training assessments will occur promptly before and after their 15 to 20-hour training regimen, including collection of functional MRI (fMRI) and structural MRI data. Cognitive outcome measures will assess capabilities for high-fidelity LTM retrieval. The a priori hypothesis is that effectiveness of the wayfinding game intervention would 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. Structural MRI measures will assess morphometric and volumetric changes from pre- to post-training assessments.

After recruitment, participants are randomly assigned to treatment arms. Participants and experimenters with whom they interact during the experiments are blind to the purpose of the randomly-assigned arm. First-level analysis performed blind to participant's treatment arm.

Multi-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive spatial wayfinding challenge. Game movement via participant ambulation wearing leg-position trackers.

Multi-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive spatial wayfinding challenge. Game movement via teleporting technique.

Multi-session cognitive intervention with handheld tablet or wireless virtual reality headset presentation of commercially available, narrative computer games.

Multi-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive rhythm training game.

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.

Multi-session cognitive intervention with head-mounted display virtual reality computer game using wireless, narrower filed technology to presents an adaptive spatial wayfinding challenge. Game movement via teleporting technique.

Head-mounted display virtual reality game designed to induce environmental enrichment in an adaptive, immersive regimen of wayfinding in novel urban and village neighborhoods.

Mnemonic discrimination task testing recognition memory for common objects, as reported in scores on a scale of the Lure Discrimination Index ranging from 0.00 to 1.00 where higher values show better performance.

Encoding and test of recent autobiographical long-term memory, as reported in scores on a scale of Percentage of Items Recalled ranging from 0.00 to 1.00 where higher values show better performance.

Changes in Volumetric-based Brain Morphometry Associated With Training-induced Changes in Mnemonic Discrimination

Structural MRI T1 data will be analyzed in terms of volumetric-based morphometry and compared between treatment arms and timepoints.

during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed

Changes in Task-based Cortical Functional Connectivity Associated With Training-induced Changes in Mnemonic Discrimination

functional MRI data will be analyzed in terms of beta-series correlations between co-active cortical regions of interest and compared between treatment arms and timepoints.

during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed

A tablet application using a speech-to-text interface to administer neuropsychological tests comparable to CVLT-II verbal memory, verbal fluency, digit span and Trail Making Test-B. Raw scores from the tasks will be transformed to z-scores, relative to population normative values, and a participant's z-scores will be the uniform measures of their performance across RCM tasks. THESE DATA WERE NOT COLLECTED OR ANALYZED DUE TO FUNDING CONSTRAINTS

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 45-minute, brisk 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

Wais PE, Arioli M, Anguera-Singla R, Gazzaley A. Virtual reality video game improves high-fidelity memory in older adults. Sci Rep. 2021 Jan 28;11(1):2552. doi: 10.1038/s41598-021-82109-3.