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). 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
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
200
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.
Commercially-available, narrative computer games marketed as cognitively enriching. Can be tablet-based or wireless VR headset-based.
Tablet computer playing Labyrinth spatial wayfinding game in 2.5D
UCSF Mission Bay
San Francisco, California, United States
RECRUITINGMDT 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)
Time frame: 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)
Time frame: 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.
Time frame: 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
Time frame: collected in association with Outcome 1, at baseline immediately before (T1) and post-assessment immediately after training regimen is completed (T2)
Remote Cognitive Module (RCM)
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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.
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
Time frame: baseline immediately before training regimen begins