Designing a spatial navigation intervention protocol informed by region-specific brain activation for individuals at risk for dementia

Abstract: With no cure available yet, lifestyle interventions to slow down cognitive decline and delay onset of Alzheimer’ disease and related dementias are essential. Up to a third of dementia cases may be preventable by engaging in protective behaviors, such as staying cognitively active, according to observational data. Yet, current cognitive training protocols to delay dementia onset often fall short. Here we argue that designing an intervention informed by specific contributions of brain regions subserving cognition will yield better results. This pilot project is focused on spatial navigation (SN), the ability to travel familiar/unfamiliar environments. Difficulties forming new and maintaining old spatial memories is a common and early sign of Alzheimer’ disease and can lead to disorientation and dependence in daily activities. Tau and amyloid-beta accumulation starts in regions subserving SN, such as mediotemporal and posterior parietal cortex. Even though SN difficulties present an important target, there are few clinical trials aimed at SN. Many trials use desktop-based SN train protocols, which deprives learners from movement-related sensory and kinematic information during active navigation. Similarly, neuroimaging requires participants to refrain from gross motor movements. To overcome these limits, we developed a full-immersive virtual-reality (VR) maze which participants learn to navigate and use Mobile Brain Body Imaging (MoBI) to synchronously record body movement with EEG to record and analyze brain activity at the source level during active movement through space. The aims of this pilot project are to 1) determine feasibility of a VR-SN maze training protocol and 2) explore training-induced neuroplasticity in older adults participating in VR-SN exercises. We seek to enroll 30 older adults with amnestic mild cognitive impairment to train twice a week for 50 min over a 4-month period. VR mazes are designed to induce different navigational strategies (allocentric and egocentric) at different periods (Stand/Encode and Walk/Navigate) of maze learning. Allocentric and egocentric spatial strategies are known to rely on mediotemporal and posterior parietal cortex regions, respectively. Hence, developing a VR-SN maze training protocol and collecting source-localized milliseconds precise brain measurements during active navigation, we enable us to identify, dissociate, and track participants’ brain dynamics applying mediotemporal-based allocentric and posterior parietal-based egocentric navigational strategies and test relationships with improvements in SN. Time required to navigate mazes will serve as our behavioral outcome. Region-specific modulations in theta (3-7Hz) and alpha (8-12Hz) power will serve as our neurophysiological outcome measures. We provide preliminary VR-MoBI maze test findings showing navigation-related theta and alpha modulations during Stand/Encode and Walk/Navigate periods. This pilot study will position us to design a future randomized clinical trial to test efficacy to improve navigational abilities, and thereby delay cognitive decline in older adults at-risk for dementia. 1