IntroductionUbiquity of Alzheimer's disease (AD) coupled with relatively ineffectual pharmacologic treatments has spurred interest in nonpharmacologic lifestyle interventions for prevention or risk reduction. However, evidence of neuroplasticity notwithstanding, there are few scientifically rigorous, ecologically relevant brain training studies focused on building cognitive reserve in middle age to protect against cognitive decline. This pilot study will examine the ability of virtual reality (VR) cognitive training to improve cognition and cerebral blood flow (CBF) in middle-aged individuals at high AD risk due to parental history.MethodsThe design is an assessor-blind, parallel group, randomized controlled trial of VR cognitive-motor training in middle-aged adults with AD family history. The experimental group will be trained with adaptive “real-world” VR tasks targeting sustained and selective attention, working memory, covert rule deduction, and planning, while walking on a treadmill. One active control group will perform the VR tasks without treadmill walking; another will walk on a treadmill while watching scientific documentaries (nonspecific cognitive stimulation). A passive (waitlist) control group will not receive training. Training sessions will be 45 minutes, twice/week for 12 weeks. Primary outcomes are global cognition and CBF (from arterial spin labeling [ASL]) at baseline, immediately after training (training gain), and 3 months post-training (maintenance gain). We aim to recruit 125 participants, including 20 passive controls and 35 in the other groups.DiscussionCurrent pharmacologic therapies are for symptomatic AD patients, whereas nonpharmacologic training is administrable before symptom onset. Emerging evidence suggests that cognitive training improves cognitive function. However, a more ecologically valid cognitive-motor VR setting that better mimics complex daily activities may augment transfer of trained skills. VR training has benefited clinical cohorts, but benefit in asymptomatic high-risk individuals is unknown. If effective, this trial may help define a prophylactic regimen for AD, adaptable for home-based application in high-risk individuals.

While walking, our locomotion is affected by and adapts to the environment based on vision- and body-based (vestibular and proprioception) cues. When transitioning to downhill walking, we modulate gait by braking to avoid uncontrolled acceleration, and when transitioning to uphill walking, we exert effort to avoid deceleration. In this study, we aimed to measure the influence of visual inputs on this behavior and on muscle activation. Specifically, we aimed to explore whether the gait speed modulations triggered by mere visual cues after transitioning to virtually inclined surface walking are accompanied by changes in muscle activation patterns typical to those triggered by veridical (gravitational) surface inclination transitions. We used an immersive virtual reality system equipped with a self-paced treadmill and projected visual scenes that allowed us to modulate physical–visual inclination congruence parametrically. Gait speed and leg muscle electromyography were measured in 12 healthy young adults. In addition, the magnitude of subjective visual verticality misperception (SVV) was measured by the rod and frame test. During virtual (non-veridical) inclination transitions, vision modulated gait speed by (i) slowing down to counteract the excepted gravitational “boost” in virtual downhill inclinations and (ii) speeding up to counteract the expected gravity resistance in virtual uphill inclinations. These gait speed modulations were reflected in muscle activation intensity changes and associated with SVV misperception. However, temporal patterns of muscle activation were not affected by virtual (visual) inclination transitions. Our results delineate the contribution of vision to locomotion and may lead to enhanced rehabilitation strategies for neurological disorders affecting movement.

Background Neuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention—one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test–retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function. Methods Healthy adults (n = 147) in three age groups (young: n = 50; middle-aged: n = 80; older: n = 17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance. Results Construct validity was substantiated by moderate correlations between the’gold standard’ pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA 0.58, tB 0.71; HMD-CTT: tA 0.62, tB 0.69). VR versions showed relatively high test–retest reliability (intraclass correlation; VR: tA 0.60–0.75, tB 0.59–0.89; original: tA 0.75–0.85, tB 0.77–0.80) and discriminant validity (area under the curve; VR: tA 0.70–0.92, tB 0.71–0.92; original: tA 0.73–0.95, tB 0.77–0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants. Conclusions The present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.

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Background: Athletes, soldiers, and rescue personnel must often perform intense, prolonged, and physically demanding activities while maintaining cognitive focus. As cognitive and physical functions are believed to share central nervous system resources, their simultaneous activation can cause reciprocal disruptions in the performance of both. Methods: In the current study, we aimed to develop and validate a virtual reality-based experimental protocol enabling rigorous exploration of the effects of prolonged high-load physical and cognitive efforts, by comparing novel cognitive tasks presented in the context of a simulated loaded march to a battery of established neurocognitive tests. We then used this protocol in a pre-post pilot study exploring the effects of high-load physical and cognitive activity on physical and cognitive performance. Twelve participants underwent a simulated 10-km loaded march on a treadmill in our virtual reality environment, with or without integrated cognitive tasks (VR-COG). At each of three experimental visits, participants underwent pre-activity and post-activity evaluations, including the Color Trail Test, the Synthetic Work Environment (SYNWIN) battery for multitasking evaluation, and physical tests (i.e., ‘time to exhaustion’). Results: In general, strong or moderate correlations (r≥0.58 p≤0.048) were found between VR-COG scores and scores on the validated cognitive tests. Together, VR-COG and CTT measures were able to successfully predict the effects of the combined physical and cognitive load on multitasking performance, as assessed by SYNWIN score. Conclusions: As virtual environments are ideal for studying high performance professional activity in realistic but controlled settings, the novel protocol is optimal for measuring the effects of prolonged, high-load physical and cognitive activity, and can therefore contribute to our knowledge on physical-cognitive interactions.

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While walking, our locomotion is affected by and adapts to the environment based on vision-based and body-based (vestibular and proprioception) cues, all contributing to an “Internal Model of Gravity”. During surface inclination transitions, we modulate gait to counteract gravitational forces by braking during downhill walking to avoid uncontrolled acceleration or by exerting effort to avoid deceleration while walking uphill. In this study, we investigated the role of vision in gait modulation during surface inclination transitions by using an immersive large-scale Virtual Reality (VR) system equipped with a self-paced treadmill and projected visual scenes that allowed us to modulate physical-visual inclinations congruence parametrically. Gait speed and leg muscle electromyography (EMG) were measured in 12 healthy young adults. In addition, the magnitude of subjective visual misperception of verticality was measured by the rod and frame test. During virtual (non-veridical) inclination transitions, vision modulated gait speed after transitions by (i) slowing down to counteract the excepted gravitational ‘boost’ in virtual downhill inclinations and by (ii) speeding up to counteract the expected gravity resistance in virtual uphill inclinations. These gait speed modulations were reflected in muscle activation intensity changes and associated with subjective visual verticality misperception. However, temporal patterns of muscle activation, which are significantly affected by real gravitational inclination transitions, were not affected by virtual (visual) inclination transitions. Our results delineate the contribution of vision to functional locomotion on uneven surfaces and may lead to enhanced rehabilitation strategies for neurological disorders affecting movement.Significance statementA crucial component of successful locomotion is maintaining balance and speed while walking on uneven surfaces. In order to reach successful locomotion, an individual must utilize multisensory integration of visual, gravitational, and proprioception cues. The contribution of vision to this process is still unclear, thus we used a fully immersive virtual reality treadmill setup allowing us to manipulate visual (virtual) and gravitational (real) surface inclinations independently during locomotion of healthy adults. While vision modulated gait speed for a short period after inclination transitions and this was predictive of individual’s visual dependency, muscle activation patterns were only affected by gravitational surface inclinations, not by vision. Understanding the vision’s contribution to successful locomotion may lead to improved rehabilitation for movement disorders.

Background Athletes, soldiers, and rescue personnel must often perform intense, prolonged, and physically demanding activities while maintaining cognitive focus. As cognitive and physical functions are believed to share central nervous system resources, their simultaneous activation can cause reciprocal disruptions in the performance of both. Methods In the current study, we aimed to develop and validate a virtual reality-based experimental protocol enabling rigorous exploration of the effects of prolonged high-load physical and cognitive efforts, by comparing novel cognitive tasks presented in the context of a simulated loaded march to a battery of established neurocognitive tests. We then used this protocol in a pre-post pilot study exploring the effects of high-load physical and cognitive activity on physical and cognitive performance. Twelve participants underwent a simulated 10-km loaded march on a treadmill in our virtual reality environment, with or without integrated cognitive tasks (VR-COG). At each of three experimental visits, participants underwent pre-activity and post-activity evaluations, including the Color Trail Test, the Synthetic Work Environment (SYNWIN) battery for multitasking evaluation, and physical tests (i.e., ‘time to exhaustion’). Results In general, strong or moderate correlations (r ≥ 0.58 p ≤ 0.048) were found between VR-COG scores and scores on the validated cognitive tests. Together, VR-COG and CTT measures were able to successfully predict the effects of the combined physical and cognitive load on multitasking performance, as assessed by SYNWIN score. Conclusions As virtual environments are ideal for studying high performance professional activity in realistic but controlled settings, the novel protocol is optimal for measuring the effects of prolonged, high-load physical and cognitive activity, and can therefore contribute to our knowledge on physical-cognitive interactions.