Using virtual reality-based neurocognitive testing and eye tracking to study naturalistic cognitive-motor performance.

Natural human behavior arises from continuous interactions between the cognitive and motor domains. However, assessments of cognitive abilities are typically conducted using pen and paper tests, i.e., in isolation from "real life" cognitive-motor behavior and in artificial contexts. In the current study, we aimed to assess cognitive-motor task performance in a more naturalistic setting while recording multiple motor and eye tracking signals. Specifically, we aimed to (i) delineate the contribution of cognitive and motor components to overall task performance and (ii) probe for a link between cognitive-motor performance and pupil size. To that end, we used a virtual reality (VR) adaptation of a well-established neurocognitive test for executive functions, the 'Color Trails Test' (CTT). The VR-CTT involves performing 3D reaching movements to follow a trail of numbered targets. To tease apart the cognitive and motor components of task performance, we included two additional conditions: a condition where participants only used their eyes to perform the CTT task (using an eye tracking device), incurring reduced motor demands, and a condition where participants manually tracked visually-cued targets without numbers on them, incurring reduced cognitive demands. Our results from a group of 30 older adults (>65) showed that reducing cognitive demands shortened completion times more extensively than reducing motor demands. Conditions with higher cognitive demands had longer target search time, as well as decreased movement execution velocity and head-hand coordination. We found larger pupil sizes in the more cognitively demanding conditions, and an inverse correlation between pupil size and completion times across individuals in all task conditions. Lastly, we found a possible link between VR-CTT performance measures and clinical signatures of participants (fallers versus non-fallers). In summary, performance and pupil parameters were mainly dependent on task cognitive load, while maintaining systematic interindividual differences. We suggest that this paradigm opens the possibility for more detailed profiling of individual cognitive-motor performance capabilities in older adults and other at-risk populations.

Differential gait adaptation patterns in Parkinson's disease - a split belt treadmill pilot study.

BACKGROUND: Interventions using split belt treadmills (SBTM) aim to improve gait symmetry (GA) in Parkinson's disease (PD). Comparative effects in conjugated SBTM conditions were not studied systematically despite potentially affecting intervention outcomes. We compared gait adaptation effects instigated by SBTM walking with respect to the type (increased\decreased speed) and the side (more/less affected) of the manipulated belt in PD. METHODS: Eight individuals with PD performed four trials of SBTM walking, each consisted of baseline tied belt configuration, followed by split belt setting - either WS or BS belt's speed increased or decreased by 50% from baseline, and final tied belt configuration. Based on the disease's motor symptoms, a 'worst' side (WS) and a 'best' side (BS) were defined for each participant. RESULTS: SB initial change in GA was significant regardless of condition (p ≤ 0.02). This change was however more pronounced for BS-decrease compared with its matching condition WS-increase (p = 0.016). Similarly, the same was observed for WS-decrease compared to BS-increase (p = 0.013). Upon returning to tied belt condition, both BS-decrease and WS-increased resulted in a significant change in GA (p = 0.04). Upper limb asymmetry followed a similar trend of GA reversal, although non-significant. CONCLUSIONS: Stronger effects on GA were obtained by decreasing the BS belt's speed of the best side, rather than increasing the speed of the worst side. Albeit a small sample size, which limits the generalisability of these results, we propose that future clinical studies would benefit from considering such methodological planning of SBTM intervention, for maximising of intervention outcomes. Larger samples may reveal arm swinging asymmetries alterations to match SBTM adaptation patterns. Finally, further research is warranted to study post-adaption effects in order to define optimal adaptation schemes to maximise the therapeutic effect of SBTM based interventions.

Studying cognitive-motor interactions using a tablet-based application of the Color Trails Test.

The Color Trails Test (CTT) is a pen and paper (P&P) test designed to measure cognitive function. The test consists of two parts that evaluate primarily sustained visual attention (Trails A) and divided attention (Trails B). Based on clinical interest in converting neuropsychological testing from P&P to computerized testing, we developed a digital version of the CTT ('Tablet-CTT'). Twenty-four young, healthy participants performed Trails A and B of both the original P&P and the Tablet-CTT. Hand kinematics were calculated using the continuous location of an electronic pen on the tablet touch screen. To compare motor control aspects, we differentiated for each test session the 'movement planning' and 'movement execution' times (accumulated across all single target-to-target trajectories). Concurrent validity was demonstrated by the high correlation between completion times of the P&P and Tablet-CTT, in both Trails A (r = 0.6; p < 0.005) and Trails B (r = 0.8; p < 0.001). Trails B yielded significantly longer completion times in both formats (p < 0.001). Examining hand kinematics in Tablet-CTT revealed that the difference in durations was mostly due to prolonged planning time, but also due to significantly lower execution velocity in Trails B (p < 0.001). Lastly, we found increased hand velocity during the planning phase in Trails B compared to Trails A (p < 0.001). This study demonstrates how transforming the CTT to a digital platform could be useful for studying cognitive-motor interactions in healthy individuals. Moreover, it could potentially serve as a diagnosis tool by introducing a more comprehensive testing method that incorporates online recordings of hand movements.

Adaptation of bilateral coordination of gait during split belt walking as reflected by the phase coordination index.

BACKGROUND: The Split belt treadmill (SBTM) has recently been used in research and rehabilitation to study and utilize gait adaptations. The Phase coordination index (PCI) is useful in assessing bilateral coordination of gait by quantifying the consistency and accuracy in generating the anti-phased left-right stepping pattern. Recently we proposed that 23 strides are sufficient to reliably characterize PCI values from regular over ground and treadmill walking RESEARCH QUESTION: Can we detect the effect of SBTM on PCI using only 23 gait cycles also from SBTM walking? METHODS: Young healthy participants (n = 13) with right side motor dominance performed SBTM walking trials. Experiment protocol began by walking in tied belt (TB) mode, followed by an incremental speed increase of one of the belts by 50 % - split belt (SB) mode. This was performed for each side. Two 1-minute segments were analyzed per participant, TB and SB. PCI analysis was carried out upon fewer strides (n = 23) and compared to PCI that was obtained based on all available strides (n = 56 ± 5). RESULTS: Clear SBTM walking effects on PCI were seen in both experiments, for example, PCI increased from 4.46 ± 1.5 % (TB) to 10.07 ± 3.6 % (SB) for left belt speed increase. Twenty three strides from each trail were sufficient to demonstrate the effect. SIGNIFICANCE: PCI can be a useful metric to characterize changes in bilateral coordination of gait during SBTM gait adaptations. The fact that 23 strides are sufficient for its reliable estimation, contribute to the continued monitoring through the adaptation process (i.e., by using time windows).

Patterns of whole-body muscle activations following vertical perturbations during standing and walking.

BACKGROUND: Falls commonly occur due to losses of balance associated with vertical body movements (e.g. reacting to uneven ground, street curbs). Research, however, has focused on horizontal perturbations, such as forward and backward translations of the standing surface. This study describes and compares muscle activation patterns following vertical and horizontal perturbations during standing and walking, and investigates the role of vision during standing postural responses. METHODS: Fourteen healthy participants (ten males; 27±4 years-old) responded to downward, upward, forward, and backward perturbations while standing and walking in a virtual reality (VR) facility containing a moveable platform with an embedded treadmill; participants were also exposed to visual perturbations in which only the virtual scenery moved. We collected bilateral surface electromyography (EMG) signals from 8 muscles (tibialis anterior, rectus femoris, rectus abdominis, external oblique, gastrocnemius, biceps femoris, paraspinals, deltoids). Parameters included onset latency, duration of activation, and activation magnitude. Standing perturbations comprised dynamic-camera (congruent), static-camera (incongruent) and eyes-closed sensory conditions. ANOVAs were used to compare the effects of perturbation direction and sensory condition across muscles. RESULTS: Vertical perturbations induced longer onset latencies and shorter durations of activation with lower activation magnitudes in comparison to horizontal perturbations (p<0.0001). Downward perturbations while standing generated earlier activation of anterior muscles to facilitate flexion (for example, p=0.0005 and p=0.0021 when comparing the early activators, rectus femoris and tibialis anterior, to a late activator, the paraspinals), whereas upward perturbations generated earlier activation of posterior muscles to facilitate extension (for example, p<0.0001 and p=0.0004, when comparing the early activators, biceps femoris and gastrocnemius, to a late activator, the rectus abdominis). Static-camera conditions induced longer onset latencies (p=0.0085 and p<0.0001 compared to eyes-closed and dynamic-camera conditions, respectively), whereas eyes-closed conditions induced longer durations of activation (p=0.0001 and p=0.0008 compared to static-camera and dynamic-camera, respectively) and larger activation magnitudes. During walking, downward perturbations promptly activated contralateral trunk and deltoid muscles (e.g., p=0.0036 for contralateral deltoid versus a late activator, the ipsilateral tibialis anterior), and upward perturbations triggered early activation of trunk flexors (e.g., p=0.0308 for contralateral rectus abdominis versus a late activator, the ipsilateral gastrocnemius). Visual perturbations elicited muscle activation in 67.7% of trials. CONCLUSION: Our results demonstrate that vertical (vs. horizontal) perturbations generate unique balance-correcting muscle activations, which were consistent with counteracting vertical body extension induced by downward perturbations and vertical body flexion induced by upward perturbations. Availability of visual input appears to affect response efficiency, and incongruent visual input can adversely affect response triggering. Our findings have clinical implications for the design of robotic exoskeletons (to ensure user safety in dynamic balance environments) and for perturbation-based balance and gait rehabilitation.

Multimodal immersive trail making-virtual reality paradigm to study cognitive-motor interactions.

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.

Novel methodology for assessing total recovery time in response to unexpected perturbations while walking.

Walking stability is achieved by adjusting the medio-lateral and anterior-posterior dimensions of the base of support (step length and step width, respectively) to contain an extrapolated center of mass. We aimed to calculate total recovery time after different types of perturbations during walking, and use it to compare young and older adults following different types of perturbations. Walking trials were performed in 12 young (age 26.92 ± 3.40 years) and 12 older (age 66.83 ± 1.60 years) adults. Perturbations were introduced at different phases of the gait cycle, on both legs and in anterior-posterior or medio-lateral directions, in random order. A novel algorithm was developed to determine total recovery time values for regaining stable step length and step width parameters following the different perturbations, and compared between the two participant groups under low and high cognitive load conditions, using principal component analysis (PCA). We analyzed 829 perturbations each for step length and step width. The algorithm successfully estimated total recovery time in 91.07% of the runs. PCA and statistical comparisons showed significant differences in step length and step width recovery times between anterior-posterior and medio-lateral perturbations, but no age-related differences. Initial analyses demonstrated the feasibility of comparisons based on total recovery time calculated using our algorithm.

Seeing Gravity: Gait Adaptations to Visual and Physical Inclines - A Virtual Reality Study.

Using advanced virtual reality technology, we demonstrate that exposure to virtual inclinations visually simulating inclined walking induces gait modulations in a manner consistent with expected gravitational forces (i.e., acting upon a free body), suggesting vision-based perception of gravity. The force of gravity critically impacts the regulation of our movements. However, how humans perceive and incorporate gravity into locomotion is not well understood. In this study, we introduce a novel paradigm for exposing humans to incongruent sensory information under conditions constrained by distinct gravitational effects, facilitating analysis of the consistency of human locomotion with expected gravitational forces. Young healthy adults walked under conditions of actual physical inclinations as well as virtual inclinations. We identify and describe 'braking' and 'exertion' effects - locomotor adaptations accommodating gravito-inertial forces associated with physical inclines. We show that purely visual cues (from virtual inclinations) induce consistent locomotor adaptations to counter expected gravity-based changes, consistent with indirect prediction mechanisms. Specifically, downhill visual cues activate the braking effect in anticipation of a gravitational boost, whereas uphill visual cues promote an exertion effect in anticipation of gravitational deceleration. Although participants initially rely upon vision to accommodate environmental changes, a sensory reweighting mechanism gradually reprioritizes body-based cues over visual ones. A high-level neural model outlines a putative pathway subserving the observed effects. Our findings may be pivotal in designing virtual reality-based paradigms for understanding perception and action in complex environments with potential translational benefits.

Virtual reality-based cognitive-motor training for middle-aged adults at high Alzheimer's disease risk: A randomized controlled trial.

INTRODUCTION: Ubiquity 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. METHODS: The 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. DISCUSSION: Current 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.

A Novel Treatment of Fear of Flying Using a Large Virtual Reality System.

BACKGROUND: Fear of flying (FoF), a common phobia in the developed world, is usually treated with cognitive behavioral therapy, most efficiently when combined with exposure methods, e.g., virtual reality exposure therapy (VRET). We evaluated FoF treatment using VRET in a large motion-based VR system. The treated subjects were seated on a moving platform. The virtual scenery included the interior of an aircraft and a window view to the outside world accompanied by platform movements simulating, e.g., takeoff, landing, and air turbulence. Relevant auditory stimuli were also incorporated. CASE REPORT: Three male patients with FoF underwent a clinical interview followed by three VRETs in the presence and with the guidance of a therapist. Scores on the Flight Anxiety Situation (FAS) and Flight Anxiety Modality (FAM) questionnaires were obtained on the first and fourth visits. Anxiety levels were assessed using the subjective units of distress (SUDs) scale during the exposure. All three subjects expressed satisfaction regarding the procedure and did not skip or avoid any of its stages. Consistent improvement was seen in the SUDs throughout the VRET session and across sessions, while patients' scores on the FAS and FAM showed inconsistent trends. Two patients participated in actual flights in the months following the treatment, bringing 12 and 16 yr of avoidance to an end. DISCUSSION: This VR-based treatment includes critical elements for exposure of flying experience beyond visual and auditory stimuli. The current case reports suggest VRET sessions may have a meaningful impact on anxiety levels, yet additional research seems warranted.

Self-selected gait speed--over ground versus self-paced treadmill walking, a solution for a paradox.

BACKGROUND: The study of gait at self-selected speed is important. Traditional gait laboratories being relatively limited in space provide insufficient path length, while treadmill (TM) walking compromises natural gait by imposing speed variables. Self-paced (SP) walking can be realized on TM using feedback-controlled belt speed. We compared over ground walking vs. SP TM in two self-selected gait speed experiments: without visual flow, and while subjects were immersed in a virtual reality (VR) environment inducing natural visual flow. METHODS: Young healthy subjects walked 96 meters at self-selected comfortable speed, first over ground and then on the SP TM without (n=15), and with VR visual flow (n=11). Gait speed was compared across conditions for four 10 m long segments (7.5 - 17.5, 30.5 - 40.5, 55.5 - 65.5 and 78.5-88.5 m). RESULTS: During over ground walking mean (± SD) gait speed was equal for both experimental groups (1.50 ± 0.13 m/s). Without visual flow, gait speed over SP TM was smaller in the first and second epochs as compared to over ground (first: 1.15 ±0.18 vs. second: 1.53 ± 0.13 m/s; p<0.05), and was comparable in the third and fourth (1.45 ± 0.19 vs. 1.49 ± 0.15 m/s; p>0.3). With visual flow, gait speed became comparable to that of over ground performance already in the first epoch (1.43 ± 0.22 m/s; p>0.17). Curve fitting analyses estimated that steady state velocity in SP TM walking is reached after shorter distanced passed with visual flow (24.6 ± 14.7 m) versus without (36.5 ± 18.7 m, not statistically significant; p=0.097). Steady state velocity was estimated to be higher in the presence of visual flow (1.61 ± 0.17 m/s) versus its absence (1.42 ± 1.19 m/s; p<0.05). CONCLUSIONS: The SP TM walking is a reliable method for recording typical self-selected gait speed, provided that sufficient distance is first passed for reaching steady state. Seemingly, in the presence of VR visual flow, steady state of gait speed is reached faster. We propose that the gait research community joins forces to standardize the use of SP TMs, e.g., by unifying protocols or gathering normative data.

Balance maintenance as an acquired motor skill: Delayed gains and robust retention after a single session of training in a virtual environment.

Does the learning of a balance and stability skill exhibit time-course phases and transfer limitations characteristic of the acquisition and consolidation of voluntary movement sequences? Here we followed the performance of young adults trained in maintaining balance while standing on a moving platform synchronized with a virtual reality road travel scene. The training protocol included eight 3 min long iterations of the road scene. Center of Pressure (CoP) displacements were analyzed for each task iteration within the training session, as well as during tests at 24h, 4 weeks and 12 weeks post-training to test for consolidation phase ("offline") gains and assess retention. In addition, CoP displacements in reaction to external perturbations were assessed before and after the training session and in the 3 subsequent post-training assessments (stability tests). There were significant reductions in CoP displacements as experience accumulated within session, with performance stabilizing by the end of the session. However, CoP displacements were further reduced at 24h post-training (delayed "offline" gains) and these gains were robustly retained. There was no transfer of the practice-related gains to performance in the stability tests. The time-course of learning the balance maintenance task, as well as the limitation on generalizing the gains to untrained conditions, are in line with the results of studies of manual movement skill learning. The current results support the conjecture that a similar repertoire of basic neuronal mechanisms of plasticity may underlay skill (procedural, "how to" knowledge) acquisition and skill memory consolidation in voluntary and balance maintenance tasks.