The study was conducted at the Heller Institute of Medical Research (The Institute for Military Physiology) and the Center of Advanced Technologies in Rehabilitation (CATR), both located at the Sheba Medical Center in Israel.
The study was primarily designed to assess the feasibility of a VR environment-based protocol that simultaneously exposes participants to physical and cognitive demands. While the protocol includes several novel elements, the focus was on comparing new cognitive tasks presented in the context of simulated loaded military missions to conventional, validated cognitive tests (primary objective). We also conducted a pilot study to assess the effects of cognitive load during a strenuous simulated 2 hour march (pre-mission effort) on physical and cognitive performance after the exposure (secondary objective). We used a crossover trial design, with participants undergoing three activity sessions in random order, each comprising one of the following conditions: simultaneous physical and cognitive load (Phys+Cog condition), physical load only (Phys condition), and rest. For our primary objective, the outcome measure was correlation between the new VR-based cognitive tasks (during the Phys+Cog condition; see Protocol below) and a cognitive testing battery presented prior to and following the Phys+Cog condition. For the secondary objective, we conducted a within-subject pre-post comparison to determine the effects of the activity conditions on physical and cognitive performance.
Twelve healthy civilians were recruited in accordance with the following inclusion criteria: 1) male; 2) 21-30 years old; 3) served in a combat position in the military, during which they experienced loaded marches; 4) self-declared ability to endure 10-km forced walking while carrying a substantial load in a backpack; 5) above average aerobic ability (maximal oxygen uptake, VO2max, above 42.4 ml/kg/min; (18)). Exclusion criteria included any orthopedic or other health issues. Mean (±SD) values of the demographic variables for included participants were as follows: age 23.9±2.0 years; weight 72.0±7.5 kg; height 170±5 cm; BMI 24.9±1.8 kg/m2; VO2max 58.3±7.9 ml/kg/min.
Participants were informed about the study's purpose and possible risks. Their final inclusion in the study was subject to medical clearance by the study's physician and signing of an informed consent form. The study was approved by the Human Use Committee of the Sheba Medical Center (SMC-2664-15) and by the Medical Corps (IDF- 1526-15).
We used the Computer Assisted Rehabilitation Environment (CAREN; Motek Medical©, Amsterdam, the Netherlands) high-end system. The system consists of a moveable platform (3m diameter) with six degrees of freedom of movement (translations and rotations). A dual-belt instrumented treadmill is embedded within the platform. This installation is placed in a dome-shaped space. A virtual visual scene is projected on the interior surface of the dome using eight projectors, creating a 360° visual display that provides a sensation of full immersion and visual depth perception. A surround sound system provides auditory stimuli congruent with the scenery. The visual flow is synchronized with the speed of the treadmill (Figure 1).
First, each participant was invited to a preparatory visit, during which his height and weight were recorded, backpack size and weight were adjusted (see Supplementary File 1, Section 1), and a VO2max test was performed (see Supplementary File 1, Section 2 for test description). Height (cm) was measured using a stadiometer (ADE, Germany; result ±1 cm), and body mass (kg) was measured using an electronic flat scale (SECA, 803 model, Germany; result ±100g). VO2max (ml/kg/min) was measured using a continuous uphill stepwise treadmill-modified Bruce protocol (19). During the VO2max test, we recorded heart rate (HR; bpm) using the Polar RS800CX heart rate monitor (Polar®, Finland). In addition, participants were familiarized with one of the baseline cognitive evaluations (SYNWIN battery, see below); they repeated the test five times with 5-minute breaks between consecutive tests. Then, as noted above, participants attended three separate activity visits, undergoing one the following protocols in each (in random order): Phys+Cog, Phys only, and rest. The physical component was a 10 km treadmill march (see details below). During the rest visit, participants sat in a room for 2 hours, during which they were exposed only to non-demanding activities such as reading a book. The time interval between visits ranged from 7 to 14 days, based on participant availability.
Each visit included the following components: a. baseline (pre-activity) assessment (see details below); b. exposure to two hours of activity/rest; and c. post-activity assessment (see details below). The pre-activity assessment included cognitive evaluation only, and the post-activity assessment included cognitive and physical evaluations. During each visit, the participants' heart rate was continuously monitored using a Polar RS800 watch with chest belt (Polar Electro, Finland), which measured the R-R time intervals.
Participants were asked to arrive to each visit in shoes and clothing suitable for athletic activity. By combining treadmill operation profiles (speed and inclinations) with congruent visual flow speed, we simulated a 10 km march at a speed of 5 km/h and 1.15° slope (2% grade) in hilly Mediterranean terrain with nearby and distant villages (Figure 1; see also video in Supplementary File 2). To simulate diverse terrain, every 20 minutes the treadmill slope increased to 3.4° (6% grade) for 5 minutes and then returned to the original slope. The duration of the march was exactly 2 hours. This is similar to the march settings used in previous research (11).
Participants were secured to the system in a manner that did not limit their mobility or cause discomfort (see Figure 1 and video in Supplementary File 2). They walked while carrying a backpack weighing 30% of their body weight.
In the Phys+Cog condition, participants also carried a two-way radio transceiver (walkie-talkie). Participants also had access to a drinking bag containing cold water, which was placed near the treadmill and not carried.
Context-related cognitive tasks during the march
In the Phys+Cog condition, participants performed cognitive tasks that simulated military tasks while marching, including: navigating, detecting and reporting “enemy forces” and static and dynamic objects of interest, and memorizing the status of allied forces to which they were exposed via ongoing radio transmission.
Prior to marching, participants memorized for two minutes the navigation route based on a map simulating aerial photos of the environment (Figure 2A). Though the map was available for use during the march, they were encouraged to rely on memory as much as possible and were notified that they would be scored accordingly. The route consisted of a number of straight walking intervals of different lengths, separated by 90° left and right turning points. The turning points were marked with noticeable landmarks, e.g., wells, road boards and old barrels, etc. These landmarks were also indicated on the map (Figure 2B).
Navigation was conducted by choosing a direction to turn (left or right) once a landmark was identified (total of five navigation decision points). The signal to turn was given by pointing a stick with a reflective marker attached to it, which was captured by a motion capture system (Vicon, Oxford, UK; sampling rate 120 Hz). Immediately after the participant pointed to one direction, the visual scenery rotated accordingly to create the illusion of turning. If a participant chose wrong, the visual scenery rotated by 180 after 10 seconds and the participant was informed of his mistake. Feedback was consistently provided using these methods to prevent a cumulative effect from previous mistakes (see the VR-based navigation process in the video in Supplementary File 2). Scoring: each navigation decision was given a score of 1 (correct decision) or 0 (incorrect decision/did not identify the turn/looked at the map), such that total score could range from 0 to 5.
This task primarily involved the following three cognitive functions (20)
(1) Visual and spatial memory – to memorize which land mark is associated with which turning direction.
(2) Attention and visuospatial skill – to continuously scan the changing VRE in search of memorized landmarks.
(3) Spatial orientation – to compare real landmarks to symbolic landmarks presented on the map, a cognitive task requiring spatial orientation and two dimensional to three dimensional translation.
Detection and reporting of visual elements (‘visual’)
Prior to the march, participants were informed that while they were walking, different objects would appear in the environment (“in the sky and on the sides of the road”), such as fighter jets, armored fighting vehicles (tanks), steel figure targets (simulating hostile combatants), and villages (see Figure 3 and video in Supplementary File 3 for visual examples). Participants were instructed to identify these objects and memorize specific information about them, such as the number and flight direction of jets (see explanation on VR compass below), the number of figure targets or armored fighting vehicles and the side on which they appeared, the number of turrets in the villages and the side of the terrain in which they appeared. To avoid misidentification, participants were shown pictures of the target objects prior to the march. Fighter jets were accompanied by a compass rose (projected on the screen in the participant’s walking direction), making it easier for participants to identify their flying direction. In addition, to alert participants that jets would be passing and to improve immersion, the jets were accompanied by actual recorded jet sounds. To evaluate participant performance of these detection tasks (in a pre-defined order), the experimenter used pre-recorded questions to ask participants to report information, via the two-way radio, regarding specific, previously seen objects. When reporting detection of armored vehicles and targets, participants had to indicate the side of the road on which they appeared. No feedback was provided as to whether responses were correct or incorrect. Scoring: each detection question was given a score of 2 (full correct), 1 (partial correct), or 0 (incorrect), such that total score could vary between 0 and 32.
This task primarily involved the following three cognitive functions:
(1) Visual scanning – to identify all of the aforementioned elements that were not accompanied by sound.
(2) Spatial orientation – to determine the flight direction of the fighter jets based on the virtual compass.
(3) Short term memory (21) – to store accumulated information for a few minutes and retrieve it upon request (e.g., radio call from field headquarters).
[Place Figure 3 about here]
Memorizing status of other allied forces (‘Calc&Mem’)
Participants were informed that there were three 30-soldier allied units walking in parallel to them, identified as the green, blue, and red units. They were also informed that they would occasionally be given updates (using the two-way radio) on the status of these forces. Each report included information about one of the units, for example, “three soldiers from the red unit have been wounded and evacuated” or, “five new soldiers have joined the blue unit.” Periodically, participants were asked to provide status reports regarding the current number of soldiers in each unit, requiring them to perform calculations upon receiving the information and to memorize the updated numbers continuously throughout the march. No feedback was provided as to whether their responses were correct or incorrect. To prevent carry-over from previous mistakes, participant reports were judged (in a post-hoc evaluation) based only on the most recent responses.
Scoring: each report was given a score of 1 (correct report) or 0 (incorrect report), such that total score could vary between 0 and 9.
This task primarily involved the following three cognitive components (22):
(1) Working memory – to continuously store information from updates on the number of soldiers in the three different allied units and periodically retrieve it to report current numbers.
(2) Short-term memory – to store the accumulated information for a few minutes and retrieve it upon request (call from field headquarters).
(3) Mathematical calculations – to add or subtract numbers to/from an existing sum.
Pre-activity and post-activity cognitive assessments
The following validated neurocognitive tasks were administered before and after the three physical activity sessions:
(1) The color version of the Trail Making Test (TMT; (23,24,25), also known as the Color Trails Test (CTT), which assesses selective attention, visual and perceptual tracking abilities, and working memory (23,24,25).
(2) The Synthetic Work Environment (SYNWIN) computerized test battery, which assesses short-term memory, working memory, cognitive concentration, visual perception, multitasking, reaction time, and data processing (26). The full battery comprises four sub-tasks, presented simultaneously in a 5-minute session: a simple memory task, an arithmetic computation task, a visual monitoring task, and an auditory monitoring task. However, in the current study, we did not use the auditory monitoring task due to technical issues, as participants were not able to clearly hear tones produced by the software. The SYNWIN battery has been used in past trials to investigate the effects of various tasks and environmental factors on cognitive performance (26,27,28,29,30).
To minimize learning effects while performing this battery, participants repeated the battery several times during the baseline visit. After confirming that no further score improvement was observed, the participant moved ahead with the protocol. No more than 5 repetitions were required to reach this stage.
(3) A VR version of the CTT test (17), the results of which are reported elsewhere in this issue.
Post-activity physical evaluation
We used the time to exhaustion (TTE) test only in the post-activity physical assessment, after 30 minutes of rest (during which the post-activity cognitive evaluation was conducted). The TTE [modified according to (11)] is conducted using a motor-driven treadmill, as follows: after a 2-minute warm-up (5 km/h, 2% slope), the pace and inclination was increased to match the participant's anaerobic threshold intensity (calculated from the VO2max test, see Supplementary File 1) and maintained for 15 minutes. If the participant managed to sustain this 15-minute stage continuously, the pace was kept constant while the inclination was elevated by 2% every 4 minutes until the participant reached subjective exhaustion. While performing the TTE test, a silicone mask was placed on the participant’s face to measure respiratory values and adjusts the intensity to match his pre-defined anaerobic threshold, until he completed the first 15-min stage. The primary outcome of the TTE test was the maximum running time achieved.
Outcome Measures and Data Analysis
Outcome measures for the primary objective
We evaluated the correlations between participant scores on the validated cognitive tests and their scores on the new ecological cognitive assessment administered during the simulated march in the VR environment (VR-COG). We checked correlations with both the pre-activity and post-activity scores on the validated cognitive tests. We also examined potential prediction of post-activity cognitive performance based on VR-COG scores.
CTT outcome measures include Part A execution time (CTTA), which measures visual and perceptual tracking and sustained attention, and Part B execution time (CTTB), which measures working memory, divided attention, sequencing skills, inhibitory control, and cognitive flexibility (23,31,32). To evaluate the effect of activity, the difference between post-activity score and pre-activity score was calculated for each part of the task (ΔCTTA, ΔCTTB).
The SYNWIN produces a composite score based on performance in the three sub-tasks (a simple memory task, ‘Memory,’ an arithmetic computation task, ‘Math,’ and a visual monitoring task, ‘Visual’). To evaluate the effect of activity, the differences post-activity and pre-activity SYNWIN total and sub-task scores were calculated (SYNWIN ΔScore, ΔMemory, ΔMath, and ΔVisual monitoring).
The VR-COG outcome measures included total score for each cognitive task (navigating, detection and reporting of static and dynamic objects, and memorizing). A composite score was calculated based on all tasks using a weighted average (in accordance with the number of task-related questions that were presented to the participants).
Outcomes measures for the secondary objective
The pre-activity and post-activity cognitive and physical performance scores for all three sessions are compared and reported as preliminary data, as customary in pilot validation studies.
Means ± standard deviations (SD) are presented. To address the study primary objective of validating the new VR-COG assessments, we used Pearson correlations between the VR-COG scores and the pre-activity and post-activity cognitive assessment scores. A multiple linear regression was conducted in an attempt to predict the SYNWIN ΔScore based on the VR-COG and pre-activity CTT scores.
To address the study secondary objective, we used a Time (pre-activity and post-activity) by Condition (three visit types) repeated measures ANOVA. Post hoc pairwise comparisons were performed using Bonferroni correction (n = 3).
To evaluate participant fatigue in response to the different experimental conditions, a repeated measures ANOVA was used to compare time to subjective exhaustion during the TTE running test. Post hoc pairwise comparisons were performed using Bonferroni correction (n = 3).
Pearson correlation analysis was used to assess the correlation between HR at rest and post-rest TTE score.
Statistical significance level was set at α = 0.05; analyses was conducted on SPSS software (SPSS Ver. 24, IBM).