Virtual Reality Tools for Assessing Unilateral Spatial Neglect: A Novel Opportunity for Data Collection
March 10th, 2021
The goal was to design, build, and pilot a novel virtual reality task to detect and characterize unilateral spatial neglect, a syndrome affecting 23-46% of acute stroke survivors, expanding the role of virtual reality in the study and management of neurologic disease.
Our protocol, investigators can design and validate novel virtual reality tools to assist in the diagnosis and characterization of unilateral spatial neglect. This technique provides a broad array of data sets for the study of unilateral spatial neglect. It also avoids possible confounding effects seen in studies of patients with acquired brain injury.
Better characterization of unilateral spatial neglect can facilitate the delivery of therapy to patients with subtle but still debilitating deficits and potentially improve their overall recovery. Demonstrating the procedure will be Sam Cason and Peter Schwab, researchers from my laboratory. To perform the Line Bisection test have the subject sit at a table directly across from the tester and provide the subject with a writing utensil and the stimulus sheet ensuring that the sheet is placed directly in front of the subject.
Instruct the subject to quickly and accurately bisect each line printed on the stimulus sheet as close to the middle of each line as possible while keeping their head and shoulders centered as much as possible. To perform the Bells Test provide the subject with the Bells Test stimuli sheet and instruct the subject to circle or cross out all of the bells on the sheet as quickly and accurately as possible while keeping their head and shoulders as centered. To perform the star cancellation test present the subject with the stimulus sheet ensuring that it is placed directly in front of them and instruct the subject to circle or cross out all of the stars on the stimulus sheet as quickly and accurately as possible with their head and shoulders centered.
To perform the Otas circle cancellation test provide the subject with the Otas circle cancellation stimulus sheet and instruct the subject to cross out or circle all of the open incomplete circles as quickly and as accurately as possible with their head and shoulders as centered. Before the first TMS session upload the subject's 3TT1 MRI scan into the neuro navigational software and create a 3D representation of the subject's brain. During the first session, have the subject sit in front of an optical tracking camera and use a headband or glasses to place a tracker on the subject.
Attach one disposable disc electrode on the subject's right dorsal interosseous, one disc electrode to the subject's second knuckle on the right pointer finger and one ground electrode to the subject's right wrist, right hand, and wrist. Plug the electrodes into an electrode adapter that inputs into an MEP tracking software program and select, new online session to open the subject's project within the neuro navigational software. Select the targets to be stimulated in this session and using a pointer registered to the neuro navigational software touch the subject's face in the same locations that the landmarks were placed.
Open the validation tab in the software and use the pointer to touch the subject in various spots on the head, ensuring that the cross hairs on the screen line up with the spot being pointed to on the subject. Plug a handheld TMS coil into the TMS machine and turn on the TMS machine. Set the instrument to single pulse and set an appropriate stimulation intensity.
Placing the handheld TMS coil on the left side of the subject's head, deliver stimuli to the motor cortex using TMS single pulses. To identify the location that stimulates the first dorsal interosseous. Alter the stimulation intensity until the stimulation elicits MEP's of at least 50 millivolts exactly five out of 10 times.
This intensity is considered the resting motor threshold. Replace the handheld coil with an air cooled TMS coil with a built-in cooling system targeting the SMG or STG for active sessions or the vertex for sham sessions and set the stimulation parameters to repetitive TMS at a rate of one Hertz for 20 minutes at a 110%intensity of the resting motor threshold. Then start stimulation of the target of interest.
To perform the virtual reality behavior test place the VR headset onto the seated subject's head with the straps secured tightly but comfortably. Give the subject both controllers and ensure that both eyes are visible by visually confirming they are centered in the pupil core software camera feeds. In the unity editor, open the virtual reality task and press the play button.
Ask the subject to look straight ahead and click the tear camera button. Click the begin tutorial button and wait for the subject to complete the tutorial. When subject is finished, click the calibrate eye tracking button and click next trial to begin the first trial.
When the subject has completed the trial click the play button again to end the task. In this analysis the average head angle was examined to determine whether the virtual reality task was sensitive enough to identify a difference between the SMG and STG groups. ANCOVA analysis of head angle differences between groups revealed a significant difference in head angle change scores between the pre and post TMS groups.
This finding from the virtual reality task is consistent with the results of the traditional paper and pencil task as both demonstrated a pattern in which the SMG group may have had a subtle neglect and looked more toward the right compared to the STG group. To specifically assess for signs of allocentric neglect on an individual target level flowers can be separated by which side of the flower contains the defective petals. In this analysis, participants in the SMG group had a tendency to look further to the right at a higher flower to head angle when searching for the short petal on the right side of the flower compared to the angle observed when the short petals were on the left side of the flower.
When the average number of seconds that participants looked at each flower were analyzed no significant difference in mean head angle change score was observed between the SMG and STG groups. This method is limited by the subtle clinical effects achieved with repetitive transcranial magnetic stimulation. So proper stimulation parameters in cortical region targeting are critical.
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Overview
This study focuses on the design and validation of a novel virtual reality task aimed at detecting and characterizing unilateral spatial neglect, a condition prevalent among stroke survivors. The approach aims to enhance the understanding and management of this neurological syndrome.
Key Study Components
Area of Science
- Neuroscience
- Virtual Reality Applications
- Stroke Rehabilitation
Background
- Unilateral spatial neglect affects 23-46% of acute stroke survivors.
- Current diagnostic methods may have confounding effects.
- Virtual reality offers a new avenue for assessment and therapy.
- Improved characterization can lead to better therapeutic outcomes.
Purpose of Study
- To develop a virtual reality tool for diagnosing unilateral spatial neglect.
- To provide comprehensive data sets for research on the syndrome.
- To facilitate targeted therapy for patients with subtle deficits.
Methods Used
- Designing a virtual reality task for assessment.
- Conducting the Line Bisection test with subjects.
- Collecting data to analyze neglect characteristics.
- Involving researchers Sam Cason and Peter Schwab in the demonstration.
Main Results
- Successful implementation of the virtual reality task.
- Collection of diverse data sets for unilateral spatial neglect.
- Identification of subtle deficits in stroke survivors.
- Potential for improved recovery outcomes through targeted therapy.
Conclusions
- The virtual reality tool shows promise for diagnosing unilateral spatial neglect.
- It may reduce confounding variables in patient assessments.
- Further research could enhance therapeutic strategies for stroke survivors.
Frequently Asked Questions
Executive Industry Relevance
This study demonstrates how virtual reality can be used to model and assess unilateral spatial neglect, a neurological condition relevant to stroke recovery. By combining VR with targeted TMS, researchers can isolate and quantify specific visuospatial deficits in controlled settings. This approach supports mechanistic de-risking in preclinical neuroscience research and offers a scalable platform for evaluating potential therapeutic interventions.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of neural circuits involved in visuospatial attention through controlled induction of neglect-like symptoms.
- Operational Value: Provides a reproducible method to assess functional outcomes following neuromodulation interventions.
Screening & Assay Development
- Scientific Value: Generates quantitative behavioral readouts such as head yaw and visual axis deviation for objective symptom tracking.
- Operational Value: Supports assay standardization through dynamic difficulty adjustment and automated data collection in immersive environments.
Translational & Preclinical Research
- Scientific Value: Models acquired brain injury deficits in healthy subjects, improving predictive validity for therapeutic screening.
- Operational Value: Bridges discovery and preclinical workflows by validating VR-based biomarkers of attentional function.
Pipeline & Workflow Integration
The VR-TMS paradigm fits within early discovery to preclinical transition, offering a platform for target engagement and functional readout validation.
- Discovery Biology: Supports hypothesis testing of cortical targets (STG, SMG) in attentional networks through measurable behavioral changes.
- Screening: Enables high-fidelity, repeatable assessment of neuromodulatory effects on spatial cognition.
- Analytics: Delivers continuous, quantitative metrics (head angle, gaze direction) for group comparisons and dose-response modeling.
- Translational Research: Aligns with clinical neglect symptomatology, supporting continuity from artificial models to patient-relevant outcomes.
- Enterprise Reuse: Establishes a reusable VR neuroscience platform applicable across multiple CNS target validation programs.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence by reducing confounding variables inherent in patient studies.
- Operational Value: Enhances reproducibility and scalability of neuropsychological assessments through standardized VR environments.
- Strategic Value: Improves go/no-go decision-making by providing early, translatable functional data on CNS targets.
- Portfolio Impact: Enables risk-adjusted prioritization of neuromodulation targets based on objective behavioral de-risking.
Implementation Considerations
- Expertise in neuroscience, virtual reality development, and TMS administration is required.
- Instrumentation includes VR headsets with eye tracking, TMS systems, and neuro-navigation software.
- Cross-team standardization is needed for stimulus design, performance thresholds, and data analysis protocols.
- Adaptation across model systems depends on validity of neglect-like phenotypes and homologous cortical targeting.
- Practical limitations include subtlety of induced effects and dependence on precise stimulation parameters.
