Movement perception in Functional Neurological Disorder (FND)

Lead Research Organisation: The University of Manchester
Department Name: School of Biological Sciences

Abstract

Functional Neurological Disorder (FND) is a common, debilitating condition often causing problems with movement and balance. It is second only to headaches as a reason for referral to a neurologist, however, it is little understood and treatments are limited, leaving people with FND with few options. In this project we will study FND from a new perspective, suggesting movement symptoms might arise due to problems with the brain systems that help us to:

i) Perceive movement in our environment from the motion arising on the back of the eye (the retina)
ii) Control our movement through the environment.

The second of these activities obviously requires the brain to estimate how we are moving, which involves combining self-movement information appropriately from a range of senses (including vision together with balance information from the inner ear). However, the first activity also relies on knowing about self-movement - the brain cannot assess how other parts of the environment are moving without taking into account our own movement first. For example, a traffic cone that is stationary in the environment will be moving on the retina if we drive past it. To establish that the cone is, in fact, 'world stationary' the brain needs to factor in and compensate for our own movement. The brain solves this this problem by rapidly predicting/estimating the motion on the retina due to self-movement and then compensating for this before interpreting the movement of other parts of the environment. Without this ability we would incorrectly interpret motion on the retina - stationary parts of the environment would seem to move and problems with balance and movement similar to those experienced in FND would follow.

With these issues in mind, we will test theories suggesting that FND movement symptoms arise from inappropriate combination of sensory information about self-movement and/or estimation and compensation for our self-movement when interpreting how other parts of the world are moving. We will focus on a subgroup of FND patients with Persistent Postural-Perceptual Dizziness (3PD), who experience particularly pronounced movement symptoms and use established experimental approaches to test our hypotheses. Crucially we will also use Virtual Reality (VR) technology, which allows us to break the relationship between self-movement and the retinal movement that normally accompanies it. Using well-established methods from sensory science we will measure (for each individual) the ability to: i) estimate self-movement and movement of other parts of the environment ii) compensate for self-movement; iii) combine different sensory information sources about self-movement. We can then consider how these measures differ in those with and without 3PD and how they might predict 3PD symptoms and problems in everyday movement tasks.

Having better understanding of the factors causing 3PD/FND movement symptoms, will then allow us to investigate novel VR-based therapies to reduce symptoms. For example, our pilot data suggest less compensation for self-movement in 3PD and we could counteract this by temporarily placing patients in VR environments where motion on the retina is slightly increased relative to what should normally accompany self-movement, gradually reducing this to normal over a period of time. Similarly, if we find that combination of self-movement information is altered in FND (e.g. too much emphasis placed on visual information) we could use VR to direct more attention towards the overlooked information source. Crucially, such approaches could be tailored to the individual.

We anticipate that our research will lead to significantly better understanding of the causes of FND/3PD and, subsequently, better and more targeted therapies. As a consequence we are confident that this work could rapidly translate into future studies demonstrating direct benefit for a large patient group with limited treatment options.

Technical Summary

Recent research on Persistent Perceptual Postural Dizziness (3PD), a subtype of Functional Neurological Disorder (FND), highlights two sensory information processing abnormalities. The first concerns a general change in predictive processing and/or interplay between feedforward and feedback sensory information. The second concerns altered sensory integration and, more specifically, suggests that atypical visual processing might be over-weighted when integrated with vestibular information. Crucially, prediction and integration mechanisms are vital for two ubiquitous perceptual tasks, namely estimating: i) self-movement (SM); ii) scene-relative movement (SRM) of other parts of the environment. We hypothesise that errors in prediction and integration supporting either or both of these tasks drive 3PD symptoms and will test these hypotheses using established methods from perceptual psychophysics together with Virtual Reality (VR) and Motion Capture technologies. In four work packages (WPs) we will:

WP1 - Characterise performance in 3PD relative to control participants in both SM and SRM visual estimation tasks.
WP2 - Investigate integration of visual and vestibular self-movement information for recovery of SM and SRM estimates using a standard cue conflict paradigm and compare this to optimal integration observed in healthy control participants.
WP3 - Investigate which metrics recovered in WP1-2 predict functional performance in a VR-based task involving avoiding obstacles in a cluttered virtual scene.
WP4 - Use what we have learned in WP1-3 to develop and test theoretically motivated targeted Virtual Reality (VR)-based therapies harnessing VR's power to break the natural relationship between observer movement and its visual consequences.

This work should lead to a step change in our understanding of the causal factors underpinning 3PD (& FND more generally) and highlight novel routes to targeted therapy.
 
Title Hear Me! 
Description An exhibition (from 1st-31st October 2024) at The University of Manchester, highlighting the invisible impact of hearing loss, tinnitus, and dizziness by showcasing the lived experiences of those affected. Hear Me! presents powerful personal stories, poetry, photography, and ink drawings, which bring to life the invisible challenges faced by many. STARDUST team member Debbie Cane was part of the organising team for this exhibition and led on the dizziness component. This was were designed to help raise general awareness of the lived experience of 3pd. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2024 
Impact The exhibition generated good feedback (see below) from attendees who were from both the student, patient and clinical communities .The event was accessed by around 100 people per day. Following on from this Debbie generated 3 posters that were designed to raise awareness during Balance Awareness Week and also to help GPs better understand how they could best support their patients. These materials were displayed at Withington Community hospital, the National Hospital of Neurology and Neurosurgery in London and also posted on the Meniere's Society's social media sites. Feedback from attendees: "The stories of people affected from dizziness are very comforting to read as someone who also suffers from dizziness. I really enjoyed reading about tinnitus as well - its great to read such a vivid description of people's lived experiences." "This was a really interesting exhibition with some impactful personal stories/artwork about deafness, tinnitus and dizziness." "I thought it was really powerful and thought provoking. It's not until you look at how patients with these conditions portray themselves/use art to express their conditions/ what it means to them, that you can truly start to understand the impact." 
URL https://sites.manchester.ac.uk/bmh-athena-swan/2024/08/22/hear-me/
 
Description PhD studentship for Neurologist Dr. Andrew Jones
Amount £15,000 (GBP)
Organisation Northern Care Alliance NHS Foundation Trust 
Sector Public
Country United Kingdom
Start 01/2025 
End 12/2027
 
Description Network of NHS sites/associated PIs 
Organisation Guy's and St Thomas' NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution The UoM research team (and PI/CI Paul Warren) are leading all aspects of this project. We are working with all the named trusts to recruit new patient participants and also to keep clinicians at each site aware of our research findings. We have had regular meetings with the team at each site to share preliminary data and update on progress as well as discuss new recruitment routes.
Collaborator Contribution Staff at each named trust are helping us to identify patient participants with appropriate symptoms. Each site has a designated PI who is a team member on this MRC-funded project. Team members at each site are providing appropriate expertise on FND/3PD Neurology in general. Team members at each site attend regular team meetings and feedback on preliminary data help to shape the project Team members at each site will contribute to all aspects dissemination of findings to academic, clinician and general populations.
Impact All outcomes associated with this project (detailed in other sections) have been facilitated by this collaboration either by sharing of knowledge/providing feedback between sites, or direct contribution to /leadership of outputs.
Start Year 2024
 
Description Network of NHS sites/associated PIs 
Organisation Manchester University
Department Biological Services Facility (BSF)
Country United States 
Sector Academic/University 
PI Contribution The UoM research team (and PI/CI Paul Warren) are leading all aspects of this project. We are working with all the named trusts to recruit new patient participants and also to keep clinicians at each site aware of our research findings. We have had regular meetings with the team at each site to share preliminary data and update on progress as well as discuss new recruitment routes.
Collaborator Contribution Staff at each named trust are helping us to identify patient participants with appropriate symptoms. Each site has a designated PI who is a team member on this MRC-funded project. Team members at each site are providing appropriate expertise on FND/3PD Neurology in general. Team members at each site attend regular team meetings and feedback on preliminary data help to shape the project Team members at each site will contribute to all aspects dissemination of findings to academic, clinician and general populations.
Impact All outcomes associated with this project (detailed in other sections) have been facilitated by this collaboration either by sharing of knowledge/providing feedback between sites, or direct contribution to /leadership of outputs.
Start Year 2024
 
Description Network of NHS sites/associated PIs 
Organisation Manchester University NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution The UoM research team (and PI/CI Paul Warren) are leading all aspects of this project. We are working with all the named trusts to recruit new patient participants and also to keep clinicians at each site aware of our research findings. We have had regular meetings with the team at each site to share preliminary data and update on progress as well as discuss new recruitment routes.
Collaborator Contribution Staff at each named trust are helping us to identify patient participants with appropriate symptoms. Each site has a designated PI who is a team member on this MRC-funded project. Team members at each site are providing appropriate expertise on FND/3PD Neurology in general. Team members at each site attend regular team meetings and feedback on preliminary data help to shape the project Team members at each site will contribute to all aspects dissemination of findings to academic, clinician and general populations.
Impact All outcomes associated with this project (detailed in other sections) have been facilitated by this collaboration either by sharing of knowledge/providing feedback between sites, or direct contribution to /leadership of outputs.
Start Year 2024
 
Description Network of NHS sites/associated PIs 
Organisation NHS Lothian
Country United Kingdom 
Sector Public 
PI Contribution The UoM research team (and PI/CI Paul Warren) are leading all aspects of this project. We are working with all the named trusts to recruit new patient participants and also to keep clinicians at each site aware of our research findings. We have had regular meetings with the team at each site to share preliminary data and update on progress as well as discuss new recruitment routes.
Collaborator Contribution Staff at each named trust are helping us to identify patient participants with appropriate symptoms. Each site has a designated PI who is a team member on this MRC-funded project. Team members at each site are providing appropriate expertise on FND/3PD Neurology in general. Team members at each site attend regular team meetings and feedback on preliminary data help to shape the project Team members at each site will contribute to all aspects dissemination of findings to academic, clinician and general populations.
Impact All outcomes associated with this project (detailed in other sections) have been facilitated by this collaboration either by sharing of knowledge/providing feedback between sites, or direct contribution to /leadership of outputs.
Start Year 2024
 
Description Network of NHS sites/associated PIs 
Organisation Northern Care Alliance NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution The UoM research team (and PI/CI Paul Warren) are leading all aspects of this project. We are working with all the named trusts to recruit new patient participants and also to keep clinicians at each site aware of our research findings. We have had regular meetings with the team at each site to share preliminary data and update on progress as well as discuss new recruitment routes.
Collaborator Contribution Staff at each named trust are helping us to identify patient participants with appropriate symptoms. Each site has a designated PI who is a team member on this MRC-funded project. Team members at each site are providing appropriate expertise on FND/3PD Neurology in general. Team members at each site attend regular team meetings and feedback on preliminary data help to shape the project Team members at each site will contribute to all aspects dissemination of findings to academic, clinician and general populations.
Impact All outcomes associated with this project (detailed in other sections) have been facilitated by this collaboration either by sharing of knowledge/providing feedback between sites, or direct contribution to /leadership of outputs.
Start Year 2024
 
Title Virtual Functional Movement Evaluation Tool 
Description We have developed a Virtual Environment that can be used to measure functional movement performance. The environment (developed in Unity) is a corridor in a figure 8 configuration such that the central region can be regenerated each time the user turns a corner. Consequently we can ask participants to walk indefinitely in a pre-defined space and encounter new obstacles to step over and squeeze past around each corner. This can be used to recover high level metrics of performance such as time to complete the course. In addition, when used with motion tracking technology, it can also be used to track the feet, shoulders and head, thereby enabling measurement of lower level performance measures such as number of obstacle collisions and minimum distance to obstacle. The software is not yet freely available but it is our intention to share this with the academic/clinical community (e.g. vi GitHub) after the project is finished. 
Type Of Technology Software 
Year Produced 2024 
Impact This software is allowing us to obtain data with our FND/3PD participants and thereby: i) evaluate/compare functional performance in patients vs controls ii) examine evidence for relationships between performance and low level sensory measures iii) test for evidence of improvements in functional performance 
 
Description Guys & St. Thomas' NHS Trust, Balance Team educational meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Team member Dr. Rosa Crunkhorn presented about the STARDUST project, it's motivation and background to her local Balance team in order to inform them about theories being tested and and methodological approaches. In addition this activity was designed to also encourage local practitioners to signpost the study for potential participants where appropriate.

15 members of the balance team from different groupings (audiology, physiotherapy and ENT) at Guy's hospital attended an online presentation introducing the stardust project and the theories behind this. This led to interest and discussion and hopefully will allow the team to consider patients for referral to the project.
Year(s) Of Engagement Activity 2024
 
Description Manchester Foundation Trust Vestibular Team presentation (Debbie Cane) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presention (by research team member Debbie Cane) to a group of vestibular clinicians from across the Manchester Foundation NHS Trust to inform them about our study aims and also encourage them to tell participants about and signpost potential participants to our study. The presentation sparked a good deal of interest and discussion about the key theories outlined from the attendees.
Year(s) Of Engagement Activity 2024
 
Description Meniere's Society Meeting (2024) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Presentation by Debbie Cane at the Annual Meniere's Society meeting. Debbie presented on the STARDUST project and theories of 3PD being studied under this MRC project. This sparked interest from patient groups and clinicians attending and we saw increased contact from participants after the meeting.
Year(s) Of Engagement Activity 2024
URL https://www.menieres.org.uk/news/entry/10123/conference-2024
 
Description NCA Neurlogy team presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Team member Dr. Josh Haynes outlined the STARDUST project (and its theoretical underpinning) to Northern Care Alliance Neurologists at their regular meeting. Discussion afterwards sparked interest in the project and the potetial underlying causal factors to be examined in the project. The team gave good feedback on the talk. Neurologists were also asked to bear the study in mind to sign post potential participants.
Year(s) Of Engagement Activity 2024
 
Description Outreach presentation to "Life on the Level" support group (Debbie Cane) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Presentation by team member Debbie Cane to the "Life on the Level"support group for people living with chronic dizziness. Debbie presented information about the STARDUST study as well as some background on the theories of 3PD/FND studied in this project. The presentation sparked interest from the support group members and we saw an increase in contact from potential participants afterwards.
Year(s) Of Engagement Activity 2024
URL https://www.lifeonthelevel.org/meeting-reports/meeting-report-sat-20th-april-2024-on-zoom/
 
Description Royal Society Event - Digital healthcare for the management of functional neurological disorders 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This discussion meeting united experts (both clinical and academic) and patient groups to develop digital healthcare solutions, enhancing FND management and accessibility. STARDUST PI Dr. Paul Warren presented a poster at the meeting and engaged with national and international clinicians and patient group representatives to inform them about the STARDUST project. Discussion after the presentation sparked interest in the project and the potential underlying causal factors to be examined in the project. Feedback on the presentation from clinicians was strong and they were also asked to bear the study in mind to sign post to potential participants.
Year(s) Of Engagement Activity 2024
URL https://royalsociety.org/science-events-and-lectures/2024/11/digital-healthcare/
 
Description Yorkshire and Humber Neurology/Neuro-ontology Regional trainee day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact STARDUST Team member Dr. Andrew Jones presented: 'Persistent postural-perceptual dizziness: diagnosis and treatment.' AIm to increase knowledge of the condition and inform on the STARDUST study. In addition Andrew used this opportunity to request for clinician referral of patients to online study information.
Year(s) Of Engagement Activity 2024