Cortical Function in Visual Dependency in Patients with Chronic Dizziness

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

In this application to the MRC for a research grant we intend to elucidate the basis for long term (= chronic) dizziness. Chronic dizziness is common, disabling and has significant social repercussions, with up 1/5 of patients in specialised hospital clinics giving up work as a result. It often starts with relatively trivial inner ear (= vestibular) disorders such as labyrinthitis (= vestibular neuritis) or common problems such as migraine. The problem is that it is difficult to predict which patients with such bening and usually self-limiting disorders will go on to develop long term symptoms. We have identified that patients with chronic dizziness are unusually sensitive to complex visual stimuli (= visually dependent) and that rehabilitation treatments adapting these patients to visual movement are effective. However, the underlying anatomical and functional basis of visual dependence in chronic dizziness are not known.

We propose to carry out studies applying state of the art brain imaging and physiological techniques in patients with acute (= recent, sudden onset) dizziness and in patients with chronic dizziness, as well as in healthy control subjects. The brain imaging techniques allow visualization of the cerebral cortical areas involved in the processing of visual and vestibular (=balance) stimuli. The neuro-physiological techniques probe the excitability of visual areas, in particular those areas that interact with vestibular areas. The imaging and physiological results will be correlated with questionnaire data of the actual symptoms in the patients so that the clinical significance of the basic (= physiological + imaging) findings can be ascertained. A specific hypothesis we have is that in patients with chronic dizziness and enhanced visual dependence, the normal inhibitory interaction between the visual and vestibular parts of the brain will be lost or attenuated. We will also see patients acutely (eg recruited in the emergency department) and followed up, to see the normal and abnormal process of recovery in well and poorly recovered patients, respectively. These findings would provide the basis for new treatments of these symptoms, including the use of non invasive modulation of cortical excitability with transcranial electrical stimulation.

Technical Summary

Research objectives: To clarify the underlying neuroanatomical and neurophysiological basis of chronic dizziness, in particular the increased visual dependence observed in such patients.

Background: Chronic dizziness is extremely common in neurology, ENT (ORL), audiology and old-age medicine. Chronic dizziness usually evolves from preceding acute, attacks of vertigo (rotatory dizziness) of viral etiology (vestibular neuritis) or recurrent episodes of vertigo (Meniere's disease and vestibular migraine). However, why some but not all patients with acute/episodic vertigo end up with long term dizziness is not known. A specific component of such chronic dizziness is an increase in visual dependence, that is, high levels of reliance on visual input for spatial orientation and balance. These patients are dizzier in environments with moving or complex visual surroundings, a syndrome called visual vertigo or visually-induced dizziness. In previous MRC cycles we have shown that vestibular physiotherapy including visual motion desensitization improves clinical outcomes in chronic dizziness but still the underlying anatomy and physiology of this important phenomenon is unknown.

Methodology: We will measure vestibular patients' symptoms with questionnaires and visual dependence with validated psycho-pshysical techniques. We will correlate such results with novel findings from visuo-vestibular functional imaging (fMRI) and human neurosphysiology studies (transcranial magnetic stimulation). Imaging and phsyiological studies will explore the known inhibitory coupling between visual motion and vestibular areas in the brain. Experimental subjects will include acute vestibular patients + follow up, patients already with chronic dizziness and healthy controls.

Application & exploitation of results: Dissemination of findings to the relevant clinical community and development of targeted therapies, including rational physiotherapies and non invasive brain stimulation.

Planned Impact

The beneficiaries from this research will be:

- Neuroscience research community: The changes induced in the brain by a peripheral vestibular lesion have always been one the best examples of lesion-induced neural plasticity. Our approach studies divergent modes of recovery following a vestibular lesion, a good outcome and a poor outcome leading to chronic dizziness and visually induced dizziness. Thus we would be expanding the horizon in this field of research and further human and animal research models may follow, turning a basic field of research into an applied one.

- Healthcare personnel: a rational basis to explain difficult symptoms in a large patient population is always welcome by healthcare practitioners, in this case in particular neurologists, ENT and audiology specialists, geriatritians, GPs and rehabilitation specialists (physiotherapists and audiologists dealing with dizzy patients).

- Healthcare resources: chronic dizziness is 'expensive'. There is a considerable waste of resources on this large patient population because patients are disatisfied and doctors worried that patients don't get better. As a result patients have unecessary expensive investigations, typically MRI/CT scans, EEG, and cross-specialist referrals, which are useless for the vast majority of these patients.

- Patients: patients will also benefit because one of the frustrating things about chronic dizziness is the general lack of knowledge by general physicians and consultants on this matter. Providing a rational basis for a complex clinical condition is always reassuring to patients, as they can understand the symptoms they experience. In addition, the findings will lead, without any doubt, to new treatments (usually targeted rehabilitation) for these patients. We often pioneer such treatment developments and actually hope to do so again during the next research cycle.

Publications

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Ahmad H (2015) Are white matter abnormalities associated with "unexplained dizziness"? in Journal of the neurological sciences

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Anastasopoulos D (2019) Large gaze shift generation while standing: the role of the vestibular system. in Journal of neurophysiology

 
Title NeuroSci-Art Image competition 
Description First prize in the Neurosci-art competition 2015. Now on permanent display in a college building and used on Brain Sciences / Centre for Clinical Translation web page. 
Type Of Art Image 
Year Produced 2013 
Impact none 
URL http://www1.imperial.ac.uk/departmentofmedicine/divisions/brainsciences/translationalneuroscience_me...
 
Description Improved Treatment of Balance Disorders
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact This REF impact case collected several lines of evidence showing how the treatments we devised had been adopted worldwide, and were cited in government health policy documents.
URL http://impact.ref.ac.uk/CaseStudies/CaseStudy.aspx?Id=42200
 
Description AMS Clinician Scientist Fellowship
Amount £700,000 (GBP)
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Bequest from Dr Dix's estate
Amount £276,619 (GBP)
Funding ID WMCT_P51150 
Organisation Otto Dix Foundation 
Sector Public
Country Germany
Start 02/2017 
 
Description EEG in small vessel white matter disease (BRC)
Amount £56,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR Imperial Biomedical Research Centre
Sector Charity/Non Profit
Country United Kingdom
Start 07/2015 
End 03/2016
 
Description MRes studentship
Amount £160,000 (GBP)
Organisation University of Chile 
Sector Academic/University
Country Chile
Start 10/2016 
End 09/2020
 
Description P18036 - Meniere's Society Project Grant
Amount £284,406 (GBP)
Funding ID P18036 
Organisation Ménière’s Society 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2008 
End 12/2015
 
Description P51150 - Spatial orientation control
Amount £29,000 (GBP)
Funding ID p51150 
Organisation Imperial College London 
Department Imperial College Trust
Sector Charity/Non Profit
Country United Kingdom
Start 01/2014 
End 12/2016
 
Description P52213 - CLRN Regis to the Barany Conf.
Amount £479 (GBP)
Funding ID p52213 
Organisation Imperial College Healthcare NHS Trust 
Sector Hospitals
Country United Kingdom
Start 03/2014 
End 03/2015
 
Description P53058 - Purchase of Frenzel glasses
Amount £2,200 (GBP)
Funding ID p53058 
Organisation Ménière’s Society 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2014 
End 03/2015
 
Description PC3403 - IC TRUST (Dix)
Amount £154,888 (GBP)
Funding ID pc3403 
Organisation Imperial College London 
Department Imperial College Trust
Sector Charity/Non Profit
Country United Kingdom
Start  
End 12/2015
 
Description PS2122 - Neural correlates of vestibular activity (BRC)
Amount £12,000 (GBP)
Funding ID ps2122 
Organisation Hungarian Academy of Sciences (MTA) 
Department Biological Research Centre (BRC)
Sector Academic/University
Country Hungary
Start 05/2013 
End 04/2015
 
Description Vitual reality video grant
Amount £12,000 (GBP)
Funding ID WMCT_P61181 
Organisation Ménière’s Society 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2016 
End 01/2018
 
Title Binocular rivalry mediated brain activation 
Description We found that combining binocular rivalry with vestibular or electrical activation of the brain creates inter-hemisphere competition. 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact some publications. 
 
Title New brain model underpinning numerical allocation 
Description A novel unifying computational model that describes how numerical magnitude allocation is subject to dynamic interhemispheric competition. That is, numerical allocation is continually updated in a contextual manner based upon relative magnitude, with the right hemisphere responsible for smaller magnitudes and the left hemisphere for larger magnitudes. Also described in the paper is a heat map method for documenting visual spatial attentional shifts. PMID: 26879093 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2016 
Provided To Others? Yes  
Impact None so far 
URL https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bhv344
 
Description Cortical processing of rotational stimuli (Perugia) 
Organisation University of Perugia
Country Italy 
Sector Academic/University 
PI Contribution Provided clinical ideas. Data analysis and manuscript writing.
Collaborator Contribution Large scale testing of patients. Provided us with a new valuble vestibular stimlus (asymetric rotation)
Impact see papers together with V.E. Pettorossi
Start Year 2011
 
Description Human spatial orientation (Marseille) 
Organisation Aix-Marseille University
Country France 
Sector Academic/University 
PI Contribution Provided research concepts and infrastructure
Collaborator Contribution Research fellows
Impact PMID:14663543 PMID:17101157 PMID:23206549
 
Description Interhemispheric conflicts in spatial processing (Oxford) 
Organisation University of Oxford
Department Department of Experimental Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided new research topics.
Collaborator Contribution Expertise in experimantal psychology.
Impact Publications.
Start Year 2013
 
Description Long term vestibular compensation (Zurich) 
Organisation University of Zurich
Department Neurology Department Zurich
Country Switzerland 
Sector Academic/University 
PI Contribution We've provided the research concept
Collaborator Contribution The Swiss team allowed access to their patient database and adapted our research tools to their environment
Impact 18604466
Start Year 2007
 
Description Mutisegmental gaze-led body movements (Athens) 
Organisation National and Kapodistrian University of Athens
Country Greece 
Sector Academic/University 
PI Contribution We've provided teh experimental protocol
Collaborator Contribution They provided novel maths-based analysis
Impact 18718325 19002676
Start Year 2008
 
Description Normal and abnormal motion sickness (Westminster) 
Organisation University of Westminster
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided our laboratory and research students to sevral projects in common
Collaborator Contribution Prof Golding, from the Univ of Westminster is a top researcher in motion sickness and a proficient statistician. His skills are used in many of our projects.
Impact 19522361 18619124
 
Description Scientific basis of neuro-rehabilitation of balance (KCL) 
Organisation King's College London
Department School of Medicine KCL
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided the research concept/question and the apparatus required
Collaborator Contribution 17538212
Impact 17538212
 
Description Small vessel white matter disease as a cause of balance disorders (Pisa) 
Organisation University of Pisa
Country Italy 
Sector Academic/University 
PI Contribution Provided the research question and clinical material.
Collaborator Contribution Provided a research fellow.
Impact None so far
Start Year 2014
 
Description Visual control of posture (CNRS) 
Organisation National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS)
Department Laboratory of Psychology and Neurocognition, University of Savoy
Country France 
Sector Academic/University 
PI Contribution We've provided the lab and technology
Collaborator Contribution They contributed the research question and manpower
Impact 18672020 19026959
Start Year 2007
 
Description Visual cortical excitability and visual dependence (Amsterdam/Antwerp) 
Organisation Free University of Amsterdam
Department Faculty of Human Movement Sciences
Country Netherlands 
Sector Academic/University 
PI Contribution Provided the research question (as described in the MRC grant application) and the laboratory facility.
Collaborator Contribution Provided two researchers to execute this project.
Impact None so far
Start Year 2014
 
Description Visual cortical excitability and visual dependence (Amsterdam/Antwerp) 
Organisation University of Antwerp
Country Belgium 
Sector Academic/University 
PI Contribution Provided the research question (as described in the MRC grant application) and the laboratory facility.
Collaborator Contribution Provided two researchers to execute this project.
Impact None so far
Start Year 2014
 
Title DVD home-based treatment of 'visual vertigo' and difficult dizziness 
Description A collection of visual motion images designed for patients to treat their dizziness, either at home or with a physiotherapist 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2013
Licensed Yes
Impact Most physiotherapist want to employ this treatment (www.bsno.org.uk)
 
Title Meniere's disease trial 
Description This is a clinical trial (RCT) of two drugs (gentamycin vs. dexametasone) delivered trans-tympanically for treatment of refractory meniere's disease. The results have changed the management of advanced Meniere's disease. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2016
Development Status Closed
Clinical Trial? Yes
Impact http://www.dailymail.co.uk/health/article-4003528/Can-steroid-jab-ear-banish-dizzy-spells-good-New-treatment-reduces-symptoms-without-risk-severe-hearing-loss.html http://newatlas.com/menieres-disease-steroid-injections/46500/ http://www.sciencenewsline.com/news/2016111712090019.html http://www.enttoday.org/article/intratympanic-corticosteroid-treatment-effective-gentamicin-menieres/ NEW YORK (Reuters Health): http://www.managedhealthcareconnect.com/content/intratympanic-steroids-effective-treating-unilateral-m-ni-res-disease 
URL http://clinicaltrials.gov/show/NCT00802529
 
Title Transcranial DC brain stimulation for gait disorders 
Description We applied tDCS as a proof of principle for the treatment of gait disorders due to leucoaraiosis and Parkinson's disease 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2013
Development Status Actively seeking support
Impact N/A 
 
Description Articles in national newspapers 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Approximately once a year the media visit our labs for one reason or another, or contact us re. publications that may catch the public's imagination (eg the 'broken escalator effect; clinical trials). This has included Daily Mail, Metro, a local West London Newspaper, Evening Standard, The Times (16/11/2004) and others.

These caused increased patient referrals to our clinical services and follow up letters in the newspapers.
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,2009,2013
 
Description BBC Radio 4 - Live Interview - Dancers 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Ballet dancers' brains adapt to stop them feeling dizzy.
Discussing the research on dancers in PMID: 24072889

Items on the BBC news, ITV news and in national and international newspapers and news websites internationally.
Year(s) Of Engagement Activity 2013
URL http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_26-9-2013-17-43-4
 
Description BBC TV - Bang Goes the Theory - Series 6 Episode 7 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Bang Goes the Theory", Series 6, episode 7 - Motion sickness. Treatment of sickness by regulation of breathing.

None so far
Year(s) Of Engagement Activity 2012
 
Description Daily Mail and Daily Mail online 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Treatment of Meniere's disease by intratympanic injection for joint centre randomised, double-blind, clinical trial on unilateral refractory Meniere's disease at Charing Cross Hospital and Leicester Royal Infirmary.

Advertised new treatments for Meniere's disease trialled at Charing Cross Hospital between the Neuro-Otology department and Ear Nose and Throat.
Year(s) Of Engagement Activity 2012
URL http://www.dailymail.co.uk/health/article-2224996/Dizzy-spells-The-jab-INSIDE-ear-stop-head-spinning...
 
Description Electrical treatment of motion sickness. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Numerous requests for interviews with the team from the media.
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/news/health-34145713
 
Description Imperial Festival Stall "How does what you see affect your balance?" 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact We had over approximately 100 participants a day. Test how their balance can be affected by visual motion, differently in both young and old.

We recruited participants for our studies and we were approached by a number of people with pre-existing balance problems who wanted to know more about the topic.
Year(s) Of Engagement Activity 2013
 
Description Imperial Fringe: The Arts Experiment. "Juggling and Neuroscience". 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Explained to an audience how your behavior can influence your brain structure.

???
Year(s) Of Engagement Activity 2013
URL https://www.imperialcollegeunion.org/whats-on/event/391
 
Description Interviewed for documentary 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview for documentary "Inside the brain of the ultimate athlete" by French-German TV channel ARTE.
Year(s) Of Engagement Activity 2016
 
Description Podcast Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Podcast Interview on research paper on motion sickness.
Year(s) Of Engagement Activity 2016
URL https://www.aan.com/rss/search/home/episodedetail/?item=3054
 
Description Podcast interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Podcast interview hosted by Vivid drinks on expertise and brain function.
Year(s) Of Engagement Activity 2016
 
Description Podcast interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Podcast Interview for Imperial College London on Visual Vertigo
Year(s) Of Engagement Activity 2016
URL https://www.imperial.ac.uk/department-of-medicine/research/brain-sciences/clinical-translation/neuro...
 
Description Response to motion sickness paper 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Many interviews from around the world and referenced on multiple international news websites and media outlets.
Year(s) Of Engagement Activity 2016
URL http://www.neurology.org/content/85/14/1257.full
 
Description Scientific consultant for play 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Scientific Consultyant for a play called "Testosterone"
Year(s) Of Engagement Activity 2016
URL http://www.rhumandclay.com/testosterone
 
Description Wonder Street Fair at the Barbican, part of British Neuroscience Association 2013 Meeting. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We had over 300 participants over 3 days. Test how their balance can be affected by visual motion, differently in both young and old.

We recruited participants for our studies and we were approached by a number of people with pre-existing balance problems who wanted to know more about the topic.
Year(s) Of Engagement Activity 2013
URL http://www.bna.org.uk/BNA2013-festival-of-neuroscience.html