Transforming Vestibular Information for Human Action

Lead Research Organisation: University College London
Department Name: Institute of Neurology

Abstract

The vestibular organs in the inner ear provide the brain with important sensory information for many motor and perceptual functions. In the past, research into understanding these mechanisms has been hampered by the inability to selectively stimulate the vestibular system without affecting other sensory systems or affecting the behaviour of interest. In recent years we have pioneered vestibular stimulation techniques that allow us to do this non-invasively in human subjects. We plan to develop these techniques further and use them to investigate some specific mechanisms in the brain that are necessary for using vestibular information to control different types of motor behaviour. Such mechanisms are vital but not very much is known about them. We plan to investigate these mechanisms in human subjects and try to understand how they work, which parts of the brain are involved, and how they are affected by neurological disease to produce functional deficits. First, we will use our vestibular stimulation techniques to develop ways of probing these mechanisms associated with the different motor systems that control the eyes, balance, or voluntary movement. We shall then use this information to study how the mechanisms break down in specific neurological diseases. To do this we will study patients who have had a stroke affecting the parietal cortex, or who have a genetic disease that disrupts the cerebellum. We shall also use a brain stimulation technique to disrupt the normal function of the parietal cortex in healthy subjects. These investigations will tell us about the roles played by these specific parts of the brain in the mechanisms, whether these brain areas control vestibular input to all motor systems equally, and the resulting functional deficits caused by stroke and cerebellar disease.

Technical Summary

The vestibular system supplies the brain with a unique and complete description of head motion and orientation in three dimensions. This information is important for many motor and perceptual functions. In recent years we have pioneered a technique for electrically stimulating the vestibular afferent system (galvanic vestibular stimulation; GVS) in isolation from other sensory systems and without interfering with natural free behaviour. This has provided us with a tool for investigating vestibular influences on action. GVS effectively evokes a virtual head motion because it is interpreted by the brain as having arisen from a real movement of the head in space, even though no such movement has occurred. We plan to develop GVS further and to introduce an additional mechanical method of vestibular stimulation (bone-tone stimulation; BTS) with the aim of being able to select from a range of possible virtual head motion vectors. We will then use these techniques to study a class of central processes that transform the vestibular input into coordinate frames appropriate for the behaviour being controlled. These are basic and powerful processes that have evolved to solve the problems introduced by the multi-jointed body, which allows almost any spatial relationship between sensory input and motor output. We will investigate in human subjects the properties and characteristics of these processes. We will also address the questions of which brain structures contribute to the processes and whether the neural substrate is the same for all motor functions and body parts. To achieve these aims we will develop experimental paradigms that allow us to probe the vestibular transformation processes that are used for the control of three distinct motor systems: the oculomotor, balance, and voluntary movement systems. Our hypothesis is that the posterior parietal cortex and the cerebellum form a network that is involved in these transformation processes. To test this hypothesis we will use a lesion-study approach to contrast the effects of specific lesions with control subjects on coordinate transformation performance for each of the three motor systems. We will study: 1) patients with posterior parietal cortex damage due to stroke; 2) patients with genetically-defined lesions of the cerebellum; 3) healthy subjects in whom normal processing of the posterior parietal cortex has been temporarily disrupted by transcranial magnetic stimulation (TMS) techniques that have been designed to produce a temporary virtual lesion.

Publications

10 25 50
 
Description ESPRIT steering committee
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description Ataxia UK Research Grant
Amount £71,496 (GBP)
Organisation Ataxia UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2006 
End 08/2009
 
Description Ataxia UK, Research grant
Amount £24,480 (GBP)
Organisation Ataxia UK 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2010 
End 03/2011
 
Description EPSRC Project Grant EP/G061653/1 Measurement and Modelling of Electric Fields Induced in the Human Body by Temporally Changing Magnetic Fields
Amount £119,199 (GBP)
Funding ID EP/G061653/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 11/2009 
End 10/2012
 
Description MRC Experimental Medicine Grant
Amount £310,000 (GBP)
Funding ID G0502136 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2007 
End 12/2009
 
Description MRC Research Grant
Amount £324,000 (GBP)
Funding ID G0802073 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2009 
End 03/2012
 
Description Research Grant
Amount £24,484 (GBP)
Organisation Ataxia UK 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2010 
End 03/2011
 
Description Wellcome Trust equipment grant (A multi-user facility for analysis of large-volume movements for investigation of motor control processes in health and disease)
Amount £192,950 (GBP)
Funding ID 084870/Z/08/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2008 
End 05/2013
 
Title 3D whole-body motion analysis laboratory 
Description design and implementation of 3D whole-body motion analysis laboratory allowing data collection of unrestrained movement over an area of 60 square metres incorporating the largest Codamotion system in the UK (8 Coda units and 96 analogue channels), co-registered with 9 force plates, 16-channel telemetry EMG, and head-free gaze tracker 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact Has encouraged new collaborations with other clinical research groups and has opened up new experimental possibilities for future research. 
 
Title Bone tone stimulation 
Description Used 500Hz vibration of bone around ear to evoke whole-body balance responses thought to be evoked by activation of the vestibular otoliths. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact Publications; award of Australian research grants. 
 
Title Galvanic vestibular stimulation 
Description Developed this technique to investigate normal processing of vestibular information for different brain functions and to probe pathological processes in patients with neurological disease. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact Publications; Led to award of research grants (Ataxia UK, MRC, EPSRC). Used in patients with Cerebellar ataxia and patients with Schwannoma. Plan to use it to investigate bio-effects associated with high-field MRI. 
 
Title Stochastic vestibular stimulation 
Description Development of a new method of electrical stimulation of the vestibular nerve in intact human subjects that uses randomly varying currents. We have applied this technique and developed a method for determining the whole-body response direction. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2009 
Provided To Others? Yes  
Impact This has resulted in publications and collaborative research with University of British Columbia, Canada. 
 
Description "Jumping stepping-stones" for assessment and rehabilitation of stroke patients 
Organisation Radboud University Nijmegen Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution Provided the method, protocol and measurement technology
Collaborator Contribution Formulated the problem and provided a research worker to perform experiments
Impact publication: Nonnekes et al. Neurorehabilitation and Neural Repair (in press)
Start Year 2008
 
Description "jumping stepping-stones" for assessment and rehabilitation of stroke patients 
Organisation Radboud University Nijmegen
Department Department of Rehabilitation Medicine
Country Netherlands 
Sector Academic/University 
PI Contribution Provided the method, protocol and measurement technology.
Collaborator Contribution Formulated the problem and provided a research worker to perform experiments
Impact Multi-disciplinary: Physiology, neurology, physiotherapy PMID: 20018932
Start Year 2008
 
Description Development and application of bone-conducted sound as a vestibular stimulation technique 
Organisation University of Sydney
Country Australia 
Sector Academic/University 
PI Contribution Provided the experimental method and technology for measuring whole-body balance responses.
Collaborator Contribution Introduced this new technique and performed experiments on patients.
Impact Multi-disciplinary: Neuro-otology, neurology, physiology, neuroscience Awarded 2 Australian grants: NHMRC (Australia) project grant [Co-applicant with Dr M Welgampola, Prof M Halmagyi, Dr R Fitzpatrick] Brain Foundation (Australia) research grant [Co-applicant with Dr M Welgampola] PMID: 16945974
 
Description Development and application of galvanic vestibular stimulation technique 
Organisation University of New South Wales
Department Prince of Wales Medical Research Institute
Country Australia 
Sector Academic/University 
PI Contribution Conceptual and experimental advances
Collaborator Contribution Contributed to a deeper understanding of the mechanism of action of GVS which has opened up new experimental approaches to investigate physiology of vestibular function.
Impact PMID: 16890526 PMID: 20026614 PMID: 20855437 PMID: 20937715
 
Description Development and application of stochastic vestimulation technique 
Organisation University of British Columbia
Country Canada 
Sector Academic/University 
PI Contribution Placed the technique in a new research context and undertook the experimental design and execution
Collaborator Contribution Brought a new experimental technique and analytical method to our laboratory
Impact PMID: 20855437
Start Year 2009
 
Description Understanding bio-effects of magnetic fields associated with magnetic resonance imaging 
Organisation University of Nottingham
Department School of Physics and Astronomy
Country United Kingdom 
Sector Academic/University 
PI Contribution Measurement and quatification of effects of high field MRI on vestibular system.
Impact Multi-disciplinary: Physiology, neuroscience, physics Awarded EPSRC research grant
Start Year 2009
 
Description BBC; Science in Action; series 
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 Interviewed at length about our research into vestibular control of balance and navigation. Interviewer acted as experimental subject to describe the experience.

None known
Year(s) Of Engagement Activity 2006
 
Description CodaMotion conference and workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation at workshop organised by the UK company Charnwood Dynamics for users of their motion analysis system, which is employed in my lab. My presentation focused on the use of this technology in neuroscience and neurological research.

Subsequent discussions and meetings with researchers from Ireland with a view to future collaboration.
Year(s) Of Engagement Activity 2008,2014
 
Description Contributor to 'Motion Times' 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Describing research projects that have involved 3-D motion analysis technology in a newsletter for the motion capture community.

None known
Year(s) Of Engagement Activity 2006,2007,2008
 
Description Discovery Channel science series "Weird connections" 
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 Media (as a channel to the public)
Results and Impact Provided filmed scientific demonstrations and talking head related to vestibular control of balance and navigation as part of one programme in this series. The programme will be shown on Discovery Channel in North America and then Europe.

None known
Year(s) Of Engagement Activity 2008
 
Description Workshop: Bodies, Objects and Rituals 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The workshop took place at the Victoria and Albert museum. It was aimed at curators and included presentations from curators, artists and performers. I was invited to give a presentation from the perspective of a neuroscientist involved in human and clinical studies. The feedback was overwhelmingly positive from this very mixed audience.

I have subsequently been having discussions with two of the artists involved in the workshop with a view to joining forces on two separate art/science projects for which Welcome Trust funding will be sought.
Year(s) Of Engagement Activity 2008