DERANGED MODULATORY FUNCTION OF THE BASAL GANGLIA IN HUMAN MOVEMENT DISORDERS

Lead Research Organisation: University College London
Department Name: UNLISTED

Abstract

Voluntary movement is fundamental to human existence. Yet impairments of movement, due to stroke, developmental disorder, and degenerative diseases like Parkinson?s Disease affect 1 in 20 of the population during their life span. Most of these disorders are likely to involve a change in the function of the basal ganglia. The latter are key but inaccessible motor centers deep within the brain. Their inaccessibility has meant that we have very little understanding of how the basal ganglia function in human disease. In this research we capitalize on the resurgence of deep brain stimulation for the treatment of diseases like Parkinson?s disease and dystonia, using this opportunity to record directly from the basal ganglia in different diseases at rest and during movement. Our goal is to understand how the basal ganglia interact with each other and with other motor structures like the cortex in organizing normal and contributing to abnormal movement. This research should provide a rational basis for the development of new treatments.

Technical Summary

Our overall aim is to define how dysfunction of the modulatory actions of the basal ganglia (BG) may contribute to movement disorders in the human, and to exploit this knowledge to develop improved pharmacological and surgical approaches to treatment. To this end we will make intra and post operative depth recordings in patients with Parkinson?s disease (PD) and dystonia. These will be complemented by recordings in rodents to answer questions of precise anatomical localisation and pharmacology and by the use of a novel correlative fMRI approach to motor disorders.

Publications

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Androulidakis AG (2008) Amplitude modulation of oscillatory activity in the subthalamic nucleus during movement. in The European journal of neuroscience

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Brown P (2008) Paradoxes of functional neurosurgery: clues from basal ganglia recordings. in Movement disorders : official journal of the Movement Disorder Society

 
Description Scientific Affairs Council
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
Impact Member of Scientific Affairs Council, International Movement Disorders Society which produces international guidelines for the diagnosis and management of movement disorders.
 
Description DANA Foundation
Amount £100,000 (GBP)
Organisation Dana Foundation 
Sector Charity/Non Profit
Country United States
Start  
 
Description EC FP6 funding
Amount £150,000 (GBP)
Organisation Sixth Framework Programme (FP6) 
Sector Public
Country European Union (EU)
Start 01/2006 
End 01/2008
 
Description MRC Program grant
Amount £1,700,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2010 
End 12/2015
 
Description Medtronic Fund Project grant
Amount £46,500 (GBP)
Organisation Medtronic 
Sector Private
Country United States
Start  
 
Description NPF Fellowship
Amount £35,000 (GBP)
Organisation National Parkinson Foundation (NPF) 
Sector Charity/Non Profit
Country United States
Start  
 
Description Parkinson's Disease UK: Fellowship
Amount £177,000 (GBP)
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Parkinson's Disease UK: Project Grant
Amount £56,000 (GBP)
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Rosetrees Trust: project Grant
Amount £30,000 (GBP)
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2008 
End 11/2011
 
Description Welcome Trust Clinical Training Fellowship
Amount £160,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2007 
End 07/2009
 
Description Welcome Trust Project Grant (A new systems approach to therapeutic target selection in degenerative neurological disease)
Amount £324,686 (GBP)
Funding ID 089603 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2009 
End 08/2014
 
Title Beta band synchrony in Parkinsonson's Disease 
Description Showed correlations between drug and deep brain stimulation induced suppression of beta activity in the basal ganglia and improvements in bradykinesia and rigidity. Also provided preliminary evidence of a causal role in the genesis of these symptoms. 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact Closed-loop brain stimulators which use beta activity for feedback are being developed (eg by Medtronic Ltd) 
 
Title Local field potential recordings from basal ganglia in patients 
Description Pioneered the recording of local field potentials during and immediately after functional neurosurgery 
Type Of Material Physiological assessment or outcome measure 
Provided To Others? No  
Impact Forms the basis of a new form of functional intra-operative localisation 
 
Title Refinement of 6OH dopamine lesioned parkinsonian rat model 
Description Able to show that with steps to induce arousal this model recapitulates same abnormal synchrony as in human disease 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact THis model now allows system wide investigation and modelling of the underpinning of these abnormal oscillations 
 
Description Dr Peter Magill, Oxford 
Organisation University of Oxford
Department MRC Anatomical Neuropharmacology Unit
Country United Kingdom 
Sector Public 
PI Contribution Signals Analysis expertise and contributions to experimental question and manuscript preparation
Collaborator Contribution Data collection and sharing of ideas
Impact 16763040 16709634 18448656 19109506 19535481
 
Description Prof Kuhn 
Organisation Charité - University of Medicine Berlin
Country Germany 
Sector Academic/University 
PI Contribution Experimental design, data collection and manuscript preparation
Collaborator Contribution Provision of research material and data collection. Intellectual input
Impact 16476944 16364953 16623853 16499911 16905134 16930593 17113373 17213215 17336961 17425586 17561827 17686048 17686426 18178569 18312587 18430031 18682201 18550758 18760276 19070616 19139047 19291224 19525877
 
Description Prof T Aziz 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Experimental design and recording. Analysis and joint manuscript preparation
Collaborator Contribution Provision of research material and intellectual input
Impact 17084697 17686426 18312587 18430031 18682201 19226423
Start Year 2006
 
Description Article-New Scientist 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Description of our work on slowing movement

Numerous other reports/articles on same subject
Year(s) Of Engagement Activity 2009
 
Description BBC news 24 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 Public/other audiences
Results and Impact Description of our recent work on slowing movement and Parkinsons

Multiple interviews and news items related to this presentation, including New Scientist
Year(s) Of Engagement Activity 2009
 
Description Lecture Brussels. The pathophysiology of Parkinson's Disease. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Lecture to European Brain Council while formulating their policy

A policy document arose
Year(s) Of Engagement Activity 2008
 
Description Visit of A-level students 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Presented experiments nd their background

Two students were more convinced that they wanted to do biomedicine and medicine
Year(s) Of Engagement Activity 2009