Quantitative, multimodal neuroimaging to investigate the mechanisms of brain plasticity

Lead Research Organisation: University of Liverpool
Department Name: Magnetic Resonance & Image Analysis Re C

Abstract

The adult brain is able to reorganise its connections. For example, after a stroke, new brain areas take on the roles of those that have been damaged. Functional magnetic resonance imaging (fMRI) and Magnetoencephalography (MEG) can measure these changes in brain organisation.
The aim of this work is to understand the mechanisms behind these brain changes. We aim to answer questions such as: How are new brain cells recruited? How are the connections between cells strengthened?
Rather than studying people who have had a stroke we will look at normal healthy people and induce changes in brain organisation in a controlled way. We will place a vibrating device on the fingertips that, after only a few hours, causes expansion of the region in the brain that senses touch. We think that the connections between two brain regions may strengthen if they are activated with synchronous vibrations.
We will use fMRI to measure the expansion of brain regions and MEG to measure the timing and co-operation between brain cells. Used together they give a clear picture of how the brain is changing. We will develop new methods to measure the strength of connections between two regions.

Technical Summary

Functional Magnetic Resonance Imaging (fMRI) using the Blood-oxygenation-level-dependent (BOLD) signal has greatly increased our knowledge of normal and abnormal brain function, through the mapping of brain areas associated with sensory and cognitive tasks. The amplitude of the BOLD signal change can provide additional information beyond simple mapping, such as the relative strength of the underlying neuronal activity, and the connectivity between brain regions.

Quantification of changes in cerebral blood flow (CBF) and the rate of oxygen metabolism (CMRO2) that contribute to the BOLD signal gives further information on how the underlying neuronal activity changes during stimulation, since CBF changes are thought to be closely related to changes in synaptic input; whereas CMRO2 provides information on the increased energy expenditure during activation. Complementary information can be obtained from magnetoencephalography (MEG), which is sensitive to the temporal coherence of active neurons. Combined, these measurements will be applied to further our understanding of the mechanisms underlying adult brain plasticity in the somatosensory system.

The somatosensory cortex is highly plastic, for example, continuous vibrotactile stimulation leads to improvements in spatial and frequency discrimination over the course of hours. The time course and nature of neuronal changes during this process, and how they relate to the behavioural changes are unclear. Long-term potentiation of excitatory synapses, following a Hebbian learning rule is one of the key candidate mechanisms causing this plasticity. Long-term experience, such as learning to play a musical instrument, produces structural changes in the brain. The mechanism and time-course of structural changes, and how these relate to short-term functional changes are largely unknown.

The objectives of this research are to: 1. Establish quantitative measurements of CBF and CMRO2. 2. Explore the possibility of measuring the dynamics of cortical interactions using fMRI. 3. Demonstrate that Hebbian activation can produce changes in synaptic strength in the human brain using methods developed in objective 2. 4. Characterize the changing neurophysiological response during continuous vibrotactile stimulation using methods developed in objective 1 and MEG, and investigate how these correlate with changes in frequency discrimination. 5. Measure long-term changes in the somatosensory cortex of normal subjects learning to read Braille using both quantitative fMRI (as developed in objective 1) and structural MRI at several time points during the learning process.

These objectives will be achieved though non-invasive neuroimaging and psychophysical measurements in normal human volunteers.

Publications

10 25 50

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Lea-Carnall CA (2016) Cortical Resonance Frequencies Emerge from Network Size and Connectivity. in PLoS computational biology

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Lea-Carnall CA (2017) Evidence for frequency-dependent cortical plasticity in the human brain. in Proceedings of the National Academy of Sciences of the United States of America

 
Description Additional University Funding
Amount £50,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 09/2012 
End 06/2013
 
Description CASE PhD studentship
Amount £80,000 (GBP)
Organisation Unilever 
Sector Private
Country United Kingdom
Start 09/2009 
End 08/2013
 
Description Efficacy and Mechanism Evaluation Programme in Very Rare Diseases
Amount £1,400,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2015 
End 05/2023
 
Description MRC momentum award - dementias
Amount £120,000 (GBP)
Organisation University of Manchester 
Sector Academic/University
Country United Kingdom
Start 10/2017 
End 03/2018
 
Description MRC/UoM Momentum award for dementia research
Amount £750,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 01/2019
 
Description NIHR clinical fellowship
Amount £584,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2018 
End 06/2021
 
Description Project Grant Unilever black tea
Amount £170,000 (GBP)
Organisation Unilever 
Sector Private
Country United Kingdom
Start 04/2010 
End 04/2011
 
Description Project grant neurovascular coupling, including Jonathan PhD
Amount £170,000 (GBP)
Organisation Unilever 
Sector Private
Country United Kingdom
Start 10/2006 
End 10/2009
 
Description Sensing and Imaging for Early Diagnosis of Dementia
Amount £1,100,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 01/2015 
End 01/2018
 
Description Alder Hey Childrens Hospital 
Organisation Hull and East Yorkshire Hospitals NHS Trust
Department Neuroradiology
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative work with Alder Hey NHS Trust has lead to the translation of a number of MRI protocols, developed in a research setting, into routine clinical use. For example, the use of diffusion tensor imaging and arterial spin labelling.
Collaborator Contribution Funds from the Alder Hey NHS Trust were provided to support a part-time medical physicist to maintain this collaboration.
Impact Use of advanced MRI techniques in routine clinical practice. Publications: Vidyasagar R, Abernethy L, Pizer B, Mallucci CL, Avula S, Parkes LM, 'Quantitative measurement of blood flow in paediatric brain tumours - a comparative study of dynamic susceptibility contrast and multi time-point arterial spin labeled MRI.' British Journal of Radiology In press [2016]. Sze M Ng, Mark A Turner, Carrol Gamble, Mohammed Didi, Suresh Victor, Jessica Atkinson, Vanessa Sluming, Laura M Parkes, Anna Tietze, Laurence J Abernethy,and A Michael Weindling, 'Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings from the TIPIT study'. Paediatric Radiology 44(8):987-996 August [2014]. DOI: 10.1007/s00247-014-2911-6 Funding: 2013 - 2014 Arterial Spin Labelled MRI - an imaging biomarker of cerebral blood flow in children. Liverpool and Manchester MRC Confidence in Concept Award.Grant Holders: Laura Parkes (PI), Dr Stavros Stivaros, Prof Graham Kemp, Dr Laurence Abernethy, Dr Rishma Vidyasagar (£50k). 2012 - 2014 Development of advanced intra-operative MRI techniques. Alder Hey Children's NHS Trust. Grant holders: Laura Parkes and Laurence Abernethy (£50k).
Start Year 2007
 
Description Infectious Diseases Group, Liverpool 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Advice and implementation of MRI techniques for multi-centre trials in encephalitis. Advice on image analysis.
Collaborator Contribution Application of imaging techniques in a patient population.
Impact Publications: Defres S, Keller SS, Das K, Vidyasagar R, Parkes LM, Burnside G, Griffiths M, Kopelman M, Roberts N, Solomon T, 'A Feasibility Study of Quantifying longitudinal Brain Changes in Herpes simplex virus (HSV) Encephalitis using Magnetic Resonance Imaging (MRI) and stereology.' in press PLOS one [2017]. Michael BD, Griffiths MJ, Granerod J, Brown D, Keir G, Wnek M, Cox DJ, Vidyasagar R, Borrow R, Parkes LM, Solomon T, 'The interleukin-1 balance is associated with clinical severity, blood-brain barrier permeability, neuroimaging changes and outcome in encephalitis.' Journal of Infectious Diseases in press. [2015]. DOI: 10.1093/infdis/jiv771 Grant funding: 2015 - 2022 Mechanism and Efficacy of Corticosteroids in Herpes simplex virus Encephalitis in Adults. MRC and NIHR 'Efficacy and Mechanism Evaluation Programme in Very Rare Diseases'. Grant holders: Tom Solomon (PI), Laura Parkes, Ava Easton, Girvan Burnside, Paula Williamson, Rachel Kneen (£1.4M).
Start Year 2006
 
Description Preston 
Organisation Royal Preston Hospital
Department Neurology Department
Country United Kingdom 
Sector Hospitals 
PI Contribution I have jointly supervised medical students and clinical fellows on dissertation projects and PhDs, providing advice on implementation and analysis of imaging measurements.
Collaborator Contribution Joint supervision of medical students and clinical fellows on dissertation projects and PhDs, providing advice on clinical mechanisms and impact.
Impact This long-term research partnership with neurologist Prof. Emsley has resulted in many publications: Al-Bachari S, Vidyasagar R, Emsley HCA, Parkes LM, 'Structural and Physiological Neurovascular Changes in Idiopathic Parkinson's Disease and its Clinical Phenotypes' Journal of Cerebral Blood Flow and Metabolism, in press [2017]. Hanby MF, Al-Bachari S, Makin F, Vidyasagar R, Parkes LM, Emsley HCA, 'Structural and physiological MRI correlates of occult cerebrovascular disease in late-onset epilepsy.' Neuroimage Clinical 9:128-133, Sept [2015]. DOI: 10.1016/j.nicl.2015.07.016 Al-Bachari S, Parkes LM, Vidyasagar R, Hanby MF, Tharaken V, Leroi I, Emsley H, 'Arterial Spin Labeling Reveals Prolonged Arterial Arrival Time in Idiopathic Parkinson's Disease.' Neuroimage Clinical 6:1-8 [2014]. DOI: 10.1016/j.nicl.2014.07.014 Gibson LM, Hanby M, Al-bachari S, Parkes LM, Allan SM, Emsley HCA, 'Late Onset Epilepsy and Occult Cerebrovascular Disease' JCBFM 34(4):564-570 April [2014]. DOI: 10.1038/jcbfm.2014.25 Maxwell H, Hanby M, Parkes LM, Gibson L, Coutinho C, Emsley HCA, 'Prevalence and subtypes of radiological cerebrovascular disease in late-onset isolated seizures and epilepsy' Clin Neurol and Neurosurgery 115(5): 591-596 May [2013]. DOI: 10.1016/j.clineuro.2012.07.009 Mohtasib RS, Lumley G, Goodwin JA, Emsley HCA, Sluming V, Parkes LM 'Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response with increasing age' Neuroimage 59:2 1143-1151 Jan [2012]. DOI: 10.1016/j.neuroimage.2011.07.092 Gibson LM, Allan SM, Parkes LM, Emsley HC 'Occult cerebrovascular disease and late onset epilepsy: could loss of neurovascular unit integrity be a viable model?' Cardiovascular Psychiatry and Neurology 2011:130406. Epub Mar [2011]. DOI: 10.1155/2011/130406 And a number of research grants: 2012 - 2016 Cerebrovascular Mechanisms of Idiopathic Parkinson's Disease; Correlations with Clinical Phenotypes and Features. Biomedical Imaging Institute Studentship. Grant Holders: Laura Parkes (PI), Hedley Emsley (£70k). 2012 -2013 Investigating comorbid cerebrovascular disease in idiopathic Parkinson's disease. Manchester Mental Health and Social Care Trust and the Neuroscience Research Institute, University of Manchester. Grant holders: Laura Parkes (PI), Hedley Emsley and Ira Leroi. (£32k).
Start Year 2006
 
Description St. Marys Childrens Hospital 
Organisation Hull and East Yorkshire Hospitals NHS Trust
Department Neuroradiology
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative work with neuroradiologists at St. Mary's NHS Trust has led to the translation of a number of MRI protocols, developed in a research setting, into routine clinical use. For example, the use of arterial spin labelling.
Collaborator Contribution Application of new techniques in patient populations.
Impact Funding: 2013 - 2014 Arterial Spin Labelled MRI - an imaging biomarker of cerebral blood flow in children. Liverpool and Manchester MRC Confidence in Concept Award.Grant Holders: Laura Parkes (PI), Dr Stavros Stivaros, Prof Graham Kemp, Dr Laurence Abernethy, Dr Rishma Vidyasagar (£50k). Multi-disciplinary collaboration involving physicists and radiologists.
Start Year 2012
 
Description Unilever 
Organisation Unilever
Country United Kingdom 
Sector Private 
PI Contribution intellectual input to joint research, leading to additional funding for a number of research students and data collection.
Collaborator Contribution Access to expertise on vascular function. Access to food substances used in intervention studies.
Impact Development of a quantitative approach to functional brain imaging, leading to 3 publications: Vidyasagar R, Greyling A, Draijer R, Corfield C, Parkes LM, 'The effect of black tea and caffeine on regional cerebral blood flow measured with arterial spin labeling' JCBFM 33(6):963-968 June [2013]. DOI: 10.1038/jcbfm.2013.40 Mohtasib RS, Lumley G, Goodwin JA, Emsley HCA, Sluming V, Parkes LM 'Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response with increasing age' Neuroimage 59:2 1143-1151 Jan [2012]. DOI: 10.1016/j.neuroimage.2011.07.092 Goodwin JG, Bulte D, Balanos G, Vidyasagar R, Parkes LM 'Quantitative fMRI using hyperoxia calibration: reproducibility during a cognitive Stroop task' Neuroimage 47(2): 573-580 aug [2009]. DOI: 10.1016/j.neuroimage.2009.04.064
Start Year 2006
 
Description Article in University magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact The article described the purpose of our research project to a wide audience.

More people interested in volunteering as research participants.
Year(s) Of Engagement Activity 2008
 
Description Big Brain 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact A 'hands-on' 2 day event for local school children aged 13 - 14. I led a theme on brain imaging with the aim of highlighting the need for physics and maths in brain imaging not just biology. Children were engaged and asked many questions. They enjoyed the day.
Year(s) Of Engagement Activity 2017
 
Description Brainbox 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The Brainbox event was held in Manchester town hall on 'Manchester day' and attracted over 5000 members of the public.
My team ran one of 8 themes on neuroimaging. Our exhibit explain how imaging techniques work (eg MRI, EEG, PET), the importance of physical scientists in this work, and the impact of imaging technologies on neuroscience research and healthcare.
Year(s) Of Engagement Activity 2016
URL https://mcrbrainbox.wordpress.com/legacy/
 
Description British Science Week 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact This was a week long event attracting hundreds of local school children (secondary and primary) to tour the exhibition. I led a theme on neuroimaging in action.
Year(s) Of Engagement Activity 2017
 
Description Imaging stand at Manchester 'Science Spectacular' 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Lots of interest in the stand.

Great feedback, eg comment: 'we all want to be scientists now'.
Year(s) Of Engagement Activity 2011
 
Description Presentation at the National Student Conference of the Academy of Medical Sciences 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact Presented on 'Imaging in neurology and neuroscience' to a group of medical students to enthuse them on the role of imaging in medical research.
Year(s) Of Engagement Activity Pre-2006,2017
 
Description School Visit as part of Manchester Science festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Schools
Results and Impact Approximately 200 sixth-form students attended. Interesting discussion afterwards.

School asked for follow-up visits to see the MRI scanner.
Year(s) Of Engagement Activity 2011
 
Description ScienceGrrl event at MOSI 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I was one of a team of female scientists at the Museum of Science and Industry. We roamed the Museum carrying gadgets and engaged children in our work and explained what we do and what the gadget is for. Specifically aimed at changing people's perception of 'what a scientist looks like' and engaging young girls in science.
Year(s) Of Engagement Activity 2015
 
Description Talk to U3A Stockport 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Presentation of Research findings to the U3A group, some of whom had participated in the research.
Year(s) Of Engagement Activity 2015
 
Description Talk to the U3A Bramhall 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact The talk sparked many questions from the audience.

After my talk I recieved an email of thanks from the organisers stating that it had been very well received. I have been invited to give a similar talk to another U3A group in 2015 as a result.
Year(s) Of Engagement Activity 2012