Neuronal- and systems-level understanding of spatial and episodic memory.

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

Abstract

Our memories define who we are and the loss of day-to-day (or ?episodic?) memory, for example as a result of Alzheimer?s disease (AD), temporal lobe epilepsy or stroke, has a devastating impact on one?s capacity to live independently and places a huge burden on caregivers and the state.
There is an enormous potential for memory to be improved, both in health and disease, via drugs (which modulate how neurons create and store memories), technological devices and memory strategies. However, our current level of understanding of memory processes means that we are a long way from being able to fully utilize these interventions. Critically, there is a gap between our understanding of memory processes at the level of molecules and cells (the neuronal level) through to the activity of populations of cells throughout the brain (the systems level).
This research is aimed at bridging this gap by providing a detailed understanding of how the actions and interactions of neurons in the brain gives rise to memory. Much of the research focusses on spatial memory, where comparable data can be collected from animals and humans. By pioneering the use of virtual reality to test memory in realistic large-scale environments we have shown that similar neuronal representations are used by humans and animals to find their way around, and that it is possible to understand memory for where things are in terms of the actions of neurons within the brain. Because loss of spatial memory is a prominent and early feature of AD, the findings will be directly relevant to understanding and monitoring the progression of this disease. As well as being a challenge in its own right, understanding the basic neuronal mechanisms by which the brain remembers the spatial context of events, will also have knock-on effects for the progress of medical and therapeutic science. For one example, it can help us to understand how new memories are triggered when a novel event occurs, and how this might go wrong so that memories are lost, and how such loss might be avoided by drugs. For another example, we will test the idea that unwanted intrusive memories in posttraumatic stress disorder occur because the representations of the sights, sounds and feelings associated with a traumatic event have become disconnected with the representations of the specific context in which they occurred.

Technical Summary

Our memories are critical to who we are, and depend on the hippocampal formation (HF) and its interactions with other areas. Damage or dysfunction in this system in dementia, epilepsy, stroke, or posttraumatic stress disorder (PTSD) can cause debilitating mnemonic impairments. The precise neuronal and systems-neuroscience mechanisms supporting memory are unknown, leaving a gap between molecular and physiological knowledge of neurons and synapses and behavioural, structural and electrophysiological measures in human health and disease.
To bridge this gap, I propose a convergent series of behavioural, neuropsychological, functional neuroimaging and electrophysiological experiments in healthy volunteers, neurological patients and behaving rodents, integrated via computational modelling. I will use spatial memory as a model system, using similar tasks in humans and rodents, to begin to understand the neural mechanisms of episodic memory and how they fail in conditions such as dementia and PTSD.
I aim to build a quantitative computational understanding of: i) The neuronal representations underlying memory for environmental spatial locations; ii) The dynamics of these representations, focussing on rhythmicity in the theta band; iii) How novelty affects the neuronal mechanisms of memory, including the creation of new representations; iv) How the mechanisms of spatial memory extend to episodic memory, including the effects of traumatic content or neurological damage.

Proposed research includes: 1) Electrophysiological recording and 2-photon microscopic calcium imaging of the activity of place cells and grid cells in rodents navigating in open environments and in head-fixed virtual reality; 2) Testing my computational model of how place cells and grid cells represent environmental locations, and developing it to include the effects of novelty, development and reconsolidation; 3) Extending the model to human spatial memory and the effects upon it of novelty, neurological damage and Alzheimer?s dementia, using fMRI and studies in neurological patients; 4) Understanding the role of theta-band rhythmicity in neural computation and the coordination of processing across brain regions, using magnetoencephalography in healthy volunteers and intracranial recording in epilepsy patients; 5) Extending the model to include the role of the HF in episodic memory: using fMRI to whether the HF supports recall by providing: attractor dynamics for recall; conjunctive codes for binding together the disparate elements of an event; pre-existing contextual associations for the formation of new memories. 6) Understanding the interaction of the HF with the amygdala and sensory systems in supporting memory for context and content of traumatic /fearful memories, and how this fails in PTSD.

Publications

10 25 50
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Barry C (2012) Grid cell firing patterns signal environmental novelty by expansion. in Proceedings of the National Academy of Sciences of the United States of America

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Bird CM (2015) Consolidation of Complex Events via Reinstatement in Posterior Cingulate Cortex. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Bird CM (2012) The hippocampus and spatial constraints on mental imagery. in Frontiers in human neuroscience

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Bisby JA (2013) Negative affect impairs associative memory but not item memory. in Learning & memory (Cold Spring Harbor, N.Y.)

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Bisby JA (2015) Extinction learning is slower, weaker and less context specific after alcohol. in Neurobiology of learning and memory

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Brewin CR (2014) Contextualisation in the revised dual representation theory of PTSD: a response to Pearson and colleagues. in Journal of behavior therapy and experimental psychiatry

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Bush D (2014) What do grid cells contribute to place cell firing? in Trends in neurosciences

 
Description Advanced grant
Amount € 2,429,964 (EUR)
Funding ID NEUROMEM 
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 10/2016 
End 09/2021
 
Description EU FP7 FET STREP
Amount € 302,691 (EUR)
Funding ID SpaceCog 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 03/2013 
End 02/2016
 
Description Principal Research Fellowship
Amount £2,242,793 (GBP)
Funding ID 202805/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2021
 
Description Comment in New Scientist 2015 
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 Comment in New Scientist on research on implanting memories during sleep, 09 March 2015.
Year(s) Of Engagement Activity 2015
URL http://www.newscientist.com/article/dn27115-new-memories-implanted-in-mice-while-they-sleep.html#.VP...
 
Description Comment in The Scientist 2013 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Commented in The Scientist on the discovery of grid cells in humans. 5 August 2013

Contact from members of the public
Year(s) Of Engagement Activity 2013
URL http://www.the-scientist.com/?articles.view/articleNo/36881/title/Mapping-Humans--Mental-GPS/
 
Description Comment on BBC News website (July 2013) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Commented on BBC News story regarding implanting false memories into mice. 25 July 2013.

Contact from other journalists
Year(s) Of Engagement Activity 2013
URL http://www.bbc.co.uk/news/science-environment-23447600
 
Description Comment on BBC news website (April 2013) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Commented on BBC News story regarding the memory benefits (or otherwise) of fist clenching. 25 April 2013. http://www.bbc.co.uk/news/health-22270716

Contact from other journalists
Year(s) Of Engagement Activity 2013
URL http://www.bbc.co.uk/news/health-22270716
 
Description Invited talk at the Kavli Institute for Theoretical Physics 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited talk at the Kavli Institute for Theoretical Physics "Neurophysics of Space, Time and Learning" Santa Barbara 1-3 Feb, 2014. Video of talk made available on website
Year(s) Of Engagement Activity 2014
URL http://online.kitp.ucsb.edu/online/neuro14/burgess/
 
Description Keynote address: Amsterdam Memory Slam 2012 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited Keynote address: Amsterdam Memory Slam, Amsterdam, Netherlands, 30-31 August, 2012.

Discussions with other scientists
Year(s) Of Engagement Activity 2013
 
Description Plenary lecture, Robotics: Science & Systems 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact • Plenary lecture, Robotics: Science & Systems, Berlin, 26th June, 2013.


Interest from roboticists regarding the neural basis of navigation
Year(s) Of Engagement Activity 2013
 
Description Report in The Guardian on grid cells and imagery 
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 Report on our research on grid cells and imagery in The Guardian, 10/03/2016.
Year(s) Of Engagement Activity 2016
URL https://www.theguardian.com/science/neurophilosophy/2016/mar/10/grid-cells-come-into-play-when-the-i...
 
Description Report on Bird et al., (2015), Today.com 2015 
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 Report on Bird et al., (2015), Today.com, 02 Nov 2015
Year(s) Of Engagement Activity 2015
URL http://www.today.com/health/want-preserve-memory-more-vividly-follow-these-steps-t52596
 
Description Report on grid cells and imagery, Wellcome Trust website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Report on our research into grid cells and imagery on the Wellcome Trust website
Year(s) Of Engagement Activity 2016
URL http://blog.wellcome.ac.uk/2016/03/21/wellcome-trust-research-round-up-21-03-16/
 
Description Report on traumatic memories in Daily Mail 
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 Report on our research on traumatic memories in the Daily Mail 11 May 2016.
Year(s) Of Engagement Activity 2016
URL http://www.dailymail.co.uk/sciencetech/article-3583047/Hindsight-isn-t-wonderful-thing-brains-trauma...
 
Description Report on traumatic memories on UCL website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Report on the UCL website about our research on traumatic memories, 11 May 2016
Year(s) Of Engagement Activity 2016
URL https://www.ucl.ac.uk/news/news-articles/0516/100516-bad-experiences-lose-context/
 
Description Royal Society Meeting 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Royal Society Theo Murphy discussion meeting "Space in the Brain: cells, circuits, codes and cognition" - organised (with Tom Hartley, John O'Keefe and Colin Lever) and spoke, 1-3 May 2013, Chicheley Hall, UK.
With publication of articles in Phil Trans Roy Soc B

The procedings are in press in a special issue of Phil Trans Roy Soc B
Year(s) Of Engagement Activity 2013
 
Description TED talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact A talk at a TED event - video on TED website. Approx 500000 views in the following year.

Various correspondence from members of the public who viewed the video.
Year(s) Of Engagement Activity 2011