Testing for material-specific effects in long-term memory: evidence from amnesia and functional neuroimaging.

Lead Research Organisation: Cardiff University
Department Name: Sch of Psychology

Abstract

A number of diseases, such as epilepsy, dementia, stroke and viral infections, result in memory difficulties, in particular our ability to remember events from the past (long-term memory, LTM). Two regions, the hippocampus and perirhinal cortex, are thought to make an important contribution to LTM as damage to either of these areas results in memory problems. It is unclear, however, whether these two brain regions work together to support LTM, or whether they play distinct roles, particularly for visual memory. The proposed research addresses this question by testing whether the hippocampus is necessary for scene, but not face or object, memory, and if the perirhinal cortex is involved in face and object, but not scene, memory.

Two different techniques are used to address this question. First, we ask patients with damage to the hippocampus and/or perirhinal cortex to perform memory tasks in which they are required to remember whether they have previously seen items from our three visual categories. We wish to know whether damage to these two brain structures results in distinct patterns of memory impairment. Second, we ask healthy participants and patients to undertake memory tasks in an MRI scanner; this allows us to pinpoint which parts of the brain are recruited during memory processing, and to see if the hippocampus and perirhinal cortex show distinct patterns of activity for different visual categories. The findings from these two parts of the grant will be used to refine current ideas about how the hippocampus and perirhinal cortex support LTM, and to develop new models and predictions, that further our knowledge of how damage to these brain areas results in memory difficulties across different diseases.

The final part to the grant aims to use the information we gather from our patient and imaging studies to improve memory in individuals with hippocampal damage. We propose to show that if patients concentrate on the individual details of objects this will help boost their memory for words referring to these objects. If we can demonstrate evidence of transfer from visual to verbal stimuli, this will help clinicians and patients develop better strategies for improving memory in everyday situations.

Technical Summary

Long-term memory (LTM) is a critical part of our ability to maintain social interactions and navigate accurately in our environment; not surprisingly, therefore, loss of LTM - common to many neurological disorders (dementia, epilepsy, stroke) - can have a significant impact on independent living and general well being. The high frequency of memory impairment after brain damage also has a major financial cost to society, and a key goal for cognitive and clinical neuroscience therefore, is (a) to understand the genesis of memory impairment, (b) to elucidate the functional role of brain regions considered necessary for memory and (c) to use this scientific knowledge to make progress aimed at intervention after memory impairment.

The proposed project contributes to these important questions by undertaking novel experiments aimed at identifying how two brain regions within the medial temporal lobe (MTL), the hippocampus and perirhinal cortex, contribute to memory for exemplars from different visual categories (faces, objects and scenes). It addresses novel data emerging from patient experiments in which amnesic patients with hippocampal damage do not show a global deficit in LTM (as predicted by most models), but instead reveal memory difficulties that are modulated by category (good memory for faces despite poor memory for scenes, Taylor et al., 2007). Such material-specific differences are not easily explained by current theories of human LTM, and there is an urgent need for more research aimed at obtaining further data to help refine these models.

The experiments proposed here involve neuropsychological and neuroimaging approaches (the latter in both patients and healthy controls) to ask under what circumstances the hippocampus and perirhinal cortex contribute to memory for different visual categories. A unique strength of the proposal is the application of the three main paradigms used in the field to measure LTM (relational processing, memory confidence and source memory); this means that we can test key hypotheses from all existing models, and ensures that we obtain definitive evidence about the role of the hippocampus and perirhinal cortex in visual memory. This knowledge is then used to undertake an experiment aimed at asking whether we can improve verbal memory in amnesia by stressing encoding of object features. This experiment has significant translational potential, and provides a stepping stone to further work aimed at remediating some of day-to-day difficulties experienced by amnesic individuals.

Publications

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Hodgetts CJ (2020) The role of the fornix in human navigational learning. in Cortex; a journal devoted to the study of the nervous system and behavior

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Hodgetts CJ (2017) Ultra-High-Field fMRI Reveals a Role for the Subiculum in Scene Perceptual Discrimination. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Hodgetts CJ (2017) Distinct contributions of the fornix and inferior longitudinal fasciculus to episodic and semantic autobiographical memory. in Cortex; a journal devoted to the study of the nervous system and behavior

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Karahan E (2019) Cognitive and White-Matter Compartment Models Reveal Selective Relations between Corticospinal Tract Microstructure and Simple Reaction Time. in The Journal of neuroscience : the official journal of the Society for Neuroscience

 
Description Neurodem Cymru Steering Committee
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Participation in advisory committee
 
Description Clinical Infrastructure Call
Amount £6,700,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2015 
End 06/2015
 
Description Clinical Infrastructure Call
Amount £40,800,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2015 
End 06/2015
 
Description Clinical Research Training Fellowship
Amount £110,000 (GBP)
Organisation Association of British Neurologists (ABN) 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2012 
End 02/2015
 
Description Global Challenges Foundation Award
Amount £500,000 (GBP)
Funding ID MR/P024696/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 03/2019
 
Description Multidisciplinary PhD Pilot Scheme
Amount £550,000 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 09/2013 
End 09/2018
 
Description Project Grant
Amount £1,400,000 (GBP)
Funding ID MR/N01233X/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2017 
End 08/2021
 
Description Wellcome Trust ISSF Scheme
Amount £24,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2016 
End 12/2016
 
Description Wellcome Trust ISSF Scheme - Fellowship
Amount £50,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2016 
End 12/2016
 
Description Wellcome Trust Strategic Award
Amount £5,900,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2015 
End 09/2020
 
Description Wolfson Foundation
Amount £1,000,000 (GBP)
Organisation The Wolfson Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2015 
End 06/2015
 
Title Hippocampal Subfields Consortium 
Description Development of standardised approaches to assessment of hippocampal subfields via engagement in international hippocampal subfields consortium 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2018 
Provided To Others? No  
Impact Bringing together researchers to work collaboratively on protocols for imaging, and in time the development of a standardised tool for the community. 
URL http://www.hippocampalsubfields.com
 
Description Dementias Platform UK 
Organisation MRC Dementias Platform UK
Country United Kingdom 
Sector Academic/University 
PI Contribution Part of the DPUK Imaging Group; contributed to discussions about approaches.
Collaborator Contribution Enabled our involvement in DPUK
Impact None yet.
Start Year 2015
 
Description Investigation in autoimmune limbic encephalitis 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborator on an MRC Clinician Scientist Fellowship on amnesia and the medial temporal lobes: an investigation in autoimmune limbic encephalitis
Collaborator Contribution Support for a MRC Clinician Scientist Fellow to undertake research on related amnesic conditions
Impact None yet
Start Year 2013
 
Description Testing memory in amnesia 
Organisation Bangor University
Department School of Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution Design of experimental tests of memory and new functional neuroimaging protocols
Collaborator Contribution Identification and testing of suitable patients for our MRC grant
Impact Multi-disciplinary - imaging and patient work
Start Year 2012
 
Description Testing memory in amnesia 
Organisation The Walton Centre NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Design of experimental tests of memory and new functional neuroimaging protocols
Collaborator Contribution Identification and testing of suitable patients for our MRC grant
Impact Multi-disciplinary - imaging and patient work
Start Year 2012
 
Description Testing memory in amnesia 
Organisation University of Oxford
Department Nuffield Department of Clinical Neurosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Design of experimental tests of memory and new functional neuroimaging protocols
Collaborator Contribution Identification and testing of suitable patients for our MRC grant
Impact Multi-disciplinary - imaging and patient work
Start Year 2012
 
Title Cognitive app 
Description A new app for the detection of dementia 
Type Of Technology Webtool/Application 
Year Produced 2020 
Impact The app is currently being used to test for feasibility of identification of dementia in low-to-middle-income countries 
 
Title Online cognitive testing battery for different memory networks 
Description We developed an online cognitive battery for collection of data linked to different brain networks involved in dementia 
Type Of Technology Webtool/Application 
Year Produced 2018 
Impact The online battery is being used to collect data in key UK population cohorts 
 
Description Cardiff Brain Games & Primary Assemblies 2015 
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 All day public engagement activity aimed at KS2 school-children and their parents, held in the Cardiff Museum. It involves presentations, workshops and demonstrations.
Year(s) Of Engagement Activity 2014,2015,2016,2017
URL http://sites.cardiff.ac.uk/cubric/3200-visitors-to-the-cardiff-university-brain-games/
 
Description Cardiff Brain Games and School Assemblies 
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 Activities and talks organised at the Cardiff Museum throughout the day, with free attendance to children and parents, as well as other members of the public

Primary School Assemblies on the Brain

Increased interest in our primary school assemblies
Year(s) Of Engagement Activity 2012,2013,2014
URL http://www.cardiff.ac.uk/news/articles/brain-games-event-success-10556.html
 
Description Cardiff SciScreen 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Discussant around a film 'Iris' about dementia and aging, also involving a presentation to the audience around diagnosis and patient needs;

Further requests to undertake involvement in public engagement activities related to dementia
Year(s) Of Engagement Activity 2014
URL http://www.cardiffsciscreen.co.uk/
 
Description Cardiff Sciscreen - Away From Her 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Gave a talk / took part in a debate regarding the film Away From Her, related to forms of dementia
Year(s) Of Engagement Activity 2016
 
Description Dementia and Stigma Debate (House of Lords) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Attendance at a high-level dinner discussion at the House of Lords, with parliamentarians, scientists, funders and the public, to discuss the impact of stigma on dementia and quality of life as we age

This event resulted in a report 'New perspectives and approaches to understanding dementia and stigma', released by the Medical Research Council and the think-tank International Longevity Centre UK (ILC-UK), in collaboration with Alzheimer's Research UK, Alzheimer's Society and supported by the drug company Pfizer.
Year(s) Of Engagement Activity 2014
URL http://www.ilcuk.org.uk/index.php/publications/publication_details/new_perspectives_and_approaches_t...
 
Description Member of the Seren Network 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Network to encourage bright sixth-formers in Wales to achieve their academic potential and gain access to information about leading Universities. Engage via mentoring and participation in events
Year(s) Of Engagement Activity 2016,2017
 
Description Newspaper article 
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 Wrote an article on different forms of dementia for major national Welsh newspaper.
Year(s) Of Engagement Activity 2017
 
Description Pint of Science, Beautiful Mind 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Took part in presentation and debate around memory and dementia for Pint of Science. Almost 100 members of the general public attended the event, and increased interest in Cardiff University research and participation in research was achieved.
Year(s) Of Engagement Activity 2017
 
Description SET for Britain 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Discussion about the science; dissemination around the topic

None noted
Year(s) Of Engagement Activity 2013
 
Description Secondary School Work Experience 
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 Schools
Results and Impact Full day work experience for secondary school children interested in Psychology and Neuroscience. Brain anatomy courses, neuropsychological testing and design of psychology experiments.

Students reported interest in following-up a career in Psychology and Neuroscience; request to do the activity again for other work experience students.
Year(s) Of Engagement Activity 2013