E1: Interactive neural systems governing emotion and social interaction

Lead Research Organisation: MRC Cognition and Brain Sciences Unit

Abstract

This project aims to understand the brain mechanisms underlying aggression and social attention (interpreting another persons focus of attention from their eye gaze, head or body orientation) and their disruption in two clinical conditions, Conduct Disorder and Autism, respectively. ||Conduct Disorder (CD) is an adolescent condition characterised by heightened levels of aggression and antisocial behaviour and has significant financial impact on society. Although CD is suspected to have a biological basis the brain mechanisms involved are poorly understood. This research uses behavioural and brain imaging experiments developed in healthy individuals to understand the brain mechanisms disrupted in CD. |A second line of research focuses on the neural mechanisms underlying social attention and their disruption in individuals with Autism Spectrum Disorders (ASD). Individuals with ASD show problems in inferring others mental states from social attention cues (i.e., that person A is interested in and may make a move towards the object that they are gazing at). However, the psychological and brain mechanisms of social attention and the aspects that are disrupted in ASD are poorly understood. The research uses behavioural and brain imaging experiments to address these issues.

Technical Summary

Understanding the neural basis of emotional and social functions in healthy individuals is crucial to understanding their breakdown in developmental or psychiatric disorders. This project uses behavioural and neuroimaging investigations of healthy and clinical populations to address the neural mechanisms underlying aggression and social attention and their disruption in specific clinical conditions. Because the project requires detailed information on the clinical groups psychiatric profiles, performance on psychological tests, and functional brain abnormalities, its success relies on the joint contribution of the MRC-CBSU and the Psychiatry Department of the University of Cambridge. ||A first series of studies focussing on aggression examines healthy individuals and a population of individuals with Conduct Disorder (CD), an adolescent condition associated with heightened levels of aggression and antisocial behaviour. The societal impact of CD is profound. Individuals with CD are at increased risk for developing mental and physical health problems and the impact of their violent and antisocial behavior is considerable. Behavioural studies are used to identify the emotional and social functions disrupted in these individuals relative to healthy controls, whereas neuroimaging investigations address the neural bases of these deficits and structural impairments that may be potential biological markers of CD. A key focus of enquiry regards an influential theory that posits that two recognised forms of CD (a childhood-onset variant in which the symptoms present prior to age 10 years and an adolescent-onset variant in which symptoms present after age 10) have different aetiological bases; specifically, it posits that only childhood-onset variant is associated with a neurological basis. Contrary to this proposal, our research to date indicates that both forms have a neurological basis. ||A second series of studies aims to understand the functional and neural mechanisms of social attention and their breakdown in Autism Spectrum Disorders (ASD) using behavioural and neuroimaging experiments. Social attention is signalled by a persons eye gaze, head or body orientation. Our perception of others social attention plays a central role in guiding social interactions. Individuals with ASD show problems in inferring others mental states from social attention cues (i.e., that person A is interested in and may make move towards the object that they are gazing at). However, the cognitive and neural substrates of social attention and the mechanisms disrupted in ASD are poorly understood.

Publications

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Beaver JD (2006) Individual differences in reward drive predict neural responses to images of food. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Beaver JD (2008) Appetitive motivation predicts the neural response to facial signals of aggression. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Bellesi M (2006) Non-convulsive status epilepticus during lithium treatment at therapeutic doses. in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

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Bishop SJ (2008) Neural mechanisms underlying selective attention to threat. in Annals of the New York Academy of Sciences

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Bishop SJ (2007) Neurocognitive mechanisms of anxiety: an integrative account. in Trends in cognitive sciences

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Bridge H (2014) Changes in brain morphology in albinism reflect reduced visual acuity. in Cortex; a journal devoted to the study of the nervous system and behavior

 
Description BB/H008217/1 BBSRC LoLa Scheme (PI L Tyler) Systems Cognitive Neuroscience of Healthy Ageing: Population-Representative Studies of Functional Plasticity and Neural Change - shared with L Tyler, F Matthews, W Marslen Wilson, J Duncan, R Henson, A Calder
Amount £700,000 (GBP)
Funding ID BB/H008217/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start  
 
Description Medical Research Council, Sir Cusrow Wadia Fund
Amount £197,751 (GBP)
Funding ID MC-A060-5PQ53 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Parkinson's Disease UK
Amount £104,746 (GBP)
Funding ID G-0603 
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description The University of Sydney International Visiting Research Fellowships/The University of Sydney
Amount £6,000 (GBP)
Organisation University of Sydney 
Sector Academic/University
Country Australia
Start  
 
Description University of Werstern Australia Programmatic Distinguished Visitor/University of University of Werstern Australia
Amount £3,696 (GBP)
Organisation University of Western Australia 
Sector Academic/University
Country Australia
Start  
 
Description Autism spectrum traits 
Organisation University of Cambridge
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution The research investigates neural abnormalities in Autism and in the extended autism phenotype (including siblings of people with autism and typical controls that show high numbers of autism traits). My research team is responsible for the design and analysis of experiments and the preparation of manuscripts, and act as collaborators on the work with unaffected siblings.
Collaborator Contribution Professor Simon Baron-Cohen has provided access to his cohort of volunteers with high functioning autism. He has also contributed his expert knowledge in this field. The collaboration has led to a further collaborative project with Dr Michael Spencer (Wellcome Clinical Fellow), Dept of Psychiatry. This work addresses neural function in children with Autism Spectrum Disorders and their unaffected siblings to study the extended Autism Spectrum phenotype.
Impact Our initial work provides the first evidence of an abnormal neural response to viewing changes in others gaze direction (posterior superior temporal sulcus (pSTS, and wider gaze network) and abnormal neural responses at rest (pSTS) in healthy, typical individuals with high levels of autism spectrum traits. In addition, we have found that variation in the number of autism traits is related to the volume of white matter in pSTS. The pSTS is associated with social function and is implicated in Autism spectrum disorders. A recent collaboration with Spencer and Baron-Cohen has shown that siblings of adolescents with Autism show a reduced neural response to viewing faces in a network of regions implicated in face perception. 20439317 22062191 Spencer, MD (Jul, 2011) A novel functional brain imaging endophenotype of autism: The neural response to facial expression of emotion, Translational Psychiatry 1, , Article number e19
Start Year 2008
 
Description Cambridge BioResource 
Organisation University of Cambridge
Department MRC Epidemiology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution The neuroimaging research is being conducted and analysed at the CBSU by my own research team. I prepared a grant application to the MRC Sir Cusrow Wadia Fund to provide administrative and technical support for the Cambridge BioResource panel
Collaborator Contribution The Cambridge BioResource (CBR) is a major initiative that has grown in the last two years into an important clinical resource. It currently comprises over 5,000 volunteers from the Cambridge region who have donated an initial blood or saliva sample for genetic analysis and have agreed to consider participating in a range of research studies. The CBR is designed to enable Cambridge researchers to select their subject sample according to their genetic make- up and demographic criteria. Funding has been obtained from the National Institute for Health Research Cambridge Biomedical Research Centre (NIHR CBRC) to support recruitment of an additional 5,000 volunteers and extraction of their DNA from blood or saliva samples over the next 4 years. Participants from CBR have been recruited for one of my own ongoing studies addressing the genetic influence on emotional brain systems. The CBR (combining both the local donor & blood donor panels) was initiated and is led by several principal investigators (PI's) across three Medical Research Council (MRC) Units or Centres, the University of Cambridge Clinical School, and the National Blood Service: Nick Wareham (MRC Epidemiology and the Institute of Metabolic Science), John Todd and CBR co- ordinator, Sarah Nutland (Medical Genetics), William Marslen-Wilson and Andy Calder (MRC Cognition and Brain Sciences Unit [CBSU]), Steve O'Rahilly and David Savage (MRC Centre for Obesity and Related Metabolic Diseases, Clinical Biochemistry, and the Institute of Metabolic Science), David Dunger (Paediatrics), Willem Ouwehand and CBR co-ordinator, Jennifer Sambrook (Haematology and NHSBT), John Bradley and Krish Chatterjee (National Institute for Health Research Cambridge Biomedical Research Centre). These PIs form a Management Committee that considers applications to access the resource volunteers.
Impact A recent grant application was successful and will be reported next year. Marslen-Wilson, W., Calder, A.J., Todd, J., Ouwehand, W., Wareham, N., O'Rahilly, S., Dunger, D., Savage, D.; Grant value: £197,751; The Cambridge BioResource: Facilitating Human Gene-Phenotype-Function Research in Cambridge: 2009 to 2013. Medical Research Council, Sir Cusrow Wadia Fund 21167188
Start Year 2007
 
Description Neural systems for anger recognition 
Organisation University of Cambridge
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided well-validated tests of facial expression recognition and have advised on other aspects of behavioural research. We have conducted, analysed and written-up experimental research addressing the neural basis of Conduct Disorder (CD) comparing both early-onset (EO-CD) and adolescent-onset (AO-CD) versions of CD. We have provided expertise in different aspects of neuroimaging to explore the neural basis of early-onset and adolescent-onset variants of CD.
Collaborator Contribution Prof Goodyer and Dr Graeme Fairchild have provided access to a cohort of participants with Conduct disorder (characterised by heightened levels of aggression and antisocial behaviour). They have also made a significant contribution to our research addressing the neural basis of emotional function in this group.
Impact 19432683 20447616 20603454 21454920 21920502 The research brings together expertise in Cognitive Neuroscience, Neuroimaging, and Psychiatry.
Start Year 2008
 
Description The perceptual representations of facial cues in healthy individuals and people with Autism 
Organisation University of Western Australia
Department School of Psychology
Country Australia 
Sector Academic/University 
PI Contribution The collaboration brings together expertise in different aspects of face perception to study perception of different facial cues in typical adults and children, and individuals with autism spectrum disorders. My own research team is responsible for the development of paradigms.
Collaborator Contribution Professor Gillian Rhodes has provided expertise in critical aspects of face perception. Her developmental laboratory also provides a means of testing young typical children and children with Autism spectrum disorders.
Impact 21333662 22072729 21199895 The research brings together expertise in cognitive neuroscience, neuroimaging, and psychiatry Top facilitate to the research I was awarded a Programmatic Distinguished Visitor, University of Western Australia Jan 2010 to Jan 2013 The research is funded by the Australian Research Council (ARC) - Center of Excellence in Study of Cognition and its Disorders, ARC, 2011-2017, $21,000,000 (Crain, Rhodes, Hodges, Coltheart, Castles, Barnier, Brock, Byrne, Demuth, Green, Johnson, Langdon, McArthur, Miller, Nickels, Piguet, Savage, Thompson, Thornton, Addis, Bishop, Calder, Halligan, Hayward, McKay, Nation, Pellicano, Rice, Young)
Start Year 2009
 
Description Visual adaptation of cues to social attention 
Organisation University of Sydney
Country Australia 
Sector Academic/University 
PI Contribution The research was conducted my research team in Cambridge. This included development of experiments, data collection and storage, data analysis, write-up of experimental results, and staff training.
Collaborator Contribution Professor Colin Clifford (University of Sydney) is a leading expert in adaptation of low-level visual properties (motion, contrast, colour, etc.). His expertise in this domain has been combined with my own expertise in face perception to examine psychological and neural mechanisms underlying the perception of facial and body cues to social attention (i.e., eye gaze, head orientation, and body orientation), and their breakdown in congenital and neurological disorders.
Impact 18473657 19254238 19467353 19223221 20661452 20016001 21078896 21873615 2010: I have secured an International Visiting Research Fellowships grant from The University of Sydney to support the collaboration 2011: Australian Research Council discovery project grant DP120102589 Title: Gaze perception and adaptation Applicants: Clifford, Prof Colin W; Calder, Dr Andrew J Total $284,000.00
Start Year 2007
 
Description ARClub Seminar Series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Presentation as part of the Autism Research Centre's seminar series to postgraduates and research staff from the Cambridge academic community.
Year(s) Of Engagement Activity 2015
 
Description Neuroesthetics Berkely 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The audience for the conference on Neuroesthetics comprises lay people, artists, and academics

The research was conveyed to a large audience of both academic and lay members, and provided an opportunity to meet with other leading researchers in the field.
Year(s) Of Engagement Activity 2007
 
Description RESUS Summer School 
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 Talk generated lots of interest and discussion

Future collaborations were discussed and joint papers were agreed
Year(s) Of Engagement Activity 2014
URL http://www.cogsci.uni-jena.de/RESUS.html
 
Description Talk - University of East Anglia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Talk generated lots of interest and questions from students

Received emails from students wishing to use my research to develop their own research
Year(s) Of Engagement Activity 2014
 
Description Talk at EPS conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact Talk at the Experimental Psychology Society Annual Meeting in London, January, 2016. Part of a symposium on the academic legacy of Andy Calder.
Year(s) Of Engagement Activity 2016
 
Description The Neurology of Emotion, Madrid 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact The event was organized by the British Council and Cosmo Caixa (Spain). I was invited to give a lecture to a mixture of health professionals, neurologists, and interested members of the lay public. Simultaneous translation was provided to make the presentation as accessible as possible.

Very good feedback from th audience regarding the interest of the research
Year(s) Of Engagement Activity 2007