Dorsal and ventral cortical stream function in normal development and in at-risk infants born prematurely

Lead Research Organisation: University College London
Department Name: Psychology

Abstract

Brain networks to interpret information from the eyes are among the earliest to develop, and so we can use measures of vision to tell us whether an infant?s brain is developing normally. Within the brain there are two major visual networks, the ?ventral stream? for identifying patterns, objects and faces, and the ?dorsal? stream which registers the movements and positions of objects to control actions such as reaching. We have found that the ?dorsal stream? is particularly vulnerable in children with certain genetic developmental disorders e.g. Williams Syndrome, autism, and in children who have suffered brain damage, often due to periods of oxygen lack around birth.

We will devise new ?brain wave? measures for infants and children alongside child-friendly computer tests to measure the normal course of relative development in dorsal and ventral streams. We will use different types of motion (dorsal) e.g. the outward movement that occurs when we move forwards, and the relative movement by which we see an object move against its background. We will compare these to children?s ability to see similar but static versions of these patterns, which are processed in the ventral stream.

We will apply these tests to study development in infants born very prematurely, who are at risk of lifelong problems, ranging from attention deficits (ADHD) to severe cerebral palsy. As clinical trials of therapies in the newborn periodwith special intervention therapies are introduced, a major difficulty is the long delay between intervention around birth, and much later ages at which these children?s abilities can be measured. We will bridge this gap by designing safe, effective tests for babies in the first months of life, to measure visual processing in the dorsal and ventral streams. We will compare our test results with MRI brain imaging analyses carried out at birth) and with development up to 18 months, to identify which brain systems are most vulnerable to damage, which can recover or be substituted, and which infant tests are the best predictors of later abilities.

Our longer term goal is to design and use these sensitive tests for specific aspects of vision to evaluate the effectiveness of early treatment in children at high risk of later problems, whether they arise from genetic disorders or early brain damage, so that effective therapies can be introduced as early as possible to reduce lifelong mental health problems and reduce healthcare and educational costs.

Technical Summary

This proposal combines basic research on the development of global visual processing in infancy and childhood, with clinical application using these methods for assessment of at-risk, very premature infants.
Global visual processing occurs beyond primary visual cortex in two cortical streams, the ?ventral? underpinning recognition of patterns, objects and faces, and the ?dorsal? stream for spatial and motion processing and visual control of actions. We have shown differential human development of these two streams in infancy and childhood, using form and motion coherence sensitivity as markers of ventral and dorsal global processing. We have identified ?dorsal stream vulnerability?, a relative deficit or delay in global motion compared to global form sensitivity in a range of neurodevelopmental disorders including Williams Syndrome, and hemiplegia. Our methods have been followed by others, extending dorsal vulnerability to autism, Fragile X and congenital cataract.
Basic research: to understand differential development and vulnerability, we will devise new behavioural and electrophysiological measures to analyse specific sub-systems within these two streams beyond primary visual cortex. We will develop and use high density VERP recording methods with a geodesic array, to distinguish the spatio-temporal signatures of specific global processes for motion and form, e.g. coherence detection, segmentation, localization of optic flow. We will investigate the functional onset of these processes in normally developing infants under 6 months of age. With psychophysical methods specially adapted for normally developing 4-12 year olds, we will track their developmental trajectory, at a time when vulnerability in developmental disorders is apparent. We will relate individual variations to other measures of visuocognitive and visuomotor performance.
Proof of concept clinical study: we will apply these new VERP measures to infants born very prematurely (under 32 weeks gestation). This will extend our previous work on premature infants using tests of primary cortical function, to test higher level visual processing in dorsal and ventral streams. Results will be compared with measures of brain structure from neonatal MRI, and neurological/behavioural development up to 18 mo. The longer term goal is to use these visual brain processing measures to assess brain plasticity and development, and so meet the need for reliable early surrogate outcome measures in the first months of life. These would predict outcome in a number of high-risk groups, including children with specific genetic developmental disorders, and so gauge the effectiveness of early intervention in improving cognitive status in later childhood.

Publications

10 25 50
 
Description Emeritus Fellowship
Amount £20,000 (GBP)
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2011 
End 05/2015
 
Description Behavioural / VEP assessment of infants born very prematurely 
Organisation Imperial College London
Department Imperial College Academic Health Science Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution We have jointly studied and followed up infants born very preamturely in the Hammersmith Hospital
Collaborator Contribution Co-operation in referral of patients and access to clinical and MRI data
Impact PMID: 18334617 PMID: 17920430 PMID: 16500047 PMID: 17513071 Multidisciplinary: Neuroscience, Psychology, neonatology, neuroimaging
Start Year 2006
 
Description Behavioural / VEP assessment of infants born very prematurely 
Organisation University of East London
Country United Kingdom 
Sector Academic/University 
PI Contribution We have jointly studied and followed up infants born very preamturely in the Hammersmith Hospital
Collaborator Contribution Co-operation in referral of patients and access to clinical and MRI data
Impact PMID: 18334617 PMID: 17920430 PMID: 16500047 PMID: 17513071 Multidisciplinary: Neuroscience, Psychology, neonatology, neuroimaging
Start Year 2006
 
Description High-density VERP study of development of global form and motion processing 
Organisation Uppsala University
Department Department of Psychology
Country Sweden 
Sector Academic/University 
PI Contribution Participation in data collaction, software development, and data analysis
Collaborator Contribution Access to VEP equipment and opprortunity to test children before our own laboratory was set up, and subsequent joint data collection
Impact Paper accepted for publication in Current Biology: "High-density VERPs show reorganization of global form and motion processing between infants and adults"
Start Year 2006
 
Description Italian ECAB 
Organisation Catholic University of the Sacred Heart
Department Pediatric Neurosurgery Unit
Country Italy 
Sector Academic/University 
PI Contribution We have provided test materials and advised on their translation into Italian
Collaborator Contribution Translation of test materials and planned evaluation with paediatric patients in Rome
Impact no outputs yet
Start Year 2012
 
Description Paediatric visual assessment suite based on eye-tracker 
Organisation Tobii Technology AB (Stockholm)
Country Sweden 
Sector Private 
PI Contribution We have advised on software specifications for the suite and collaborated in evaluation of pre-prototype with infants in our laboratory
Collaborator Contribution Loan of equipment that has given us experience in automated infant eye tracking
Impact We have identified developments that are required to implement this as a paediatric assessment suite and have advised the company on development. We have collaborated with Dr Peter Jones and others at IoO in development and evaluation of an application of the Tobii eye tracker for visual acuity assessment which has led to one publication and another submitted, and advised on a current PhD project by Ms Eliza Burton.
Start Year 2008
 
Description Paediatric visual assessment suite based on eye-tracker 
Organisation University College London
Department Institute of Ophthalmology UCL
Country United Kingdom 
Sector Academic/University 
PI Contribution We have advised on software specifications for the suite and collaborated in evaluation of pre-prototype with infants in our laboratory
Collaborator Contribution Loan of equipment that has given us experience in automated infant eye tracking
Impact We have identified developments that are required to implement this as a paediatric assessment suite and have advised the company on development. We have collaborated with Dr Peter Jones and others at IoO in development and evaluation of an application of the Tobii eye tracker for visual acuity assessment which has led to one publication and another submitted, and advised on a current PhD project by Ms Eliza Burton.
Start Year 2008
 
Description Pediatric Longitudinal Imaging, Neurocognition, and Genetics 
Organisation University of California, San Diego (UCSD)
Department Centre for Human Development
Country United States 
Sector Academic/University 
PI Contribution Provision of visual testing methods and protocols and analysis of data arising from these
Collaborator Contribution recruitment of particpnats, collection of other behavioural and demographic data, neuroimaging and analysis
Impact Schork AJ, Madsen KS, Baare WFC, Akshoomoff N, McCabe C, Newman E, Atkinson J, Braddick O, Bloss CS,Murray SS, Schork NJ, Jernigan TL. (2012, October). Common repeat polymorphism in the dopamine transporter gene SLC6A3 is associated with stop signal reaction time (SSRT) and motion coherence threshold (MCT). Society for Neuroscience Annual Meeting, New Orleans, LA.
Start Year 2012
 
Description Visual function in premature and at-risk infants 
Organisation University of Oxford
Department Department of Paediatrics
Country United Kingdom 
Sector Academic/University 
PI Contribution VEP and behavioural testing of (a) healthy infants born very prematurely (b) infants at risk or diagnosed with cerebral palsy, participating in a trial of neurotrophic dietary supplement. Follow up of neurocognitive development of these groups with tests we have developed of components of children's attention, and visual global form and motion processing
Collaborator Contribution Access to patients and clinical information
Impact PMID: 18007197 and conference presentations. Project (b) is currently underway (started 2009) Multidiscipinary: Paediatrics, nutrition, neuroscience
Start Year 2008
 
Title ABCDEFV 
Description Test battery for evaluating fuctional vision in children aged 0-4 years. Offered to test publishers for commercial evaluation 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2010
Development Status On hold
Impact
 
Title ECAB 
Description Test battery for attention in pre-school children 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2010
Development Status On hold
Impact demonstration of distinctive profiles of attentin ability in Williams' and Down's syndrome 
 
Description Advice to families & patient group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact Families with children at rsik for neurodevelopmental disorders who participate in our research receive individual advice and reports on their children's visual and visuocognitive assessment Presentation to Williams Syndrome Association, Bristol, 2008 Membership of Professional Committee of Williams Syndrome Association

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Year(s) Of Engagement Activity 2006,2007,2008,2009
 
Description Advise Chilean neonatologists on assessment 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Senior Neonatal staff from major Santiago hospital discussed their needs with us.

Funding proposal based on our advice submitted to Chilean government
Year(s) Of Engagement Activity 2011
 
Description Child Vision Research Society, London 2007, Cardiff 2009 & Amsterdam, 2011 
Form Of Engagement Activity A formal working group, expert panel or dialogue
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 Keynote speaker + 4 other presentations in 2007 Invited speakers + 2 other presentations, 2009; 2 presentations, 2011

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Year(s) Of Engagement Activity 2007,2009,2011
 
Description European Academy for Childhood Disability, Newcastle 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? Yes
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Health professionals
Results and Impact presentations to audience of paediatricians and therapists. EACD Conference Gateshead, 10-12 Oct 2013.
Platform presentation: A novel visual evoked potential latency measure identifies deficits of cortical development in infants with perinatal brain injury
M Andrew, C Montague-Johnson, J Lee, A Kopuri, P Sullivan, J Parr, J Wattam-Bell, J Atkinson, O Braddick.
Poster presentation: The fixation shift test identifies early attentional deficits in infants with perinatal brain injury. M Andrew, C Montague-Johnson, A Kopuri, J Parr,
P Sullivan, J Wattam-Bell, O Braddick, J Atkinson

New methods of infant testing communicated to a wide proifessional audience
Year(s) Of Engagement Activity 2013
URL http://eacd2013.org/
 
Description Review chapter for healthcare professionals 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Health professionals
Results and Impact Atkinson, J., & Nardini, M. (2008). Visuospatial and visuomotor development. In J. Reed & J. W. Rogers (Eds.), Child neuropsychology. Oxford: Blackwell.
Atkinson J, Braddick O (2010) Objective behavioural and electrophysiological measures for assessing visual brain function in infants and young children. In G N Dutton & M Bax (eds) Visual Impairment in Children Due to Damage to the Brain London: MacKeith Press
Atkinson J, Braddick O (2011). Linked brain development for vision, visual attention and visual cognition in typical development and developmental disorders. In Riva D (ed.) Brain Lesion Localization and Developmental Function: Frontal Lobes, Limbic System, Visuo-Cognitive System Mariani Foundation Paediatric Neurology Series 26, John Libbey Eurotext Ltd.
Braddick O, Atkinson J (2011). Neurophysiological and behavioural aspects of visual assessment: correlation with neuroimaging. In Riva D (ed.) Brain Lesion Localization and Developmental Function: Frontal Lobes, Limbic System, Visuo-Cognitive System Mariani Foundation Paediatric Neurology Series 26, John Libbey Eurotext Ltd.
Atkinson, J., & Braddick, O. (2012) Visual and visuocognitive development of children born very prematurely. Ch. 32 (pp. 543-566) in: Preedy VR (Ed.) Handbook of Growth and Growth Monitoring in Health and Disease. New York: Springer.


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Year(s) Of Engagement Activity 2008,2010,2011,2012
 
Description presentations to optometrists & child neurologists 2007-12 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Invited lectures to Child neuropsychology Courses in Oxfordshire & London, Nova Southwestern School of Optometry (Florida), University Hospital Vall d'Hebron Barcelona; Keynote presentation at the World Congress on Optometric Globalization, 2008; Invited presentation at European Assocn for Childhood Disability, Rome, 2011; Invited presentation at 4th Int'l Conference on Cerebral Palsy, Pisa 2012;

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Year(s) Of Engagement Activity 2007,2008,2009,2010,2011