Dr Marko Nardini

Researchers at IoO and Moorfields are developing new treatments for currently incurable eye disease.

Genetic mutations disrupting the retinal transduction cascade lead to dysfunction and degeneration of photoreceptors. In the world's first clinical trial of retinal gene replacement therapy, young adults with defects in the gene encoding the RPE65 protein had healthy copies of the missing gene inserted into the cells of the retina, leading to sight improvement. A major goal is to evaluate this type of treatment in children, who have less advanced retinal disease and so are most likely to benefit. News on the clinical trial.

Research Questions

Behavioural consequences of inherited retinal disease: relating genetic mutations to structural and functional changes via ocular imaging and psychophysics.

Developing new tests for early retinal and cortical visual function; evaluating new trials of treatment.

Plasticity of cortical visual processing after interventions to treat sensory impairment at the retina.

Collaborators

Profs Tony Moore, Gary Rubin, Robin Ali, Mr James Bainbridge, Profs Graham Holder, Andrew Stockman (UCL-IoO / MEH)

Dr John Wattam-Bell, Profs Janette Atkinson and Oliver Braddick (Visual Development Unit, UCL / Oxford)

Funding

2011-14 Understanding the developmental course of retinal dystrophies: from genes to behaviour. Fight For Sight project grant.

2009-14 Special Trustees of Moorfields Eye Hospital, Moorfields Eye Hospital / Institute of Ophthalmology NIHR Biomedical Research Centre.

Related publications

Bainbridge, J. W. B. et al (2008). Effect of Gene Therapy on Visual Function in Leber’s Congenital Amaurosis. N Engl J Med 358 2231-2239 [PDF]

Sensory information is uncertain. Two means of reducing uncertainty are integrating multiple estimates (e.g. vision and touch), and interpreting present information in light of prior knowledge. Human adults use such strategies to reduce the uncertainty in their sensory estimates of physical properties, and to maximise reward in simple visuo-motor tasks.

Research Questions

How do abilities to integrate multiple information sources to reduce sensory noise develop?

How is statistical information about the world collected and integrated with sensory information to reduce uncertainty?

How does the ability to take own sensory and motor capabilities into account when choosing a course of action develop in childhood, while these capabilities are changing rapidly?

What is the neural basis for development of mature sensory integration?

Collaborators

Prof Denis Mareschal (Birkbeck), Rachael Bedford (IoE)

Funding

2011-14. Economics of perceptual and motor decisions in childhood. ESRC, grant RES-061-25-0523.

2008-11 Learning to combine sense and experience for optimal perceptual judgments. ESRC, grant RES-062-23-0819 (with Denis Mareschal).

2010-11 Integration of information for 3D shape perception in the developing visual brain. University of London Central Research Fund.

2008-11. PhD studentship: prior knowledge and sensory integration. ESRC (with Denis Mareschal).

Publications

M Nardini, R Bedford, D Mareschal (2010). Fusion of visual cues is not mandatory in children. Proc. Natl. Acad. Sci. U. S. A. 107 (39), 17041-17046. [PDF]

R Thomas, M Nardini, D Mareschal (2010). Interactions between "light-from-above" and convexity priors in visual development. Journal of Vision, 10(8):6. [PDF]

M Nardini, P Jones, R Bedford, O Braddick (2008). Development of cue integration in human navigation. Current Biology, 18, 689-693. [PDF]

Spatial cognitive development raises three central questions. First, to what degree are different spatial concepts either innate or dependent on experience? Second, do our representations of space use only the egocentric reference frames dictated by our sensory and motor systems, or do we also possess more abstract, viewpoint-independent representations? Third, given that the human brain seems to encode spatial information in several parallel systems that may develop at different rates, how do these representations interact, and how are they selected or integrated to guide behaviour?

Major new insights into these problems come from recent work characterising the neuronal basis for spatial representation and behaviour in model organisms and humans. Spatial tasks are closely comparable between species, and direct comparisons increasingly show close correspondence in their neural bases. For example, the role of the hippocampus in spatial memory and navigation has been characterised in rodents, in human patients, and in healthy humans imaged via functional magnetic resonance imaging (fMRI) while navigating in virtual reality. It has also very recently become possible to study the functional development of neuronal populations encoding spatial information in very young rats.

Studies of development of human spatial cognition have found striking dissociations in the maturation rates of different representational systems. Those enabling simple body-referenced and view-based recall emerge early; those enabling flexible landmark use and integration of multiple spatial information sources appear much later in childhood. Developmental research is increasingly using cue controlled environments enabling isolation of spatial representational systems identifiable with distinct neural substrates in animal models and human patients. The major challenge is to bring these approaches close enough to relate human developmental behavioural data directly to neural mechanisms of developmental change.

 

Collaborators

Prof Neil Burgess, Dr John King (UCL), Dr Hugo Spiers

Funding

2010-16. Development of human spatial cognition.
James S. McDonnell Foundation Scholar Award.

Previous funding

2007-08. Young children's use of visual landmarks: view matching or cognitive mapping? ESRC, grant RES-000-22-2486 (with Janette Atkinson).

2006-07. Perception/action interactions in children's spatial representations. ESRC, grant RES-000-23-1474 (with Oliver Braddick).

2006-07. Interactions between landmark and self-motion cues for navigation. John Fell OUP Research Fund (with Oliver Braddick).

Publications

J Bullens, M Nardini, C F Doeller, O Braddick, A Postma, N Burgess. (2010). The role of landmarks and boundaries in the development of spatial memory. Developmental Science 13, 170-180. [PDF]

M Nardini, R Thomas, V Knowland, O, Braddick, J Atkinson (2009). A viewpoint-independent process for spatial reorientation. Cognition, 112, 241-248. [PDF]

M Nardini, J Atkinson, O Braddick, N Burgess (2008). Developmental trajectories for spatial frames of reference in Williams syndrome. Developmental Science, 11, 583-595.[PDF]

M Nardini, J Atkinson, N Burgess (2008). Children reorient using the left/right sense of coloured landmarks at 18-24 months. Cognition, 106, 519-527. [PDF]

M Nardini, N Burgess, K Breckenridge, J Atkinson (2006). Differential developmental trajectories for egocentric, environmental and intrinsic frames of reference in spatial memory. Cognition, 101, 153-172. [PDF]