Neural Systems and Circuits for Binocular Vision

When we see a child of 18 months reach out and pick up a toy, we are witnessing in this everyday event a most remarkable skill. The child's brain uses vision to direct a movement to the position and depth of the toy that the child desires. The child's grasp needs to be correct for the object: small toys need fingers; large ones may need two hands.

Our laboratories study one important component of this skill, namely judging the depth of objects. In looking towards an object, we use our left and right eyes in co-ordination. The centre of each eye points accurately towards the object. In this way, the most sensitive part of each eye points directly at the object. If the object is close to us, then each eye rotates a little bit inwards, towards the nose, to achieve this.

As well as controlling the movement of the eyes very accurately, the brain also puts together the visual images from the left and right eyes and uses these in co-ordination as well. The separation of the two eyes means that each eye gets a slightly different picture of the visual scene: the bigger the difference between the images, the bigger the change in depth out in the visual world. These differences in the images are called "binocular disparity" and the entire process is called "binocular vision".

Binocular vision gives us a sense of depth; it can tell the brain how far away objects are, what size they are and where one object sits in relation to another. We are now improving our understanding of what actually happens in the brain when we see things in depth. Whilst solving this puzzle is an interesting problem in itself, it turns out that binocular vision often goes wrong during development. About 1 in 50 people have a problem with their binocular vision and the problem is often apparent as a squint or "lazy eye".

Large numbers of children have surgical operations on their eyes to get them straight again: there is about one operation every 25 minutes of each working day in the UK alone. At present, most of this surgery is cosmetic: the eyes end up without a squint but they do not work properly in co-ordination. Even after the corrective surgery, the nerves leaving one eye may never make their proper connections with the rest of brain and the person may become blind in that eye for the rest of their life. Sometimes later in life, people suffer an injury or disease in the other, "good" eye and become totally blind. All of this implies a large health care cost and a significant burden of disease, partly because these problems are so common.

Nobody really knows whereabouts in the brain the necessary connections are disrupted. For a while, many scientists thought that this disruption happens exactly at the point where the nerves from the eyes first reach the cerebral cortex. It is now clear that this is only a partial explanation. Our aim is to find out exactly where and how binocular vision happens in the brain.

Part of our strategy uses brain imaging with humans. We will be able to use a new and more powerful brain scanner provided by the MRC to Oxford. We will use this to find out how the human brain responds to binocular depth by studying normal individuals and comparing them with people who have problems with their binocular vision. Although we work with human brain imaging, investigations with animals are also part of our research strategy. Here we can examine directly the neural signals and circuitry that are responsible for binocular depth.
Once we have this new knowledge we will be able to understand how problems with binocular vision begin in early life, what parts of the brain are affected and whether we can propose some specific eye training that could help to prevent or even alleviate the problems.

Design of Studies
1) Parametric assessment of brain's response to binocular depth: this involves collection of brain signals (BOLD fMRI in the case of human studies; electrical activities of nerve cells in the case of animal studies) with simultaneous performance of a behaviourally relevant task. Change of behavioural state will be a parameter in the studies. The human studies will include the investigation of former patient groups. Conservative estimates of required statistical power can be gained from large number of studies conducted with these techniques before.
2) Identification of brain regions processing depth. High-field MRI at 7-Tesla will be used to measure the response of cortical areas and sub-compartments within those areas. Structural and functional measures will be used to gain converging evidence.

Technical Measurements
1) High-field MRI at 7-Tesla: BOLD & fMRI, diffusion tensor imaging, multi-voxel pattern analysis, objective identification of cortical areas, visual behaviour within the scanner
2) Multi-electrode neurophysiology in identified locations in experimental animals: statistics of neural firing, correlated firing within populations, identification of "brain signatures" of perceptual events, linking neuronal signals to functional MRI.

This research has the capacity to benefit three areas of activity, outside of the immediate network of systems neuroscientists, who study the encoding of information by neuronal cells and circuits within the brain.

First, understanding the brain is important for translational neuroscience: the application of scientific studies of the brain to clinical problems. In our own case, elements of the proposed work will build on our current collaboration with John Elston (Hospital Consultant: Oxford Eye Hospital) to examine vision in individuals who have been treated for disorders of binocular stereoscopic vision. This is a common childhood disorder: correction of squint is the second-most common reason for elective surgery in childhood in the UK. This project will provide basic knowledge about how the brain processes visual depth and 3-D shape, which can be applied in the context of the ongoing translational studies.

Second, there is a wide community of scientists and technologists who are interested in the encoding of information, particularly the question of whether studies of the nervous system can provide any novel insights that they could exploit in their own work. These scientists and technologists are in the fields of computer science, intelligent devices and the knowledge-based economy. They will be the driving-force behind new technological developments, which are acknowledged as an important factor in creating new economic growth in established Western economies, like the UK. The studies proposed will be significant for this group.

Third, the wider public continues to have a fascination with understanding the workings of the brain, as evidenced by the large number of popular science books and media presentations. This research will ultimately feed into this activity, thereby enhancing public understanding of science and contributing to the social and cultural life of the UK.

Transfer of the benefits of this research will be facilitated in a number of ways: publication of papers, interdisciplinary communication of results and sharing of data will be the main route for the clinicians, scientists and technologists in related fields; wider discussion of neuroscience and appropriate use of public media will be the route for the general public; and pursuit of applied and translational research will be main route for involving more health practitioners.

The time scale on which these benefits will begin to be felt is likely to be 3 years in respect of the health practitioners, scientists and technologists in related fields and perhaps 4-5 years in respect of the other groups. However, this project is addressing a major scientific issue about the functioning of the brain and it is reasonable to argue that the impact of this project is likely to be prolonged, lasting hopefully some 10-15 years after the initial benefits have been felt.