Craters, blisters and Pringles: Do small irregularities on the brain surface give us clues about its functions?
The shape of the brain could tell us much about its function, but it may be the details that are important, as Professor Paul Fletcher explains.
Franz Gall, the originator of phrenology believed that the shape of the brain determined the shape of the skull and that careful measurement of the latter could be used to assess the characteristics of the mind. While phrenology has, for good reasons, fallen into disuse, there is still wide interest in the importance that the shape of the brain may have for its function and dysfunction. This is reflected in the fact that many neuroscientists spend a great deal of time examining variations in the folding and thickness of the brain surface.
There are good reasons for this. After all, the brain’s shape is governed by how it develops, and many abnormalities of mental function are thought to arise from changes in this development. Perhaps through assessing its shape we may learn more about these abnormalities.
To the eye, the surface of the brain consists of a complex system of hills (gyri) and valleys (sulci), some shallow, some several centimeters deep. These folds in the surface emerge as the brain grows. It is possible to compute an overall measure of this folding-tendency and to see if it differs between healthy people and patients with a range of illnesses such as schizophrenia and Alzheimer’s disease.
Several theories have been put forward to explain why the surface folds as the brain grows: some centre around the space-saving properties of a neatly folded structure (after all, the brain needs to fit into the skull and larger skulls would be very inconvenient), while others relate its folding to the development of important connections between nerve cells. The possibility that the folding does relate to development of connections in the brain, and that this folding is measurably abnormal in cases of neurological and psychiatric illness, may tell us how these connections are altered in such illnesses.
My Cambridge colleague, Dr Lisa Ronan came up with the idea that it may be more informative to look not at the big (centimeter scale) hills and valleys but rather at the subtle (millimeter scale) variations in shape that are apparent across the entire surface. In a paper published in the current issue of International Journal of Neural Systems, These small-scale variations demonstrate that if we tried to unfold the brain surface (the cortex) we would not be left with a flat surface, but rather a very uneven one consisting of an array of small bumps and dimples. More specifically, there are many areas that are positively curved (small mounds) and even more that are negatively curved (saddle- or Pringle-shaped). Studies that explore overall folding (gyrification) ignore these small-scale properties but, it is suggested, these smaller curves may more closely reflect the development of the connections in the cortex.
The paper is the result of an international collaboration between Cambridge, Oxford, Edinburgh and Massachussetts, led by Dr Ronan and myself, at the Brain Mapping Unit, Department of Psychiatry. We speculate that it may be possible to infer how the cortex has grown by exploring the relative distributions of positive and negative curvature.
Perhaps these subtle changes in curvature arise from uneven growth during development. For example, if we imagine a small patch of the surface, if the centre part grows faster than the surroundings, it will protrude like a blister (positive curvature), whereas if the surrounding grows more quickly, it will ruck up (like a saddle or Pringle). We think that these changes could have important implications for the connection lengths on the brain surface and this, in turn may have important implications for the efficiency of processing. In the paper, we provide an initial test for this hypothesis, showing that profiles of small-scale curvature differ across species with more marked degrees of curvature (especially negative curvature) in humans.
While the proposed link between small-scale intrinsic curvature and connectivity within the cortex is speculative, our approach suggests novel ways of exploring brain structure in patient groups, thereby providing information about development of connectivity patterns in the healthy and unhealthy human brain.
Professor Paul Fletcher is Bernard Wolfe Professor of Health Neuroscience and a Wellcome Trust Senior Research Fellow in Clinical Science at the University of Cambridge.