The story of Grey Level Index: forty years of misleading consistency?

1. Why the history of GLI technology is important today?

In 2018 all progressive mankind interested in quantitative neuroanatomy and cortical mapping celebrated 40th Anniversary of a rather significant scientific event: the first publication of quantitative approach to analysis of the laminar structure of brain cortex, called “Grey Level Index”, or GLI. Today the significance of this and similar approaches to quantitative analysis of cortical profile is explained by increasing demand for precise anatomical localization of cortical activity measured by modern functional and structural brain imaging studies.

The method was published by Axel Schleicher, Karl Zilles and professor Hans-Joachim Kretschmann in 1978, practically at the same time, in two different papers . One paper was entitled “Automatische Registrierung und Auswertung eines Grauwertindex in histologischen Schnitten” (Automatic registration and evaluation of a gray standard index in histological sections, Schleicher, A., Zilles, K. & Kretschmann, H.-J., Verh. anat. Ges. (Jena), 72, 413, 1978), and the second – “A quantitative approach to cytoarchitectonics. I. The areal pattern of the cortex of Tupaia belangeri. (Zilles, K., Schleicher, A. & Kretschmann, H.-J., Anat. Embryol. 153, 195. 1978). The registration of the grey level index was described as “a new, automatic, high resolution measuring procedure” developed for quantitative evaluation of the laminar pattern of different cortical areas. By the way, Tupaia belangeri, also known as northern tree shrew (take a look, for example, at this paper), is a rather cute-looking and very interesting animal. Regarded as one of the closest relative of primates, it is famous for many reasons, including size (shrews are, actually, smallest known mammals), remarkable circadian rhythm of body temperature, and similarity of the eye structure to human eye; however this is quite another story.

Our story is about modern approach to human brain cortex mapping. Recently I was very surprised by finding the reference to my old paper (Istomin, Shkliarov, 1984) in the article published in Neuron by professors Katrin Amunts and Karl Zilles.  The paper “Architectonic mapping of the human brain beyond Brodmann” (Neuron 88, December 16, 2015, 1086-1107) outlines a challenging roadmap for the future development of cytoarchitectonic brain mapping, and allegedly describes novel “imaging and optical methods, 2D and 3D quantitative architechtonics, as well as high-performance computing, including analyses of big data.”

Despite its goal to discuss future challenges, careful reading of this paper reveals an interesting fact: criteria for defining borders between cortical areas in “modern” computerized 3D cortical map – a super-challenging task which supposed to use super-power of supercomputing, and incorporate tera- and petabytes of super-high resolution images is actually based upon… a 40 years-old technology of GLI profiling in 2D sections, slightly modified by more recent, but still quite 20 years old improvements in statistical testing.

Puzzled by this inconsistency, I decided to analyze the history of GLI-related publications in order to understand current status of this technology.

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