BRODMANN, KORBINIAN

(b. Liggersdorf in Hohenzollern, Württemberg, 17 November 1868,d. Munich, Germany, 22 August 1918)

comparative neuroanatomy.

Brodmann is best known for his advocacy of the view that the mammalian cortex consists of six fundamental layers and for his creation of neuroanatomical maps of the mammalian brain. He took this structure to be fundamental in the sense that the cortices of all mammals are supposed to be diverse modifications of this basic six-layer structure. Further, insofar as these six layers differ over the surface of the brain in a given species, they provide a neuroanatomical basis for dividing the brain of any given species into a large number of distinct brain regions. These regions are smaller than the frontal, parietal, temporal, and occipital lobes of the brain. Brodmann’s division of the brain into distinct regions continued in wide use in the early 2000s.

Like those of many neuroscientists of his day, Brodmann’s career involved medical training, clinical practice, and periods of scientific investigation. Brodmann received his license to practice medicine in 1895, after study at the Universities of Munich, Würzburg, Berlin, and Freiburg. Practicing briefly in Munich, he contracted diphtheria. Treatment for his illness led him into an appointment as an assistant in the Neurological Clinic in Alexanderbad in 1896. At the clinic he devoted some time to the study of hypnotherapy, eventually producing a literature summary and two papers on hypnotic therapy for early volumes of the Journal of Hypnotism. Seeing this work, the clinic director, Oskar Vogt, encouraged Brodmann to abandon plans for a medical practice in favor of further education in preparation for a scientific career. Brodmann thus turned to neurology and psychiatry in Berlin, then to pathology in Leipzig where, in 1898, he received his medical doctorate with a dissertation on chronic ependymal sclerosis.

For his residency, Brodmann worked at the University Psychiatric Clinic in Jena, under the direction of Otto Binswanger, then at the Municipal Mental Asylum in Frankfurt am Main. At Jena, Brodmann used measures of blood flow as an indicator of brain volume when a person falls asleep, sleeps, and wakes. Brodmann next took up a suggestion by Alois Alzheimer to undertake microscopic investigations as a means of understanding the biological basis of psychiatric disorders. Using Weigert’s glial stain to make cells visible to light microscopy, Brodmann studied a case of thalamic gliomas. These tumors to the supporting glial cells of the thalamus were associated with behavioral impairments ranging from changes in personality to dementia. In this study, he argued for the existence of an important class of glial cells, the astrocytes. In other work, Brodmann also used a light polarization microscope to study the structure of nerve fibers. This kind of technical work was excellent preparation for his future research.

During the time Brodmann was completing his doctoral degree and his residency, Oskar Vogt had moved to Berlin, where he founded his Neurobiological Laboratory in 1898. At the laboratory, Vogt and his wife Cécile were investigating, among other things, the myelinated fiber systems of the brain. This was the standard biological project of making an anatomical determination of the structure of an organ. What was distinctive was that the brain was not just any organ. It had long been recognized as the primary organ of the mind and implicatexsd in psychological disturbances. In addition to the intrinsic interest of the brain, the work was an important response to the technical challenges to microscopy. For much of the nineteenth century, the delicacy of brain tissue and the translucence of its cells limited the quality and reliability of microscopic investigations. By applying stains that selectively colored the myelinated fibers of the brain, the Vogts hoped to overcome some of the obstacles facing previous investigators.

As the laboratory was developing nicely, the Vogts were able to recruit Brodmann to the laboratory to work on a complementary project. Brodmann was to fix brain sections in formalin, embed them in paraffin, then apply a cresyl violet staining technique developed a few years before by Franz Nissl. The relatively simple technique stains the RNA in the cytoplasm of neurons, thereby enabling an observer to determine the number, size, and form of nerve cells in the sample. This was the study of the cytoarchitectonics of the brain. Thus began the work for which Brodmann came to be best known. From 1901 to 1908, Brodmann produced a series of six papers on the structure of the cortex in distinct mammalian species. This comparative work spanned the mammalian orders of the primates, prosimians, chiropterans, insectivores, rodents, and marsupials. In some cases, such as with the rodents, several species within the order were investigated. The series culminated in his treatment of histological localization in the human cerebral cortex. These papers formed the basis for Brodmann’s 1909 monograph on the comparative anatomy of the cerebral cortex in mammals.

Brodmann maintained that, in general, it is not possible to make reliable demarcations of distinct regions of the brain by exclusive reliance on the types of cells to be found in a region. In other words, “elemental localization” was not generally reliable. The one exception to this rule that Brodmann recognized was the existence of exceptionally large pyramidal cells found anterior to the central sulcus in the motor cortex. These so-called “Betz cells” were first reported in 1874 by Vladimir Betz. Brodmann also maintained that one could not rely exclusively on distinctive characteristics of particular layers to demarcate brain regions. This technique might work to delimit the early visual processing region of the brain with its stria of Gennari, but the method is not generally reliable. According to Brodmann, the most reliable method available at the time was topographic localization, in which a region is identified by a homogeneous intrinsic structure that is heterogeneous with respect to adjacent regions. A transition of this sort is marked with a small arrow in Figure 1 One can clearly see a number of features of this transition. For example, in moving from left to right across the transition, one finds that in layer I the number of darkly stained cells in the upper portion of the layer decreases dramatically, that layer III is greatly reduced in thickness, and that layer IV subdivides into layers IVA, IVB, and IVC.

Prior to Brodmann’s research, the emerging view was that the cortex has a layered structure. Differences of opinion, however, remained concerning the number and location of the proposed layers. Some authors proposed only five layers, others as many as seven. All authors recognized the layers Brodmann identified as layers I and IV, with layer I being the closest to the surface of the brain and the other layers lying deeper. Other authors, however, either lumped or further subdivided the layers Brodmann identified as layers II and III and lumped or further subdivided what were to become Brodmann’s layers V and VI. In particular, Brodmann’s colleague Oskar Vogt faulted Brodmann for failing to recognize a seventh layer. Among those who contributed to the theory of laminar structure were Theodore Meynert, Bevan Lewis, Vladimir Betz, Santiago Ramon y Cajal, Alfred Walter Campbell, and Frederick Walker Mott. Based on developmental and comparative data, Brodmann proposed that, in mammals, the cerebral cortex is a modification of a basic six-layer structure. Brodmann maintained that the six-layer structure could be modified by having individual layers split, by having individual layers disappear with more or less completely (by fusion), and by having individual layers change in their thickness, cell density, cell size, and cell shape.

Brodmann informed his comparative anatomy with the theory of evolution in many ways. To justify his use of both comparative and developmental data to argue for the six basic layers of the cortex, he appealed to Ernst Haeckel’s biogenetic law that embryological development (ontogeny) in a species represents an abbreviated recounting of the evolution of the species (phylogeny). Brodmann also maintained that valid comparisons of neuroanatomical features, such as layer thicknesses, cell sizes, and cell densities, in distinct species must be comparisons of homologous structures; that is, they must be comparisons of structures that are modifications of a single brain structure possessed by an ancestor common to the distinct species. This is not to say that Brodmann found simple applications of evolutionary theory to all he examined. In fact, he rejected many earlier hypotheses as simplistic, insufficiently well supported by observation, and at times contradictory. For example, it had been proposed both that the more evolutionarily advanced a species the thicker its cortex would be and that the more evolutionarily advanced a species the thinner its cortex would be. Brod-mann maintained that neither such simple rule held true. Similarly it had been proposed both that the more evolutionarily advanced a species the greater its cell density would be and that the more evolutionarily advanced a species the lower its cell density would be. Again Brod-mann argued that neither such simple rule was correct. Further, he maintained that even when comparing homologous cell types, such as the Betz cells, there is no simple relation between cell size and position on an evolutionary scale. Nor is there any simple relationship between cell size and such properties as an organism’s body size, length of axon, or size of a dependent muscle.

Brodmann was consistent in the application of his general methodological principles to histopathology. He rejected earlier hypotheses that one could find modifications of individual neuronal elements corresponding to particular psychiatric or psychological problems. Instead he maintained that psychiatric and psychological disorders should be attributed to multiple changes in all the components of a given brain region, including the glial cells and vascular and connective tissue.

Brodmann also recognized one of the most fundamental features of brain mapping, namely, individual variation. Individual organisms of a given species differ, sometimes dramatically, in both intrinsic properties, such as the thickness and cell density of particular regions of the brain, and in extrinsic properties, such as the size, position, and shape. For example, in humans, there are regions of the brain that range in thickness from 1.5 to 4.5 millimeters, so that some individuals have cortices three times thicker than others. The need for methods for accurately representing this degree of variability in brain maps is part of Brodmann’s legacy.

At the end of Localisation, Brodmann turned directly to the complex issue of the possible anatomical and physiological localization of functions in the brain. When Brodmann wrote, the idea that distinct psychological functions might be performed by distinct regions of the brain had been around for about a century and had already been the subject of extensive debate. Despite the intense interest in the topic, experimental methods had largely been inadequate to the task of associating particular brain regions with particular psychological functions. One marked success had been achieved with the motor cortex, in which electrical stimulation of the exposed surface of animal brains enabled researchers to correlate regions of the brain with specific motor capacities. Among the leaders in this area were David Ferrier, Eduard Hitzig, Victor Horsley, and Herman Munk. Another success was the recognition of a role for the left parietal lobe in linguistic processing. This was spurred by Pierre Broca’s discovery of correlations between brain damage in this region and particular language deficits. Brodmann believed that his neuroanatomical findings definitively established that there must be some form of functional localization in the brain. Anatomical differences in general imply functional differences; objects with different structures carry out different functions. Given this principle, the numerous anatomical differences among the many regions of the brain he had studied implied that there must be corresponding functional differences. What, therefore, remained to be done was to work out just exactly what those functions were.

During his time at Vogt’s Neurobiological Laboratory, Brodmann was never appointed to a permanent university position, but was instead sustained by a series of grants and a heavy burden of clinical work in neurology. In addition, Brodmann assisted the Vogts in editing the Journal für Psychologie und Neurologie, which the Vogts had founded in 1902. The financial hardship on Brod-mann was exacerbated when the faculty of medicine at the University of Berlin rejected his habilitation thesis on the cytoarchitectonics of the prosimians (a suborder of primates that includes the lorises, lemurs, and tarsiers). This thesis, over and above that written for his doctoral degree, was meant to certify Brodmann’s ability to conduct independent scientific research and to prove his qualification to hold a more significant teaching appointment at the university. To all appearances, both Brodmann and Vogt remained quite bitter about this rejection for the remainder of their careers.

In search of greater economic security and more supportive colleagues, Brodmann moved to the University of Tübingen in 1910. By 1913, his habilitation thesis was accepted and Brodmann was given a professorial appointment where he taught courses on the significance of brain localization from anatomical, physiological, and clinical perspectives. In ddition to his teaching and research obligations,Brodmann retained clinical responsibilities. He served as an assistant physician, then later chief physician,of the anatomical laboratory of the psychiatric clinic. This clinical work drew his attention to various cognitive deficits, including aphasia, agnosia, and apraxia. The outbreak of the First World War placed additional demands on Brodmann’s time, which included his volunteering for work in a military hospital. In May of 1916, he assumed an appointment as the prosector at the Nietleben MentalAsylum in Halle an der Saale. Here he met the much younger Margarete Franeke, an assistant at the asylum,whom he married on 3 April 1917. Although rodmann’spersonal life was much enriched, Germany’s growing military losses in the war brought Brodmann’s scientific work to a halt.

BIBLIOGRAPHY

WORKS BY BRODMANN

“Beiträge zur histologischen Lokalisation der Grosshirnrinde. VI.Mitteilung: Die Cortexgliederung des Menschen.” Journal für Psychologie und Neurologie 10 (1908): 231–246.

Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Principien, dargestellt auf grund des Zellenbaues. Leipzig: Johann Ambrosius Barth Verlag, 1909. (2nd ed., 1925.) English translation, with biographical introduction and editorial notes, by Laurence J. Garey: Brodmann’s“Localisation in the Cerebral Cortex.” Smith-Gordon, 1994;Imperial College Press, 1999; 3rd ed. Springer Verlag, 2006.

OTHER SOURCES

Danek, A., and J. Rettig. “Korbinian Brodmann (1868–1918).”Schweizer Archiv für Neurologie und Psychiatrie 140 (1989):555–566.Vogt, Oskar. “Korbinian Brodmann.” Journal für Psychologie und Neurologie 24 (1919): 1–10.

Ken Aizawa