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Wednesday, November 4, 2009

Constantin von Monakow & Brain Plasticity

Constantin von Monakow was born in Bobresovo, Poland at that time, on this day in 1853.  He was to become one of the most eminent neuroanatomists, neurologists and psychiatrists of his age.  Below I attempt to highlight some of his achievements, relying mainly on Mario Wiesendanger's informative article in the Comptes Rendus Biologies (Wiesendanger, 2006).

Von Monakow spent most of his life in and near Zürich, Switzerland, where his family moved in his youth. He studied medicine, worked with Eduard Hitzig at one of the first psychiatric research clinics in continental Europe, the Burghölzli. The principal investigators at the clinic led by Auguste Forel had fully recognized the role of cerebral organization in mental illness.  Hitzig and Gustav Theodor Fritsch were among the first to localize function in the cerebral cortex with electrical stimulation electrodes.  Hitizig hired von Monakow as assistant and taught him histological methods.  At a brief visit with the famous anatomist Bernhard von Gudden in Munich, he familiarized himself further with silver impregnation methods that permitted him to visualize degenerating nerve fibers. Injury to brain tissue, precipitated by hemorrhagic bleeding, stroke or trauma, results in the degeneration of the nerve cell connections between the affected location with other parts of the brain.  Tracing degenerating nerve fibers, therefore, could be used to examine pathways among brain structures.

Von Monakows independent research would begin under small and unusual circumstances as attending physician at St. Pirminsberg, a psychiatric asylum near Bad Ragaz, a spa not far from Zürich.  One day, while inspecting the premises, he discovered a brand new microtome stowed away in an unused closet.  He knew how to use the microtome and turned the pantry into a small histological laboratory to get a series of experiments off the ground that would uncover the brain's visual pathway.  The faculty of the University of Zürich accepted the publication of the results of these experiments as qualification for the right to teach (habilitation), and he started to give lessons at the university without salary, while attempting to maintain a private practice for neurology and general medicine in the city.  The practice barely supported him. Yet he managed to continue his research in a small laboratory he sat up for himself.

Eventually in 1894, von Monakow received a call from the University of Innsbruck, Austria, to assume a chair in psychiatry.  The offer compelled the government of Zürich to make a counterproposal which von Monakow happily accepted, although the appointment was only at the level of associate professor. Despite the lower rank, the new post permitted him to continue his research in his laboratory, which became known as the Brain Institute and serve as the director of a psychiatric policlinic.  Finally, 17 years after he graduated from medical school, he had garnered a stable position, securing financial support for his research and a stable income.

Von Monakow worked full-time at the university until his retirement at the age of 70, and continued another four years as honorary professor and director of his laboratory, which became known as the Brain Institute. During his years as professor, he maintained an active journal club, enjoying regular visits from a number of eminent scientists and physicians. Among others, the fourth director of the Burghölzli, Auguste Forel, and the famed neuroanatomist and neurologist Constantin von Economo were in attendance as much as the founder of psychotherapy, Carl Gustav Jung, whose long-hidden self-analysis, known as The Red Book, has just been published. 

Constantin von Monakow passed away in 1930 at the age of 77, and his former responsibilities were divided among several successors.  In 1962, Konrad Akert succeeded in recreating Von Monakow's Brain Institute as The Institute for Brain Research, which has remained a vibrant site for world-class neuroscience research to the day. 

Constantin von Monakow was a prolific writer and published a long list of scientific articles, book chapters, books, hand books and anatomical brain atlases.  His work entitled "Die Lokalisation im Grosshirn und der Abbau der Funktion durch kortikale Herde" (Localization in the Cerebral Cortex and Loss of Function Produced by Cortical Lesions) arguably became one of his most notable contributions.  In this book, he laid out comprehensively the principles of chronogenic localization and diaschisis.

Von Monakow's observations suggested that the cortical and subcortical components of a brain pathway cooperate in precisely timed sequence to synergistically effect coordinated brain function, though the components may not necessarily be situated near each other.  He called the cooperative, yet distributed localization of brain function chronogenic localization.  His concept ran counter to the widely-held belief at the time that brain function was localized in circumscribed centers dedicated to particular tasks.  Phrenology represented the most extreme and popular variation of that idea.  History would prove von Monakow right.  The functional brain imaging studies conducted today commonly render multiple loci of activation in cerebral cortex when the participants execute a task, confirming that brain functions are indeed carried out by distributed nerve cell networks involving a number of cortical areas.

For example, using functional magnetic resonance imaging, my colleagues and I observed numerous foci of activation scattered across cerebral cortex when people with severe visual disability read Braille with their fingertips (Melzer and others, 2001). Intriguingly, cortical areas in the occipital lobes were involved that process visual information in sighted people. The animation below shows these foci in a 36 mm slice through cerebral cortex. The poles of the occipital lobes point to the bottom at the finish.


As another significant finding, von Monakow observed that acute damage to one component of a brain system immediately depressed the function of the system's unharmed components, disabling their coordinated cooperation.  He called this immediate loss of adequate control over integrated brain function diaschisis.

Von Monakow noted furthermore that with time functionality would return, though a residual deficit almost always remained. Differences in the timing of the recovery of various aspects of the lost function would bare its chronogenic localization.  The recovery would help identify each component's contribution to the integrated function.  Nerve cell plasticity would permit the unharmed components to reorganize and reintegrate. However, he could only speculate on the underlying cellular mechanisms.

Von Monakow proposed that the increased use of existing, undamaged collateral nerve cell connections within cerebral cortex stimulated the development of new connections, recruiting nerve cells in other cortical areas for the recovery of lost function. Furthermore, he recognized that exercise benefited recovery, suggesting that exercise-related stimulation facilitated the growth of new, more extensive nerve cell connections. As a consequence novel behaviors would be learned to compensate for residual deficits.

In own research, my colleagues and I observed that nerve cells in the vicinity of a stroke lesion in the cerebral cortex respond to sensory input only at short latency in the days after the infarct.  By contrast, responses at long latency were suppressed (Melzer and others, 2006). Inputs from intracortical nerve cell connections are thought to drive the long latency responses.  The observed suppression is entirely consistent with von Monakow's diaschisis.

Von Monakow's concept of distributed nerve cell networks underlying brain function was astoundingly modern.  His ideas of recovery of function were profoundly forward looking.  More than a century after their inception, his ideas are still inspiring intense research.

References
  • Melzer P, Maguire MJ, Ebner FF (2006) Rat barrel cortex as a model for stroke analysis. Soc Neurosci Abst:583.13.
  • Melzer P, Morgan VL, Pickens DR, Price RR, Wall RS, Ebner FF (2001) Cortical activation during Braille reading is influenced by early visual experience in subjects with severe visual disability: a correlational fMRI study. Hum Brain Mapp 14:186-195.
  • Monakow von C (1914) Die Lokalisation im Grosshirn und der Abbau der Funktion durch kortikale Herde. J.F. Bergmann, Wiesbaden.
  • Wiesendanger M (2006) Constantin von Monakow (1853-1930): a pioneer in interdisciplinary brain research and a humanist. C R Biol 329:406-418.
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