Elsevier

Brain Research Reviews

Volume 59, Issue 1, November 2008, Pages 74-95
Brain Research Reviews

Review
Thomas Graham Brown (1882–1965), Anders Lundberg (1920–), and the neural control of stepping

https://doi.org/10.1016/j.brainresrev.2008.06.001Get rights and content

Abstract

Thomas Graham Brown (1882–1965) undertook experiments on the neural control of stepping in the University of Liverpool laboratory of Charles Sherrington (1857–1952) in 1910–13 and his own laboratory in 1913–15 at the University of Manchester. His results revealed the intrinsic capability of the spinal cord in the guinea pig and cat to generate a stepping output pattern whose timing did not depend upon descending or sensory inputs. This idea was then revolutionary because the prevailing viewpoint was that the stepping rhythm was generated by spinal reflexes. Sadly, Graham Brown's GBR peers gave little credence to this seminal accomplishment, except perhaps Sherrington, who waxed but largely waned on the potential significance of the work. It remained for the Swedish neuroscientist, Anders Lundberg (1920–), to rescue Graham Brown's concepts from obscurity: in seminars presented in several countries between 1957 and 1980, and in widely read articles and reviews (1965–1981). Graham Brown had proposed mutually inhibitory connections between a pair of intrinsically active flexor and extensor “half-centers” on each side of the spinal cord, with the rhythmic output modulated by sensory proprioceptive input. Lundberg, Elzbieta Jankowska (1930–), and their colleagues provided seminal, compelling evidence for spinal half-center interneuronal circuitry implicated in the control of stepping and Lundberg and Ingemar Engberg (1935–2005) made behavioral EMG observations on unrestrained cats that supported a central generation of the rhythm. Subsequently, models of the spinal pattern generators for mammalian locomotion have become progressively more complex but they mostly still include a half-center component.

Introduction

In current reports on the neural control of terrestrial locomotion, much emphasis is placed on the capability of interneurons (INs) in the spinal segments innervating the limbs to generate the main features of the locomotor rhythm, including its flexor and extensor phases and the timing of each muscle's activity during each step. Such IN circuitry for each limb, now commonly termed a central pattern generator (CPG),1 is confined to relatively “low-level” ganglia in invertebrates and the spinal cord in vertebrates. It can express a locomotor rhythm that is not dependent upon ongoing descending input from higher centers and sensory feedback from passive and active body parts (for recent reviews, see Clarac, 2008, Clarac and Pearlstein, 2007, Grillner et al., 2008a, Grillner et al., 2008b, Orlovsky et al., 1999, Stuart, 2007a). Prior to the 1960s, the favored viewpoint was that locomotor rhythmicity was elicited by spinal reflex action2 even though evidence of a central nervous system (CNS) control component was available (Delcomyn, 1980). Such evidence was sporadic for invertebrates but quite substantial for mammals prior to 1920 as provided by Thomas Graham Brown (1882–1965) and later in the 1930s for non-mammalian vertebrates, most notably by Eric von Holst (1908–1962) and Paul Weiss (1898–1989).

In this brief historical article, we review the academic career and research accomplishments of Graham Brown (Fig. 1A), reflect on why his ideas on spinal pattern generation languished in near-total obscurity for so long, and document how his ideas were brought to the forefront of locomotion research in the 1960s by the Swedish neuroscientist, Anders Lundberg (1920–) (Figs. 1B,C).

A preliminary account of some of this material has been presented (Stuart, 2007b).

Section snippets

Graham Brown's academic career and research contributions

Graham Brown remains an enigma to modern-day movement neuroscientists. On one hand, his academic career had initial elements of success. He was the Professor of Physiology at the University of Cardiff from 1920 until 1947 and became a Fellow of the Royal Society in 1927. On the other hand, he published little of value to neuroscience after the early 1920s, had no pre- or postdoctoral trainees, and his seminal spinal locomotion work was rarely cited until the 1960s.

Anders Lundberg's academic career and research contributions

In sharp contrast to Graham Brown, Anders Lundberg's initial and subsequent research has had a profound impact on his neuroscientific peers for the full 53 years of its publication (1947–2000). Table 1 shows that throughout this period he mentored 14 PhD students and co-authored research articles with 60 other collaborators from 23 countries.13

Further developments and the current state-of-the-play on the spinal contribution to stepping

Speculation on how history may have developed had this or that not occurred is not a prominent branch of science but it is clearly of heuristic value to reflect on such issues (see, e.g., Kuhn, 1996). In this vein, what would be the current understanding of the contribution of the spinal cord to the overall control of locomotion without Graham Brown's discoveries that were certainly the primary motivation for Lundberg's work on the DOPA-released spinal locomotor network?

In attempting to answer

Acknowledgments

Some of the above was presented by D.G.S in a poster at the IBRO World Congress of Neuroscience, Melbourne, Australia, July 12–17, 2007 and at a Congress Satellite Meeting, “Motor Control at the Top End”, Darwin, Australia, July 18–21, 2007. For the preparation of our article we thank Anders Lundberg and John Bowles for providing some historical details, Rauni Larsson, Elzbieta Jankowska, and Lars-Gunnar Pettersson (together with innumerable others) for their help with Table 1, Nga Nguyen (AHSC

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