Walking down the rabbit hole

Thomas Graham Brown is a colorful and largely forgotten figure in the history of neuroscience. He was unknown to me before I encountered a rabbit hole that, as is my wont, I could not resist. Rabbit holes are always surprises and the path that leads to them is a big chunk of the fun. Here is my path to theThomas-Graham-Brown-rabbit-hole:

  • Need to prepare a new lecture on social neuroscience for my undergraduate class on Tuesday
  • Look up social neuroscience review on Pubmed
  • Read several interesting reviews and get several useful leads, have new thoughts
  • Then I see an eLife piece by the great neuroscientist Eve Marder, who never fails to articulate an interesting and important point in spectacularly clear and entertaining fashion
  • I click on said article which is happily open access (all articles in eLife are)
  • I read about grandma elephants and Eve’s (not only is Eve a great scientist but also a warm and good friend to innumerable others, including luckily me; I just cannot refer to her as anything but Eve) concern that we overlook how earlier scientists were “able to extract deep insights into biological processes with simple experiments and clear thinking”
  • To illustrate her point, Eve points to Henry Dale and Thomas Graham Brown
  • I know about Dale’s clever experiments, beautifully described and contextualized in Elliot Valenstein’s The War of the Soups and the Sparks: The Discovery of Neurotransmitters and the Dispute Over How Nerves Communicate
  • I don’t know about Thomas Graham Brown and his “[anticipation of] much of what we understand about the spinal cord circuits that are important for walking”
  • I like walking and spend a fair amount of time thinking about walking
  • I google-search Thomas Graham Brown walking

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  • Second to a I’m-sure-very-worthwhile wallpapering firm is a link to a history of Thomas Graham Brown
  • Click —- Rabbit hole alert!!! 

Rabbit holes

Going down the proverbial rabbit hole started with Lewis Carroll’s indomitable character, Alice. Alice was a little bored as she sat next to her sister who was reading a pictureless and conversation-less book – what is the use? was her thought. She entertained the notion of making a daisy chain when she saw the White Rabbit run by, muttering to himself. Alice was “burning with curiosity” as she followed the White Rabbit and saw him disappear down a rabbit-hole. Then “Alice had not a moment to think about stopping herself before she found herself falling down what seemed to be a very deep well.” And that, my friends, is how it (falling down a rabbit hole) is done. Easy as burning curiousity and impetuousity. Prior boredom not necessary.

For me, I wasn’t bored in the slightest when I saw enough – walking, mountaineering, physiology – so that I, like Alice, found myself falling down into a rabbit-hole before I could stop myself. The rabbit hole is an article entitled Thomas Graham Brown (1882-1965): Behind the scenes at the Cardiff Institute of Physiology, written by J Gareth Jones, EM (Tilli) Tansey, and Douglas G Stuart and published in the Journal of the History of Neurosciences (vol 20, pp 188-209) in 2011. This post draws nearly entirely from this outstanding article.

Thomas Graham Brown was both important and colorful

Thomas Graham Brown was a valued friend and colleague of Sir Charles Sherrington a 1932 Nobel laureate. Brown published up a storm in the 1910s and ’20s and invented the concept of a central pattern generator or CPG. He was Sherrington’s intellectual equal and was elected to the Royal Society for his scientific contributions. However, shortly after this election, Brown “lost interest” in physiology, opting to spend most of his remaining life as a mountaineer, climbing in the Alps as well as in Alaska and the Himalayas. He was never married. He maintained his connection to the University College Cardiff, even as he gallavanted around mountaineering, and lived alone in the turret above his laboratory in the Cardiff Institute of Physiology for more than a decade. Brown’s contributions were rediscovered and lauded by Anders Lundberg, a modern guru of CPG who recognized the value of Brown’s work.

Brown was a colorful character, not wanting for self-confidence. He had a picture of himself and another Professor with the future King Edward VIII. Brown “inked out [the offending Professor] and [had] the picture rephotographed! Just him and the King-to-be, nothing else to see here, keep moving!

During WWI, Brown was part of the medical corps. He decided to go for a walk and shells started to fall around him. He was advised to run, which he did not do, reasoning that the situation was “not very dangerous because the Bulgars don’t often shell a single man.” Additional evidence of his nonchalance to personal danger comes from his continued scholarship during the war. He even proofread “a 100-page article… in Salonika with 8-inch Howitzer shells bursting around his mosquito-ridden tent.”

Thomas Graham Brown and the concept of a central motor command

Brown’s most important contribution was to demonstrate that walking did not depend on a chain of reflexes, as Sherrington initially considered, but rather on a central circuit. Brown keyed in two key features of this circuit, now termed a CPG. First, the spinal cord alone is capable of producing the rhythmic gait. The spinal cord does not need input from the brain but is fully capable of producing stepping on its own. Second, the spinal cord can produce walking even without any sensory feedback. So much for the chain of reflexes idea!


This figure shows alternating flexion (top) and extension (bottom) produced by spinal cord stimulation. At right is Graham’s model for a CPG, showing separate flexion and extension half-centers that mutually inhibit each other. This figure was adapted by Jones et al (2011) from Graham Brown’s 1911 article entitled The intrinsic factors in the act of progression in the mammal, published in Proc R Soc B 84:308–319.

At the time that Brown was working, methods to interrogate central circuits were lacking. Nonetheless, Brown advanced the field by proposing a heuristic model for how a stepping CPG could work. He postulated that separate flexion center and extension half-centers mutually inhibited each other so that as flexion occurred, extension was prevented from occurring and then as the inhibition of extension ran down, extension occurred and flexion was suppressed. The details are not accurate but the basic idea is spectacularly and presciently correct.

Brown published voraciously during the 1920s until he was elected to the Royal Society. Then Brown’s published output, although not his research, stopped on a dime. No more. He turned his attention principally to mountaineering.

But Brown dabbled in science. He continued to teach. He also built a contraption that he could use to film cats as they walked at different speeds and inclines, a fancy treadmill. And he made films. Decades later, in the 1960s, these films were re-discovered and analyzed by Lundberg. Brown never published anything about his treadmill work and thus it is difficult to imagine what he was thinking. Yet, the observation of locomotion at different speeds and in different patterns points to a fundamental truth of CPGs, viz that one CPG can give rise to many related movements at a range of speeds.

The concept of CPGs today

Brown hit darn close to the mark of our modern conception of central pattern generators. Today we consider a central pattern generator to be a central circuit (aka a connected group of central neurons) that can produce a default movement such as locomotion or chewing or swallowing and so on. Activation of the CPG can produce this default movement even if the CPG is cut off from both descending inputs from the brain and sensory inputs from the periphery. In other words, the CPG is a field commander that can operate even in the absence of direction from Headquarters or information from the local patrols. Of course, input from HQ and from patrols is useful and the field commander’s actions will be better conceived and executed with these inputs. Similarly, a CPG puts out a movement such as walking that works in ideal circumstances but is likely to fail under the most trivial of challenges, such as walking from linoleum to carpet, in the absence of sensory feedback and descending control.

There is one more key feature of CPGs. As discovered by Eve Marder and others, working primarily in invertebrate preparations (Eve studied the digestive rhythm in the stomatogastric ganglion of the lobster; Sten Grillner studied leech swimming), CPGs are versatile as heck. The same CPG can put out closely related movements such as running and walking, trotting and galloping. All that is required is a little neuromodulation – a monoamine here, a neuropeptide there and voilà, walking becomes running or jogging becomes sprinting.

Most CPGs are in the spinal cord or brainstem. As Brown showed, cats have a spinal CPG that allows for stepping. We have one too. So why is walking such a challenge for patients with spinal cord injury? A large piece of the answer is that as nice as being bipedal is for us, it is accompanied by a big problem – that of balance. Balance requires the hindbrain, including the cerebellum. The spinal cord alone cannot keep us upright. In addition, our spinal CPG for locomotion is not as complete as that in quadrupedal mammals such as cats. So even if a spinal cord-injured patient were kept upright, s/he would not step as robustly as would a spinalized cat, for example.

Brown’s approach to mountaineering is CPG-inspired

In their excellent history of Thomas Graham Brown, Jones and colleagues describe Brown’s approach to mountaineering:

“The essential characteristic he brought to the sport was a force of will with an outstanding strategic aptitude. His approach was scientific. During the winter, in his room in the CIP, he meticulously thought out new routes after careful study of the available evidence.”

When I read this description of Brown’s strategy, I immediately thought of Ian Waterman, about whom I recently wrote. In brief, Ian Waterman had a viral illness at age 19, after which he had lost all touch and proprioceptive feedback from the neck down. Although there was absolutely nothing wrong with his motoneurons or his muscles, Ian could not move when his condition first appeared. He slowly taught himself to move, as long as he could see his body.

Today, Ian is the only one with such a sensory loss (out of roughly a dozen known cases) that can stand or walk independently. [Only in the light!! He has to be able to visually check supervise his own movements since he gets no other sensory feedback from his own movements.] Essentially, Ian gets his brain to activate CPGs and then makes sure that the CPGs are working properly by using vision.

Imagine that Ian wants to drink some tea. To do this, he must not only reach the cup, grasp it, and bring it to his face; but do all this without falling over. So first Ian figures out how to ensure his balance in the face of a shifting center of mass. Then he figures out how to reach, grasp, and carry the cup. Accomplishing the grasp and carry of the cup is complicated by the fact that Ian does not get any information about the weight of the cup. Here is Ian’s blow-by-blow description of how he reaches “for a cup of tea,” as quoted by Jonathan Cole in Losing Touch (Oxford University Press, 2016):

“I am initially being aware of my body position to hang it all off. Sitting down, my legs are in a tripod, sitting on a chair, and I have a mental image of this. Having my arm resting on the table is a good triangle position, and I know I can then reach the cup. Once the framework is safe and I can monitor hand out and in, then I can begin. I see it all except what the fingers are doing behind the cup, but I have learned to do this [by grasping without using the handle]. I don’t know how heavy the cup is, so pick it up and monitor it visually. I need to see my arm up to my face, but then I can feel the cup with my face…. This is all very controlled and involved.”

I will say that is indeed involved. All that to reach for a cup of tea. And all of that is absolutely needed because CPGs work using sensory feedback. CPGs don’t need sensory feedback for their default output but their default output is useless for any real life movement.

I see a great similarity between Ian’s planning to drink a cup of tea or to walk and Brown’s planning an upcoming mountain ascent. Both require cognitively demanding plans that are deliberately and consciously thought out ahead of time. Ian gives walking the same attention as Brown gives mountaineering. [I do wonder if Brown recognized any connection between his approach to mountaineering and what he had learned about CPGs.] The similarity is acknowledged in the title of Jonathan Cole’s first book about Ian: Pride and a Daily Marathon (MIT Press, 1991). For Ian, every day of getting up, standing, walking, reaching, carrying and so on is a mental marathon, an accomplishment that is incredibly hard won.

Rabbit hole concluded. That was fun. Now back to social neuroscience….

1 Comment »

  1. Maybe he was impressed enough with the elegance of the cpg that he decided to use his to walk rather than to study walking. Or maybe his love of walking drove him to study the mechanism.


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