My name is Roger Lemon, I am a just-retired Professor of Neurophysiology at the Institute of Neurology, UCL, where I worked for 22 years, after university posts in Sheffield, Melbourne, Rotterdam and Cambridge. I am a Fellow and past Council Member of the Academy of Medical Sciences.
My main research interest is the control of skilled hand movements by the brain and is prompted by the need to understand why hand and finger movements are particularly affected by damage to the cortex, and its major descending pathways, for instance as a result of stroke, spinal injury and motor neuron disease. My experiments involve the use of purpose-bred non-human primates, since these provide the best available model for the human sensorimotor system controlling the hand.
My research is complemented by parallel studies in normal human volunteers and in patients: interactions between discoveries gained from work in monkeys and understanding the effects of neurological disorders on hand function in patients has been an important part of my career, especially when working at the Institute of Neurology, a world centre for the treatment of neurological disorders. I have helped to develop better ways of studying the human motor system, to understand the process of recovery after injury and to investigate therapies that might enhance recovery.
I am firmly of the opinion that we still need some research in monkeys to understand the complex functions of the human brain. This is fundamental research aimed at understanding normal brain function in, for example, learning, memory, emotion and, my own research area, motor skill. I believe that this work should only be carried out with careful regulation that ensures responsible, high-quality research and requires the highest possible welfare standards, driven by application of the 3Rs.
I am also keen to explain that without supporting this basic type of research, we will not get the translational benefits that results from a small but important fraction of the work that leads on to impact on the clinical conditions such as those listed above.
So I am a strong advocate for better engagement between scientists and the public about how we use animals in science, which has been vital for much of my own research.
This is my first AMA, I’m here to talk about the neuroscience of skilled movement, the miracle of the human hand, and how it is disrupted by disease, about animal research, particularly research in non-human primates, and well Ask Me Anything!
This AMA has been organised by Understanding Animal Research.
EDIT: I've now finished. Thanks for all the interest and fascinating questions. I only hope I went some way to answering some of them.
Hkw has human hand writing affected the brain over the course of the last few thousand years?
I've read about non-human primates being able to learn some sign language, is it possible that they could ever learn to write?
I am not an expert on language but it is true that both apes and monkeys can learn some forms of sign language and there have even been some studies of some rhesus monkeys where they draw and copy simple outlines (such as a figure of 8).
I have family that suffers from cerebral palsy and it is a very debilitating condition (more so in some than others) has this disorder ever been a focus of any of your research? I have never thought to ask this but is this only a human disorder or something that you have seen in primates and thus been able to study?
As a researcher do you ever find yourself anthropomorphizing your testing animals? Has there ever been a test that you struggled to perform out of empathy?
I have not directly contributed to understanding of cerebral palsy. Although I have worked with paediatricians caring for these children and I think my work has helped to explain the primacy of the motor cortex for human hand control and why this structure is so vulnerable to damage early in life. I am not aware that cerebral palsy regularly presents as a condition in nonhuman primates, but there are certainly scattered reports of monkeys with poorly-developed cortex. In terms of anthropomorphising: yes of course. I think I have always avoided the infliction of unnecessary pain to the animals in my care. If such a procedure was needed, I think I would generally try and find another way of using a less painful test or avoiding it altogether. I am very much aware that all biomedical research inflicts some harms on the animals used and it is our duty as scientists to try to minimise those harms and at all times to make sure that the benefits of the research justify the harms inflicted.
Dr Lemon, I kinda feel intimidated by all the other questions since mine is more rudimentary, but I'm gonna ask anyways. I'm playing guitar since 10 years now, and one of my goals is to play 16th triplets at 180bpm; that'd be 18 single movements of my left Hand in a second, but even after trying for a year now, I can't seem to nail a Solo that fast. Would you say (in general) that there is a maximum speed your fingers can move?
Fascinating, I think your performance is probably close to the limit. My understanding is that the limit is set not by the brain but by the response of the muscles in the hand and forearm where the maximum frequency is limited by the time it takes to develop a mechanical contraction in response to the neural control signal. This is probably in the order of 40-50 milliseconds i.e. around 20 hertz. I think this is the speed that violinists can exhibit during a vibrato sequence.
Hi Dr. Lemon, thanks for doing this AMA!
In regard to your belief that we need more research done on non-human primates' brains in order to understand more of our own, how similar are our brains motor cortex's compared to those of non-human primates?
Are there evolution gaps that you have to take into account when studying brain scans, etc.? What kinds of data can you take from a study on a non-human primate's brain and make relevant to a human's brain?
EDIT: non-human primate
There are important differences and similarities between the human brain and the brain of, for example, the rhesus monkey, which is the main model which I have used in my research. The similarities include the fact that both human and monkey brains are very similarly organised in terms of the motor map within the brain and the connections the motor cortex makes with the spinal cord and the motor neurons the control the muscles. But there are differences including the sheer size of the human motor cortex which is larger than expected (on the basis of bodyweight) and in having some unique connections, for example, with areas of the brain which are concerned with tool use which are either not developed or not developed in monkeys. What we do know is that the so-called “new” motor cortex is greatly expanded in humans. This is the region of the motor cortex which is directly connected to the muscles operating the hand and digits and particularly the thumb.
Yes, there are evolutionary differences and so it is always the case that we cannot take it for granted that a result obtained in a monkey brain will be directly applicable to the human brain. However, I am absolutely certain that our knowledge of the human motor system would be very poor indeed without the wealth of neuroanatomical and neurophysiological studies carried out in monkeys. We would not know where to start.
Will your research be applicable in creating prosthetics to replace missing fingers and hands? It is possible to make a prosthetic that is close to a true analog of a human hand and capable of fine motor skills?
My research has not been directly concerned with the design of prosthetics for missing fingers and hands. There are some very interesting developments in this area for example touchbionics. What we have achieved is a focus on the importance of sensory feedback in controlling such a prosthesis. A completely different aspect of this research is that concerning stroke patients or patients with spinal injury who have an intact hand but completely lost neurological control of it. My research has helped to develop the techniques which are now being used for a brain/machine interface to help patients of this kind. For example, braingate.
In one of Robert Sapolsky's lectures, he mentions that moving one finger is actually a command to move all fingers but suppressing all of the ones you don't want to move. Is this true and can you give some detail on this?
Yes, I think this is probably true insofar that it is impossible to move one finger without actively suppressing movement in all the others. This is partly due to the way the hand works biomechanically in that some muscles have actions on more than one digit, and partly because of the way the brain is wired up to the hand in that single neurons in the motor system connect with more than one muscle. But certainly, suppression of unwanted movement is an important part of skilled motor control.
Hi Dr. Lemon, thanks for doing this AMA.
What can researchers do to help the public understand the importance of nonhuman primate research?
I often find myself unwilling to broach the subject with non-scientists because I don't want to risk drawing up hostility towards myself, my lab, or my institution; especially since, in the past, activists have gone so far as to commit acts of terrorism against monkey researchers. Not to mention people may assume things about you even if they don't turn outwardly hostile, e.g. this person doesn't care about animals (personally, I love animals) or this person is arrogant because they believe that sacrificing a monkey or performing invasive procedures on them can be ethical. This is especially problematic because any lack of transparency makes the problem worse and further reduces the public's faith in science. One further complication is that your average person doesn't really have the background to fully understand the limitations of human and rodent research. So how do you balance your concern for your personal safety and reputation with the need to be transparent about your research?
During the course of my career I have experienced quite a lot of personal hatemail and demonstrations against my work. I always found this very upsetting and I could only continue because I have a deep belief that what I was doing was fundamentally useful. In the UK we have come through a period of intense anti-vivisectionist terrorist activity and have moved onto a more of a peaceful debate about the rights and wrongs of animal experiments. Of course I am grateful for that change. The UK now has the lowest levels of animal rights extremism that it is ever had. So it's important to use the current opportunity to try and persuade the public of the importance of medical research including that involving Non-human primates. When I look at the contributions made by monkey research in areas such as infectious disease and neurological and neuropsychiatric disorders, I am more than ever convinced of the importance of retaining the monkey model. I am also convinced that by being increasingly open and forthcoming about the research that I do, I am actually decreasing the chances of my being personally targeted by the more violent members of the antivivisection community. In the UK, the increasingly open and transparent approach to talking about the issue (see, for example, The Concordat on Openness), has helped push up public acceptance (whereas in other countries it has not). A great example of this openness can be seen with the recent Lab Animal Tour.
Hi Dr. Lemon, thank you for taking the time for this AMA. A couple of questions if I may.
Can you elaborate on "purpose-bred" primates? Would they be generalized research primates or specifically bred for your research? Do you think there are any significant differences in using purpose-bred research animals, especially as the level of intelligence increases, as compared to the wild forms?
Specific to your research, you state that damage to the cortex particularly affects hand and finger movements. Do we see little to no effect on the legs, feet, and toes based on evolving away from using them as often and as deftly as other primates?
In the UK all monkeys that are used for basic research are purpose bred in the UK. The numbers involved are usually in the order of 250 monkeys per year. For work in neuroscience a great deal of effort has gone into preparing rhesus macaques to be suitable for use in experiments which typically require a great deal of skill and intelligence to perform challenging cognitive and motor tasks. For example, monkeys are introduced at a young age to positive reinforcement techniques in which they are rewarded for performing simple actions such as pressing a button or touching a particular part of the cage. Remarkably, these monkeys can be conditioned to every requirement of the experiment provided you are willing to be patient long enough for the monkeys to understand what has to be done in order to obtain a reward. I have never done any research with wild caught monkeys so I cannot comment on any differences. I can say that purpose-bred macaques are amazingly smart and much faster than humans. For example, we trained monkeys to use a rake to obtain food rewards that were placed out of their reach and they learned this task within 12 sessions and were able to collect many rewards within a minute with no trouble.
I have not done research involving permanent damage to the cortex, but generally others have shown that damage to the hand area has its main effect on hand function with little effect on the feet and toes. Of course it depends on the size of the lesion and we know that in human stroke patients, for example, a major stroke affects all parts of the motor system including the face, speech, hand and foot function. I think there is good evidence that cortical damage in humans is far more devastating than in any animal model. Evolution has put all its eggs in the cortical basket, which has been very important for many different areas of human cultural and technological advance. However, the price we pay is that cortical damage has a proportionally more disabling effect.
I'm interested on your thoughts on the boy who had a double hand transplant.
Like you, I have been completely enthralled to see the footage of this boy. It is a remarkable achievement when one thinks of all of the connections: vascular, muscular and nervous that must be re-established by the surgeon when making these transplants. Perhaps the most amazing thing is how the boy's brain has taken on board a completely foreign set of hands and adapted its control signals to allow him a normal and dexterous daily experience.
Pool Billard Player and coach here. Do you have knowledge and explanation on, how many times some movement with hand or arm needs to be repeated, until it is automaticly possible to repeat without thinking about it? I assume for thinking, by this I mean active brain control of my hand, the nerves are too long and it takes too much time. Like the same with speech, it runs fluid without thinking how to speak one word in detail. Thank you for this ama, very interesting!
I’m sure you understand that this very much depends on the speed, skill and accuracy of the movement. If I can give you one extreme example, I believe it is true that it takes 10 years to learn how to perfectly roll a Havana cigar. But of course simpler movements can be perfected much more quickly. However, I am not sure that movements ever occur completely automatically, for example people of my age, when walking, often experience falls when they get distracted by, say, an incoming phone call (or something else in the visual horizon).
What's your favorite book to recommend to someone who has almost little to no background in this topic?
Yes indeed, have a look at The Hand: A Philosophical Inquiry into Human Being by Raymond Tallis
Have you come across primates that could be called ambidextrous? What other differences did they exhibit from the other primates of the same species who weren't?
I have no great expertise in this area although I can tell you that most of the monkeys we work with seemed well able to perform the skilled tasks with either hand. I think it is generally recognised that monkeys show hand preference for particular tasks e.g. using a tool, but they do not show hand dominance (which means you always use one hand, right or left, for all the tasks you carry out). Humans show hand dominance, but monkeys show hand preference. They may change their preferred side according to the task they are carrying out.
What sections of the brain control hand movement, and are they the same sections that control the rest of our voluntary movement? Do the more fine controls (like dexterity) result from the same region that regulate non-finely controlled movement? The brain is amazing.
Thanks for the AMA!
Noninvasive human brain imaging has revealed that there are many different brain areas involved in hand movements. These include the cerebellum, the basal ganglia and the cerebral cortex. Neurologists who study patients with damage to these different areas have concluded that none of them is absolutely essential, but damage to any of them will degrade the quality of the movement made. For example, cerebellum damage will induce uncontrollable tremor and cortical damage leads to a poverty and weakness of movement. There is evidence that one particular region of cerebral primary motor cortex, which we refer as new M-1, is particularly important for hand movement. It gives rise to many of the direct projections that go to the hand muscles involved and these direct projections are only found in humans and other highly dexterous primates.
I'm a laboratory animal veterinarian who regularly works with and treats non-human primates. What kinds of species did you work with? Can you describe your model and the tasks your animals were asked to perform? What are your favorite and least favorite things about working with primates?
Most of my research was carried out using purpose-bred Macaca Mulatta (Rhesus) or Macaca Nemestrina monkeys. The tasks we used were designed to elicit the most skillful hand movements we could from these monkeys. In many studies monkeys were presented with manipulanda which required independent movements of the index finger and thumb to move levers into a narrow target zone and hold them there for a second or so. Successful trials were rewarded with either fruit, nuts or pulses (e.g. sunflower seeds). Highly trained monkeys could complete up to a thousand trials of these tasks in a day and so you can imagine we had to carefully control reward size to avoid them becoming obese.
Most favourite aspects of working with monkeys is that they are amazingly curious and friendly animals with whom you can build up a really strong working relationship over the period of the experiment, which was often several years. As you can imagine the major downside of this research is when the experiment has to come to an end. I should point out that post-mortem studies were always essential to confirm the areas of the brain from which we had been collecting data. In these experiments monkey undergo a number of complex surgical procedure. All of these procedures are carried out under deep general anaesthesia with full aseptic control (i.e. sterile conditions) and with a full programme of post-operative painkillers. Over the course of my career I have seen that new methods of anaesthesia and surgery have resulted in monkeys being able to make faster recoveries after surgeries.
What exactly ARE the regulations around the safety of the animals you use for testing? How is it that you examine the effects of neurological damage and motor control without injuring the animals in question, do you have ways to remotely shut down parts of their brain?
in the UK, research in Non-Human Primates (NHPs) is quite rightly very carefully regulated. NHPs can only be used in scientific research when no other species is appropriate. There are extra controls on issues such as breeding, weaning, transport, accommodation, health and welfare of experimental monkeys. Every licence for NHP work is subject to rigorous assessment from the Animal Ethical Review and Welfare Body (AWERB) and subsequently by the UK Home Office. Because of the sentient and valuable nature of NHPs, the standards for care and welfare are constantly being revised and upgraded. In particular, scientists and institutions are taking on board new procedures which refine the use of primates in experiments. In the course of my career I have seen a lot of really important changes in this area. Probably the most important change has been the introduction of social housing for all experimental monkeys (where all monkeys share their cage with at least one other). I should point out that nearly all of my research has involved monkeys carrying out trained tasks for food rewards. Training the monkeys is done with positive reinforcement and we never use aversive, or painful, punishments for poor performance. Most monkeys welcome the opportunity to perform their tasks, since they are naturally curious and task performance represents a break from a relatively boring cage life. Despite the fact that their cage environment is enriched and constantly changed, they still seem more than happy to come out and work when required.
In terms of safety, the UK legislation makes it a requirement of the scientists and their institutions to report to the Home Office any unanticipated welfare events, such as sudden development of weakness. All institutions using non-human primates have expert veterinarians who regularly visit the animals and are available 24/7 in the event of an emergency.
I should also like to point out that none my research has involved making lesions in a monkey and the work has primarily been directed at a fundamental understanding of how the brain controls a normal hand movement. There are reversible techniques for interfering pharmacologically in specific regions of the brain and I have used these techniques in the past. Recovery from injections of Muscimol, for example, is complete within 24 hours.
Are there any popular misconceptions you'd like to address about the use of NHPs or other animals in scientific research?
An unfortunate legacy of the past conflict between scientists and antivivisectionists is the continuing presence, on the internet, of gruesome pictures of monkeys in experimental procedures. A popular misconception is that these procedures are still going on today. My experience, in the UK, is completely the opposite, and that our research is now characterised by a great deal of new refinements that have reduced the harms and improved the lives of our experimental subjects. Once again I refer you to the Virtual Lab Tour and to the Macaque pages on the NC3Rs website. I think we are now moving into a more open way of explaining to the public the work we are doing, and why we are doing it. As a result I hope that these old, outdated, and misleading images will be recognised for what they are.
How do you feel about fidget spinners?
Since Tom is is writing the answers here, I can afford to sit here and twiddle my thumbs since I can't afford a fidget spinner, but to be serious I do think it's interesting that many people feel compelled to use their hands consistently through the day. Try knitting instead.
Hi, medical sciences student here. Many fields of scientific research are currently moving towards using less animals in their laboratory work and finding new innovative ways to carry out their research, such as 3D in vitro cell cultures. Could something like this be applicable to your field of research (not necessarily now, but perhaps in the future)? Also, do you think that something like this will someday be the norm, or will animal models always be necessary in medical research?
Take a look at the EU's SCHEER report. This report concluded that research in nonhuman primates will continue to be needed, but also lays great emphasis on alternative non-animal approaches. If you look at the numbers of monkeys used in basic research over the last few years you can see a steady decline in numbers that fits with the use of these alternative methods. I personally believe that a better term for these approaches is 'complementary' because we need to combine research in the monkey with, for example, computer modelling and noninvasive work in human volunteers and patients. For example, it was work in monkeys that discovered the fundamental role played by Dopamine in brain activity related to rewards and this work has been incorporated into very successful computational models and these models can help to explain how the reward system malfunctions in various brain states such as depression. If you are interested in this look at the work of Schultz, Dayan and Dolan who together won the Brain Prize 2017.
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