This week I had some fun time getting some basic research projects on the go, a welcome break from my now almost full time management life, as much as I enjoy it. I was asked to comment on a theoretical article that suggested that the prefrontal cortex is important in pacing and fatigue processes, and write a review article on brain function regulating activity, by my good friend and world leading physiologist and exercise scientist, Professor Andy Jones, and both of these got the neurons firing in pleasant way. For most of my career I have been a researcher, and while I describe my main research interest as understanding generic regulatory control mechanisms when asked about it, my research passion has always been the brain and how it functions, and creates ‘us’ and what we see, feel and experience as ‘life’. I will never forget the ‘buzz’ I got when working at the NIH in Washington DC, with Austrian neurologist without peer, Dr Bernhard Voller, when we put a needle electrode into one of the muscles controlling eye movement of a subject and heard the repetitive ‘clicks’ of each action potential as it fired in order to control the muscle’s movement, or when we used transcranial magnetic stimulation to stimulate the motor cortex (basically a magnet placed on the skull which ‘fires’ electromagnetic waves into the brain) and saw muscles in the finger or foot twitching when we selectively targeted different regions of the motor cortex. I will never forget the feeling of excitement when with Dr Laurie Rauch at the University of Cape Town we first got good quality EEG traces from folk and saw the EEG change frequency and complexity when someone put their hands on the folk being tested. I will also remember the wonder I felt (tinged with a degree of sadness for the rats which were sacrificed) working with Professor Viv Russell and Dr Musa Mabandla when we saw quantitative differences in neurotransmitter levels in areas of the brain of rats associated with motivation and drive that had run to exhaustion compared to more ‘lazy’ ones that simply refused to run as much as others did. Having said all this, it’s amazing that after all these years, and so much research performed on the brain by so many top quality folk all round the world, we still have almost no idea of how the brain functions, how and where the mind is and how it relates to the physical brain structures and processes, and where ‘we’ and our ‘soul’ are in relation to this most complex organ in our body.
As everyone knows, the brain is an odd shaped organ situated in the skull which consists of billions of neurons which connect with each other and with nerve fibres that ‘flow’ out to the body and which regulate all our body systems, processes and functions. Information is sent through neurons via electrical signals (called action potentials) which create ‘coded’ messages and commands. In a somewhat strange organizational structural process, there is a gap between each neuron where they connect to each other (called a synapse) and chemical substances called neurotransmitters fill the gap when electrical activity comes down the neuron and allows the ‘message’ to be transferred to the next neuron with great fidelity, though the synaptic neurotransmitter activity can also amplify, moderate or attenuate the signal passing through it, in a manner which is still not well understood, but related to the type of neurotransmitter that is secreted at the synapses. The brain also ‘secretes’ chemical substances such as hormones and regulatory factors that go via the bloodstream to various peripheral organs in the body and can control their function in a slower but longer acting way.
Though we do have some knowledge of basic output and input functions of the brain, such as vision and hearing processes, and sensory inputs and motor outputs from and to the body, there is currently no unifying theory of how neural activity in the brain works in its entirety to control or create the complex activities associated with life as we know it, such as thinking, memory, desire, awareness or even basic consciousness. Before the 1700’s it was assumed that the brain functioned as a type of ‘gland’, based on the theories of the Greek physician Galen. In his model, the nerves conveyed fluids from the brain to the peripheral tissues (so he was right at least about the ‘secretory’ function of the brain). In the 1800’s, using staining techniques and the (then) recently developed light microscope, Cayal and Golgi showed that neural tissues were a network of discrete cells, and that individual neurons were responsible for information processing. Around the same time Galvani showed that muscles and neurons produced electricity, and von Helmholtz and other German physiologists showed that electrical activity in one nerve cell affected activity in another neuron it was in contact with via a synapse in a predictable manner. Two conflicting views of how the brain uses these electrical-based neuronal systems to send commands or information were developed in the 1800’s. The first was reductionistic, suggesting that different brain regions control specific functions. This concept was based on the work of Joseph Gall, who also suggested that continuous use of these different brain regions for specific tasks caused regional hypertrophy (increased size). Gall suggested that this regional brain hypertrophy created bulges in the skull, which could be associated with the specific function of the underlying brain tissue. While the skull theory of his has ‘fallen by the wayside’, in later years Brodmann described 52 separate anatomically and functionally distinct regions of the cortex, and Hughlings Jackson showed that in focal epilepsy, convulsions in different parts of the body were initiated in different parts of the cerebral cortex. These findings were supported by the work of Penfield, who used small electrodes to stimulate different areas of the motor cortex in awake neurological patients and induced movements in different anatomical regions of the body (similar to the work we did at the NIH, albeit we did it in a more indirect / less invasive way).
The second and opposing view was that all brain regions contribute to every different mental task and motor function in an integrative and continuous manner. This theory was based on the work of Flourens in the 1800’s, and was described as the aggregate field theory. Recent research has shown that large areas of the brain communicate with each other continuously using electromagnetic waves of different frequency during any task. Further support for the aggregate field theory comes from the concept that no activity is ever simple, and even a ‘simple’ motor task such as moving the hand to get something is the final common output of multiple behavioural demands such as emotional context, prior experience, sensory perception and homeostatic requirements, and therefore cannot be attributed solely to any specific / single region, except from a final output perspective. While the aggregate field theory fell into disfavour in the late 1900’s, due to the development of MRI, CT and PET scanning of the brain and these techniques ascendancy to being ‘the in thing’ in neuroscience / brain research over the last few decades, the ‘snapshot’ methodology associated with brain scanning using MRI and these other image-based techniques have contributed very little real understanding of how the brain functions, apart from creating ‘pretty’ pictures that show that certain brain regions ‘light up’ whenever a task is performed. Unfortunately, often the same areas of the brain are shown to be active when using these techniques during very different testing protocols, which creates a confusing and complex ‘picture’ of what is happening in the brain during even simple tasks.
Incredibly therefore, we still know so little about how the brain works that this basic argument between ‘regional’ versus ‘general’ brain functionality has not been resolved, despite all the technological development in the last few decades, such as those described above. Even more mysterious is how the ‘mind’ works, and there is still active debate of what the ‘mind’ is, and how it relates to physical brain structures. The mind is defined as the cognitive faculties that enables consciousness, perception, thinking, judgement and memory. As will be obvious, this definition of the mind can at best be described as a conceptually ‘hazy’ one and does not help much clarify things, but basically the mind is what ‘we’ are – the ‘me’ that makes our life feel as if it is ‘ours’ and that we are unique and our experiences and thoughts are ‘our own’. The debate still rages about whether the mind is ‘in’ – the monist or materialist doctrine – or ‘out’ of the brain tissue – the ‘dualist’ doctrine. The monist / materialist doctrine posits that everything we think, feel and ‘are’ can and is found in the functioning and activity of the neural cells and neurons in the brain. The dualist theory posits that ‘we’ are an immaterial ‘spirit’, as described by Rene Descartes, that is related to but exists ‘out’ of the brain and body – a more spiritual interpretation of what ‘we’ are and a theory which allows for concepts such as ‘soul’. The clearest evidence for a strong relationship between physical brain matter and the mind is the effect of physical agents such as psychoactive and anaesthetic drugs and alcohol on the ‘mind’, and the effect of traumatic brain injury in certain areas of the brain on mental function and the mind. But, given that we have absolutely no idea where memories are stored in the brain or how they are stored, how ‘thought’ happens, or even what consciousness ‘is’, it is difficult to completely refute the dualist approach, even as a hard-nosed scientist, although it is the ‘death sentence’ for many a neuroscientist’s career for one of us to suggest a belief in dualism is a scientifically possible entity. Religion is perhaps in many ways a derivative of this ‘explanatory gap’ between mind and brain function, and will continue to flourish until science eventually (if possible) proves the materialist / monist theory to be true or refutes the dualist theory with more evidence than we currently have.
So what do we know of the brain, the most brilliant and puzzling organ in the body, and its function. Sadly, after 25 years studying it, I have to be honest and say almost nothing, and anyone who says differently, is not being honest or is deluding themselves (which of course would be an irony of note). Us neuroscientists are in many ways beholden to and ‘straightjacketed’ in developing our brain and mind theories by the laboratory investigative techniques that are currently available which allow us to examine whatever our area of interest is, and unfortunately in the brain research area, these techniques are just not subtle enough, or conversely not complex enough, to allow us to have any more understanding today of how the brain works than in many ways was known one or two hundred years ago. It’s amazing that we know so much about heart, liver, and muscle function – indeed any organ of the body – and so little about the brain, which is such a seemingly impenetrable mystery. Most neuroscientists like myself eventually focus on examining specific areas of brain or mind function, perhaps to protect ourselves from a sense of being abject failures in our chosen discipline – which is why I describe my main area of interest as control theory rather than ‘brain function’ research to those that ask. But, it surely will be some scientist, working with some new recently developed piece of equipment that we are not yet aware of, that will have the ‘eureka’ moment for neuroscience similar to what occurred with genetics / molecular biology in the 1950’s with the breakthrough in the understanding of the structure of DNA that in turn led to how quickly molecular biology developed in the subsequent 60 years to its current status, and we will have a clear understanding of how the brain works and how the mind fits in to the puzzle. Whoever does have this ‘eureka’ moment will very much deserve their Nobel Prize. Until that time, I, and probably most research folk who are interested in basic brain function, will keep on telling our new neuroscience / physiology / exercise science students each year that as scientists us neuroscientists are dismal failures / the least successful of all the research folk working in academia, given how little of brain and mind function we know and understand, despite all our valiant endeavours and countless hours in the lab, trying to work it all out.
But, having said this, I will also continue to marvel at the brain and mind, and be thankful that I had, and have, the career from a research perspective that I do, trying to work out and understand something as truly amazing as the brain, which is the ‘root of all life as we know it’, whatever life and our part of it is. In the mass of neurons in our brains, which work in some mysterious way and using codes we still need to ‘crack’, ‘we’ exist, feel, live and die. Unless of course the dualists are right, and us research folk have been fooling ourselves for a long time, and ‘we’ are just spirits that exist in our bodies for the length of time we are alive, before heading off for another adventure, either in another body, or in another world. Time, hard work, and perhaps a good dose of luck, will allow us neuroscience folk to eventually have a definitive opinion either way – however at this point in time, the mind is willing, but the contemporary brain appears to be too ‘weak’ to make or find that elusive ‘eureka’ breakthrough and know what itself, and indeed ‘we’, are all about!