Two experienced neuroscientists, Bertie and Arnold, decide to go for a lunch picnic but this time they bring along a doctoral student, Christina. Christina works in both labs of the neuroscientists, who are her joint mentors supervising her doctoral thesis. She is an unusually perceptive student, and has always seen her role in both labs as a “go-between”. Her demeanor is always one of high intellectual and emotional intelligence, and a concern for its general application. As they settled in for their lunch, Christina wondered how long it would be before the two men started competing. After all, science was just one long battle of ideas, and not always the best idea won, but perhaps the most persistent, or worse, the loudest or most advertised.
“Bertie, I was struggling with the idea of how our brains are wired up. Seems at many levels just to be a messy tangle but somehow it gets the job done” started Arnold. Bertie, of course, knew that this was a wild tease, of false modesty, just to hurl down the gauntlet. He was, however, not easily goaded into a topic that was not his best. But he just could not resist. “Arnold, you know it is nothing like that simple. If it were, we would have been able to hook our brains together, and we would not even have to talk to convey our thoughts”, replied Bertie. “Now that’s a fascinating thought Bertie, once we figure out how to do that, we could have a true collective consciousness” said Arnold. Bertie finished his sandwich, drank his coconut water, and gave Arnold that well known “come on” glint but he knew he had to be careful to be civil lest Christina think the worst of them. “Arnold, you know that understanding how the brain is connected is one of the big controversies in neuroscience. As early as the 19th century, neuroanatomists were fascinated by the localization of certain functions in the brain. Say, for example, where language is located is named after the French physician Piere Paul Broca. Not a lot of people know he graduated in Medicine at the age of 20 years, a year earlier than me, incredible! But, sadly, he died at the tender age of 56 years from a cerebral hemorrhage (https://en.wikipedia.org/wiki/Paul_Broca). Talk about being ill fated – to die from a disease of the organ that you were so brilliant at describing” said Bertie. “And he also was an anthropologist” chimed in Christina. “May I continue” asked Bertie?” He did not like being interrupted when getting into his full flow. Arnold and Christina shrugged their shoulders. Bertie continue – “What Broca was describing was that the brain seems to have structural elements that are related to certain functional tasks. This is called structural or anatomical connectivity. But we all know that you cannot actually map very many functions of the brain because they are not structurally static. Indeed, our brains are highly neoplastic, and structural relationships are always changing. We know even more about this from the experience of individuals with head injuries who can regain some functions seemingly by accessing other parts of the brain.
Nowadays, we work with two other concepts. They are called functional connectivity and effective connectivity”. “Hold on” interrupted Arnold, this is getting a bit complicated. “Not for me” said Christina with a smile. She continued “Functional connectivity is like a statistical concept really (http://www.scholarpedia.org/article/Brain_connectivity). At its core, what it is measuring is the relationship vs. the variation between neuronal activity in their spatial relations or orientations. Put simply, it is an attempt to measure the activity of the brain in space and time but what makes it difficult is that neurons are in different time phases, from just a few milliseconds, and others lasting many times longer in a phenomenon known as long-term potentiation, which is critical to understanding the neuroscience of many mental disorders including depression. Because of this, our current theories are scant with directional elements. Let me give you truism, even if we could measure all the electrical activity in the brain, we still could not simulate what the brain does because it will be electrical nonsense”. Bertie and Arnold looked at each other and smiled. Christina was a smart student. Not only did she know her stuff but she knew exactly when to introduce it. But Christina was not finished – “Two technologies are really helping us to build this map of brain function, which is a first step to understanding how our brain works. One is called fMRI (Functional Magnetic Resonance Imaging) and the other is called TMS (Transcranial Magnetic Stimulation). It is a painstaking process, and the National Institutes of Health describe this as the “connectome” project. We do know now that almost 80% of the brain appears to be in close connectivity, and there are formulas that can seemingly describe the relative strengths of the contribution of different brain areas by their distance, density, orientation, and connectivity. The brain is a great big orchestra. All parts talking to one another to create symphonies. And it also has its own built-in audience of side-kicks that can jump in and replace some of the active players. This is not the idea of our forefathers where the brain was an organ that executed isolated functional goals as targeted activities”.
“But” interrupted Bertie, “even that will not be enough. We would also need to be able to put some kind of direction to these effects in the brain, and that brings us to the idea of effective connectivity. If you like, it is the union between structure and function”. But this story becomes even more fascinating as some scholars have eschewed the directional concepts and have given consideration to what is called a model-free concept. That is, the information gleaned from the changes in the brain by virtue of its function determine the true directionality. Indeed, this idea also creates the idea of brain states such that for example, your brain reading this work differs greatly from that when you get up and make yourself a cup of tea. A giant in this area of thought was Clive Granger who tried to model causality. In other words, cause and effect relationships. Philosophers have been trying this for thousands of years! His theory did not relate to neuroscience but to economics, and indeed, he won the 2003 Nobel Prize for economics. But the idea is so powerful that it can be applied to neuroscience. The formulas are simple and gorgeous at the same time. And what is more, by expanding the idea of Granger’s G-Causality using Fourier Methods, you can arrive at equations for Spectral G- Causality. Direction, time, and space, all defined elegantly (http://www.scholarpedia.org/article/Granger_causality). Let me show you a diagram from a recent article to show how these different ideas work so it is really clear
Modes of brain connectivity. Sketches at the top illustrate structural connectivity (fiber pathways), functional connectivity (correlations), and effective connectivity (information flow) among four brain regions in macaque cortex. Matrices at the bottom show binary structural connections (left), symmetric mutual information (middle) and non-symmetric transfer entropy (right). Data was obtained from a large-scale simulation of cortical dynamics (see Honey et al., 2007 Network structure of cerebral cortex shapes functional connectivity on multiple time scales. Proc Natl. Acad Sci. USA 104: 10240-10245. The image above and legend are copied directly, and in full form, and complete credit also to: http://www.scholarpedia.org/article/Brain_connectivity and further referenced to Olaf Sporns (2007), Scholarpedia, 2(10):4695.
This work is so astounding that it allowed Bernasconi and Konig in 1999 (In: On the directionality of cortical interactions studied by structural analysis of electrophysiological recordings. Biol Cybern 81, 199-210), and later in 2001 Liang and colleagues (In: Causal influences in primate cerebral cortex during visual pattern discrimination. Neuroreport 11, 2875-80) to describe and understand vision in the cat and monkey, respectively. I still remember being excited about reading this at the time. Finally, there is another idea, called transfer entropy by Schrieber 2000 (In: Measuring information transfer. Phys Rev Lett 85, 461-4.) based on the concept of probabilistic changes in mutual transformation (http://www.scholarpedia.org/article/Mutual_information ), whereby direction is determined by the history of exchange of information between inputs. It is, however, a binary model and, thus, it does have limitations in understanding our tri-dimensional brains.” Arnold, who had been quiet for much of this time decided to speak. He got up and adjusted his clothes like a man who had just come out of a tightly packed box. He began to speak “I still think this is all very complicated. But I have been intrigued by the work of the brilliant Carl Friston, and in his recent article, he takes apart and tries to explain all these concepts, although some might say he is a bit harsh on Granger’s causality. Still, this is all part of science. What I like about his ideas are that he does seem to come up with more dynamic and dimensional understandings. (http://www.fil.ion.ucl.ac.uk/~karl/Functional%20and%20Effective%20Connectivity%20A%20Review.pdf). A simpler yet elegant description of brain connectivity and its potential implications also can be found in an article by Tanya Lewis (http://www.livescience.com/40855-brain-connections-no-neuron-is-an-island.html)”. Strewth! Arnold was definitely no scientific lightweight!
Bertie, always wishing to have the final word continued to speak: “One wonders where all this would lead us. Some of the more immediate applications of information on brain connectivity is coming from our understanding of autism (https://spectrumnews.org/news/infants-who-develop-autism-show-distinct-brain-connectivity/; https://health-innovations.org/2015/07/15/multiple-neuroimaging-studies-point-to-brain-connectivity-changes-in-autism/), which is associated language impairments. Here structure and function do meet. We also know that social impairments like poverty also can impair brain connectivity and adult development (http://www.spring.org.uk/2016/01/growing-up-poor-changes-brain-connectivity-and-depression-risk.php). So, the characters in this story of Pierre Broca and economic theory are all sort of intertwined with brain connectivity. Science can be beautifully strange. Notably, however, some of this is becoming reminiscent of science fiction in which we can transfer thoughts and impressions to other people through our thoughts without speaking to them. Indeed, I remember an episode of Star Trek the Next Generation called Night Terrors where Counselor Deanna Troi has to convey the image of a hydrogen atom to another ship so they can release it to spark an explosion to free both the Enterprise and the other ship (https://en.wikipedia.org/wiki/Night_Terrors_(Star_Trek:_The_Next_Generation). That was true telepathy but that is not where we are today. Where we are appears not to be true telepathy but exploring a human-in-silico-human interface for communication (https://www.extremetech.com/extreme/188883-the-first-human-brain-to-brain-interface-has-been-created-in-the-future-will-we-all-be-linked-telepathically). Not even sure how good or great this research is. But I am a skeptic of human nature. I am sure that type of technology would be first used for “dark” or military purposes rather than in medicine or science to heal. As for collective thought, that is still in the realms of philosophy and even ethics. Not sure I would be comfortable with everyone knowing my thoughts. And as for consciousness, that really is like the Ghost in the Machine (https://en.wikipedia.org/wiki/Ghost_in_the_machine)”. “Come on professors Christina ushered – “time to get back to the School and do some real work!”. They all then broke out in laughter and headed back. A great day is one in which you learn something new!
COVER IMAGE OF ATYPICAL BRAIN CONNECTIVITY IN AUTISM IS CREDITED TO RADU JIANU AT BROWN UNIVERSITY. GRAINER’S CAUSALITY EQUATION IS CREDITED TO GOOGE IMAGES