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The Connectome and the Quest for Self

In my fourth novel, “The%20Law">The Law,” which takes place in the same galaxy order emerged after the events narrated in the Daimones Trilogy, a main crucial scientific element of the story revolves around the ‘connectome.’

If you search on google, the first entry for the word is from Wikipedia, which says: “A connectome (/kəˈnɛktoʊm/) is a comprehensive map of neural connections in the brain, and may be thought of as its “wiring diagram”. More broadly, a connectome would include the mapping of all neural connections within an organism’s nervous system.”

Various studies and research from neuroscientist aim at understanding, mapping, and interact with the connectome.

While writing “The%20Law">The Law,” I had several contacts with neuroscientists, read articles, and absorbed the main lines of thought on the subject and extrapolated them into new realms of possibility.

In the novel, scientists finally succeed to fully understand the connectome, map it precisely in order to discern how behavior and stimuli relate to it, alter it to inject memories, action/reaction patterns, change personality, and more.

At a recent reading session with a Book Club in Geneva, one of the attendees was a young neuroscientist researcher and, afterwards, we had interesting conversations around this fascinating subject. Today, researchers in neuroscience aim at understanding the connection between biology and personality, phobia and neurons networks, short linkage and long distance connection between different areas of the brain, and ultimately are along the same scientific journey which in “The Law” is fully accomplished.

Allow me to introduce you to Doctor Ewa Miendlarzewska, PhD University of Geneva and University of Lausanne. Ewa agreed to answer a few basic questions on the connectome from me, and agreed to answer questions you might also have on the subject for a little while.

Ewa, thanks for the continuing exchange and chat on this amazing real of discovery and mystery such as the Human brain is.

Many years have passed and gone since the brain was only known as amorphous ‘grey matter,’ today we understand that the network of neurons firing together, send excitation messages to other areas, repetitive behaviour trigger changes and evolution in the brain, which is a formidable bio-puter that, most probably, still holds its most precious jewels hidden.

Modern neuroscientists have evolved at the same pace as the discoveries and new perspective in this scientific domain. Ideally, neuroscientists would like to trace the actual “wiring” of the brain: the dendrites and axons that form the synaptic connections between neurons, and map them with traits of personalities, and behaviour.

Q1) The amount of data required for the above probably will reach easily terabytes and petabytes for even a tiny part of the actual connectome but it would constitute the realisation of the wildest dream of science fiction writers. In your opinion, will neuroscientists achieve, in our lifetime, the mapping of the wiring of critical areas like the hippocampus, or the retina, for example?

Ewa) We are well on our way when it comes to mapping the structure, Massimo! The rat somatosensory cortex (aka, the barrel cortex), mouse visual cortex have already been mapped by the Human Brain Project (nota bene, with a seat at Campus Biotech in Geneva). Project MindScope, which closely collaborates with the HBP, has been working on the mouse retina but I don’t know how far they’ve gotten. The hippocampus is a more tricky beast. I don’t know how advanced the efforts are in this direction.

This is rodent research but I suppose you are more interested in the human brain. Well, there is good progress on microscopic mapping of ex vivo human hippocampus but I guess your question refers to real-life and real-time visualization of what’s inside the skull. We are very far from “real-time” because of computation cost, for the moment. Even with supercomputers (as in the HBP), it takes months to years to put the pieces together.

As far as “real-life” goes, the technology for noninvasive brain imaging (ultra high-field MRI) in the human is pretty impressive (we can now image something like a 1mm cube of neurons at 7T, as far as I remember) but we cannot image single cells without actually implanting electrodes inside the brain and that greatly limits data collection. So we can make human connectomes but the nodes in the network are not single neurons – they could be at most populations of neurons that occupy a voxel measuring >=1 cubic mm, at the moment. With that said, I do believe we will be able to visualize (and maybe even use for diagnosis and prognosis) such cortical column-based connectomes with fairly high accuracy in the next 10-20 years.

Q2) Fascinating. So, Science Fiction of today can really become Science of tomorrow. The assumption in “The Law” is that the connectome may hold the key to the basis of personality, intelligence, memory, and maybe even mental disorders. How far off science fiction is from science in this case?

EwaA short answer – it does. Today this is not sci-fi, it is science.

Presently, a lot of exciting things are happening in human network neuroscience which links the structural (obtained with DTI) and functional (typically, with resting-state fMRI) human brain maps with cognition. I foresee that this is where the biggest impact of neuroscience on daily life is going to come from in the near future. To cite a small example, a network property measure called resilience (which defines the degree of network robustness, i.e., its ability to still sustain undisturbed function after removal of some x% of connection), has been shown to correlate with fluid intelligence.

We simply need large-scale projects and many many more brains to be scanned in order to have reliable estimates for connectomics of cognition (personality, task performance, etc.), and this laborious effort is going to take time and international collaborations.

Q3) You’re right. This is highly exciting and, yes, it will have a tremendous impact on daily life of people. If you were to give a short answer about why, today, neuroscientists believe it is so important to study neurons and the connections between them, what would you tell us?

EwaIt has always been important. It is the basis of neural science since the discovery of the Hebbian learning principle. What do you mean “today”?

Q4) Indeed, we non-expert tend to believe neuroscience is only a few years old, while instead it has decades of research and studies. With an approach related to the concept from Information Technology of neural network, in the novel scientists approached the problem as reweighting, reconnection, rewiring and regeneration of new patterns (through lots of lost ‘patients’ and brains, I have to say). How might we go about learning a new skill, remembering something, recovering from an injury. Is current research on the path of figuring out one day what I call connectome code breaking?

Coloring the Connectome

EwaI like the term “connectome code breaking” – by which you probably mean a set of principles that dictate which neurons are going to (re-)wire together? In network science this is called link prediction (and please note – I know this not because I am a neuroscientist but because I’ve spent some time with network scientists. The sexy term for studying biological networks these days is “Biocybernetics”).

Real neural networks in the human brain still hold a lot of mysteries before scientists because they are so incredibly complex. There are so many levels of biological tissue that come together to determine where and what kind of connection is going to be made or broken, that – also here – multidisciplinary efforts are needed for scientists to bring together the knowledge from different levels of study, i.e. from peptides and molecules flowing through clefts and channels of a single neuron, through synaptic gating and tagging, to multiple neuron network dynamics, to columnar organization in the cortex, to intra-cortical communication, and up to consciousness (which is also probably determined by some network state) and cognition…

To give you an example from my home topic – memory: The difficulty is not so much in understanding “if these conditions are met – let’s say, you have dopamine present at the synapse at the time of stimulation – then there is a high probability of these several neurons forming strong synaptic connections”. The relevant question would then be “does this mean the animal will remember better?” And then of course, we are not yet talking about a human brain in this case.

It appears that ”human connectome code breaking” is still a remote dream, at least in the direct manipulation sense that you might envision. We can, however, observe progress in traumatic brain injury recovery, for example, by just looking at the brain. A very exciting example is the prediction of recovery of consciousness in patients in coma from resting-state data, which illustrates the amazing potential of applying network science to brain data.

Q5) I like those terms, “link prediction” and “Bio-cybernetics.” You really depict a scenario that involves the need of multi-skills and concomitant and diversified research teams from many branches of science to maximize the chances of a breakthrough. Speaking of which, what excites you most in terms of future challenges and outcomes?

EwaVery hopeful news about the human brain is that the atlasing is getting more fine-grained and major advances come to light every year. We are still mapping, in a way, but many mapping initiatives include the third dimension – linking the structure to cognition.

It’s becoming difficult to catch up with the scientific progress, unless you’re within this sub-branch of human neurosciences! I am not – I am an experimentalist and I work on emotions, memory and decision making, but I found out that, for example, we now have a detailed multimodal (including cytoarchitecture) atlas of the human neocortex that has been produced by the Human Connectome Project. It combines data obtained through various techniques – invasive (such as ex vivo microscopy) and noninvasive, such as MRI, DTI and all other cool things you can do with an MR scanner.

Personally, I am most excited about the applications, not about the methods of obtaining data. We won’t be able to directly manipulate the connectome – as you’d envision – by injecting and removing memories anytime soon (although this has already been done in the mouse) but we may soon be able to use these databases to predict task performance, probability of developing some brain diseases and understanding inter-individual differences with some accuracy. In a way, we are still on the same quest: “to know thyself .“ And I think we are not that far away from the sci-fi vision you’re painting…

Well, folks, wasn’t that exciting? Can you imagine what the future holds, maybe not for us but for our children’s children?

Thank you, Ewa, for being with us, here, and folks, don’t be shy, it’s a rare opportunity offered from this page. Fire your questions.

Ewa Aurelia Miendlarzewska is still interested in how we learn and how to optimize it: first it was organizational learning (MSc No.1), human emotional memory (in applied research and in MSc No.2), then modulation of memory formation in the hippocampus (PhD in Neurosciences). Now she studies learning from financial information in an interdisciplinary lab at the University of Geneva (post-doc). She’s an attempting sci-fi writer, tango argentino and egyptian belly dancer and Paleo baker. She wants to inspire people, apply her research to optimize how we learn and teach, and encapsulate the rest of her futuristic ideas in books and movies.

Speaks 4 ½  languages, highly sensorially sensitive, high-maintenance (gets easily bored and tired unless propelled by love and passion).

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The Connectome and the Quest for Self


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