“Finding the Unfair Advantage in Neuroscience through the Paradigm of Connectomics By Blake Endres”

I would like to begin this section of the paper with a brief introduction to my perspective
on the methodological error that psychology commits by assuming that everyone’s personality will fall under, a specific set of traits, or characteristics, based on questions that could have multiple interpretations, by each existentially “unique” individual. Every person will interpret all variables differently, this is enforced empirically, by the now intensively studied field of connectomics, which is tracing the four quadrillion synaptic connections that reside within each individual’s neuronal network, which also as a conceptual structure itself is being completely rethought and rediscovered. Rather than just assuming that each individual will be stimulated in the same functional neuronal unit, by each subjective question, and also create a unique output that is according to their personality. A specific segment of research that has intrigued me, and
also brought me to write this paragraph, happened to be discovered during a search for the target cells that were triggering epileptic seizures in a patient of a UCLA neurosurgeon named Itzhak Fried. as the patient was in a Fmri, Fried noticed that a particular neuron, was being stimulated, surprisingly every time the patient was looking at Jennifer aniston( the actor), even more startling, That same neuron was reacting to even distinct traits of jennifer aniston(chin, smile, eyes, nose).

Now in my mind, the question of “ to what informational potential, can individual neurons contain. And what is the variability that each functional neuronal network can differ amongst each person. And could these individual neurons be studied in vivo, to look at variables such as action potential strength, inhibition tolerance, excitability, or secretion of specific neurotransmitters, that will enable direct measurement for the importance of this jennifer aniston neuron, to this specific person, or even the effect on its corresponding synaptic connections, for example the content of G-coupled protein receptors for site-specific neurotransmitters, could
help us examine disorders like depression by localizing a specific neuron that is only responsive to depressing stimulus ”. With this new perspective in mind, the interpretation of these variations of site-specific or network sites, could prove extremely insightful towards, the formation of psychological/neurological disorders, personality, cortical injury, and possibly some cancers, if neuroglia can react in a similar fashion to neurons. This demonstrates that connectomics as emerging perspective, is producing a vast amount of empirical data on the immense proportions of variables that can come from synaptic connectionism, but also provide great empirical instruments for psychologist to reinvent the interpretation of personality, by finding an actual
meaning to the traits that each unique person may exhibit, and letting their own brain cells provide the information.

I. History and clarification
At first, I would like to clarify a few preliminary definitions of the topics in this essay to
be as concise as possible before the introduction of an eminently new paradigm, Connectomics, strongly advocated by the Massachusetts Institute of Technology’s professor of computational neuroscience, Sebastian Seung. Neuroscience, as a practice, is relatively new considering its predecessors; physiology and psychology, which have made their own distinct marks upon the texts of literature since as far back as classical era greece. But it was not till around 1865, until neuroscience as discipline began to take form, and completely separated itself from the falsified
and criticized grip of psychology. This was in part due to an intelligent medical graduate student at University of pavia, Italy, named Camillo Golgi. Golgi was interested in microscopy of neuronal tissue, but like most cellular components, they are even difficult to view in clarity and resolution with the aid of microscopes. So Golgi resorted to probing neural tissues with silver nitrate, a method that was deemed inadequate for neuronal tissues, by physiologist and biologists in the latter part of the 19th century. Golgi’s results were as he called a “Black reaction”, which allowed the microscopist a elaborate visualization of the structures and architecture that neuronal cells had established. Golgi’s discovery was very confounding, because he took a simple staining
method, albeit with a new goal, and created an astounding new concept and understanding of neurobiology. But to his contemporaries, who were well shocked by the use of silver nitrate to expose neuronal tracks, it would have been considered an “ unfair advantage” if he did not publicize his method. Now that neurons could be visualized and tracked through their large schematic of networks, it allowed for the availability of that structure to be studied and consequently a theory on how neurons interacted, where they interacted, and most importantly why they interacted in such a fashion. This important question posed an even more important
goal: determine the functionality of said network, and its individual parts. But it was not
necessarily Golgi who figured out key elements to the question, but rather a Spanish scientist named Santiago Ramon Y Cajal, who found this discovery more than captivating. Cajal experimented with the “Golgi method” of staining neurons with silver nitrate, and soon contributed his own thoughts to the newly developing discipline. Cajal had suggested ‘the neuron doctrine’, in which he described the fundamental function of a neuron, the capability of polarization in neurons cell bodies, which travel down axonal appendages, and propagate a new polarization in the following neuron. During this time Cajal had been recognizing certain characteristics that occurred in his experiments with neuronal synapses, he noticed that some neurons, specifically in the cerebellum and hippocampus, that neurons could abruptly disconnect synapses with others, which was contrary to the present belief that the nervous system was reticular, in that it somehow connected and fluid with each and every other neuron, virtually all were one, and one where all. But if neurons could detach synaptic connections, then that would
mean, as Cajal said “ Contiguity over continuity”, that all neurons could be sharing the same extracellular matrix, and be smushed together, but also not necessarily making all neurons, essentially 1 object.

II. Connectionism

What is connectionism? you may say, it is how things are connected, or the state of being
connected, or even the principle of connection. All of these are correct, but when applied to such a complex and abstract field of neuroscience, they are all wrong. In neuroscience, Connectionism is implicitly complex. For one simple reason, everyone is different, from genetics, learning experiences, relations, environment, etc. Everything makes everyone different. One could say that people learn the same way ( auditory, visual, etc) , everyone has relations, everyone is exposed to environment, but does that mean that everyones neuronal synaptic connections will be the same? absolutely not, the nervous system is comprised of roughly 100 billion neurons, with a ratio of neurons to neuro glia at 1:10, which astrocytes also play a role in synaptic connectivity, via control of neurotransmitters precursor material and reuptake.

This equates to around 10^24 synaptic connections within the central nervous system. Since all learning is unique to the individual, why would our neurons connect even remotely in the same chains? The answer is, they will not. But that uniqueness has qualities that could result in extremely efficient & accurate results, once we find ways to harness the individuality of each patient and their target neuronal chains, with methods and devices that the paradigm of Connectomics will produce. And with the current extensive research well underway at this very moment, that focus on studying the extremely formidable and challenging tasks, such as: Grandmother neuron, (ambien) non benzodiazepine hypnotics effect on stroke victims with partial/complete brocas aphasia, FTLD-TDP43, which are just a few dire projects that are giving rise to new concepts, and even more( for lack of a better word) revolutionary initiating, methods of instrumentation and technology. Without any doubts, it could always be said that instrumentation is the key to a revolution, for example pertaining to neuroscience, Golgi’s Silver nitrate stain. A simple chemical formula, that was known for at least four decades before Golgi thought of using it as a means to view a world that no one has ever seen before, and Cajal as well implemented a technique of using double impregnation with silver nitrate to view astrocytes, a type of neuroglia.

Other discoveries that lead to revolutions in the same manner, were called “ unfair advantages” by Sebastian Seung in his book Connectomics some examples are Antione van leeuwenhoek’s invention of a superior compound microscope, that allowed him to view cellular structures with much higher magnitude than any of his contemporaries, making him the proponent of the cell theory. Now Connectomics on the other hand, will require much more than simply increasing the magnitude of our Fmri, PET, and Voxel based neuronal imaging scans. If we hope to trace and map the entire connectome of the human central nervous system, it will require advanced technology that will allow for: 4-dimensional viewpoint, neuron startpoint/endpoint targeting for neuronal chain tracing, combined with the inherent properties of an electron scanning

III. Unfair Advantage

Thomas S Kuhn, the author of ‘ The Structure of Scientific Revolutions’, said that “paradigms can lead to new methods of instrumentation”, from this context, it implies the methods or production of certain devices, that later on help distinguish the paradigm by attributing a specific advantage that will add more information and specificity. Now, is this the case with all paradigms? most likely not, I believe there must be adequate information in the paradigm as a prerequisite for such inventions and devices to be conceived. But in the case with neuroscience, inventions were in a sense, borrowed from very similar fields such as chemistry, in example: radioisotope glutamate markers, Protein markers, receptor agonists/antagonists, neurotransmitter mimetics. now could concepts and instruments be taken from other fields and applied to Neuroscience as well, in hopes of finding the answer to our dilemma of how to go about mapping 10^24 synaptic connections in the nervous system? Well, for example, Magnetic Resonance Imaging was discovered by Herman Carr, a Physicist, but it was Raymond
Damadian, a medical scientist who realized its use for visualizing metastasized tumors in vivo. So my interpretation of this extremely profitable occurrence, leads me to believe that if any characteristics in a method of instrumentation/ device is useable in some fashion that aides in solving a problem in the discipline of an unrelated or related field alike is worth using to its fullest potential. Do these inventions and methods only originate from random occurrence, or could there be a sort of algorithm to its creation. Well, in retrospect, Golgi’s dilemma,was his goal was to find any method to view the functional units of the nervous system, what would dictate the limitations? for it is a goal that is unprecedented, with algorithms and trial-and-error being mostly useless because of the fact. Since Golgi was already aware and well practiced with tissue staining methods, he was experienced with its reagents, and the respected chemical
properties that they retained. So, Gogi’s Discovery could have been merely simple problem solving method of heuristics.

IV. Construction of a possibility

In a rough schematic of function, I have theorized an attempted model that most likely would not work for mapping, but in expectations it would be exclusively, only 1- millimeters superficially of the cerebral cortex, with the combined use of

● Focused High Intensity ultrasound
● polycationanion
● fluorodeoxyglucose
● PET Scan

This theory would only work on a patient who suffered considerable anoxia, resulting in
neuronal oxidative damage, and would have to be done within ~ 20 hours of the stroke. It would begin with intraarterial injection of fluorodeoxyglucose via carotid artery, somehow coupled with a polycationanion. Since the neuronal bodies in the penumbra(area of effect) would have been recently necrotized, the polycatioanions should be able to attach somewhere on the neuronal soma, via G-coupled protein receptor, given microglia are not already active. Then the patient will undergo a PET scan, that should only be able to couple to the necrosed neurons, due to connection of the polycationanion, it will inhibit metabolism by live neurons and astrocytes.
The patient would then be subjected to High intensity focused ultrasound, which would be guided in conjunction with the PET scan computer system. The goal of the HIF ultrasound is to ‘scan’ over affected area, and when focal point comes in contact with the chemical tags, the sounds waves are reverberated back. ( the sound waves still need a way to be converted into a HD image, then be able to be imaged via Electron scanning microscope, it would have to be along the lines of sound transduction into some form to be susceptible to the electron beam).

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