Publications 

For peer-review

Vadakkan K.I. (2022) A new explanation for flash-lag effect using a testable mechanism for first-person inner sensation of perception. OSF Preprints. (When a flash is briefly presented in a specific location adjacent to the path of a uniformly moving object, the former is perceived to lag the latter. Different experimental conditions carried out to qualify this flash-lag effect (FLE) have led to several seemingly unrelated first-person reports from which several constraints are available to arrive at a testable mechanism for FLE. Using a derived mechanism for generation of first-person internal sensation of perception, present work explains FLE and provides interconnected explanations for various findings associated with FLE). Article (v2).

Vadakkan K.I (2022) Golgi staining of neurons: Oxidation-state dependent spread of chemical reaction identifies a testable property of the connectome OSF Preprints. (Camillo Golgi observed reticular nature of the nervous system by his staining method. Ramón y Cajal modified this protocol to obtain staining limited to individual neurons that supported cell theory. Close examination shows that Golgi used one oxidizing agent to pre-treat the brain tissue before the staining reaction and Cajal used an additional oxidizing agent for the same step. It shows that oxidation state of the tissue has a crucial role in determining the spread of Golgi chemical reaction between neurons. Since dye injected to a neuron is restricted to the cytoplasm of that neuron and since it is possible to grow individual neurons in primary culture, these provide very specific constraints that can guide us towards understanding system. Since blood oxygenation level dependent (BOLD) signals are present in specific locations in the brain that peak around 4 seconds after learning, oxygen has some functional role in the structural changes during learning. Are there gates formed during learning? Since learning can be completed within milliseconds and memory retrieval can also occur in milliseconds, what is oxygen doing to those gates? For the duration of existence of the learning-generated gate, it should allow propagation of depolarization from a cue stimulus across it to generate both internal sensation of associatively learned item and provide potentials sufficient to generate motor action. This gate should not allow mixing of cytoplasmic contents between neurons. These constraints led to the derivation of an oxidation state-dependent crucial connection that defines the connectome). Article

Vadakkan K.I (2018) Extreme degeneracy of inputs in firing a neuron leads to loss of information when neuronal firing is examined. PeerJ Preprints. (A very small fraction of input signals out of all possible inputs is able to fire a neuron. In certain circumstances (e.g. when a neuron is held at sub-threshold activation states short of a fraction of one postsynaptic potential), even fraction of a single postsynaptic potential can fire a neuron. The importance of degeneracy of codons in the genetic code reminds us that there is a background utility behind this observation. Furthermore, the unitary operational mechanism of the system is expected to lie in the neighborhood where degeneracy is observed. This work shows that information storage and retrieval should be taking place at the level of the dendritic spines and the findings of semblance hypothesis match this observation). Article

Vadakkan K.I (2018) A learning mechanism completed in milliseconds and capable of transitioning to stabilizable forms can generate working, short and long-term memories - A verifiable mechanism. PeerJ Preprints. (Based on semblance hypothesis, the learning-induced change in physiological timescales of milliseconds remains as the core change sufficient for retrieving memory as a first-person internal sensation during working memory. Maintaining this learning-induced change by its stabilization allows continued retrieval of the same memory after short time and longtime intervals). Article

Peer-reviewed

Vadakkan K.I (2021) Framework for internal sensation of pleasure using constraints from disparate findings in nucleus accumbens. World Journal of Psychiatry. Previously, it was possible to explain memories as first-person inner sensations generated from a structural change that can occur during learning. Using this as a reference, disparate findings in nucleus accumbens (NAc) such as 1) long-term depression (LTD) in naïve animals, 2) impaired ability to induce LTD in addicted state, 3) attenuation of postsynaptic potentials by both cocaine and dopamine, and 4) reduced firing of medium spiny neurons in NAc by dopamine were viewed as pieces of a puzzle that need to be solved. This led to the identification of a further verifiable mechanism that can generate internal sensation of pleasure & explain all the above findings in an inter-connectable manner. Furthermore, potential changes that can occur in addicted state were also found. Article

Vadakkan K.I (2021) Neurological disorders of COVID-19 can be explained in terms of “loss or gain of function” states of a testable solution for the nervous system. Brain Circulation. (Covid-19 spike protein is a fusion protein that in addition to generating fusion pores in the host cell membrane for viral entry, also forms inter-cellular fusion between host cells. Inter-postsynaptic functional LINK (IPL) is the linchpin mechanism derived by semblance hypothesis. When virus exits a cell by vesicle exocytosis, it can cause fusion of the hemifused area of IPL, which is a bilayer structure. Based on semblance hypothesis, an adaptation mechanism that can prevent progression of hemifusion to fusion (Vadakkan, 2020) is expected to deteriorate during aging and may prevent reversal of IPL fusion. Since transcriptomes of even adjacent neurons of same type are different in the cortex, inter-cellular fusion can lead to protein precipitation within the spines that can lead to spine loss and eventual neuronal death. Furthermore, formation of non-specific IPLs can lead to “gain of function” changes responsible for some of the neurological features of COVID-19. Article

Vadakkan K.I (2020) A derived mechanism of nervous system functions explains aging-related neurodegeneration as a gradual loss of an evolutionary adaptation. Current Aging Science. (The last stage of ontogeny is expected to remain throughout adulthood. Examination shows that a neuronal circuitry where IPLs can form, and function can be evolved from simple excitable cells. It also shows that the last stage is preceded by a transient inter-cellular fusion event and is expected to "turn on" the expression of specific proteins that arrests fusion at the intermediate stage of hemifusion. Based on the semblance hypothesis, every event of learning relies on this mechanism to prevent inter-spine fusion. Since any deficiency in this mechanism can lead to inter-spine fusion and since spine loss is a common finding in age-related neurodegeneration, it prompts us to ask the questions, "Is this what determines neuronal life span?" "Will it not limit our ability to learn as we age?" "Can we understand this event better so that we can try methods to artificially maintain the ability to stabilize the inter-spine hemifusion stage to prevent age-related neurodegeneration and increase our longevity?" Article

Vadakkan K.I (2019) From cells to sensations: A window to the physics of mind. Physics of Life Reviews. This paper summarizes derivation of the mechanism that generates first-person inner sensations of various higher brain functions using constraints from large number of findings of the system from different levels. It explains a testable mechanism by which nervous system generates mind. Several testable predictions are provided. Article

Vadakkan K.I (2018) A potential mechanism for first-person internal sensation of memory provides evidence for the relationship between learning and LTP induction. Behavioural Brain Research. (Long-term potentiation (LTP) is an electrophysiological finding first observed at the synaptic region between entorhinal cortex and dentate gyrus (perforant path). This finding has provided several correlations with learning & memory. It has been our realistic hope for the last 50 years that we will be able to use these correlations to figure out the mechanism of memory retrieval taking place in millisecond timescales. By viewing memories in their true nature as first-person inner sensations, this work has explained how a derived mechanism of natural learning occurring in milliseconds can get scaled-up during experimental LTP induction. Since such scaling-up events take time to manifest, it explains the time-delay of 20 to 30 seconds and even up to a minute or more for LTP induction following stimulation. Predictions that were possible from this finding can be verified.  Article

Vadakkan K.I (2016) Substantive nature of sleep in updating the temporal conditions necessary for inducing units of internal sensations. Sleep Science. (Sleep is part of the substance of the nervous system. The system becomes operational only in the presence of sleep. Without sleep, the system cannot continue to function. In fact, without sleep, there is no system! This finding provides evidence for the hypothesized mechanism). Article

Vadakkan K.I (2016) Neurodegenerative disorders share common features of "loss of function" states of a proposed mechanism of nervous system functions. Biomedicine and Pharmacotherapy. (This work was carried out with a simple idea that just by sitting in a workshop and watching how defects of the cars are being repaired for a period time, one will get some idea how a car works normally. In the case of the nervous system, the observations in various neurodegenerative disorders match with the defects in the hypothesized mechanism). Article

Vadakkan K.I (2016) Rapid chain-generation of inter-postsynaptic functional LINKs can trigger seizure generation: Evidence for potential interconnections from pathology to behavior. Epilepsy & Behavior. (This work provides an opportunity to triangulate constraints from large number of findings in seizure disorders to arrive at a mechanism for both generation and rapid spread of seizures from its primary focus) Article

Vadakkan K.I. (2016) The functional role of all postsynaptic potentials examined from a first-person frame of reference. Reviews in the Neurosciences. (Explained how a neuronal soma is flanked by a large number of internal sensory processing units and their relationship with neuronal firing). Article

Vadakkan K.I (2015) A framework for the first-person internal sensation of visual perception in mammals and a comparable circuitry for olfactory perception in Drosophila. SpringerPlus. (This work explains and interconnects several third person findings in visual perception and optics. Presence of a comparable circuitry in a different sensory system (olfaction) in a remote animal species (Drosophila) provides support for the semblance hypothesis). Article

Vadakkan K.I (2015; Revised 2017) The necessity for the observer to examine the system from a first-person frame of reference to trace the path of generation of inner sensations. F1000 Research. (This paper explains that first-person properties need to be viewed from a different frame of reference than our current third person approaches). Article

Vadakkan K.I (2015) A pressure-reversible cellular mechanism of general anesthetics capable of altering a possible mechanism for consciousness. SpringerPlus. (This paper explains several previously unconnectable findings in anesthesia research field through a possible derangement of normal operations explained by the semblance hypothesis. For e.g.1) reduced anesthetic requirement in the presence of dopamine that causes enlargement of dendritic spines, 2) how pressure reversal of anesthetics work, and 3) correlation between lipid solubility of anesthetics and their anesthetic action). Article 

Vadakkan K.I (2014) An electronic circuit model of the inter-postsynaptic functional LINK designed to study the formation of internal sensations in the nervous system. Advances in Artificial Neural Systems. (This article describes how a basic electronic circuit can be built to generate first-person properties) Article

Vadakkan K.I (2013) A supplementary circuit rule-set for the neuronal wiring. Frontiers in Human Neuroscience. (This work explains a unique circuit feature that can operate in unison with the synaptically-connected neurons and at the same time generate first-person inner sensations. This theoretically arrived new connection needs to be verified to understand the functional connectome). Article

Vadakkan K.I (2012) A structure-function mechanism for schizophrenia. Frontiers in Psychiatry (This work has identified rapidly reversible, yet stabilizable membrane hemi-fusion as a possible mechanism for inter-postsynaptic functional LINKs). Article

Vadakkan K.I (2012) The nature of "internal sensations" of higher brain functions may be derived from the design rules for artificial machines that can produce them. Journal of Biological Engineering. (This article explains how signal propagation in neurons is different from that in an electric conductor. It further explains how a unique circuit arrangement in neuronal systems can generate first-person properties. Article

Vadakkan K.I (2011) Processing semblances induced through inter-postsynaptic functional LINKs, presumed biological parallels of K-lines proposed for building artificial intelligence. Frontiers in Neuroengineering. (This article explains how inter-postsynaptic functional LINKs proposed by the semblance hypothesis matches with the expectation of K-lines proposed by Marvin Minsky. Author was not aware of the K-line paper until the last part of 2010. Readers may sense this from the first-edition of the semblance hypothesis book and two previous papers) Article

Vadakkan K.I (2011) A possible mechanism of transfer of memories from the hippocampus to the cortex. Medical Hypotheses. (This paper explains a mechanism for the apparent transfer of locations of memory storage from the hippocampus to the cortex over a period of time). Article

Vadakkan K.I (2010) Framework of consciousness from semblance of activity at functionally LINKed postsynaptic membranes. Frontiers in Psychology. (This paper provides a framework of a mechanism for the inner sensation of consciousness. A further expansion of the framework is given in 2015 paper on anesthesia). Article

Books

Vadakkan K.I (2010) Semblance hypothesis of memory. 3rd Edition. ISBN: 978-1-4502-5620-9

Vadakkan K.I (2008) Semblance hypothesis of memory. 2nd Edition. ISBN: 978-1-4401-0754-2

Vadakkan K.I (2007) Semblance of activity at the shared post-synapses and extracellular matrices - A structure function hypothesis of memory. ISBN:978-0-5954-7002-0 Book

Patents

Artificial neural circuit forming re-activatible functional link between the postynaptic terminals of two synapses. U.S. Patent. Article

Presentations

Center for Neuroscience, Indian Institute of Science, Bangalore. August 11th, 2017. Title: Why did Camillo Golgi disagree with the Neuron doctrine?

Society for Neuroscience annual meeting - Satellite event. October 17th, 2015. Title: Examining nervous system functions from a first-person frame of reference using the semblance hypothesis.

Society for Neuroscience annual meeting - Satellite event. November 17th, 2014. Title: Exploring the mind using the semblance hypothesis.

Society for Neuroscience annual meeting - Satellite event. November 2013. Title: Internal Sensations, Artificial intelligence and the semblance hypothesis.

Florida State University, Department of Scientific Computing seminar. February, 2013. Title: Transferable units from natural Intelligence: Proof requires AI development.

University of New Mexico, Department of Computer Science colloquium. January 2013. Title: Natural intelligence to artificial intelligence - A new route that can be taken. I apologize to molecular biologists for my comment that discoveries in molecular biology were over. It is the lack of matching advancement in neuroscience that made me to say that).