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
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 subthreshold
activation states short of a fraction of one postsynaptic potential), even fraction of a sigle 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
neighbourhood where degeneracy is observed. This work shows that information storage and retieval
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 time-scales of milliseconds remains as the core change
sufficient for retrieving memory as a first-person internal senation
during working memory. Maintaining this learning-induced change by its
stabilization allows continued retrieval of the same memory after short
time and long time 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 hypotheiss. 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 expectedd 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 time-scales. By viewing memories
in their true nature as first-person inner sensations, this work
has explained how a derived mechanism of natural learning ocurring
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, we 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 hypothesised 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 large number of findings from different
levels to examine a possible normal operational mechanism of the system)
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
in a remote animal species provides support for the presented mechanism).
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.
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 how
anesthetic requirement is reduced in the presence of dopamine that
causes enlargement of dendritic spines).
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.
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).
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.
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.
Vadakkan K.I (2011) A
possible mechanism of transfer of memories from the hippocampus to the
cortex. Medical Hypotheses.
Vadakkan K.I (2010) Framework of
consciousness from semblance of activity at functionally LINKed
postsynaptic membranes. Frontiers in Psychology.
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
Patents
Artifical 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. (video). 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).
Society for Neuroscience annual meeting -
Satellite event. October 15th, 2012. Title: Reducing internal sensation of
retrieved memories using the semblance hypothesis.
Society for Neuroscience annual meeting -
Satellite event. November 13th, 2011. Topic: Semblance hypothesis of memory:
Computational modelling and development of artificial circuits.
Society for Neuroscience annual meeting -
Satellite event. November 14th, 2010. Topic: Semblance hypothesis of memory - Transfer
of memories from the hippocampus to the cortex.
Society for Neuroscience annual meeting -
Satellite event. October 18th, 2009. Topic: Semblance hypothesis of memory - A
presentation.
Abstracts
Vadakkan K.I (2013) A structural unit of
brain network that can operate in unison with synaptic connections and
can impart needed functions. Cell symposium on the topic "Networked
Brain" at the Society for Neuroscience meeting November 8
Poster
Vadakkan K.I (2012) Induced p-semblances as
a possible mechanism for the internal sensation of pain. Society for
Neuroscience Annual meeting, Oct.16. Abstract
674.25/HH10
Vadakkan K.I (2012) Perception as the
integral of semblances formed by re-activation of existing previously
formed functional LINKs between the postsynapses. Cognitive Neuroscience
Society meeting, April 3rd, Abstract H90
Vadakkan K.I (2011) Semblions induced
through inter-postsynaptic functional LINKs, biological parallels of
K-lines, as basic units of internal sensations. Society for Neuroscience
conference, Abstract 722.16/XX68
Vadakkan K.I (2010) Framework of
consciousness from the semblance hypothesis of memory. Toward a science
of consciousness Conference, Tucson, University of Arizona. Abstract No:
P-8
Vadakkan K.I (2009) Delusions, cognitive
impairment and the therapeutic effect of dopamine receptor antagonists
in schizophrenia - An explanation through the semblance hypothesis of
memory. Society for Neuroscience conference, Poster Abstract: 644.3/U18
Vadakkan K.I (2008) Oxidation-state
dependent interconnections between dendritic spines provide early
evidence in support of semblance hypothesis of memory. Society for
Neuroscience conference, Abstract: 239.19/E16
Vadakkan K.I (2008) Examination of the
premises of semblance hypothesis that can explain retrieval-efficient
mechanism of memory at appropriate time-scales. Second Canadian
Association for Neuroscience annual meeting, Montreal.
Abstract A-G 118