Semblance Hypothesis

Objective: To understand how first-person inner sensations of higher brain functions occur either independently or concurrent with the third-person observed behavioral motor actions.

How to understand something that cannot be accessed by our sensory systems? A method used in physics

Perception from a first-person frame of reference

Without sleep, there is no system! An explanation

Internal sensation - A comparison with electromagnetism

Why do we need a first-person neuroscience?

In simple words, what is semblance hypothesis? Systems in the body are being studied by observing them from outside (e.g. pumping of heart, filtering by kidneys, structure of DNA and synthesis of proteins). Third-person approaches are suitable for their studies. In contrast, functions of the nervous system such as perception, memory and consciousness are first-person inner sensations to which only the owner of the nervous system has access. However, we have been studying these functions by examining the nervous system from outside by third-person approaches at various levels (biochemical, cellular, systems, electrophysiological, imaging, and behavioral) and trying to find correlations between these findings with an aim to understand the system. By these approaches, the first-person internal sensations of all the higher brain functions remain unexplored. The reality is that the examiner should become an insider in a subject's nervous system (and become part of the system) to sense the first-person internal sensations! This is not practically possible. This means we are facing a “frame of reference” problem in our current approaches to understand its operations. This can be overcome by undertaking a theoretical approach. Since it is a universal operational mechanism, we should be able to find it without much difficulty if we are in the right path. We had no previous experience of examining for a biological mechanism that gives rise to virtual first-person inner sensations. This should not hinder our examination in any way. In fact, we must prepare ourselves to look for a unique mechanism that has the ability to evade our attention! By keeping these in mind, a theoretical examination was carried out to arrive at a specific location where such a unique mechanism can be expected to take place. Further examination of this location has enabled identification of a set of unique features necessary for a feasible operational mechanism whereby the system can generate units of inner sensations at specific conditions (that are physiologically present). This mechanism is expected to interconnect all the findings made by third-person approaches at different levels. Until now, results using this observation are able to explain and interconnect several findings from different levels. Pathological changes of the expected cellular mechanism can explain several neurological and psychiatric disorders. Predictions made by this hypothesis are testable.                                                                                      

There are several unsolved problems in neuroscience (Adolphs, 2015) and they have been observed from different levels (Edelman 2012; Gallistel & Balsam 2014; Sejnowski et al., 2014). The challenges in understanding the nervous system can be viewed in different ways as follows. Nervous system functions observed at different levels are being studied by different faculties of science - biochemistry, cell biology, electrophysiology, systems neuroscience, psychology and consciousness studies. The system is similar to a puzzle lying in multiple dimensions. Solving it requires finding the correct pieces of the puzzle at the right level with the right operational function so that it can be used to build the system from which formation of all the functions can be explained. Solving the system is also required to troubleshoot its disorders, for example to treat psychiatric disorders. If we examine only one or a few levels of the system, we might find some solutions that will allow fitting together pieces of the puzzle, but only for those few levels. Features of the unexamined levels will remain unexplainable and we won't find the solution for the system. The diverse nature of different functions strongly indicate that the solution is going to be a very unique one. At the same time, it is also expected to be a simple one. In order to solve the system and find out the correct operational units, it is necessary to simultaneously examine representative functions from all the levels.

    A second view of the problem can be described as follows. It begins by examining the following situation: The heart pumps the blood and the kidneys filter the waste materials from the blood; these functions are observed by us from a third-person perspective. We understood their functions quite well as evidenced by our ability to develop methods to replace their functions - using artificial heart and dialysis. What functions does the nervous system carry out? It creates an inner sense of the external world during perception, stores sensory information by associative learning and later produces the internal sensation of retrieved memories of the learned item when the associatively learned cue stimulus arrives at the system, induces thought process to connect different items from different sets of learning for solving problems – all of which are first-person properties that cannot be accessed by others, the third-persons. The only sensory stimuli from the owner of the nervous system that are available to a third-person are from the surrogate markers consisting of motor activity - specifically, speech and behavior. Therefore, the pieces of the puzzle mentioned in the above paragraph should be capable of explaining both first- and third-person detectable functions.

 

    A third view of the problem become evident when examined from the view point of a builder. Here, the job is to replicate the nervous system in an engineered system. The real problems in solving the system will become very clear by taking this approach. Since intentionality to feed and carry out all the actions for survival and reproduction are present even among the members of lower level animal species, a robust evolutionarily conserved circuit mechanism for generating internal sensations is expected to be present in all the nervous systems. Since the first-person properties cannot be accessed from a third-person approach, they cannot be studied using biological systems. Therefore, we should keep replication of the mechanism in engineered systems as the gold standard proof. These systems need to be built to provide readouts for the first-person internal sensations that can be accessed by the third-persons. As a builder, we will feel the pressure to know how system can operate all the different functions. We are forced to speculate all the possible mechanisms and figure out the correct one. We will be concerned mostly to explain the formation of internal sensations at physiological time-scales. Before building the system, we need to make sure that we can draw a sketch of the systems operations.

 

A fourth view becomes possible when we observe the “loss of function” states of the system occurring at various levels. Mother Nature has provided us with this excellent toolset of “loss of function” states that can help understanding the nature of the pieces of the puzzle. Early years of genetics research have gained valuable information from "inborn errors" of metabolism that provided guidance to understand the alleles of genes. In this context, examining the neurological and psychiatric disorders can help understanding the nature of the operational mechanism. Since the exact pathological features of many of these diseases are not yet known, it is expected that the loss of function of the operational units that induce both the first- and third-person features should be able to provide information about the nature of their pathologies from which the function can be deduced.

 

Based on the above challenges, a conclusion can be arrived that for arriving at an operational mechanism that can explain both third- and first-person properties, a theoretical approach is the most efficient method. This led to the development of the semblance hypothesis. Of the different higher brain functions, memory has a special advantage in that it can be tested at various levels (induction, storage, maintenance, and retrieval at the structural and functional levels). Studies were carried out by examining how the first-person internal sensation of memory is formed at physiological time-scales using electro-physiological properties compatible with cell biological features. Further examinations were carried out to test whether the same mechanism or its derived operations can explain findings from different fields of neuroscience research. These included findings that are unsolvable when examined by third-person observations. A hypothesis was published first as a book in 2007 (a copy is uploaded in Publications section). Revised editions were published in 2008 and 2010.

Among different brain functions, memory has the advantage in that experiments can be carried out both to associatively teach the system and then verify how learning-induced changes are used during memory retrieval. Large amount of experimental data are available in the field of memory research. Retrieved memories are assessed using behavioral motor changes such as speech or motor activity occurring at the time of memory retrieval. Since no cellular changes are observed during memory retrieval, the memory retrieval is likely taking place by a passive reactivation of a learning-induced change. Since molecular or electro-physiological changes are not observed during memory retrieval, current studies are limited to examining changes taking place at the time of associative learning. Memories were classified into working, short-term and long-term memories based on the differences in the period of time, following learning, during which they can be retrieved. Studies have been carried out with the assumption that the cellular mechanisms during learning that leads to memories classified in this manner are different. Since qualia (virtual first-person internal sensations) of these retrieved memories are almost same, it prompts one to ask, "What if a) a common cellular mechanism is taking place during learning, and b) the retrieval of different types memories (currently classified) can be explained by reactivations of learning-induced changes that are retained for different durations?" One may also ask, "Can we directly examine the memories themselves instead of examining the motor activity such as behavior and speech at the time of memory retrieval?" This will also eliminate our dependence on correlating memories with slow molecular changes occurring after learning. In this context, it is necessary to re-examine the question: "What are memories?" Memories are first-person virtual internal sensations induced within the nervous system (in response to a cue stimulus or occurring spontaneously). Can we search for a mechanism that can induce virtual first-person internal sensations of memory?

Large number of features observed by different branches of neuroscience and psychology are required to be explained by a solution for the system (Table 1). Since these features are very diverse, only a unique cellular mechanism will be able to explain all of them. This unique mechanism is expected to be a unique structure-function mechanism occurring at the intersection between the third-person observed features and first-person properties. In other words, it is a structural feature that can provide the basic units of first-person internal sensations of different higher brain functions. It is necessary to verify whether the derived solution can explain findings from different specialized faculties within the large fields of neuroscience and psychology and test whether the explanations are inter-connectable. Since our current research efforts in each field are moving towards more specialized and super-specialized areas, finding and verifying the unique solution (to put the pieces of the puzzle together) requires an effort in the opposite direction. Anticipating this is the most important requirement for solving the system. It is necessary to explain how the nervous system functions occurring at different levels such as - a mechanism that directs potentials to induce internal sensation concurrent with the activation of motor neurons at physiological time-scales (inter-connecting central mechanism), dendritic spine changes, long-term potentiation, place cell firing, consolidation of memory, and association of memory with a feasible framework for consciousness - are interconnected. The constraints provided by findings from various levels (Table 1) were used both to derive a testable mechanism that can explain and interconnect findings made by different faculties of brain research and to verify its suitability. For the first time, the present work put forward a testable mechanism occurring during learning that can be reactivated at the time of memory retrieval to induce basic units of internal sensation whose computational product can form memory. Structural and electro-physiological changes that are expected to occur from these changes were explained using experimental results from different laboratories.

Findings

Constraints offered by these findings that direct the enquiry towards a correct solution/ What needs to be explained?

Nervous system is made of synaptically-connected neuronal circuitry Mechanism should operate synchronous with the synaptically-connected neuronal circuitry
Learning-induced changes occur at physiological time-scales (in milliseconds) A learning-inducible change that can occur (and completed) at physiological time-scales (to explain the ability to retrieve memory instantly following learning)

When exposed to a cue stimulus, internal sensation of memories takes place at physiological time-scales (in milliseconds)

A mechanism that uses learning-induced change to induce internal sensation of memory at physiological time-scales (should be able to complete within this time)

Absence of cellular changes during memory retrieval

A passive reactivation of the changes that occurred during learning should be getting used at the time of memory retrieval to induce units of internal sensations. This should take place at physiological time-scales.    

Operates at a certain range of frequency of extracellularly recorded oscillating potentials

Expected mechanism to provide vector components of the oscillating potentials

Storage of very large number of memories

Since neurons and their processes are finite in number, for storing very large number of learning induced changes, an efficient operation becomes possible if each memory gets induced from a combination of unitary mechanisms              

Instant access to very large memory stores

Reactivation of large number of specific combinations of learning-induced changes in response to large number of specific cue stimuli should be able to induce specific memories at physiological time-scales

Motivation promotes learning

Role of a specific factor and a specific action to promote the learning induced change and possibly to retain this change for longer period of time than that occur in its absence

Internal sensations of working, short and long-term memories have similar qualia

A mechanism to retain learning induced change for different lengths of time

Working memory lasts only for a very short period of time Learning induced change must have a quickly reversible mechanism

Retrieval of memories very long period of time after the learning

A feasible mechanism for long-term maintenance of learning induced change

Simultaneous existence of previous two conditions (above two rows) within the system Learning induced mechanism should be able to accommodate a quickly reversible change that if prompted can progress towards a stage where it can get stabilized for long period of time

Ability to induce internal sensation of memory in a cue specific manner

How cue features can induce specific features for the internal sensation of memory?

Ability to store new memories without needing to overwrite the old ones

How specific features of different memories can be maintained by retaining previous learning-induced changes or an equivalent mechanism?

Consolidation of memory

How gradual transfer of locations of learning-induced changes occur and how memories can still be induced?

Mechanism to use schemas inter-changeably

How changes induced by one learning  are shared by another learning event and how these shared changes are used at the time of memory retrieval?

A constantly adapting dynamic circuit mechanism is expected Mechanism should be able to make large number of changes to accommodate large number of new learning and at the same time should match with the observed variations in the number of synapses

Framework of a mechanism that can generate hypothesis by the system

How two internal sensations produce internal sensation of a relationship between them?        

Place cell firing in response to specific spatial stimulus

How internal sensation of memory for a location is linked with firing of a set of CA1 neurons?

System needs an unconscious state of sleep for nearly one third of its operational time

Substantive nature of sleep in the operation of the system. In other words, it is necessary to explain why the system won't be able to exist without sleep

Firing of an ensemble of neurons during a higher brain function

The mechanism should be able to explain this observation

Firing of a set of neurons during a specific higher brain function (for example, during both learning and memory retrieval)

How both learning and induction of internal sensation of memory are associated with firing of specific sets of neurons?

Firing of a cortical neuron (axonal spike) is possible by summation of nearly 40 postsynaptic potentials (inputs). These cortical neurons have tens of thousands of dendritic spines where postsynaptic potentials can get generated These neurons have to be maintained at a sub-threshold state at the background state and the mechanism of induction of internal sensation has to be associated with providing additional postsynaptic potentials for crossing the threshold for firing of these neurons
Dendritic spikes occur by the summation of nearly 10 to 50 postsynaptic potentials at the dendritic region What is their functional significance?
Oscillating extracellular potentials While synaptic transmission provides one vector component, what constitutes the other vector component/s that is/are expected to take place nearly perpendicular to the direction of synaptic transmission?
Apical tuft regions of all the cortical neuronal orders are anchored to the inner pial surface resulting in crowding of the dendritic arbors of neurons from different orders What purpose does it serve by having dendritic spines of neurons that belong to both the same order and that belong to different neuronal orders close to each other?
On an average, inter-spine distance is more than the spine head diameter What is occupying the inter-spine region and what possible functional contribution can they make? Based on the above row, what are the possible implications?

Following learning, initially there is conscious retrieval of memory and eventually this becomes sub-conscious after repeated retrievals

Must be able to explain at least as a framework of a mechanism

LTP has several correlations with behavior associated with memory

The mechanism behind these correlations

Learning takes place in milliseconds, whereas LTP induction takes upto 30 seconds and even more time Cellular level mechanism is necessary to explain this discrepancy

Blockers of membrane fusion blocks LTP

Need to explain the cellular location where they act          

Induction of LTP at the CA2 area of the hippocampus becomes possible by the removal of the peri-neural net proteins chemically

Specific mechanism at the extracellular location by which the mechanism of LTP induction (that is related with natural memory) gets affected

Relationship between LTP, kindling and seizures

Need an interconnecting explanation

Loss of dendritic spines after kindling

Specific reason to explain the loss of spines

CA2 area of the hippocampus is resistant to seizures

How peri-neural net proteins can block the mechanism of seizures, which is related with kindling and HSV infection?

Seizures and memory problems by herpes simplex viral (HSV) encephalitis

Mechanistic explanation for both these features is expected to provide some information about the relationship between these two features

Mechanism of neurodegenerative disorders

How contiguous spread of pathology cause spine loss and neuronal death. Provision for the sporadic occurrence of these changes?

Dementia in neurodegenerative disorders

How loss of spines can lead to dementia – loss of internal sensation of various higher brain functions and behavior?                

Perception as a first-person internal sensation

How a variant or a modification of the mechanism of induction of internal sensation for memory can explain perception?

Flash lag delay, apparent location of the percept different from the actual location, homogeneity in the percept for stimuli above the flicker fusion frequency, mechanism for object borders and generation of pressure phosphenes

Matching explanations using the mechanism of induction of units of internal sensation for all these features

Inner sensation of consciousness

A testable mechanism for the generation of inner sensations that depends on/contributes to the frequency of oscillating extracellular potentials. Explain what contributes latter's vector components and their role.

Loss of consciousness by anesthetics

All the known properties of anesthetics and how they alter the framework of consciousness

Loss of consciousness during a generalized seizure and its reversal

How the explanation for seizure generation is linked with alteration of the framework for consciousness?

Changes in consciousness with the alteration in the frequency of oscillating extracellular potentials How a specific range of frequency contributes to the state of normal consciousness? How does the vector components contribute to this?

Effect of dopamine in augmenting anesthetic action

Explain a mechanism how dopamine augments anesthetic action. Now verify if this explanation matches with the explanation how dopamine augments learning

Mechanism for innate behavior that enables survival

A mechanism evolving from heritable changes to explain innate behavior in response to a stimulus

Comparative circuitry in a remote animal species

Comparable features that show relationship of a mechanism that induces units of internal sensation using synaptically-connected neuronal circuitry among different species of animals  

Neurodegeneration resulting from repeated general anesthesia

How mechanism of loss of consciousness by anesthetics, if induced repeatedly, cause loss of spines and other features of neurodegeneration?

Certain functions appear to be located at certain specific brain regions based on the findings of lesions/lesion studies These minimum locations that cause loss of function are most likely locations of convergence of inputs (they can also be locations of converging fiber tracts)
Astrocytic pedocytes cover less than 50% of perisynaptic area in nearly 60% of the synapses in the CA1 region of hippocampus Suitability of the distribution of astrocytic processes in the operational mechanism
Present nervous systems have evolved over thousands of years and are also the results of certain accidents. They have different survival features It is expected to find certain features suggestive of these. It is also expected to find possible advantages of inducing inner sensations

Table 1. Features of the system from different levels that need to be explained independently and in an inter-connectable manner using a derived solution. Even though several possibilities can be excluded (for example, biochemical reactions that occur slower than the physiological time-scales at which learning takes place (from which memory can be retrieved), which can help exclude candidacy of several biochemical intermediates as storage molecules), a systematic approach is necessary to find the correct solution. Please note that the listed findings are so disparate and the constraints offered by them are so strong that there can only be one unique solution. In other words, this unique solution for the system should be compatible with all the previous experimental observations. Constraints provided by each of the observations help to narrow down the possibilities to arrive at the solution. A subset of above list of observations can be used to derive the solution and the rest of the features can be used to verify whether the derived solution is correct or not. Please note that we cannot arrive at a solution using few mathematical equations. Once we have a unitary solution, we need to understand the principle of their computations where mathematics is expected to have a major role.

 

A complete understanding of the operational mechanism leading to the first-person properties will only be achieved by carrying out the gold standard test of its replication in engineered systems. Even though replication of motor activities to produce behaviorally equivalent machines may seem adequate, the work will not be complete until first-person properties of the mind are understood. Engineering challenges in this approach include devising methods to convert the first-person accessible internal sensations to appropriate readouts. Experiments to translate theoretically feasible mechanisms of its formation both by computational and engineering methods are required. Feasibility to explain various brain functions both from first and third-person perspectives qualifies it as a testable hypothesis. Research findings from different laboratories have been examined in terms of the semblance hypothesis. The present work resulted from curiosity to understand the order behind the seemingly complex brain functions. In this attempt, I have used some freedom to seek a new basic principle in order to put the pieces of the puzzle together. This work wouldn't have become possible without a large amount of research work painstakingly carried out by many researchers over many years. Even though the present hypothesis is compatible with experimental data, it must be considered unproven until verified.

 

Video presentations

1. A testable hypothesis of brain functions

2. How to study inner sensations? Examples from mathematics

3. Neurons and Synapses

4. List of third person findings and the derivation of the solution for the nervous system

5. Constraints to work with

6. Induction of units of inner sensation

7. Why do we need to sleep?

8. A potential mechanism for neurodegeneration

9. LTP: An explanation by semblance hypothesis

10. A framework for consciousness

11. A potential mechanism of anaesthetic agents

--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

The challenge: "What I cannot create (replicate), I do not understand" - Richard Feynman

The reality: We are being challenged to find a scientific method to study the unique function of the nervous system - i.e. how different inner sensations are being generated in the brain. We cannot directly study them using biological systems. But we can use all the observations to try to solve the system theoretically followed by verifying its predictions.    

The expectation: We are likely able to solve the mechanism of the nervous system functions in multiple steps. First, using the constraints offered by all the observations it is necessary to derive a solution (most likely a first principle) that can unify those observations. This can be followed by further verifications by triangulation methods and examining comparable circuitries in different animal species. Once identified and verified, we can expect to replicate the mechanism in engineered systems.

The hope: We will give everything we can. Together we will explore it!