Theory’s summary
A. cognitive self part
we are not living in the real world but inside a balloon of inner mental images those are consistent with the outerworld ones and had been performed gradually during different developmental stages.
what is Alzehiemer disorder?
it's a process of gradually vanishing of these mental images.
patient is conscious with almost intact sensory organs but cannot recognise the world around.
The internalisation of outerworld images started by fractal process.
which means each particle (bit of sensory information) has its own specific intraneuronal ensemble ) this defined by intra/extracellular ratio of ions (na+ ,k+and ca+) we can call it ( ionic print ) ionic print will be activated each time the consistent outerworld image particle presented this means it has specific intraneuronal pathway.
OwenN.Vickery et al 2018:-
(na+ ions respond to voltage changes from -150 mv to +150 mv ) (na+ ion exchange is the key step in activation of GPCR)
Benchiam et al 2o13:
(physiologically relevant mv can elicit functional and conformational changes in several independent GPCR)
Are GPCRs act as voltage sensors? as R.p Costa 2015 asked.
During the developmental journey The appearance of GPCRs in Central nervous system is the announcement for transformation of ionic signal fractions into a mental image.
The diverse types of GPCRs responsiveness with the development of (heteroreceptors) lead to formation of specific circles that integrate networks activity responsible for association of cognitive, emotional and motor self parts in one union, as we shall explain.
GPCRS having diverse ligands, diverse transduction pathways yielding diverse specific responsiveness in highly selective manner review ( J A Boutin 2024-biased agonist).
The diversity of ligands including ions, neurotransmitters, nucleotides, peptides, cytokines, amines, vitamins natural products, hormones pharmacological agents, photons and odrants review (D.Wacker 2017)
The diversity of transduction pathways and its specificity depend on the different α (alpha) subunits that targeted the signal to its specific pathway that has been assigned for specific responsiveness.
For example (G αs, G αi/o ,and G αq)
G αs stimulating adenylyl cyclase which increasing CAMP leading to stimulating PKA.
G αi/o reduces Adenylyl cyclase activity.
So G αs and G αi/o working on current temporal scale for adaptation to incoming sensory information (cognitive self part) at any current moment.
G αq working on phospholipase C (PLC) to stimulate PKC through triphosphatidyl inositol (IP3) pathway.
PKC lead to cell proliferation and then circuit formation.
So PKC working on developmental temporal scale.
GPCRs are 5 classes but regarding to cognitive self part We contribute to class A (rodopsin class).
The class allowing the retina to go from light based cycle (photon perception) into pattern based cycle (complexity of image and its motion)
not only that :
N Y leung 2017:-
showed roles of opsins in light independent functions like:-
Temperature sensation and hearing although they are light receptors
also they can detect light in skin, brain and blood vessels.
Also The presence of opsins in parapineal body (E.H Choi 2021)allowed the association of incoming sensory information to diurnal rhythm which constitute the concept of time in our brain.
N Y Leung 2021:-
(Opsins are polymodal sensory elements)
How all these GPCRs circuits are organised for allowing our brain to work in one connectome?
It's a matter of associvity, cooperativity (heteroreceptors),and specificity (agonist baised ligands).
It's the same Hebbian laws but at the subcellular level.
So the mental image formation started by fractal process.
Minis=(postsynaptic current corresponding to a single vesicular release)
it's a unit of chemical and electrical activity per signal unit of sensory input.
while cerebral avalanches reflected electrical cerebral activities during signal fractions collection.
how signal fraction (mental image particle) can recognise its own specific miniature?
Its a gradual process occurs through kinase/phosphatase balance
(I Somly 2017) and synaptic tagging capture plasticity (Diego Moncada 2015) during developmental journey
It's the process allowing each neuron to learn its own receptive filed with respect to cell type and brain area.
The collection of signal fractions into a coherent mental image occurs when the outerworld image presents its own consistent mental image.
It seems like piece puzzle each bit should put beside the previous suitable one we postulate the sensory information sending from neuronal presynaptic portion to dendrites are submitted to 4-intraneuronal processes
1st process
1- recognition and differentiation of signals into novel and familiar
the novel signal fractions will occupied newly ionic grade pathway while familiar ones are submitted to inhibition because they have already their ionic print (review novelty detection Schulz et al 2021 )
2- 2nd process is the precise arrangement of signals in graded mode according to their ionic print.
This process occurs through excitatory-inhibitory balance at subcellular , neural and circuit level.
3- 3rd process is addition process:
the addition process meaning the ability to add novel signal to its previous suitable one according to the degree of ionic print
4- 4th process:
it's a collective process gathering all signals or signal fractions allowing them to pass as one ensemble inside the neuron
- Shira Sardi 2017:( each neuron functions as a collection of. independent threshold units summate asynchronous electrical signals).
- we postulate the recognition and arrangement processes occur throughout the ping-pong interplay between soma and dendrites to the degree confirm there is a soma memory for extra/intracellular ionic print allowing specific pathway for every signal fraction.
- review: (I Segev 2ooo - RAJ Van Elburg 2010- G.Stuyt 2022).
the addition and collection processes (3rd and 4th) occur in axonal initial segment (review I Segev dendrites axon interplay).
At the end of the former processes if collected signal fractions reach the threshold point the signal transmission will be (digital ) while the subthreshold fractions will be transmitted through (analogue ) form (D.Debanne2013).
At cognitive level digital transmission represents the focused signal while analogue performing back ground signals(the back ground particles of the scene).
Through digital/analogue transmission no signal fraction will be dismissed.
Its (signal to noise ratio)
In brain language:- signal_ represents the degree of :
attention and concentration while noise_ represents: the back ground particles which may be overlooked.
So, deterministic / stochastic noise ratio reflects
subconscious /unconscious signal detection (the overlooked signals).
Felix Droste 2015 :- (signals from different sensory modalities can converge in a single neuron)
Its the primary step of circuit formation.
When a single neuron carry different sensory modalities.
So a single neuron receives information from different sources and distributes them to different targets where dendrites and soma constitute the convergent portion and nerve terminals constitute the divergent one that distributes signals to other neurons those will share in performing a coherent mental image, this is the meaning of circuit.
Through developmental journey Hebbian laws like
Associativity, cooperativity and specificity are working in neuronal population leading to well established specific circut formation it’s the primary stage for classification of sensory input into categories by adding all sensory pieces (multimodal) in a collective coherent image according to their congruent characters.
allowing classification of information into for example (birds, animals or humans when shared characters are more than difference).
Notice that these groups were collected according to shared characters like (faces, foots and hands) this meaning that subgroups, groups and grouping started in fractions and fractal process.
The cognitive self part is dynamic and expanding till adulthood by adding novel parts of outerworld images to the previously retained ones
Here the 1st question will arise
What about linearity of this expanding that reflected by long-term potentiation where nonlinearity either in function or structure and energy saving are the two major roles governing brain work?
In the brain always there are two forces appearing as working against each other although they are integrated :
1. The balance between phosphatase/kinase at subcellular level and
2. Excitatory/inhibitory balance at the level of circuits (eg GABAergic inhibitory plasticity) or at neuronal level (Everton J.Agnes-Tim P.Vogles 2024) Also.
3. The balance between long-term potentiation and long- term depression (G. Antunes 2o16).
Finally
The reduction process through dendritic pruning and switching of functional hubs from primary sensory areas to associative areas (S.Oldham 2019) is the most dynamic process during developmental journey.
All the former processes prevent linearity and saving energy while cognitive self expansion (increasing knowledge volume).
The most obvious process for energy saving is the reduction process :-
Alexis Wnnk : (dendritic pruning lead to brain shrink ),(notices it prevents linearity of structure ).
Dendritic pruning that leads to brain shrink occurs between age 30-40y) this is the age when novelty becomes rare ( C.Kirch 2021-Karsen Gill 2018(dendritic pruning require less energy) again this reduction process is a matter of energy saving.
We should note that while reduction process works mainly for linearity prevention and energy saving the excitatory inhibitory balance working mainly for precise arrangement of signal or signal fractions this precise arrangement during developmental journey allows keeping the grouping process(cognitive self part expanding by adding novel parts) it a matter of energy saving while energy consumption increases.
The 2nd question?
How neurons adapt to contextual change of sensory information without need for new circuit formation?
This is the adaptability for environmental changes that is going every moment .
It occurs only by modulation of neural activity through changes in neuneurotransmitter release
R.P Costa:_ (the neuron can learn each receptive filed and could rapidly relearn the acquired receptive filed just by increasing P)
Where P is the probability release of neurotransmitter
So just by increasing or decreasing the amount of neurotransmitter the recognition of original stimulus preserved whatever change in position or subtle changes in shape.
The Spike timing dependent plasticity represents the:
electrical activity accompanying the contextual change or novelty detection and addition
Also R.P.Costa 2015:(unified presynaptic and postsynaptic timing dependent plasticity allows learning information while retaining traces of prior experience).
We can conclude that the main function of neurotransmitter:
is modulating neuronal activity in order to recognise the primary mental images in their newly form specially when novelty addition became rare at adulthood (no more mental images could be added)
The 3rd question:-
In what range the changes in stimulus context can be tolerated?
Its the range of tolerability if exceeded the anxiety disorders will be arised and if strongly violated post-traumatic disorder will be appearing.
The range in which mental image particles could be gathered whether at neuronal, circuit or network level within two set points of Turrigiano (review synaptic scaling, local and global homeostatic mechanisms
G Turrigiano and Melanka)
The 4th question:
What is preserving the stability of synaptic connectivity during continuous change in synaptic strength due to continued environmental contextual change?
At neuronal level:
The bidirectional and mutual information between presynaptic and postsynaptic connectivity (eg.nitrious oxide and cannabinoid in case of hpo-hyperactivity respectively keeping this stability (R.P Costa 2015-Daniela Gandolfi 2020), (balance between excitatory and inhibitory activity in addition to heterosynaptic transmission and neuromodulators keep stability and conservation of synaptic strength) L. Caya Bissonnette 2020)
At network level:
The purpose of this work is keeping fine arrangement of signal fractions which keeps the consistency between the presented mental image with the primary one (what’s coming with what has been came) it’s one of our brain miracles to work on different temporal scales at same time.
Edmund T. Rolls 2021:-
3 classes of excitatory input into pyramidal cells :-
a. forward input from previously cortical area.
b. Backward projection from the following cortical one.
c. current signals from nearby synapses.
That’s will guard bottom- top predictive coding (what’s coming)
If we add Daniel Fine English 2017.
(connectivity between neurons and local interneurons lateral inhibition is believed to gate afferent drive and control local synchrony)
It’s top-down predictive coding and the integration between bottom-top and top-down performing
the (corrective predictive coding) reflects the submission of mental images to priming it’s the result of neural adaptation ( T.P Reber 2023).
Frazisk Gerken et al 2024:(decoding performance is driven by feature selective single neurons when decoding visual transitions such as camera cut ) also (medial temporal lobe contains category selective cells).
The familiarity means the formation of Archetype archive in cognitive self part (priming) these Archetypes elucidate.
The psychological phenomena like continuity, and completion , deviation from Archetype lead to mismatch negativity phenomena performing mistakes alarm.
This archives of archetypes allowing the child to recognise his father image with or without moustache- with or without beard
So the fragmented sensory information (fractal process at neuronal or circuit level allowing sensory input to keep the recollection of the primary image even if it is not completed in addition to readjust the presented image during the contextual change
The visual system development is the most impressive example of development from fractal to coherent mental l image while keeping the precise arrangement of Signal fractions during transmission from one brain area to another:
1. developmental mode of retinal light perception from( light) based cycle into (pattern ) based cycle.
2. similarity between visual fields in retina and lateral geniculate body (Rathon2010-Bee Reese2011)(it’s the keeping precise arrangement during signals transfer from one brain area to another .
3. The retinotpoic organisation all through the visual pathway even in the visual cortices (M.S Beau Champ 2020) again this is preserving the stability of precise arrangement of signal fractions all through visual pathway.
4. Finally the discovery of complex cells in V1-V3 that respond to summation of several receptive fileds that have been integrated from many simple cells (T. Huff et al2023 )
It’s a highly collective process gathering scene particles orderly results in a coherent mental image with respect to the developmental stage
The question that will be arise:
How recognition would appear before mental images completed? Before visual system maturity?
Recently (fetus can respond to his mother and father voices)
Robstein 2017 Sharah Knapton 2017 ,Lozier institute 2023
The recognition system occurred through the sense of audtion and olfaction allows the Archetype formation even before visual system maturity.
Review role of rhinal cortex in declarative memory
Another wonderful brain miracle is the ability to represent the mental images in the form of symbols and signs ,it’s the reductive process (Hagena ,Manahan Vaughan 2011: (exposure to novel environment facilitate the long-term potentiation where as addition of landmarks facilitate long-term depression at CA3 synapses)
so the ability to represent symbols, signs and cues it's a matter of energy saving.
language is a matter of symbols and signs used spoken, written even mathematical Symbols and signs ,it’s a type of representation of outerworld images in reductive format even in the absence of their significant image (neuroimage 2016 -Giacomo-Handjares et al )
This constitute the internal representation which is the ability to represent in the absence of sensory organs stimulation (imagination)
We postulate the trophic units are the building blocks of symbols and signs with their corresponding codes ,in addition to their ability to modulate neuronal responses through glial neuromodulators integration,
( Pereira and Furlan) : Mainly sensory, cognitive and emotional patterns transmitted from spatially distributed neuronal and glial populations can result in activation of astrobiology ca+ waves)
Review: Maha Elsyed, Piere J Magistertti 2015 (mental illness glial involvement Biological science 2013 )
( one neuron can encode many informations)
So how many information a Tripartite synapse can encode!
Reflected outerworld images and the ability to represent them either faced or through their symbols and signs constitute a half of cognitive self part
What about the other half ? Which is the body image
Our body parts have already an inherited mental image in motor area, and body related to space define by parietal lobe,while body current state is coming through thalamus, cerebellum and basal ganglia so body image can be detected at any current moment
.
The body ,mental image/ outerworld image constitute the cognitive self part at any moment
Neuronal activity reflected that the neuron can deal with different temporal states at same time
one is the current state (what’s coming ) while the other is comparing the current state with prior activity for addition the novel part or completion the deficient one.
We postulate PKA mainly working on current state while PKC working mainly on developmental way (addition process) to perform at the end a coherent mental images consisting of outerworld images.
Finally we can summarise the biological events inside any neuron at any current moment as follows
1. The events start by changing in extracellular and intracellular NA+,K+ ca+2 ratio
2. This ionic ratio will be translated into changing in intracellular Ca2+ (resting, transient or residual) according to the nature of incoming sensory information
3. Changing in ca2+ state is controlling the degree of vesicular release of neurotransmitter r leads at the end to:
4. changing in AMPA number through AMPA endo/exocytosis and changing in AMPA/NMDA ratio that constitute the trial to regain the prior activity level it’s a matter of homeostasis
In our postulation regarding to cognitive self part The last two processes (AMPA endo/exocytosis and AMPA/NMDA ratio reflects the two major processes of working memory) we call them (reflection) and( representation)
for example:-
If you stand in front of a mirror when you realise there is an image this the reflection but when you recognise this image it’s yours this is the representation
We postulate the AMPA endo/exocytosis is responsible for reflection while AMPA/NMDA ratio for representation
(AMPA play a role in normal ongoing transmission while NMDA play a role in development of cortical circuit) Kirk Wood and Bear 1994.
When a single neuron carry different sensory modalities.
We postulate :-
The ability of AMPA to change subunits composition not only control the
intracellular Ca2 but also control the degree of mental image particles contrast .
Siqiong June lieu , R. Suzanne Zukin 2oo7
(Glutamate R2 lacking AMPA mediated ca2+ signalling is
Rapid compartmentalised owing mainly to fast local ca2+ extrusion pumps
It is instrumental in synchronous firing in neocortex layer 2,3(gamma oscillations)
interneurons during gamma oscillations involved in transmission of information to distant regions of the brain)
We should note the AMPA over expression after cases involving the loss of consciousness e.g :-
After myocardial infarction and cerebrovascular accidents or epileptic status ,also in some chronic cases like drugs abuse and depression that involve the distortion of outerworld images reflection , ,Review:-Casto Rivadulla et al 2001 (direction selective responses in visual cortex)
Changes in AMPA/NMDA ratio during drug use and depression
Review(TARP crucial for antidepressant action of ketamine) SG Xue 2o23 TARP crucial for endo and exocytosis of AMPA
The ability to reflect and represent the body/self image and outerworld images consisting the current consciousness
We suppose reflection occurs mainly through AMPA endo/exocytosis while AMPA/NMDA ratio constitute representation.
Clinical application respect to cognitive self.
Schizophrenia disorders :
Start by distortion of outerworld images reflection and body/self image representation responsible for positive symptoms (e.g delusions and hallucinations).
Affective disorders
1- Bipolar disorders
start by distortion of body/self image reflection then outerworld representation
2- Unipolar disorders
Characterised by distortion of body/self representation which leads to inconsistencies between reflection and representation also distortion of outerworld images representation
Like Anxiety disorders but in Anxiety disorders the body image is more distorted than self image.
3- Alzehiemer disorder
In early stages the representation of outerworld images is deficient and going gradually where reflection and representation for both outerworld images and body image will be distorted.
4- Autism
disorder of impaired outerworld images reflection from the start
Rendering the Archetype formation and preventing corrective predictive coding formation (primary images)
Experience involving the sense of self confidence which is the result of retaining the previous motor reactions outcomes with their associated emotional load and the suggested motor reactions with their predictive emotional load
Reasonable self confidence is bringing out by balance between adaptation and accommodation throughout developmental journey
Early excessive adaptation lead to fear of body/self image distortion
e.g OCD ,paranoid trait
early excessive accommodation lead to appearance of authoritative traits or psychopathy
we postulate the cognitive self part (incoming sensory information) is working through vertical and horizontal networks to perform predictive coding and once associated with emotional and premotor or motor self parts the whole brain is working through circular networks
Here two questions are arising:-
.
Kapoor showed how an emotional moment had been performed
But we postulate each emotional moment in subcircut specific way with its assigned cognitive part has represented inside the insula and the collection of these moments will perform what we call emotional loads archives
.