Luc Turpin

A sense of smell or a pair of legs do not make choices in trying to achieve a certain outcome. However, intelligence makes this possible. Your sense of touch allows you to "sense" the keys on your keyboard, but its your intelligence that allowed you to know that you were typing an "A" and allowed you to type this text asking a very valid question. I do not know if there is an "end game", but there is at least an immediate purpose. In many cases, its' about finding food to stay alive, and this is best done with a bit of intelligence on your side, because doing it only by trial and error is costly in the survival game.

No parent! As evolutionists would say, intelligence is an emergent property of life; as life is an emergent property of matter.

Will avoid posting

My contention is that bringing mind into a discussion on the evololution of living organisms is essential, not off topic. It has an effect-impact on evolution. As for defining and explaining, you are correct that it should occur elswhere.

Mind, my favourite topic. I believe (backed by evidence) that most if not all living things show some sense of intelligence (a substrate of mind to me) and that if we are to discuss evolution in living things, then we cannot not bring it into the discussion! Intelligence in living things provides partial vision to the blind watchmaker. Also, intelligence is only one piece (although an important one) in the puzzle that we call evolution in living things. And yes, it is guided evolution that we like it or not. Even if we allow only humans to possess it and that it is only an emergent property, it is still influencing evolution. If the discussion remains on non-living things, then please disregard my comment.

This comment opened the door for me. Mind is my favourite subject. I am entirely in agreement with the above indicated statement. If you assume, as I do (backed by evidence), that there are varying degrees of intelligence (a substrate of mind for me) in all living things, then it follows the there is only one kind of evolution; guided evolution; not the one guided by a supreme being, but by intelligence (primitive at first in small living things) that gives a bit of vision back to the blind watchmaker. However, intelligence is only a single piece (important one though) in the complex puzzle that is evolution. Note: If the conversation remains on non-living things, then, by all means, disregard my comment!

We both agree to disagree on terminal lucidity and both agree on the extraordinary nature of our physiology.

I am not looking for a miracle, but a more satisfactory understanding of terminal lucidity and possible ramifications in the on-going debate on mind-brain connection.

I think that your last post speaks to the crux of the matter. I agree that there should not be any behavioral expressions without sufficient brain function and connectivity. But the data may be (not definitive, but may be) telling us that at a critical junction (between life and death), something else or something more is at play. Let's make the following postulates for end-stage AD: cortico-thalamic link sufficiently maintained; thalamus sufficiently functional; brain still benefiting from plasticity and still seeking homeostasis. Why then do we not see progressively diminishing periods of behavioral expressions followed by progressively increasing periods of non-behavioral expression? Not linear, but average regression! What we usually see in late-stage AD is a long period (months, year) of almost complete non-behavioral expression (typical of significant brain degradation) followed by a brief (hours, day), robust (near full functional) and very-late (close to death (hours, days)) spontaneous burst of behavioral expression. Near death appears to be, but not always, a determining factor here. I am sure that you can find counter points to my points. But isn’t it strange that these things called terminal (hours) or paradoxical (days) lucidity happen mostly near death, when the body is maximally degraded by AD! Also, I am not looking for a miracle to explain what is going on, but a mechanism. Maybe electro-magnetic wave bursts; very speculative. Maybe sheer willingness to survive; also, very speculative. Finaly, I do not think that we can settle this matter as we would need data that is currently unavailable to do so.

AD dysregulates the connection and exchanges between the neocortex and the thalamus "We present here several lines of evidence that suggest that dysregulation of the corticothalamic network may be a common denominator that contributes to the diverse cognitive and behavioral alterations in AD." " However, alterations in the corticothalamic network are most likely responsible for a number of other deficits that accompany AD such as sleep fragmentation, attention deficits, cognitive processing deficits, and non-convulsive seizures. Notably, many of these other symptoms become evident even prior to memory deficits." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854522/ AD degrades the thalamus’ ability to rewire and adapt its function to limited cortical function "Impaired functional connextivity of the thalamus in Alzheimer's disease and mild cognitive impairement: a resting-state fMRI study" https://pubmed.ncbi.nlm.nih.gov/23905993/ Our DTI analyses indicate that the integrity of thalamic connectivity is progressively disrupted following cognitive decline in AD and that DTI parameters in the column and body of the fornix show promise as potential markers for the early diagnosis of AD and for monitoring disease progression. https://pubmed.ncbi.nlm.nih.gov/26141074/ AD and dementia degrades thalamic function "Thalamus pathology is an important contributor to cognitive and functional decline, and it might be argued that the thalamus has been somewhat overlooked as an important player in dementia. In this review, we provide a comprehensive overview of thalamus anatomy and function, with an emphasis on human cognition and behavior, and discuss emerging insights on the role of thalamus pathology in dementia." When the central integrator disintegrates: A review of the role of the thalamus in cognition and dementia - Biesbroek - Alzheimer's & Dementia - Wiley Online Library "Increasing evidence points to the thalamus as an important hub in the clinical symptomatology of the disease, with the ‘limbic thalamus’ been described as especially vulnerable." "The results showed widespread thalamic nuclei atrophy in EOAD and LOAD compared to their respective healthy control groups, with EOAD showing additional atrophy in the centromedian and ventral lateral posterior nuclei compared to YHC." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313877/ I have not found any evidence corroborating this suggestion. It may be a valid hypothesis, but remains unsubstantiated. I have not found either any evidence on these statements either. The following link summarizes many of the diverse effects of alzheimer on the thalamus, its function and connectivity to other brain areas. Here is one excerpt of The effect of alzheimer's disease of the thalamus "The thalamus is one of the earliest brain regions to be affected by amyloid deposition in AD (Ryan et al., 2013). Our review shows that AD impacts both the thalamus itself (e.g., decrease in volume and cell loss), as well as thalamus’s connections to other brain regions, including hippocampus, Papez circuit, the retrosplenial cortex, and other cortical areas." https://www.researchgate.net/profile/Rasu-Karki/publication/354341403_The_effect_of_Alzheimer's_disease_on_the_thalamus/links/6419001b92cfd54f84186534/The-effect-of-Alzheimers-disease-on-the-thalamus.pdf I reiterate, within a severe disease context, how can the brain even be able to temporarily mount a very fast broad-span adaptation and almost full reboot of itself, do so with severely damaged hardware and software, and then go completely off-line before dying? You believe that current knowledge explains terminal lucidity and I do not. To me, something is amiss. Respectfully!

Correction: taking a respite from long posting only.

I do not contest the validity of any of the affirmation in your referenced text. Written with clarity and conciseness. We also agree that “the crux of my inquiry appears to question how a brain with severely degraded structure produces behaviors that suggest full functionality and lucidity”. Upon reading and re-reading carefully your text, I remain unconvinced that a brain evolution-plasticity perspective and current understanding of brain function can explain terminal lucidity in Alzheimer’s patients for example. In the context of imminent death, at the highest point of AD degradation, barely maintaining life, being unresponsive prior to lucidity, with numerous brain areas affected and dysfunctional repair systems, the brain is able to almost suddenly mount a late-minute surge to near normal functionality lasting for a few hours or more then suddenly extinguish itself as quickly as it came into being and, all this, just in time for death. I investigated what happens to an AD brain. Most if not all brain regions are irreversibly affected at the end-stage of the disease: neocortex, limbic system, hippocampus, thalamus, hypothalamus, corpus callosum, cerebellum, even the brain stem. Other hallmarks of AD are severe brain shrinkage, plaques and tangles blocking communication, severed neuronal connections, cell death, fibrous astrocytes, axonal swelling and transport disruptions, dysregulation of homeostatic firing and synaptic plasticity, disruption in brain wave pattern, rampant inflammation, major metabolic changes, etc. I reiterate, within the context described above, including the effects of multiple impacts of end-stage AD on the brain, how can it (the brain) even be able to temporarily mount a very-very fast broad-span adaptation and almost full reboot of itself, do so with severely damaged hardware and software, and then go completely off-line before dying? You believe that current knowledge explains terminal lucidity and I do not. To me, something is amiss. However, that we have divergent views on this matter is a suitable “état de fait”. Finally, I will be taking a respite from posting as I have other duties to attend.

We would have to dig much deeper to get to the bottom of this. However, I, at least, and some others in the field find it particularly interesting that a man with such a deficiency is able to even function in the world. i do not challenge that AD can adapt; i am only saying that in terminal lucidity where going from highly dysfunctional to almost fully functional in a matter of moments, appears to not involve adaptation. i should have said with the prevailing theories of brain, functional specialization, theory of chemical transmission, neuronal connection, etc. I am having issues with my computer, who sent this reply without it being verified. Sorry!

Not full functionality, but much more than one would anticipate with a thin sheet of brain. Adaptation plays a significant role for the man wtih the thin sheet of brain, but not in AD patients. Furthermore, your example of brushing teeth with your toes is still done with an intact brain. With our current knowledge of brain function, a man trying to do this with a seriously incapacitated brain should not be able to do so. Such as? Lots of hypotheses out there. I might present a post on leading ones.

I admit to have read too much into the data. So much so that I forgot about the man having only a thin sheet of actual brain with a 75/100 IQ, a job, family and normal life, which concurs with your perspective that continued functionality is maintained in damaged brains. You also present hydrocephaly, leucotomy and other conditions as additional examples of maintained functionality. Nonetheless, how does a man with a large part of his brain missing maintain almost full functionality and lucidity? Or how does an AD patient with significant brain atrophy, widespread damage, neuronal death and severed neuronal connections between various brain regions suddenly recover almost full functionality and lucidity? Other examples given raise similar issues. At play here is the role of brain size, specialized brain areas, neuronal count and neuronal connections on cognition. The brain may be trying to return to an homeostatic state through neuroplasticity in all of the stated examples, but it may be far from the full picture. Something else might also be at work. Findings like these call into question our conviction of knowing with quasi certainty how our brains work. Happy holidays!

You bring up good points. Unavailable for now, but will get back to you tomorrow or the day after

Joyeux Noel, you 'feminised" it 😊 I went on Google Scholar and picked at random five more studies (deleted only those that were too old) and most talked of multi-modal, multi-target effect, while one was talking of the thalamus and cortical region only, without mentioning if other regions were involved or not (another study thow seemed to indicate that the thalamus was a secondary target). Still, another study was a review of literature (multi-modal) and another one talked about theory moving away from localised in the past to moving toward global with more recent findings. Some studies still talked about the mystery of how anesthetic works. During the holiday season, I will try and get a table together on this.

Will do further search You forgot the ‘ce’ in n’est ce pas

Both

Very well explained; I understand better invariance of scale, self similarity, the need to specify what property is being scaled, from similarity to affinity. And the main point for me is that peninsulas are not exact shape copies of larger ones and that this is the difference between a material world fractal and a mathematical world like the koch snowflake. For me, this is a "revelation" (Joigus - we are losing the patient) moment 😉

I appreciate greatly our discussion. This article says that (AD) is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation of multiple adverse factors, accompanied by dysregulation of numerous intracellular signaling and molecular pathways in the brain. At the cellular and molecular levels, the neuronal cellular milieu of the AD brain exhibits metabolic abnormalities, compromised bioenergetics, impaired lipid metabolism, and reduced overall metabolic capacity, which lead to abnormal neural network activity and impaired neuroplasticity, thus accelerating the formation of extracellular senile plaques and intracellular neurofibrillary tangles. https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-023-00364-y#:~:text=AD patients have defects in,impairment and dementia [25]. As for the article in question, it does say that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics. It also says the considering AD as a kind of metabolic disease, we suggest insulin, adiponectin and antioxidants as having mechanistic links. Furthermore, glucose is the main fuel of the brain and ketones used only in the absence of glucose. Intranasal injections were performed on mild cases with no mention of size effect. As for plasticity, it is impaired in AD patients (see first reference) and I am not aware that it could function fast enough and completely enough to bring a patient from almost a vegetative state to partial or full lucidity. Respectfully! . Doing this work when I have time to do it; so not much time at hand. First four search links strongly suggesting that it is the whole brain. As for being biased, we all are!

I will have a second look at the reference. Also, point well taken on the definition of terms. And, interesting comment on brain plasticity. I will also look into it. Will try and find others.

There is still debate as to how general anesthesia works, but it seems to affect multiple regions of the brain down to individual neurons and the sedative floods the entire brain, including the brain stem: 1- "Anesthetic drugs cause brain circuits to change their oscillation patterns in particular ways, thereby preventing neurons in differnt brain regions from communicating with each other". https://www.google.com/search?q=surgery+anesthesia+effect+on+brain&rlz=1C1CHBF_enCA997CA997&oq=surgery+anesthesia+effect+on+brain&gs_lcrp=EgZjaHJvbWUyBggAEEUYOTIICAEQABgWGB4yDQgCEAAYhgMYgAQYigUyDQgDEAAYhgMYgAQYigUyDQgEEAAYhgMYgAQYigUyDQgFEAAYhgMYgAQYigXSAQkxNDExMWoxajeoAgCwAgA&sourceid=chrome&ie=UTF-8 Brain areas that influence general anesthesia - PubMed nlm.nih.gov 2- 'In a study published in April in the online journal eLife, Brown’s team used electrodes to study the neurons deep inside the brains of monkeys undergoing anesthesia. The work shows, for the first time, how individual neurons in multiple regions of the brain respond as they become flooded with the sedative, and that their impulses slow by 90 to 95 percent'. This Is Your Brain Under Anesthesia wired.com 3- 'We suggest that hypnosis during general anesthesia may result from disrupting the wake-active neuronal activities in multiple areas'.... https://pubmed.ncbi.nlm.nih.gov/25172271/ 4- This document reviews the literature on local brain manipulation of general anesthesia in animals, focusing on behavioral and electrographic effects related to hypnosis or loss of consciousness. Local inactivation or lesion of wake-active areas, such as locus coeruleus, dorsal raphe, pedunculopontine tegmental nucleus, perifornical area, tuberomammillary nucleus, ventral tegmental area and basal forebrain, enhanced general anesthesia. Anesthesia enhancement was shown as a delayed emergence (recovery of righting reflex) from anesthesia or a decrease in the minimal alveolar concentration that induced loss of righting. Local activation of various wake-active areas, including pontis oralis and centromedial thalamus, promoted behavioral or electrographic arousal during maintained anesthesia and facilitated emergence. Lesion of the sleep-active ventrolateral preoptic area resulted in increased wakefulness and decreased isoflurane sensitivity, but only for 6 days after lesion. Inactivation of any structure within limbic circuits involving the medial septum, hippocampus, nucleus accumbens, ventral pallidum, and ventral tegmental area, amygdala, entorhinal and piriform cortex delayed emergence from anesthesia, and often reduced anesthetic-induced behavioral excitation. In summary, the concept that anesthesia works on the sleep-wake system has received strong support from studies that inactivated/lesioned or activated wake-active areas, and weak support from studies that lesioned sleep-active areas. In addition to the conventional wake-sleep areas, limbic structures such as the medial septum, hippocampus and prefrontal cortex are also involved in the behavioral response to general anesthesia. We suggest that hypnosis during general anesthesia may result from disrupting the wake-active neuronal activities in multiple areas and suppressing an atropine-resistant cortical activation associated with movements. https://pubmed.ncbi.nlm.nih.gov/25172271/ Some even stay awake during anesthesia https://www.cnn.com/2010/HEALTH/05/17/general.anesthesia/index.html

Universal was indirectly ascertained in my line of questioning without necessarily mentioning it 'self-similarity (synonym of scale invariance)' 'It's a mathematical pattern rather than a process.' from Joigus and probably misinterpreted his words. Will gladly go back to school and will be reviewing our discussion about linear mathematics. Got the point about pretending for a short while that curved is linear. And yes, I defer to Exchemist on the science of mineralogy.

On invariance of scale, I am not saying that it is universal, but trying to determine if it is. Noted that it is a mathematical pattern rather than a process. As for exchemist excellent question, he knows much more than I. In trying to understand, I probably referenced the wrong articles or did not understand them well enough. In my defence, I did say "seem" as in not entirely sure.