Sunday, June 30, 2013

Melzack&Katz, Pain. Part 11d: The NEW brain model!

The paper, Pain

Most recent blogposts: Part 11: We need a new conceptual brain model! Part 11b: Intro to a new conceptual nervous system Part 11c: Older brain models just don't cut it

SEE ALL PREVIOUS BLOGPOSTS IN THIS SERIES LISTED AT END

SOURCE: EXUBERANT ANIMAL
Is this not the best picture ever?
Doesn't it just totally capture the way we are as a species?

Picking up where we left off yesterday, we were portaging around some rapids to get back to the river, a slow and gruelling but necessary detour in our examination of Pain 2013 by Melzack and Katz, dropping back at strategic intervals into Melzack 1989 to flesh out his revolutionary ideas better.

I included that image, not just because I like it, but because I think it relates to the topic. I like to think the guy standing on the crooked ladder is Melzack, thinking. I like to think the crooked ladder represents his path through pain research.

Melzack did examine the devastation left in the wake of the old brain models. He did examine the contradictions they posed, to humans, to humans with pain, in excruciating detail. Then he looked beyond, abandoned them in order to create a better model.

M&K:

Conceptual reasons for a Neuromatrix

"It is difficult to comprehend how individual bits of information from skin, joints, or muscles can all come together to produce the experience of a coherent, articulated body. At any instant in time, millions of nerve impulses arrive at the brain from all the body's sensory systems, including the proprioceptive and vestibular systems. How can all this be integrated in a constantly changing unity of experience? Where does it all come together?"

As Lorimer Moseley would say, "That's a great, great question."

There weren't any answers. Old brain models could not account for the experience of being in a body. Melzack observed "We don't need a body to feel a body."

"Melzack18,19,21 conceptualized a genetically built-in neuromatrix for the whole body, producing a characteristic neurosignature for the body which carries with it patterns for the myriad qualities we feel. The neuromatrix produces a continuous message that represents the whole body in which details are differentiated within the whole as inputs come into it. We start from the top, with the experience of a unity of the body, and look for differentiation of detail within the whole. The neuromatrix, then, is a template of the whole, which provides the characteristic neural pattern for the whole body (the body's neurosignature) as well as subsets of signature patterns (from neuromodules) that relate to events at (or in) different parts of the body."

It might seem kind of creepy, but it appears that the brain ignores the "real" body (flesh, bone,

Source

mesodermal derivative, and all peripheral neurons involved in reporting from there) pretty much all the time. It has its own built-in maps of "reality", including bodily physicality, to which it refers, which it "feels," instead, i.e., the so-called "phantoms" and the "virtual bodies." It prefers, trusts those a lot more than the physical body it is embedded within, perfect reflections of reality, subject to perturbation. And this inner landscape is dominated by vision more than by kinaesthesia. Why? because we have primate brains. And that inner landscape is really all that "we" ("I"-illusions embedded inside the brain) have access to. When we shut our eyes.

[A word about this image. Maurits Escher has to be one of the most insightful artists the world has ever enjoyed. "His artistic expression was created from images in his mind, rather than directly from observations and travels to other countries" - Wikipedia. In other words, he was making art from examining his own inner landscape. He captured the inherent paradoxes beautifully I think. (In my 20's, my walls were covered in cheap abundantly available Escher reproductions, greeting cards, postcards.... maybe that's why I have no problem being riveted by Melzack's work.)]

M&K

"These views are in sharp contrast to the classical specificity theory in which the qualities of experience are presumed to be inherent in peripheral nerve fibers. Pain is not injury; the quality of pain experiences must not be confused with the physical event of breaking skin or bone. Warmth and cold are not ‘out there’; temperature changes occur ‘out there’, but the qualities of experience must be generated by structures in the brain. There are no external equivalents to stinging, smarting, tickling, itch; the qualities are produced by built-in neuromodules whose neurosignatures innately produce the qualities."

True... these views are in sharp contrast.
[I can't throw away peripheral neurons altogether just yet though. Why? Because they are made

from neural crest. So what? Well, so are brain glia. Again, so what? Well... I dunno. Maybe it will turn out that peripheral neurons (not the motor neurons with their cell bodies inside the spinal cord, which are really therefore central nervous system neurons..),
I'm talking real peripheral neurons, sensory and autonomic motor neurons, i.e., ones that have cell bodies in dorsal root ganglia and similar ganglia within the brain - those neurons - the ones made out of neural crest cells; i.e., NOT the CNS nerve cells made of neural tube. Maybe they communicate somehow with glia in the brain, outside the conventional route, e.g. through long range neurocrine or endocrine signalling pathways not yet determined. Glia are also made from neural crest, and they run all the brain's synapses, so...

Just a stray thought. Back to regularly scheduled programming...]

"When all sensory systems are intact, inputs modulate the continuous neuromatrix output to produce the wide variety of experiences we feel. We may feel position, warmth, and several kinds of pain and pressure all at once. It is a single unitary feeling just as an orchestra produces a single unitary sound at any moment even though the sound comprises violins, cellos, horns, and so forth. Similarly, at a particular moment in time we feel complex qualities from all of the body. In addition, our experience of the body includes visual images, affect, ‘knowledge’ of the self (versus not-self) as well as the meaning of body parts in terms of social norms and values. It is hard to imagine of all of these bits and pieces coming together to produce a unitary body-self, but we can conceive of a neuromatrix which impresses a characteristic signature on all the inputs that converge on it and thereby produces the never-ending stream of feeling from the body."

Ah yes, the orchestra metaphor!

A single instrument cannot a symphony produce.

"The experience of the body-self involves multiple dimensions—sensory, affective, evaluative, postural and many others. The sensory dimensions are subserved, in part at least, by portions of the neuromatrix that lie in the sensory projection areas of the brain; the affective dimensions are subserved by areas in the brainstem and limbic system. Each major psychological dimension (or quality) of experience is subserved by a particular portion of the neuromatrix which contributes a distinct portion of the total neurosignature.18,19,21 To use a musical analogy once again, it is like the strings, tympani, woodwinds and brasses of a symphony orchestra which each comprise a part of the whole; each makes its unique contribution yet is an integral part of a single symphony which varies continually from beginning to end."

Our "I" illusion just sits back and watches the symphony. It is spared all behind the scenes drama that went on through all evolutionary time prior to the Grand Production.

"The neuromatrix resembles Hebb's ‘cell assembly’ and Bindra's ‘gnostic organization’ by being a widespread network of cells that subserves a particular psychological function. However, the neural networks proposed by Hebb22 and Bindra23 developed by gradual sensory learning, whereas Melzack, instead, conceived the structure of the neuromatrix to be predominantly determined by genetic factors, although its eventual synaptic architecture is influenced by sensory inputs. This emphasis on the genetic contribution to the brain does not diminish the importance of sensory inputs. The neuromatrix is a psychologically meaningful unit, developed by both heredity and learning, that represents an entire unified entity."

SOURCE

Musicians may come and go, but the music itself plays on.

Next, we'll examine the action-neuromatrix.

............

Previous blogposts

Part 1 First two sentences Part 2 Pain is personal Also Pain is Personal addendum., Neurotags! Pain is Personal, Always.

Part 3a Pain is more than sensation: Backdrop Part 3b Pain is not receptor stimulation Part 3c: Pain depends on everything ever experienced by an individual

Part 4: Pain is a multidimensional experience across time

Part 5: Pain and purpose

Part 6a: Descartes and his era; Part 6b: History of pain - what’s in “Ref 4”?; Part 6c: History of pain, Ref 4, cont.. : There is no pain matrix, only a neuromatrix; Part 6d: History of Pain: Final takedown Part 6e: Pattern theories in the history of pain Part 6f: Evaluation of pain theories Part 6g: History of Pain, the cautionary tale. Part 6h: Gate Control Theory.

Part 7: Gate control theory has stood the test of time: Patrick David Wall; Part 7b: Gate control: "The theory was a leap of faith but it was right!"

Part 8: Beyond the gate: Self as mayor Part 8b: 3-ring circus of self Part 8c: Getting objective about subjectivity

Part 9: Phantom pain - in the brain! Part 9b: Dawn of the Neuromatrix model Part 9c: Neuromatrix: MORE than just spinal projection areas in thalamus and cortex Part 9d: More about phantom body pain in paraplegics

Part 10: "We don't need a body to feel a body." Part 10b: Conclusion1: The brain generates its own experience of being in a body Part 10c:Conclusion 2: Your brain, not your body, tells you what you're feeling Part 10d: Conclusion 3: The brain's sense of "Self" can INclude missing parts, or EXclude actual parts, of the biological body Part 10e: The neural network that both comprises and moves "Self" is (only)modified by sensory experience

Saturday, June 29, 2013

Melzack&Katz, Pain. Part 11c: Older brain models just don't cut it.

The paper, Pain

Most recent blogpost: Part 11: We need a new conceptual brain model! Part 11b: Intro to a new conceptual nervous system

SEE ALL PREVIOUS BLOGPOSTS IN THIS SERIES LISTED AT END

OK, here we are, back from lunch and ready to hoist our canoes for the trek through brush, uphill, so we can find a place to enter the river once again, continue our paddling up to headwaters.

We left off just as Melzack evoked Hebb in his 1989 Hebb Memorial Lecture, to explain why he thought we needed a new conceptual model of the nervous system. Thirty-four years had sailed by. For 34 years, Melzack had been away from Hebb's lab, out in the world, working with Scottish terriers, working with Wall, getting the gate theory together.

My favorite bit from Hebb's 1955 reference is this:

"About 1930 it began to be evident that the nerve cell is not physiologically inert, does not have to be excited from outside in order to discharge (19, p. 8). The nervous system is alive, and living things by their nature are active. With the demonstration of spontaneous activity in c.n.s. it seemed to me that the conception of a drive system or systems was supererogation.For reasons I shall come to later, this now appears to me to have been an oversimplification; but in 1945 the only problem of motivation, I thought, was to account for the direction taken by behavior. From this point of view, hunger or pain might be peculiarly effective in guiding or channeling activity but not needed for its arousal. It was not surprising, from this point of view, to see human beings liking intellectual work, nor to find evidence that an animal might learn something without pressure of pain or hunger.The energy of response is not in the stimulus. It comes from the food, water, and oxygen ingested by the animal; and the violence of an epileptic convulsion, when brain cells for whatever reason decide to fire in synchrony, bears witness to what the nervous system can do when it likes. This is like a whole powder magazine exploding at once. Ordinary behavior can be thought of as produced by an organized series of much smaller explosions, and so a "self-motivating" c.n.s. might still be a very powerfully motivated one." - Don Hebb 1955

Hebb is the famous Canuck whose Hebbian theory about learning is remembered most easily as "Neurons that fire together wire together." Reference 19 goes to The Organization of Behaviour, a book he wrote in 1949. Melzack was one of his students.

Picking up Melzack 1989 (cont.):

"Our present knowledge of the number of brain cells and their connections makes the imagination reel (Hoyenga & Hoyenga 1988). There are, it is estimated, 100 billion nerve cells in the brain (a 10-fold increase over the number in most textbooks only 5 to 10 years ago) and the number continues to rise."

Actually I think at last count it was 86 billion. Still a heck of a lot. Weird to think, though, that earlier people thought there were so many fewer. And remember, we still aren't counting glia, which outnumber neurons 10-1, and do a whole pile of important computational activity of their own, plus run all the neuronal synapses.

Melzack:

"If we recognize that many neurons in sensory projection systems may have synaptic connections with tens or hundreds of thousands of other neurons, and if we carry our computation through the cortical layers and their projections to deeper levels which may, in turn, project to the cortex again, the number is astronomical."

Yeah. Something like more possible connections than there are particles in the universe or something... Here's Ramachandran - I'll let him explain this in his 10 minute TED talk.

Melzack:

"To think that we are even close to an understanding of brain functions and their relation to experience and behaviour is absurd. At this stage, as Don Hebb so wisely told us, we can only speculate and try to build reasonable neural models - in short, a "conceptual nervous system." Our old concepts of the brain are totally inadequate in their ability to explain phantom limb phenomena and it is time to sketch out a new one. First, however, let us look at earlier conceptual nervous systems to explain phantom limb behaviour."

[Can you feel the strain of carrying that canoe, and everything you had stowed in it, up the hill? taking care to avoid snagging it on tree branches? Having that happen anyway? taking care to avoid stumbling on tree roots and rocks? Having that happen anyway? How are your mental knee caps doing? Isn't thinking fun? It's hard work, but isn't it also exhilarating? Are you sweating yet?]

Source

Earlier theories included:

peripheral mechanisms - nope - See Melzack and Loeser 1978
hyperactive deafferented cells in the spinal cord - nope - Dorpat 1971 reported the specific urge to void in patients entirely without bladders, and Jankovic and Glass 1985 reported phantom limb tremor with metoclopramide IV. Hyperexcited spinal cord cells can't account for phantom limbs' seamless coordination with other limbs or the coherence and unity of the experience.
body schema? Simmel in 1956 and Weinstein et al in 1964 proposed "body schema" located in the homunculi mapped by Penfield (1937) in the somatosensory cortex, based on Head and Holme's concept back in 1911-12. But Melzack doesn't much care for this idea either.

"First, the idea of "body schema"is too vague to provide an explanation of any of the phenomena. Second, there is no postulate by Head and Holmes on the actual neural mechanisms that comprise their postural "body schema" apart from identifying a tactile schema with the somatosensory cortex. They also deny any relation between postural "body schema" and "body image." The latter, they say, is a visual image while the former is a somatic neural mechanism. Thus, the role of vision in the phantom limb is left unexplained even though we know that the phantom limb experience, in terms of position and other qualities, is powerfully influenced by vision. It is clear that, while phantom limbs obviously have a neural substrate, they are not explained by Head and Holmes conceptual "body schema."

identifying phantom limb experience with the post-central somatosensory cortex? Nope. Erroneous.

"The early reports that a phantom is eradicated by ablating a portion of the post-central gyrus have not been supported; a later evaluation (White and Sweet 1969) of excisions of the somatosensory cortex for phantom limb pain shows that, with time, the phantom limb and pain both return. In addition, if the phantom limb is to be identified with hte somatosensory cortex, we now know that there are at least 7 projections of the body surface at the cerebral cortex (Merzenich and Kaas 1980), which leaves out known additional projections to brainstem areas, the limbic system, and the cerebellum. All of these presumably play a role in the phantom limb experience. But how? It is evident that a new theory is needed."

Weirdly, the Merzenich and Kaas paper has no link anywhere that I could find. However, it's been cited in many papers - here is the whole citation.

Merzenich, M.M. and J.H. Kaas (1980) Principles of organization of sensory-perceptual systems in mammals. Progress in Psychobiology and Physiological Psychology 9:1-42.

A lot of the papers it's cited in are about cortical columns, etc.

Just the other day, a new paper

SOURCE

came out in Science that challenges long held ideas about cortical columns that were based only on neuroanatomy. It used to be thought that all the info from thalamus coming into cortical columns arrived at level 4. Turns out the thalamus sends about a fifth of it to layer 5, separately, for completely different processing. Not sure yet what it all means.. apparently Level 5 is pyramidal cells, according to this Wikipedia entry, anyway.

Christine M Constantinople, Randy M Bruno; Deep Cortical Layers Are Activated Directly by Thalamus. Science, Vol 340, No 6140 28June2013 pp1591-1594

Part 1 First two sentences Part 2 Pain is personal Also Pain is Personal addendum., Neurotags! Pain is Personal, Always.

Part 3a Pain is more than sensation: Backdrop Part 3b Pain is not receptor stimulation Part 3c: Pain depends on everything ever experienced by an individual

Part 4: Pain is a multidimensional experience across time

Part 5: Pain and purpose

Part 6a: Descartes and his era; Part 6b: History of pain - what’s in “Ref 4”?; Part 6c: History of pain, Ref 4, cont.. : There is no pain matrix, only a neuromatrix; Part 6d: History of Pain: Final takedown Part 6e: Pattern theories in the history of pain Part 6f: Evaluation of pain theories Part 6g: History of Pain, the cautionary tale. Part 6h: Gate Control Theory.

Part 7: Gate control theory has stood the test of time: Patrick David Wall; Part 7b: Gate control: "The theory was a leap of faith but it was right!"

Part 8: Beyond the gate: Self as mayor Part 8b: 3-ring circus of self Part 8c: Getting objective about subjectivity

Melzack&Katz, Pain. Part 11b: intro to a new conceptual nervous system

The paper, Pain

Most recent blogpost: Part 11: We need a new conceptual brain model!

SEE ALL PREVIOUS BLOGPOSTS IN THIS SERIES LISTED AT END

Beyond the Gate: continued

The next section is "The Body-Self Neuromatrix." Here is M&K:

"The body is felt as a unity, with different qualities at different times."

Sometimes it feels charged, ready to rock and roll, and other times it feels like a lazy hound dog.

M&K:

"The brain mechanism that underlies the experience also comprises a unified system that acts as a whole and produces a neurosignature pattern of a whole body.18,19,21"

Same three references as yesterday.

M&K:

"The conceptualization of this unified brain mechanism lies at the heart of the theory, and the word ‘neuromatrix’ best characterizes it."

"The neuromatrix (not the stimulus, peripheral nerves or ‘brain center’) is the origin of the neurosignature; the neurosignature originates and takes form in the neuromatrix."

I guess this means the brainstem isn't it? Sorry Damasio. I thought "brainstem" might be it (see yesterday's post, which I edited to include a picture from the TEDtalk), but Melzack is saying, there isn't any "center" to any of this - it's the whole thing operating. It's the verb of it, not the noun.

Maybe it's the so-called "Default Mode" then...

M&K

"Though the neurosignature may be activated or modulated by input, the input is only a ‘trigger’ and does not produce the neurosignature itself."

Input represents a perturbation of it.

M&K:

SOURCE
Mmmm... chocolate donuts..
"Packaging Machine wraps delicate food products"

"The neuromatrix ‘casts’ its distinctive signature on all inputs (nerve impulse patterns) which flow through it."

I can't help but think of a factory situation.

M&K:

"Finally, the array of neurons in a neuromatrix is genetically programmed to perform the specific function of producing the signature pattern."

Certain cells operate with very little stimulus - I do recall Buzsaki talking about spindle cells.

[Here is a link to a page in a book, discussing the matter. A link to the book itself.Here is a transcript I wrote up for Ginger Campbell's interview with him. Here is a series I wrote in 2008 about Buzsaki's book.]

M&K:

"The neuromatrix, distributed throughout many areas of the brain, comprises a widespread network of neurons which generates patterns, processes information that flows through it, and ultimately produces the pattern that is felt as a whole body."

So.. it's not strictly thalamus, brainstem, hippocampus.. although I bet those are where the pacemaker systems will be found. And we shouldn't forget about locus ceruleus. Here are some notes I made about LC, back when I was avidly studying up on it.

M&K:

SOURCE

"The stream of neurosignature output with constantly varying patterns riding on the main signature pattern produces the feelings of the whole body with constantly changing qualities."

Yeah... I'm a bit lost right now. It looks like we have come to some rapids that we'll have to portage around. I'm going to go to the Hebb lecture, see if I can find a way to proceed. Everybody out of the river - we have to make a portage around some falls now. Yeah.. I know. Sucks, but we can't really paddle up the rapids as if we were agile salmon.

Melzack 1989:

In the section just after his 4 conclusions, Melzack opens with a short paragraph, titled "Sketch for a New Conceptual Nervous System":

"Phantom limb phenomena confront us with the most challenging problems in psychology: awareness; the self; the qualities of experience; the nature of knowledge and reality. These ancient problems have been debated throughout the centuries and continue to elude us. In recent years we have tended to ignore them, explain them away, even deny their existence. We can no longer evade them if we want to find an answer to phantom limbs."

He continues:

The Conceptual Nervous System

"Before I embark on a search for a new understanding of brain function, it is essential to recognize the importance of Don Hebb's (1955) insight that psychologists who seek global answers to major problems can deal only with a conceptual nervous system."

The reference goes to Hebb, DO; Drives and the CNS (Conceptual nervous system) Psychological Review 62, 243-254. (Full text here!) Aha. This looks like a nice place to stop and have lunch:

"The problem of motivation of course lies close to the heart of the general problem of understanding behavior, yet it sometimes seems the least realistically treated topic in the literature. In great part, the difficulty concerns that c.n.s., or "conceptual nervous system," which Skinner disavowed and from whose influence he and others have tried to escape. But the conceptual nervous system of 1930 was evidently like the gin that was being drunk about the same time; it was homemade and none too good, as Skinner pointed out, but it was also habit-forming; and the effort to escape has not really been successful. Prohibition is long past. If we must drink we can now get better liquor; likewise, the conceptual nervous system of 1930 is out of date and -- if we must neurologize -- let us use the best brand of neurology we can find.
Though I personally favor both alcohol and neurologizing, in moderation, the point here does not assume that either is a good thing. The point is that psychology is intoxicating itself with a worse brand than it need use. Many psychologists do not think in terms of neural anatomy; but merely adhering to certain classical frameworks shows the limiting effect of earlier neurologizing." - Hebb 1955

Later we'll go back to Melzack 1989 (our portaging) and find out more about what Melzack thought about this, and why he brought it up. [It was probably more than just a polite nod to the occasion itself, the official D.O. Hebb Lecture... he says it was an important insight.]

.......

Previous blogposts

Part 1 First two sentences Part 2 Pain is personal Also Pain is Personal addendum., Neurotags! Pain is Personal, Always.

Part 3a Pain is more than sensation: Backdrop Part 3b Pain is not receptor stimulation Part 3c: Pain depends on everything ever experienced by an individual

Part 4: Pain is a multidimensional experience across time

Part 5: Pain and purpose

Part 6a: Descartes and his era; Part 6b: History of pain - what’s in “Ref 4”?; Part 6c: History of pain, Ref 4, cont.. : There is no pain matrix, only a neuromatrix; Part 6d: History of Pain: Final takedown Part 6e: Pattern theories in the history of pain Part 6f: Evaluation of pain theories Part 6g: History of Pain, the cautionary tale. Part 6h: Gate Control Theory.

Part 7: Gate control theory has stood the test of time: Patrick David Wall; Part 7b: Gate control: "The theory was a leap of faith but it was right!"

Part 8: Beyond the gate: Self as mayor Part 8b: 3-ring circus of self Part 8c: Getting objective about subjectivity