Mo on the "Connectome": "Not so fast"

Mo from Neurophilosophy linked to an article, Not so fast, written for seedmagazine.com re: his perspective on the ambitious project of mapping all the pathways and connections there are in the brain.

He says confounding factors include neuroplasticity, ignoring the functions of neuroglia, and ordinary small-scale variations that occur:

"the connectome apparently ignores the phenomenon of neuroplasticity.

Plasticity refers to the brain’s ability to physically alter its structure in response to experience. Far from being immalleable, as was once thought, the brain is a highly dynamic organ. Neurons can sprout new connections within minutes of a given stimulus, and entire neural pathways can be rerouted so that function is recovered after a brain injury.

The connectome also disregards the functional importance of neuroglial cells, another class of cells which are found in the nervous system and which outnumber neurons by at least 10 to 1. Once thought to merely provide structural and nutritional support for neurons, glia have, in recent years, come into their own as key players in the brain. As well as performing the roles initially ascribed to them, glia carry out a whole host of other vital functions, including monitoring neuronal health, identifying damaged neurons, and regulating synaptic plasticity. They are also known to be capable of communicating not only with one another, but also with neurons. A map of brain connectivity cannot therefore be complete without taking glia into account.

Finally, although the large-scale connections are very similar among individuals, there are significant variations at smaller scales."

My bold.

Michael Merzenich's video on re-wiring the brain

This is an excellent overview on brain development and neural plasticity.
Merzenich is a pioneer in research on the topic and in finding practical ways to work with it, e.g., his development of cochlear implants.

1. Michael Merzenich's blog, On the Brain

2. BrainSciencePodcast #54 with Dr. Ginger Campbell, Interview with Michael Merzenich on Neuroplasticity

Apotemnophilia

Recently I read the article Brain Games by John Colapinto in the New Yorker. It's a wonderful portrait, 13 or so pages long, of V.S. Ramachandran, the father of mirror therapy for phantom limb pain (according to me, at least). It provides the reader with a biographical account of Ramachandran, glimpses into his childhood, how he thinks (like Sherlock Holmes), a window into his personal life (can't remember his wife's birthday, forgets where he parked the car), and an account of his professional trajectory through life, how he ended up with a dinosaur fossil named after him, discussions of his interest in mirror neurons, synesthesia, ichthyology.

Lately he's been studying a patient, dubbed for the article, "Arthur Jamison". I am going to provide excerpts from the article now, direct quotes:

"Jamieson is seventy years old and lives in the Midwest. He is a physician and an amateur cellist, and has been married for forty-seven years. He also suffers from a rare and bewildering condition called apotemnophilia, the compulsion to have a perfectly healthy limb amputated--in his case, the right leg, at mid-thigh."

"After interviewing several apotemnophiliacs--Jamieson is the fifth person with the disorder whom he has studied--Ramachandran was struck by the fact that all of them said they became aware of the compulsion in early childhood, that it centered on a particular limb (or limbs), that they could draw a line at the exact spot where they wanted the amputation to occur, and that they attached little or no erotic significance to the condition. Furthermore, none rejected the limb as "not belonging" to them, as some stroke victims do in the case of a paralyzed arm or leg, and as Ramachandran had predicted they might. Instead, they said that the limb over-belonged to them: it felt intrusive. "If you talk to independent apotemnophiliacs, they say the same bloody things," Ramachandran told me. " 'The line for cutting is here.' 'It started in early childhood.' 'It's over-present.'
They're not crazy.""

"Asked where he would make the cut line for the amputation, Jamieson unhesitatingly drew an index finger across the middle of his right thigh. As to whether he felt that his leg didn't "belong" to him, Jamieson was emphatic. "Somehow, for me, that just doesn't compute, that kind of language," he said. "I have always been fascinated by amputation and wished that I had one. Why? Who the hell knows?"

"Ramachandran and other researchers have shown that the brain is what scientists call "plastic"--it can reorganize itself. Not only are different regions of the brain engaged inongoing communication with one another, with the body, and with the surrounding world; these relationships can be manipulated in ways that can reverse damage or dysfunction previously believed to be permanent. Ramachandran's work with patients at U.C.S.D. has led to one of the most effective treatments for chronic phantom-limb pain and to a new therapy for paralysis resulting from a stroke. (In both instances, his treatment involves only a five-dollar household mirror.) It has also provided suggestive insights into the physiological cause of such mystifying syndromes as autism."

"In the seventies, Michael Merzenich became expert at using microelectrodes to map the sensory cortex of monkeys. In one experiment, he mapped a monkey's hand area in the brain, then amputated its middle finger. Some months later, he remapped the monkey's hand and discovered that the brain map for the missing finger had vanished and been replaced by maps for the two adjacent fingers, which had spread to fill the gap. The results, published in the Journal of Comparative Neurology in 1984, were decisive proof that the brain can reorganize itself--at least across very short distances of one to two millimetres."

"After interviewing Jamieson in his office, Ramachandran led him to a lab for a Galvanic Skin Response, or GSR, test, which would reveal how Jamieson's legs reacted to a mild pain stimulus... David Brang, one of Ramachandran's graduate students, attached a sensor to the middle two fingers of Jamieson's right hand using a Velcro strap. The sensor would measure the reaction of Jamieson's sympathetic nervous system by monitoring the sweat on his fingers. With a sterilized pin, Brang pricked Jamieson's legs at random points, waiting a few seconds between each prick. A scrolling graph on the computer screen registered Jamieson's responses.

The unaffected leg--the left one--and the right leg above where he wished to have it amputated showed a normal response: the graph at first shot upward with each prick, but with further pricks it ceased to rise, then began to flatten out, indicating that Jamieson's nervous system was getting used to the stimulus. But when Brang pricked Jamieson anywhere on the leg below the amputation line, his nervous system responded with increasing distress, the graph climbing higher and higher with each prick.

The experiment seemed to support Ramachandran's theory about the disorder. He believed that people with apotemnophilia had a deficit in the right superior parietal lobule, where the body-image map is assembled. According to this notion, Jamieson was missing the neurons in the map that corresponded to his right leg from the mid-thigh down. He had normal sensation in the unwanted part of his leg--he felt the pin prick. But when the pain signal travelled to the right superior parietal lobule there was nothing in the body-image map to receive it.

"So there's a big discrepancy--a clash--and the brain doesn't like discrepancies," Ramachandran said."When a discrepancy comes in, it says, 'Shit! What the hell is going on here?,' and it kicks in and sends a message to the insular part of the brain, which is involved in emotional reactions--so you're getting this crazy GSR." In apotemnophilia sufferers, the discrepancy causes a feeling of distress that is no less agonizing for being below the level of conscious awareness.

In the past two years, Ramachandran has tested four other apotemnophiliacs using MEG brain scans. "You touch them anywhere in the body and the right superior parietal lobule lights up, as you would expect," Ramachandran said. "But if you touch him here"--he gestured to a point on Jamieson's leg below the amputation line--"nothing happens." Ramachandran said that the experiment needed to be repeated by other researchers, but, he added, "This takes a spooky psychological phenomenon and, as Shakespeare said, gives it a 'habitation and a name.' " Furthermore, the findings suggested to Ramachandran a possible method for alleviating the oppressive sensations in the unwanted limb.

Later, he asked Jamieson to stand in a corner of his office and placed a three foot-high mirror in front of him, in such a way that in place of his right leg Jamieson saw his left, which he held bent at the knee. Jamieson gazed into the mirror. "Astonishing," he said. For a moment, the leg looked "right.""

This is fascinating stuff. I was reminded of reading Michael Gershon's book The Second Brain, about the gut and enteric nervous system, how if neural crest cells didn't make it in to colonize the large intestine, Hirschsprung's Disease (Megacolon) is the unfortunate result. So much depends on exquisite timing during embryological unfoldment. Miss one little beat and some batch of baby neurons won't exist, and the resulting human organism can end up with major deficit. It can affect the body, and maybe, as in the case of Apotemnophilia, one's sensory perception of one's body.

As I checked out Apotemnophilia online, I saw it was quite consistently coupled with notions of a sexualized nature with heavy overtones of psychiatric implications.

About this, Colapinto writes:

"Jamieson, who was born and raised in New York City, first remembers having an unusual relationship with his right leg when, at around the age of seven, he was waiting for a bus. He found himself thinking that if he stuck out his leg it would be crushed and severed by the bus. "What came to me was not 'No, I don't want to do that' but 'How would I ever explain this?' " he told Ramachandran. In recounting his childhood memories, he said, "One of the things that's astonishing to me is how clear these recollections are."

"These things are very salient," Ramachandran said... "It's interesting to contrast these very clear-cut descriptions with these vague, Freudian notions about this whole phenomenon--that it's primarily connected with sexual stuff."

"Yeah," Jamieson said with disgust. "I've got no desire to cozy up to anyone with a stump. It's psychobabble.""

That it could be due to some embryologic formation error makes more sense. The thigh is actually the last part of the leg to form. Feet (in the form of ectodermic limb buds) poke out first, from the body wall. As toes begin to form, these feet, already containing vasculature and neural structure, begin to lengthen away from the body wall, and the "lines" of supply (vasculature) and communication (nerves) must grow to keep pace. Within the lengthening limb buds, bones begin to condense from cartilaginous masses which have formed from prior condensations of mesoderm; neural and vascular structures must simultaneously penetrate these condensations. Pathways of sensation of a limb to a brain include not just large diameter fibers from skin, but also many sorts of receptors, some very tiny, which report on all sorts of tissue, including vascular tissue (nervi vasorum). Some of these report on the sensory nerves themselves (nervi nervorum). Lots end up just inside the spinal cord, while others get all the way up as far as the insular cortex (1). The brain uses information coming in from many parallel kinesthetic channels(3) as well as visual ones, to construct its sense of self and body awareness/embodiment, to learn who is touching its organism, how it feels about that, what salience to assign in that moment. Apparently some sort of reverse processing occurs between afferents that go to the somatosensory cortex and those that go only to the insula(2). Apparently those going to the left insula are processed differently from those which go to the right (4).

All it would take would be some little screw-up in neural crest implantation into either the limb itself or else at the other end, in the brain itself (it would seem that quite a bit of "peripheral" "nerve", from neural crest, goes all the way into the brain, into some of its very touchy touch processing areas), so I can see how neural crest mishaps could be connected with body perception problems. Perhaps neural crest abnormality might become a target of investigation for body perception disorders some day.

1. Unmyelinated tactile afferents signal touch and project to insular cortex (Olausson et al.)
2. Unmyelinated tactile afferents have opposite effects on insular and somatosensory cortical processing. (Olausson et al.)
3. Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin. (Olausson et al.)
4. Coding of pleasant touch by unmyelinated afferents in humans. (Löken et al.)

Neuroplasticity with Michael Merzenich

A friend and fellow PT, Jon Newman, recently sent me a link to a TED video released for public viewing only in April, it seems - Michael Merzenich on rewiring the brain. If you have ever wondered what neuroplasticity is, check this out. It runs about 23 minutes and I guarantee you'll come away with a deeper grasp of what the brain is and does.

Here is an excerpt I thought was particularly interesting:

"Now, one of the characteristics of this change process is that information is always related to other inputs or other information that's occurring in immediate time, in context. And that's because the brain is constructing representations of things that are correlated in little moments of time, and that relate to one another in little moments of successive time. The brain is recording all information and driving all change in temporal context.

Now, overwhelmingly, the most powerful context that occurred in your brain, is "you". Billions of events occurred in history that are related in time to your "self" as the receiver, your "self" as the actor, your "self" as the thinker, your "self" as the mover.

Billions of times, little pieces of sensation have come in from the surface of your body, that are always associated with "you," the receiver, and result in the embodiment of "you". "You" are constructed. Your "self" is constructed from these billions of events; it's constructed, it's created in your brain and it's created in the brain by physical change. This is the marvelously constructed thing that results in individual form, because each one of us has vastly different histories, and vastly different experiences, that drive into us this marvelous differentiation of self, of personhood."

I love this video. It makes me glad I picked the sort of work I did. I quite like the idea that when I put my hands on someone else, I'm helping them learn more about who they are, helping that brain add to its construction of "self" outside of a pain construction (if I'm careful, and I am). I like that I'm adding more "little pieces of sensation" to their temporally correlated process of embodied self, minus nociceptive input, i.e., more "danger" signals. Yeah, I can live with that.

I also like the idea that I learn more about/add to my own self-construct at the same time, as "little pieces of sensation" from my own skin (on my hands) enters my brain and is temporally correlated to what is already in there.

What is already in there? Circuitry routes, billions of neurons, receptor sites on them (lots and lots of receptors that can change to different ones, alter what they are sensitive to, thanks to "synaptic plasticity") and transmitters. There are convergence zones and arborizations, ascending and descending fibers, switchback and feed forward stations, and lots of somatotopic representational areas (brain maps of body parts). There is brain behaviour, and parts or areas that light up for pain as well as for other functions on fMRI, a vastly complex ecosystem, embedded within another outer ecosystem called the "body," with which it is completely integrated, both of which must exist co-mingled and learn to help each other within the greater outer planetary ecosystem, via a construct called "self."


Additional Reading

1. Michael Merzenich's TED bio
2. A page from my website, About Pain


Older blogposts on Neuroplasticity

1. Neuroplasticity (Dec 11, 2007)
2. Learning (Dec 12, 2007)
3. History of Neuroplasticity (Dec 12/2007)
4. Paradigm (Dec 16, 2007)
5. About mirror therapy (Dec 16, 2007)
6. Get your game on, ease your pain (Dec 17, 2007)
7. The devil is in the details (Dec 18, 2007)
8. A few types of Learning (Dec 18, 2007)
9. Cart ruts: More about UN-doing something (Dec 29, 2007)
10. And it's about brain parts: like hippocampus (Dec 30, 2007)
11. Function only (January 15 2008)
12. Smart prosthetics, smart nerves, smart brains (February 10, 2008)
13. Nervous System Basics VIII: PLASTICITY (May 10, 2008)
14. More about neurogenesis (June 7, 2008)
15. "Dialogues in Clinical Neuroscience" online (August 23, 2008)

The ABCDEFGHI of Persisting Pain

Here is a link to a write-up I did recently on the topic:

The ABCDEFGHI of Persisting Pain.

I hope it is helpful to anyone who has any.

"Dialogues in Clinical Neuroscience" online

A reader, Kent Schnake, sent me a link that looks very good - it's to Dialogues in Clinical Neuroscience, which appears to be open access, for past issues, anyway.

Here is a link to the 2004 issue on neuroplasticity. In it is an article by Fred Gage, downloadable.


Here are some posts that have included discussion of Fred Gage's work:

1. Nervous System Basics VIII: PLASTICITY
2. History of Neuroplasticity

I now pronounce you....

In the book "The Brain That Changes Itself" by Norman Doidge the author recommends that those of us who help others by bringing about change in the nervous system call ourselves Neuroplasticians. A great name! But, what kind of neuroplastician am I?

In "Musicophilia," Oliver Sacks describes going to a concert and seeing the crowd move in unison to the music and being overtaken by the urge to move himself as well. He said it was as if the music joined together the nervous systems of the entire audience as one. He called it Neurogamy, which means the joining of 2 (or in the case of the concert, many) nervous systems. Sacks goes on to describe how this is one of the many amazing qualities of music.

I began to think about other examples of Neurogamy. Diane has often spoken of 2 nervous systems interacting during the patient encounter and I can also recall David Butler describing the patient's nervous system is processing you just as yours is processing them. It seems important for happy Neurogamy to take place during therapy. But what about unhappy Neurogamy? There are plenty of unhappy marriages in the world, why would the marriage of nervous systems be any different? Driving in traffic. A similar task forces a neurogamous relationship with strangers who have limited communication abilities with eachother. When this relationship is bad we see road rage.

I think that we could come up with many characteristics of good and bad Neurogamy that would be useful in the context of therapy. In the meantime, I'm happy to have thought of a name for my breed of Neuroplastician. We are clinical neurogamists!

More about neurogenesis

There are some other posts here that include the topic of neurogenesis:
1. History of Neuroplasticity
2. And it's about brain parts: like hippocampus
3. Nervous Systems Basics VIII: PLASTICITY

Here is a new study on the matter; Spatial Relational Memory Requires Hippocampal Adult Neurogenesis.

Abstract: The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning.

(Thank you, Deric Bownds at Mindblog.)

The best general reader book I've found on the topic of neuroplasticity and neurogenesis is the one by Sharon Begley, Train Your Mind, Change Your Brain: How a New Science Reveals Our Extraordinary Potential to Transform Ourselves .

The best general reader book I ever found on the topic of spatial brainmaps is Sandra Blakeslee's book,The Body Has a Mind of Its Own: How Body Maps in Your Brain Help You Do (Almost) Everything Better. (This same author helped Ramachandran write his now-classic Phantoms in the Brain: Probing the Mysteries of the Human Mind.)

Both these authors' books have been discussed or the authors have been interviewed by Ginger Campbell at Brainscience Podcast; there are links to a discussion of Sharon Begley's book (episode 10), and Sandra Blakeslee's interview (episode 23, also #21), and others on neuroplasticity.

More reading:
1. The Reinvention of Self, a 2006 article by Jonah Lehrer in Seed about Elizabeth Gould's pioneering research into neurogenesis in marmosets

Nervous System Basics VIII: PLASTICITY

Angevine's 7th attribute is plasticity:

"Plasticity
Highly reliable in a healthy person, the human nervous system has inherent modifiability, though in adulthood this attribute cannot approach that in invertebrates (moths and snails) or certain other vertebrates (teleosts and amphibians). In mammalian development, neural plasticity is striking. In continues postnatally. Abnormal visual experience at certain sensitive periods profoundly affects ocular dominance and orientation columns in the visual cortex. If an eye is closed at birth, ocular dominance columns for the other eye enlarge at the expense of adjacent blind eye columns, with thalamic fibers arriving in the cortex expanding terminal fields into them. If, shortly after birth, visual stimuli are restricted for a few weeks or even days to stripes of one orientation, cortical cells develop a response preference to lines of that orientation.

In humans, PET imaging studies of cortical blood flow show that tasks requiring tactile discrimination activate visual cortex in people blind at birth or having lost sight in childhood. This suggests that cortical connections reorganize after blindness: that afferent fibers to nearby cortical areas serving polymodal sensory integration usurp the bereft visual cortex. Such plasticity may explain the well-known tactile acuity of the blind.

In later development, neural plasticity operates on many levels, as in fine-tuning circuits to changing body dimensions. Depth perception is recalibrated as the skull enlarges and interpupillary distance increases. Even in adulthood, plasticity persists. Vilayanur Ramachandran has shown that a stroke with a cottonswab on the cheek of a young man who had accidentally lost his left arm led him to feel touch on his missing left hand. Later, the whole hand could be mapped on his face. The findings suggest that the deprived somatosensory cortical region for the hand becomes innervated by fibers from the adjacent face areas and that secondary input to a cortical neuron's broad receptive field becomes functional when primary input is lost.

After injury to the CNS, intact neurons form new terminals, by axon sprouting, to replace those of other neurons lost to trauma and thus reoccupy vacated synapses. Such reactive synaptogenesis, the clinically proven effectiveness of long-range regrowth of PNS axons, and the evident potential for axon regeneration in the CNS (as in teleosts and amphibia) hold promise for circuit reestablishment. But in mammals, these factors are thwarted by myelin debris, glial scarring, usurpation of sprouts, unresponsive injured neurons, and complex central connections. Developmental neuroscience now focuses on the cerebral cortex. The human nervous system appears to learn very rapidly by using preconstructed circuits and by locking neurons into specific types and functions after cell origin."

About that last paragraph suggesting that deliberate neurogenesis is difficult in mammals, check out this new blogpost Growing new neurons by Kevin McHenry at painonline.com:

"Wernig et al in Proc Natl Acad Sci U S A May (2008) have achieved a real breakthrough. They have been able to convert fibroblasts to neurons. These converted cells form into neurons, glia, and even dopaminergic cells. There has always been concern that converted cells might form tumors, but these scientists painstakingly separated the cells turned into neurons from pluripotential cells with fluorescent stains."

Seems like ordinary cells can be turned into neurons if they can be recoded, using appropriate transcription factors, "Oct4, Sox2, Klf4, and c-Myc"

Also, work by Peter Eriksson and Fred Gage showed that neurogenesis is intrinsic to the human brain, even in elderly people on the brink of death (see this history module, The Growth of New Neurons in the Adult Human Brain).

Neuroplasticity has been a favorite topic on this blog. It's starting to dawn on a few of us PTs that this is what "improved outcomes", be they pain reduction or increased function, strength etc, have always been all about. Here are some old posts with extensive links:

1. Neuroplasticity Dec 11/07
2. Learning Dec 12/07
3. History of neuroplasticity Dec 12/07
4. About mirror therapy Dec 16/07
5. The devil is in the details Dec 18/07
6. A few types of learning Dec 18/07
7. Cart ruts: More about UN-doing something Dec 29/07
8. It's all about movement Dec 30/07
9. And it's about brain parts: like Hippocampus Dec 30/07
10. Function only Jan 15/08
11. Smart Prosthetics, smart nerves, smart brains Feb 10/08

A Few Types of Learning

In reference to The Devil is in the Details:

Learning seems to be a recurring theme in this blog, so let's take it even further. Kandel says, "learning is in the synapses". How many kinds are there? Probably more than I have listed here, but this is a start:

1. Long Term Potentiation

Lately I've become caught up with Geörgy Buzsáki and his book Rhythms of the Brain. In chasing down things I've spotted in that book, namely the role of the hippocampus, the connection between theta rhythm and movement, orientation (space maps), memory and learning, it seems long term potentiation is A main if not THE main mechanism. "Learning" requires receptor breakdown and building, a process that is going on all the time anyway.. but when a signal comes in, repeatedly, the receptors will strengthen around the signal. (This is true for pain reduction, which is another sort of "learning", extinction learning, point 5.)

There is a very nice article from "Go Animal", a website linked in this blogpost by the same name. It's called "The Greatest Discovery You've Never Heard Of" by physical educator Frank Forencich.

Longterm potentiation (LTP) relates back to one of the other "tenets of neuroplasticity",

4. Initial changes are just temporary. While the brain can learn through impact (a powerful experience), usually it learns through lots of repetition.

In fact, we likely do NOT want to have to learn too many things through impact - such learning would tend to retain a heavy emotional overlay I should think, which could mess up integration, create large "hooks" for future learning of an inappropriate or counterproductive sort. Remember this other tenet:

5. Brain plasticity is a two-way street; it can change itself in positive or in negative directions. E.g., chronic pain, bad habits

... which leads us to another form of learning,


2. Sensitization

We know about this one from pain science, but its origins are with Kandel according to this Wiki page. This is described as short-term memory formation.

One of the most troubling (and confusing) aspects of pain states is mechanoreceptor sensitization, discussed in the Textbook of Pain, 5th ed.. This has led practitioners on merry goose chases after "the tissue at fault" (structure as opposed to function) for decades, centuries...

Sensitization can be "un"-learned, and quite rapidly, by something as easy as mirror therapy.

To overcome sensitization, and to utilize longterm potentiation, a "graded exposure" approach is usually recommended - this is a cognitive-behavioral approach which breaks down a learning or an un-learning movement objective into small, easily assimilative bits.

This ties in with

3. Habituation

This type of learning seems to be about just adapting to (learning to ignore) something in the environment or inside, consciously or unconsciously, be it initially positive or negative, although psychology definitions hold out for "decline in the response elicited by repeated stimulation, not due simply to adaption". My pick is "A decrease in the behavioural response to a repeated, benign stimulus." This would be best avoided in treatment of pain. I doubt we want our patients to "habituate" to either us OR our treatment. Which is why we should stay nimble and novel, in my opinion.

Habituation is classified as non-associative in psychology, which takes us to ..

4. Learning by Association, or Classical Conditioning

Here, the relationship between a stimulus and a response is strengthened, or (see above) "sensitized".

Here is one more:

5. Extinction Learning
We are now back with definitions that involve proteins at the neuron level of memory.

While this little list of definitions hops around among scholarly domains and perspectives, it is important to realize that, as per Kandel, nothing can happen with learning and memory regardless of domain, unless neurons and their receptors change. When dealing with patients whose overriding issue is persisting pain, the "locus of control" (another one of those catchy psych terms) must be with the patient at all times. They must be given ample opportunity to "learn" to downregulate their not-very-successful prior sensitization learning, given support, and sufficient time, especially if manual treatment (a form of exteroceptive neuromodulation) is involved.

Matthias, can you think of any other types of neural learning to add to the list?

The Devil is in the details

Reply to: Neuroplasticity

I want to expand on this thought a bit more:

1. The focus, the inner attention, has to be on the process of learning the action, not the desired action itself.

There are several studies out there that shows how important this is and how we can use this during treatment:

Lorimer Moseley for example has done it again - a study published in Pain, January 2008 in CRPS shows that there is a big difference in how attention influences treatment.

It's been known for some time now that attention is the driving force behind cortical plasticity - the same stimulus is able to produce two different outcomes - depending on how much attention is directed towards the stimulus.

Stimulus discrimination (paying attention to what and where a stimulus is applied) - changes the cortex in a completely different way than simple passive tactile stimulation.

The process of attention is crucial in treating chronic pain; unfortunately the mental processes behind it are as yet poorly understood and there is a lot of controversy about even defining this mental capacity.

For us - PT's and others who work with patients we can focus on making the tasks we give the patient meaningful, functional and fun - that should be more than enough for now. ;-)

Visual Feedback for Backs

Response to Visual Feedback.

Matthias, I can see how treating could be done right now, with the right equipment.. much like your idea about treating paraplegic central pain.
I was thinking of something perhaps a bit more ambitious and potentially devious, however; how one might design a study to determine if back pain could be treated virtually, using these "virtual back" studies as a point of departure.

Think of the possibilities: if it could be shown that back pain/neck pain could be treated visually/virtually instead of being the huge treatment morass it is right now, several ramifications might ensue.

1. Heavy, structurally based manual therapy could potentially be made obsolete in the future. (:D)

2. Potential big cost savings for everyone; patients wouldn't have to suffer as much for as long. Employers would save insurance costs. Insurers would save on disability claims. Aspiring professional human primate social groomers wouldn't feel obliged to pay out huge $ for manual therapy courses of under-studied or dubious quality taught by greedy "gurus".

3. Humans might actually suffer, overall, less low back pain as an industrialized, domesticated species, in the future.

Just some wild and crazy thoughts. Dare to dream I say..

History of Neuroplasticity

Matthias, I agree. And thanks for introducing Dean Kamen. Seems pretty clear his work designing arm prostheses that can "feel", will make the wider PT/OT rehab role lots easier. :)

You highlighted him as a good example of someone who is not afraid of "learning" and gave some of the important characteristics of that:

"creativity, an ability for lateral thinking, the ability to make connections between seemingly unrelated fields (of science) - and disrespect for authority."

I agree although I would translate "disrespect for authority" into "an ability to recognize and bypass conventional dogma or "groupthink" in favor of considered scientific reflection of all possibilities."

On the topic of neuroplasticity, Sharon Begley, in her book Train Your Mind, Change Your Brain, recounts how difficult it is for dogma to be overturned in favor of counter-information. She traces the history of the scientific study of neuroplasticity starting with William James, who said, in 1890: "organic matter, especially nervous tissue, seems endowed with a very extraordinary degree of plasticity", meaning, according to Begley, "a structure weak enough to yield to an influence". No one picked up on this at the time. Ramón y Cajal was in the forefront of neuroscience, and had dazzling, substantive, convincing and irrefutable research work to offer up. His opinion on fixedness, immutability, unchangingness in the nervous system was pretty much conflated with his actual research for the next century.

In the 1940's, Donald Hebb at McGill came up with

"When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased"

..which became known as Hebbian learning, and gave rise to the quip, "Neurons that fire together wire together."

Along came researchers like Fred Gage (a shirttail relative, apparently, of the famous Phineas, according to Begley), who runs a lab at the Salk Institute in La Jolla, California.

Starting in the 1960's, other researchers, like Joseph Altman at MIT, Michael Kaplan at Boston U., and Fernando Nottebohm who studied birds that produce new songs continually throughout their lives, William Greenough, showed evidence that went against dogma, but weren't able to budge it. Elizabeth Gould showed in the 1990's that primates demonstrated neurogenesis. Slowly, the dogma finally started to dissolve.

Then researchers tried to figure out how to show neuroplasticity exists in the human brain - they wanted to know not just if the human brain could rewire itself, but also if it could grow new cells. It was hard to deal with all the ethical dilemmas involved, but they finally got permission to look at brains of a group of people who were terminally ill, at autopsy. Specifically, Peter Eriksson and Fred Gage worked together to determine that new neurons are born constantly, even in the brains of old and sick humans. You can read more about how the dogma was made to melt down in this history module.

Suffice it to say, human neuroplasticity is a fact of life, and cannot be pushed back into the shadows. From a physiotherapist point of view, this is good news! It shows that our work, i.e., helping people, helping patients in pain, bolstering them and supporting their efforts to improve, now has irrefutable science to back it. Now we can show people studies (should we have to) to prove they can recover from even the most debilitating injury, but even more so we can turn around and challenge various dogmas that still exist right in our own profession, dogmas about pain and how best to help relieve it, help move the profession from one that is still mesmerized by structure into one that smoothly understands and supports function.

Learning

Diane, I think that one of the most important statements from that program is this:

1. The focus, the inner attention, has to be on the process of learning the action, not the desired action itself.

That means that you have to learn how to learn.
If you develop good learning skills - you can apply those anywhere and everywhere - all your life.

If you look at a genius like Dean Kamen - a great inventor - you will see what I mean.
He is creative and simply doesn't give up.

All geniuses throughout history have shown some or all of the same skills:
creativity, an ability for lateral thinking, the ability to make connections between seemingly unrelated fields (of science) - and disrespect for authority.

Only by letting your mind wander to places that don't exist - by freeing yourself from the constraints society and/or peer pressure impose upon you can you really become creative and innovative.

In this case it's more important to un-learn constraining patterns of behavior than to learn new ones!

So where does pain fit in?

Learn to observe yourself - use Metacognition to identify situations, thoughts, habits, .... that aren't helpful. Start today.
Because if you learn to develop this crucial skill to it's full potential, you can use it - as stated above - anywhere, everywhere, anytime.

You have to realize that chronic pain is (mostly) a learned condition. The brain learned to be in pain all the time on it's own - what's called maladaptive plasticity.

But - by learning how to learn - and thus making use of "good" neuroplasticity - one can unlearn chronic pain.

Neuroplasticity

Matthias, maybe we could start with neuroplasticity. One of the best sites online on this topic is On the Brain.com. The brain seems to be, basically, a big learning machine. One learns, slowly, to take control of its plasticity. The frontal lobes of humans are not fully formed until into the third decade of life.

What does neuroplasticity have to do with Pain?
You could say pain can happen if/when neuroplasticity gets out of control. Pain is noted as being a "dark side" of neuroplasticity. But, if the brain can learn its way into pain, it can learn its way back out.

I recently watched a PBS program (and took a few notes) on the topic of neuroplasticity in general and aging in particular - how to keep one's brain young, and how to help it if it became damaged. It featured Dr. Merzenich from the site mentioned higher up. According to the program, four fundamentals had to be in place for gaining control, "harnessing" this ordinary activity the brain does all the time anyway:

1. The focus, the inner attention, has to be on the process of learning the action, not the desired action itself.

2. The heart has to be in good shape. Cardiovascular capacity needs to be there. The brain needs lots of oxygen when it's in learning mode. Deep breathing can help.

3. Training must be incremental, and just a little bit taxing. (Does this not sound just like any form of "exercise"?) The brain will build itself best on a sense of consistent accomplishment.

4. The desired goal needs to be interesting.



The program listed seven tenets of neuroplasticity.

1. Change can occur only when the brain is in the mood: alert, on the ball, ready for action.

2. Change strengthens connections between neurons engaged at the same time. The brain builds on its successes.

3. "Neurons that fire together wire together" (-Donald Hebb, psychologist from McGill Uni. Montreal) This helps the brain get better at its predictive capacity. Associations can be made more easily.

4. Initial changes are just temporary. While the brain can learn through impact (a powerful experience), usually it learns through lots of repetition.

5. Brain plasticity is a two-way street; it can change itself in positive or in negative directions. E.g., chronic pain, bad habits

6. Memory is crucial for learning. Where you put your attention is important. Practicing something while distracted won't help the brain change.

7. Motivation is a key factor. The program told the story of Paul Bach-y-Rita's father, who sustained a huge stroke. Eventually he learned to get around, crawling at first - his motivation was that he hated being dependent. He gradually recovered most of his function! Later, after an autopsy, Paul Bach-y-Rita was able to see his own father's brain, could see how enormous the damage had been, and marveled at the recovered function his father had gained.


Also featured on this program was Sharon Begley, who has written a book called Train your Mind, Change your Brain, which I am currently reading. It reads like an historical novel, a huge wedge of perspective back through time into all the scientific background leading up to current research on neuroplasticity, some of the best neuroscience news in the last twenty years. In a nutshell: if your brain has "learned" pain, it can "unlearn" pain.

Matthias, I think each one of these points could probably grow into a whole post series, but I'll just leave it here for now. If you think this is a good jump off point, feel free to expand.

P.S. (Dec. 15):
Here are a couple of Dr. Ginger Campbell's podcasts on neuroplasticity:
Brain Science Podcast #10: Neuroplasticity- how our brains change throughout our lives - (discusses the Sharon Begley book, Train Your Mind, Change Your Brain)

Brain Science Podcast #26: More on Plasticity-an interview with Dr. Norman Doidge (Doidge has written a book on neuroplasticity called The Brain that Changes Itself.)