Friday, May 22, 2009

Four ways neuroplasticity operates

I picked up a book this morning called Neural Plasticity and Disorders of the Nervous System, by Aage R. Møller, who works in Texas.

On page 17 he has listed these four ways neuroplasticity operates:

"1. By (functional) changes in synaptic efficacy, the extreme of which is unmasking of dormant synapses, or masking of efficient synapses.

2. By reducing or modifying protein synthesis and proteinase activity in nerve cells.

3. By creation of new anatomical connections (sprouting of axons and dendrites) or elimination of existing connections or by altering synapses morphologically.

4. By elimination of nerve cells (apoptosis)."

Additional reading:

1. A quick search of blogposts re: neuroplasticity on Deric Bownd's Mindblog
2. A quick search of blogposts re: neuroplasticity on Mo's Neurophilosophy blog (and some others).
3. A quick search for neuroplasticity on this blog, Neurotonics.
4. A related blogpost, System Proteomics

Tuesday, May 19, 2009

Fabulous Interactive Brain Science Site: Genes2Cognition

I have added a new link to the menu to the right, Genes2Cognition. Very impressive, one of the best I've ever seen. You can click on ANY of dozens of balloons, drag them around, click on them to bring up deeper levels of information. I picked "Perception" which led to "Cognition" which led to "Inattentional Blindness" which led to a wonderful short little video I had seen before, connected to a TED talk by Michael Shermer, which disappeared... but now looks like it's back!

You can take a look at brain parts, look into different levels of the brain, turn it all around, flip it upside down or look into it through the top.

You can click on and explore different conditions, or different functions.

I found the G2C site at the brain portion of the Dana Foundation website. I found the brain portion of the Dana Foundation website by clicking on the main page. I found the main page by clicking on the link provided by Deric Bownds in his new post, Arts and the Brain. Thank you Deric!

Sunday, May 17, 2009


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.)
Unmyelinated tactile afferents have opposite effects on insular and somatosensory cortical processing. (Olausson et al.)
Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin. (Olausson et al.)
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)

Monday, May 11, 2009

"Higher" emotions have neural correlates too

Check out this post at Deric Bowds Mindblog, Brain correlates of self-transcendent emotions, based on this paper by a group which includes the Damasios: Neural correlates of admiration and compassion.

Bownds writes:
"Antonio and Hanna Damasio and collaborators have now observed brain activities associated with our internal loftier emotions that transcend self-interest, such as elevation and admiration. These are hard to measure because they don't correlate obviously with facial expressions or body language."

Writers at PNAS (again, from Deric's blogpost) provide an overview, put the paper into context:
"Emotion research has something in common with a drunk searching for his car keys under a street lamp. ‘‘Where did you lose them?’’ asks the cop. ‘‘In the alley,’’ says the drunk, ‘‘but the light is so much better over here.’’ For emotion research, the light shines most brightly on the face, whose movements can be coded, compared across cultures, and quantified by electromyography. All of the ‘‘basic’’ emotions described by Paul Ekman and others (happiness, sadness, anger, fear, surprise, and disgust) earned their place on the list by being face-valid. The second source of illumination has long been animal research. Emotions that can be reliably triggered in rats, such as fear and anger, have been well-studied, down to specific pathways through the amygdala. But emotions that cannot be found on the face or in a rat, such as moral elevation and admiration, are largely abandoned back in the alley. We know they are there, but nobody can seem to find a flashlight. It is therefore quite an achievement that Immordino-Yang, McCall, Damasio, and Damasio managed to drag an fMRI scanner back there and have given us a first glimpse of the neurological underpinnings of elevation and admiration."

My bold.
Here is the abstract of the paper itself;


In an fMRI experiment, participants were exposed to narratives based on true stories designed to evoke admiration and compassion in 4 distinct categories: admiration for virtue (AV), admiration for skill (AS), compassion for social/psychological pain (CSP), and compassion for physical pain (CPP). The goal was to test hypotheses about recruitment of homeostatic, somatosensory, and consciousness-related neural systems during the processing of pain-related (compassion) and non-pain-related (admiration) social emotions along 2 dimensions: emotions about other peoples' social/psychological conditions (AV, CSP) and emotions about others' physical conditions (AS, CPP). Consistent with theoretical accounts, the experience of all 4 emotions engaged brain regions involved in interoceptive representation and homeostatic regulation, including anterior insula, anterior cingulate, hypothalamus, and mesencephalon. However, the study also revealed a previously undescribed pattern within the posteromedial cortices (the ensemble of precuneus, posterior cingulate cortex, and retrosplenial region), an intriguing territory currently known for its involvement in the default mode of brain operation and in self-related/consciousness processes: emotions pertaining to social/psychological and physical situations engaged different networks aligned, respectively, with interoceptive and exteroceptive neural systems. Finally, within the anterior insula, activity correlated with AV and CSP peaked later and was more sustained than that associated with CPP. Our findings contribute insights on the functions of the posteromedial cortices and on the recruitment of the anterior insula in social emotions concerned with physical versus psychological pain.

I deliberately bolded the bit about the anterior insula, because of how involved it seems to be in pain production or at least pain perception.