Who *isn't* afraid of Alzheimer's?

I have found microglia interesting to learn about in the past, and have written here, here, here, here, and here, about their proposed relationship to pain.

Yesterday I saw a news story about researchers in Germany who carefully studied the relationship between microglia and neurons undergoing Alzheimer-like changes in mice, Dangerous custodians: Immune cells as possible nerve-cell killers in Alzheimer's disease,
and was immediately intrigued.

An advance online publication of the paper, Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease, is freely accessible, at least for now.

That stressed neurons exude the chemokine, fractalkine, or that this substance attracts microglia, isn't fresh news. Like a bunch of little cellular opportunists, microglia catch the "scent" and begin moving toward it. Like any bunch of scavengers converging on a picnic, in this case, the amyloid-β forming and piling up, they also secrete/excrete (while gorging and multiplying, I suppose). What they signal/secrete/excrete isn't really explained, but what is news, is that it, or else just the sheer numbers of microglia converging, apparently sickens the affected neurons even more, kills them, according to this story.

In the paper, the authors, Fuhrmann etal., state,

"In Alzheimer's disease, microglia represent a double-edged sword. On the one hand, microglia can have a beneficial effect by secreting neurotrophic factors and phagocytosing amyloid beta (Aβ)², the latter of which remains controversial³. On the other hand, microglia may also be neurotoxic⁴. Little is known about the neurotoxic role of microglia in Alzheimer's disease. Human peripheral blood monocytes that are stimulated with Aβ induce neuron loss in vitro⁵. Neurons cultured without microglia are resistant to Aβ-induced neurotoxicity⁶."

The authors decided to interfere, genetically, with the receptors in the microglia that allow them to sense fractalkine; CX₃CR1,

"the unique receptor for fractalkine/CX₃CL1, which is expressed in neurons and presumably acts as a membrane-bound adhesion molecule and/or cleaved chemoattractant and is important for recruiting CX₃CR1-expressing microglia to injured neurons^{9, 10}."

They managed to show that it was definitely the microglia causing the neuron death, not any other factor. Furthermore, knocking out the ability of microglia to "smell" fractalkine didn't seem to interfere with their ability to clear the amyloid material associated with Alzheimer's. Moreover, the same treatment of the microglial receptor gives inconclusive results in other kinds of conditions - only in Alzheimer's does it seem to be a helpful intervention.

Supplementary information for this paper.

Fuhrmann, M., Bittner, T., Jung, C., Burgold, S., Page, R., Mitteregger, G., Haass, C., LaFerla, F., Kretzschmar, H., & Herms, J. (2010). Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease Nature Neuroscience DOI: 10.1038/nn.2511

Multiple sclerosis and news buzz about it

I must admit that as a young PT student and newly minted PT who thought I was coming down with whatever new thing I learned about, or had the opportunity of meeting/treating people who had x or y condition, MS probably freaked me out the most. Of late, a very nice massage therapist I know personally, ended up with this diagnosis.

How wonderful that this ailment is currently being highlighted as a condition which could be, potentially at least, reversible with a simple surgical procedure. Who'd have thunk? After all these decades?

Here are the news stories I've come across so far:

CTV W5 The Liberation Treatment
Medpage Radical MS Theory Stirs Interest
BBC: Multiple sclerosis 'blood blockage theory' tested


Nov. 30/09
Edit: I'm back in this post to add a link to Dr. Zamboni's website, Fondazione HILARESCERE.
Some of his papers can be found there. At least for now.

Ego tunnels, conscious entities, virtual bodies and so on.

I have yet to read the book by Thomas Metzinger, The Ego Tunnel, but it's in the cart. Meanwhile I came upon a blog post, two in fact, by Peter Hankins at Conscious Entities blog, that set off a little speculative burst in my own brain.

Part I, and Part II.

In particular, this got my attention;

"There are many interesting details in this account, quite apart from its value as part of the overall argument. Metzinger briefly touches on four varieties of autoscopic (self-seeing) phenomena, all of which can be related to distinct areas of the brain: autoscopic hallucination, where the subject sees an image of themselves; the feeling of a presence, where the subject has the strong sense of someone there without seeing anyone; the particularly disturbing heautoscopy, where the subject sees another self and switches back and forth into and out of it, unsure which is ‘the real me’; and the better-known OBE."

It makes sense to me that multiple self-constructions/constructions of self would exist, given that there are many different body representations all throughout the brain, not just the big S1 map stretched over the top of the cortex, the famous one Wilder Penfield mapped out, and I didn't realize there were names already ascribed to the elicitation of their specific distortions..

A body misperception can be the absence of a familiar body sense just as well as it can be one that's displaced onto a mannequin or onto someone or something else entirely, or floating above.. in each case there will be a corresponding shift in neural traffic flow, the brain not operating in its own familiar manner, and part of it noticing that shift and confabulating predictive perceptual fantasies as to possible reasons why. As in the Charlie Rose Brain Series Part II, in which all the various visual perceptual distortions were touched on, body sense is subject to perceptual distortion. The science on this is younger, but is definitely happening, mostly in Europe, mostly referred to as research of virtual bodies, rubber hand illusions, etc etc. discussedmany times on this blog. It's all very fascinating, and likely to have a lot to do with learning to handle human pain issues much more adeptly with fewer drugs at some point.

Meanwhile, it won't be a bad idea to practice feeling your own normal body better, practice using normal brain pathways, strengthen them so that your brain maps don't get all out of whack some day, and in some misguided attempt at trying to locate body parts, make them spasm or make them hurt to be able to find them more easily - the neurological equivalent of lighting flares to see along a dark path.

Other reading:
1. Book review at Naturalism.org

Moving a humanantigravity suit around

I confess that my usual perspective on the nervous system is from outside in - I consider what happens when I put my hand on someone else's body part, and consider ensuing movement output as a consequence, as a nervous system's direct response.. there's almost always that idea of my inputting some sort of talented (or not) sensory input - first. That's how my treatment brain works - it uses the "operator"/"interactor" model, by default, usually, and my conceptualizations end up being informed by it.

I've been away from clinical work for over 4 months now, and my brain is learning to think in different ways. So, when I think of "movement" now, I'm seeing it in more abstract terms. Lately several papers and blogposts about movement have come to my attention. I don't know how they synthesize, yet.. but I'm paying attention to the process, at least. I'd like to outline a few thoughts about them, bearing in mind the role of the brain as predictor, oscillator, simulator. First though, I'm going to just link them here.

1. The Brain in its Body: Motor Control and Sensing in a Biomechanical Context The Hournal of Neuroscience

2. Podcast interview of Barrett Dorko by Rod Henderson, May '09

3. A sensory source for motor variation Nature

4. Physiologically impossible movement of phantom limbs explained at Body in Mind blog (Lorimer Moseley)

5. Tiny Laser-scanning Microscope Images Brain Cells In Freely Moving Animals Science Daily

6. Two Wrongs Make a Right – Abnormal Brain Circuitry May Stop Abnormal Movement BrainBlogger

7. A head of time: For the first time, neuroscientists find brain cells that keep track of time with extreme precision. MIT - Everything gets a timestamp.

8. NOI Notes on Movement as Antigen David Butler's blog/newsletter

9. Primate anterior cingulate cortex: where motor control, drive and cognition interface. 2001

Moving into a robotic hand

Here is another wonderful Mindhacks post: Inhabiting a robot hand Thank you Mindhacks.

This relates to all the posts here to do with robotics, haptics, virtual bodies, virtual body manipulation through mirror therapy or video, and rubber hand illusions. NOI twittered about the Mindhacks post in conjunction with Graded Motor Imagery, the virtual treatment they are promoting. Definitely worth boosting here as well.

Forty Years of Neuroscience

I want to thank MindHacks for constructing such an informative post. Here it is, complete with all its links to Journal of Neuroscience.
Around the Brain in Forty Years.

Self-amputation

There must be dozens of stories of this. A few years ago Oprah had as a guest a young woman who, trapped in a car which had gone off a bridge, hidden from view and possible rescue, self-amputated a leg to escape. About 5 years ago a young man hiking in the Grand Canyon became trapped when a rock tumbled and pinned his hand. He cut off the hand to escape.

It really makes one wonder what pain is, exactly.

In this story from yesterday (twittered by Mo of Neurophilosophy), a young man's leg was pinned by a concrete girder. He managed to cut most of it off himself, but a friend nearby had to help break the bone.

His brain decided the threat to his ongoing existence was greater than any threat from any upcoming nociception. It was capable of downregulating its own sensory input enough to allow him to remain conscious and focused and on task, as it realized this was its organism's only shot at surviving. In this way the seemingly impossible becomes possible, without loss of consciousness, and in spite of what must be a large loss of blood.