Wednesday, October 17, 2018

Ongaro and Kaptchuk 2.1

This blogpost deals with the first reference in the introduction of the paper I'm currently reading and absorbing (Ongaro, Giulio, Kaptchuk, Ted J., 2018, Symptom perception, placebo effects, and the Bayesian brain. PAIN, Aug 6, 2018. (To read the full paper, click on "Article as pdf").

The references are cited in the last sentence of the intro:

"It expands on recent high-quality empirical work on predictive processing (1,7,19,24) and outlines, more broadly, how Bayesian models offer an altogether different picture of how the brain perceives symptoms and relief."

The first reference is 
Anchisi D, Zanon MA. Bayesian perspective on sensory and cognitive integration in pain perception and placebo analgesia. PLoS One 2015. First, the authors
Davide Anchisi and Marco Zanon are both in Italy. Italy is a hotbed of placebo research (Fabrizio Benedetti* is in Italy as well). Both authors are at Department of Medical and Biological Sciences, Università degli Studi di Udine, Udine, Italy, according to PubMed, although Zanon may be in Bologna now.
Here is a 
list of publications by Anchisi;  Anchisi is an MD and PhD.Here is a list of publications by Zanon;  Zanon is a post-doc research fellow with the psychology department. 


1. "How can an inert treatment cause a response?"
This is the first sentence. Good question. My follow-up question is, who decided that any given treatment was "inert"? What were their criteria? They certainly left out a lot of info or maybe their info was incomplete. Right? An awake alert human brain is always going to respond to context of said treatment, so nothing can ever truly be "inert." But I digress.  

2. "... living organisms and their perceptive systems deal with uncertainty and face transposed conditional probability problems: they have to infer the features of activating stimuli (related to the state of the world) from nervous signals elicited by those stimuli, and come to a reliable perception (i.e., make an effective decision) in spite of the noisy and incomplete information that sensory signals provide about the world."
Yup, that's pretty much what the nervous system is doing from the moment it switches itself on as an embryo to the day it dies.

3. ".. experimental and theoretical work showed that perception is a multisensory task and support the hypothesis that, in perception, different pieces of information are near optimally combined in a Bayesian way."
Note to self: learn whatever I can grok about "Bayesian." This link states: 

"Bayesian statistics is a system for describing epistemological uncertainty using the mathematical language of probability. In the 'Bayesian paradigm,' degrees of belief in states of nature are specified; these are non-negative, and the total belief in all states of nature is fixed to be one. Bayesian statistical methods start with existing 'prior' beliefs, and update these using data to give 'posterior' beliefs, which may be used as the basis for inferential decisions."
Apparently there was a guy in 1763, Thomas Bayes, who came up with this.  

4. "
In this study we focused on the placebo effect because it is one of the best examples of experimentally controllable modulation of pain experience, and has been extensively investigated in recent decades." OK...

5. "Our aim was to develop a Bayesian framework which could describe and explain pain perception and its modulation....As we argue here, the nociceptive signals are not the only source of information used to compute the inference: past experience and cognitive information also play a role."
As Melzack's Neuromatrix framework states.

6. "
A total of 55 healthy human volunteers (mean age ± s.d.: 21.40 ± 1.03; 29 females) were recruited by advertising at the University of Udine (Italy) and randomly divided into two groups: Experiment 1 (n = 24); and Experiment 2 (n = 31)." And then they "conditioned" the subjects (gave a bunch of twentyish-year-olds the opportunity to organize their expectations), and applied TENS.

7. "
The main findings of this study concern not only the placebo effect but a wider range of effects also due to past experience." I wonder what results would look like if the subjects were in their 60's or 70's? Just a thought.

8. "
The Bayesian decision model we developed comprises three key elements: the prior probability, which conveys previous experiences and expectancy (e.g. through information derived from the context); the likelihood function, which implements the sensory inputs and also information from multiple sources (whether sensory, cognitive or psychological); and the decision process, which eventually determines if and to what extent pain is perceived."

9. "
The model we developed shows how the placebo effect results from the evaluation and integration of nociceptive stimuli with context information, and how the relevance of the context (through expectation/conditioning) comes, at least in part, from past experience. The process of information integration would be at the very base of pain perception, and would lead to the placebo effect and to other phenomena such as those predicted by the fBD model.

Overall, our findings support the hypothesis that pain perception can be described according to the rules of Bayesian probabilistic reasoning."

Ongaro and Kaptchuk 1: Intro 
Ongaro and Kaptchuk 2: Intro

*I spent a great deal of time with Benedetti's book, The Patient's Brain, read it cover to cover, made lots of notes; I also had the pleasure of hearing him speak about his work at the San Diego Pain Summit in 2016.

Monday, October 15, 2018

Ongaro and Kaptchuk 2: Introduction

See Ongaro, Giulio, Kaptchuk, Ted J., 2018, Symptom perception, placebo effects, and the Bayesian brain. PAIN, Aug 6, 2018. (To read the full paper, click on "Article as pdf") This is all the introduction.

What I like about it (so far) and the predictive processing model for looking at the brain is that it treats the brain as a verb, not a noun.

First line of the introduction:

"The standard and ideal biomedical model of symptom perception treats the brain largely as a passive stimulus-driven organ."

Yup, that's the Cartesian way of looking at another human being.
Lest we forget, "being" is a verb. Or at least a gerund.

Second sentence:

"It embraces the notion that the brain absorbs sensory signals from the body and converts them, directly, into conscious experience."

It may do that before it has any experience to also draw on, e.g., within the first few months of life..

Third sentence:

"Accordingly, biomedicine operates under the assumption that symptoms are the direct consequences of physiological dysfunction and improvement is the direct consequence of the restoration of bodily function."

Yup, very convenient. Also useful. Has been successful to a large extent.
Also very Cartesian. Easy to blame the patient if their particular "pain" doesn't fit into the model, i.e., "the patient must be crazy"

Fourth sentence:

"Despite its success, the biomedical model has failed to provide an adequate account of 2 well-demonstrated phenomena in medicine: (1) the experience of symptoms without pathophysiological disruption, and (2) the experience of relief after the administration of placebo treatments."

Yup. E.g., (1) phantom limb pain, and (2) resolving it by stabbing a screwdriver into the artificial limb (one of the stories in Painful Yarns by Lorimer Moseley).

Fifth sentence:

"This topical review advances the idea that “predictive processing,” a Bayesian approach to perception that is rapidly taking hold in neuroscience, significantly helps accommodating these 2 phenomena."

At last!!

Sixth sentence:

"It expands on recent high-quality empirical work on predictive processing (1,7,19,24) and outlines, more broadly, how Bayesian models offer an altogether different picture of how the brain perceives symptoms and relief."

Ah yes... inevitably, there is always going to be a ton of side reading to do. Not that I mind side reading when motivated! I see we will have to go to blogposts 2.1 - 2.4.

7. Büchel C, Geuter S, Sprenger C, Eippert F. Placebo analgesia: a predictive coding perspective. Neuron 2014;81:1223–39.
19. Grahl A, Onat S, Büchel C.The periaqueductal gray and Bayesian integration in placebo analgesia. Elife 2018;7:e32930.
24. Kaptchuk TJ. Open-label placebos: reflections on a research agenda. Perspect Biol Med 2018;61:311–34.

.......................... Other blogposts in this series

Ongaro and Kaptchuk 1

I am currently reading this paper: Symptom perception, placebo effects, and the Bayesian brain - so juicy. I stumbled upon a blogpost by Tim Cocks at Noijam that mentioned it.

I have decided to give it a "full treatment" - a full, line-by-line treatment. This is because I would love to understand Bayesian thinking better, I'm a beginner, pain has always been a way into understanding life in a body better, and this paper promises to do all that.
Plus, on Facebook, there are two bright minds who want to debate the paper.

As usual, this blog will be my private (well, probably not private, but I can pretend it is) workspace - a place for me to work on my own thinking about it, reflect on the conversation as it unfolds on Facebook, ruminating, pondering, storing all the links and analyzing WhatItAllMeans, to me.

As usual, I will be looking at all of it from the perspective of a manual therapist and neuromatrician who works with peoples' nervous systems directly to help them overcome pain problems.

This is the first of many blogposts I will write about this paper as I try to grok all of it.

I had a moment of clarity yesterday (few of these moments, so it felt sharp!)
I sent out a thought.
Here is the thought I had:

"Here's a thought (spurred by a conversation with Hsieh Hsing Wu *):  
1. Kinesthesia is to proprioception as pain is to nociception.
2. Pain is awareness of (danger signaling perceived as if coming from) the body, top-down. Nociception is sensory input, bottom-up.  
3.Kinesthesia is awareness of (movement of) the body, top-down. Proprioception is sensory input, bottom-up.  
4. It is not appropriate to mix up any of these."

I based it (and will base subsequent thoughts) on these items, which clarified many things for me:
1. Anil Seth's TedTalk on predictive processing: Your brain hallucinates your conscious reality
2. Anil Seth's TedTalk, truncated.
3. A wonderful article in New Scientist that I refer to endlessly:  
Understanding Body Ownership and Agency. 

Proprioception is likely more about ownership, whereas kinesthesia is more about agency.
Manual therapy is something I now regard as "exafference" (from the Liepelt and Brooks article) an environmental influence on the system) that creates compelling enough perturbation that the system can change its own predictions. 

1. Ongaro, Giulio, Kaptchuk, Ted J., 2018, Symptom perception, placebo effects, and the Bayesian brain. PAIN, Aug 6, 2018. (To read the full paper, click on "Article as pdf")

2. Cocks. T, 2018, The ‘Bayesian brain’ for beginners, by way of placebo. Noijam blogpost Oct 9, 2018

Your brain hallucinates your conscious reality Ted Talk, Anil Seth, video, 17 minutes, April 2017

4. Your Brain Hallucinates to Create Your Reality. Ted Talk, Anil Seth, truncated to 3 minutes, June 4, 2018, TED Facebook

5. Roman Liepelt, Jack Brooks, 2017,  Understanding Body Ownership and Agency.  New Scientist May 1, 2017

*Hsieh Hsing Wu is a physio in Taiwan who I met 14, 15 years ago in online forums. He lived in Australia at the time I met him. He attended my DNM class in Taipei this past May, and is interested in becoming a DNM workshop instructor there.

Friday, October 12, 2018

So many papers and other good stuff lately!

I lack motivation, which is why I haven't been blogging much this past year. But I do notice many things as I drift by them in my mental inner tube, and just now, I decided I had enough energy to list the sort of stuff I see daily - an avalanche of great stuff, semi-organized.

In the peripheral nervous system:

1. Concept of acute neuropathic pain. The role of nervi nervorum in the distinction between acute nociceptive and neuropathic pain.  This one comes from Brazil, 2016. It eluded me until now, possibly because it had not been translated into English before, but is now. Really interesting, everything you ever wanted to know about nociceptive neurons in the periphery. Well, a lot at least.
And how they can be bothered on the inside of nerves.
My whole manual therapy worldview rests on this idea - that if nociceptive neurons inside nerves get riled up for any reason, e.g., mechanical deformation of the nerve OR the vessels that feed and drain it, the nerve itself will get plenty cranky, sensitize, and make a signal large enough to eventually overcome normal descending inhibition, whereupon the spinal cord will obligingly amplify said signal, compounding it with central sensitization through several mechanisms.

Entrapment of middle cluneal nerves as an unknown cause of low back pain. The author is Japanese - Yoichi Aota. My Japanese colleagues have met him in person. 

In the central nervous system:

1. Thalamus: 
A long-overlooked brain region may be key to complex thought
This one is not about pain per se, but about how the thalamus's job is much more than just relay. 

2. Cerebellum: The Cerebellum, Autism, and How The Human Brain Gets Organized - New Research.    This is a half-hour video with Peggy Mason and Aaron Freeman at U Chicago, who shed all sorts of light on this structure and its contribution to developing brains.

3. Pain as maladaptive plasticity, by DevraJoy Sheldon. I had the pleasure of meeting Dera Joy at the last San Diego Pain Summit. What a great blogpost!

"Moseley et al 2009 noted that when individuals with CRPS crossed their upper extremities, the unaffected extremity became cooler than the involved limb. It wasn’t the limb, but the hemispace that was relevant. This is very much like a stroke with hemispatial neglect (an inattention to the environment on the involved side.) And what do we do with individuals who experience neglect, even extreme forms of it including anosognosia (denying the limb is theirs)? We help them attend to the limb and environment. We involve the limb in care and therapy. We apply stimulus to the limb to help the brain “tune in” to it and we encourage attention to the hemispace in which the limb resides. We do this to drive neuroplastic change."

She's right, that's exactly what we do.

4. The autonomic system: 
Professionalism-Autonomic Disorders: David S. Goldstein, MD, PhD He Could Have Been a Cartoonist. He Became an Expert in Autonomic Disorders Instead. Sounds like this may be the researcher to whom we owe a debt for elucidating dysautonomias. Note to self: look up all his work!

The ‘Bayesian brain’ for beginners, by way of placebo. A super good paper is linked into this blogpost.  Here it is: Symptom perception, placebo effects, and the Bayesian brain. Click on "Article as pdf" to get full text.

Studying the two together:

Skin nonlinearities and their effect on user perception for rotational skin stretch. This is REALLY exciting for me - someone has built a skin twizzler machine.  Now maybe someone can design a (really GOOD) research project to study DNM! 

Studying the therapeutic relationship:

A framework for establishing connections in physiotherapy practice. This new paper is by Maxi Miciak et al in Alberta. (* Don't miss her at the next San Diego Pain Summit where she'll be a speaker alongside Damasio!) I love how she geeks out the various components of therapeuttic relationship into an actual diagram.

Remember, for accessing beyond a paywall, scihub is our friend. 

Shin and Yoshi

In September I had visitors from Japan, two nice young men, one of whom translated my book into Japanese and the other who is a physio - together they plan to start teaching DNM in Japan and maybe elsewhere too - I couldn't be more relieved to hear that. It will save wear and tear on me to not have to travel so much, and at some point, I'll be able to just stop. 

Shin Iwayoshi, the translator and massage therapist, and I in front of a fountain in front of the courthouse in the small prairie city I live in. 

Yoshiro Morimoto, the physio, and I. 

Exciting times.