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UK Research Collaborative Conference in Newcastle: 13th - 14th October

Cheshire

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@Jonathan Edwards
I'd like to know how /if the hypothesis of Mark Edwards fits with the rituximab trials results and with the autoimmune theory.
Like others, I'm a bit afraid of the "interpretation" that could be drawn from this study within the frame of the "functional disorder" basket.
 
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@Jonathan Edwards
I'd like to know how /if the hypothesis of Mark Edwards fits with the rituximab trials results and with the autoimmune theory.
Like others, I'm a bit afraid of the "interpretation" that could be drawn from this study within the frame of the "functional disorder" basket.
I am not sure that Mark Edwards has a particular hypothesis for PEM. His hypothesis was about movement disorders. But even so I see no conflict. At any one time there may be immune loops or neural loops or both.

I really don't think you need to worry too much about the functional terminology. As Mark Edwards indicate sin his presentation he is really only interested in biochemical and neural mechanism. In this sense functional means working abnormally without any evident structural change. One could call autoimmunity functional in the same sense - there is no structural change in the bone marrow or lymph nodes and the cells are quite normal in the way they go about things. It is just that the functional outcome is disastrous.

I cannot see why people are being so negative about choosing people with PEM. Edwards is a neurologist. Harrison knows all about ME classification and PEM - he is not new to the field. Why would they want to do a study on PEM without making sure they had appropriate patients?
 

Large Donner

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I
I cannot see why people are being so negative about choosing people with PEM. Edwards is a neurologist. Harrison knows all about ME classification and PEM - he is not new to the field. Why would they want to do a study on PEM without making sure they had appropriate patients?
What is an appropriate patient?
 
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The boundary conditions of a 'mind' are set arbitrarily, but it sure is convenient to examine a whole brain to see whether it has the properties of a 'mind'. But this is always an abstraction. Examination of that mind relies it to be operating dynamically, which means it will be responding to external signals.The concept of mind only makes sense in the context of the scale in which you examine the system, but I don't see this as a drawback. It makes little sense to consider mind as, say, a single neuron, because neurons only function as neurons in a biological system with a large number of other neurons.

The same philosophical debates are held in physics about emergence during regular thermodynamic phase transitions.
http://www.pitt.edu/~jdnorton/Goodies/reduction_emergence/red_em.html (with some discussion of biology too)

I don't see why you are against the concept of emergence.
I said soul not mind. Mind is a tricky word that I tend not to use (I actually think it is worse than useless for scientific work). And soul in this case is not a religious concept but a biophysical one, as per Descartes's 'Passions of the Soul' (passion here does not mean what we now use the term to mean, it means receptivity). We need to be using terms the same way to have a useful dialogue.

As indicated above, emergence does have a useful meaning in condensed matter physics and thermodynamics but its application to neural networks (particularly by Walter Freeman and Giuseppe Vitiello) is inappropriate. Emergence cannot solve the locality problem for phenomenal experience however much people from Crick to Tononi might want it to. But we need to talk about this in community lounge or something. It is off topic here.
 

MeSci

ME/CFS since 1995; activity level 6?
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Yes, Newton does have a specialist interest in fatigue, but are you sure it's accurate to say that she doesn't study ME/CFS at all? Her studies do include CFS patients.

I don't think it's [POTS] widely recognised in the UK. Almost the only time I've ever seen it mentioned is on these forums, and I had to look up its meaning.
I know two people in the UK diagnosed with POTS - in the UK AFAIK. One may have been diagnosed by Julia Newton but I'm not sure.

This is the NHS patient page on POTS.
 
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I know very little about neurology, but I don't understand why 'mind' must be much more local than the brain.

Are you saying something like: Even if neural networks lead to the development of a thought, there needs to be one point in the brain where the thought is either there or not? Or one part of the brain which assesses whether thought are there or not?

Is there any vaguely easy to follow article on this you could link to?
As indicated in a post above, mind can be considered the same as brain, or even to extend out into the world if you are thinking of it as a functional computational unit. But conscious thoughts or experiences have to occur in a single 'event-domain'. That already sounds like abstruse jargon because one has to go through a whole lot of stuff about how the laws of locality have changed in modern physics to make this intelligible in common sense terms. But it is actually not that hard to put into common sense. The trouble is that there is very unlikely to be just one point in a brain where a thought is, which means there probably have to be several 'copies' at once. That is what I meant by things getting weird. There will also be other parts of the brain that assess if a thought was just thought, but these may then inform the places that have the thoughts so that they can think the thought that a thought had just been thought. And the weirdness goes on but it is tractable.

I hope that my website (Google Jonathan Edwards and UCL) is vaguely easy to follow at least in the introductory bits, but it has 600 pages of material on it, some of which will be less so! I need to dash to a seminar but at some point we can open a community thread.
 

Sidereal

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So the other chap on the Edwards grant, Harrison:

Psychiatric manifestations of Joint Hypermobility Syndrome

08 February 2011
Jessica A Eccles
ST2 Academic Clinical Fellow
Neil A Harrison, Hugo D Critchley
Sussex Partnership NHS Foundation Trust, Sussex Education Centre, Millview Hospital, Hove BN3 7HZ, U


Ross and Grahame have highlighted that hypermobility is just one visible feature of joint hypermobility syndrome. They have detailed the breadth of physical complications including dysautonomia, premature osteoarthritis and intestinal dysmotility suggesting a broader multi-system phenotype. We would like to draw readers' attention to the frequent
psychiatric co-morbidity associated with joint hypermobility. In particular, individuals with joint hypermobility syndrome are over-represented in panic and anxiety populations presenting to psychiatrists (1). This excess is suggested to be a large as a 16 times greater risk in patients with joint hypermobility compared to non-hypermobile controls(2). Joint hypermobility is more frequent in panic-disorder, where the degree of hypermobility predicts the severity of anxiety(3). Joint hypermobility is also linked to a number of psychosomatic disorders including Irritable Bowel Syndrome(4), Chronic Fatigue Syndrome (5) and fibromyalgia.

Individuals with joint hypermobility exhibit similar autonomic cardiovascular abnormalities to those with Postural Tachycardia Syndrome (PoTS) (6, 7). A defining characteristic of PoTS, regardless of its association with joint hypermobility, is an abnormally reactive autonomic nervous system, in particular a sharp increase in heart rate on standing. A phenomenological overlap, if not direct association, is also recognized between PoTS and anxiety disorders (8).

These findings suggest that constitutionally determined brain-body interactions may underlie this psychosomatic vulnerability and that joint hypermobility may represent a subphenotype of anxiety disorder.
http://www.bmj.com/rapid-response/2011/11/03/psychiatric-manifestations-joint-hypermobility-syndrome
 

Bob

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I cannot see why people are being so negative about choosing people with PEM. Edwards is a neurologist. Harrison knows all about ME classification and PEM - he is not new to the field. Why would they want to do a study on PEM without making sure they had appropriate patients?
Probably because we are a weary, cynical, battle-hardened bunch of patients who are sick to death of word games, half-truths and deceit. If we see a specialist in functional disorders getting involved in ME, we can't help but think "oh, here we go again". I think we need to see the study methodology before we are pacified.
 

user9876

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Many thanks and to Russell in particular.

Now we know what we are talking about. It looks brilliant to me. Neil is superb and he clearly has a big input. It is all about inflammatory and neural pathways and specifically about PEM so all that stuff about Oxford criteria can go in the bin. Presumably they will even correlate findings with the degree of PEM. This is proper science. They have even thought of the confounding problems of what people will be thinking because they are in an experiment - and will control for that be switching around the order of events.

I think this is a seriously important move forward in the science. The right people are focusing in on the most likely place to find some clues. And the cytokines and things will be measured as well it sounds like. It fits with the point made on both sides of the Atlantic that we should be studying people during PEM and looking at the abnormal response to exercise rather than just looking at PWME at any old time.
It looks like he is planning to take a bunch of patients and controls, scan them with an fMRI scan whilst performing a task and then have an exercise protocol and scan them 24 hours later. I get the impression that he is interested in parts of the brain associated with control signals from the body but I'm not quite sure about this. He is also doing some (unspecified) blood tests at least prior to the exercise.

So it does sound interesting. My big concern would be when bringing people in for the scans the travel etc could already be quite an activity and hence he may not get to test people in a inactive paced state.

I think it would be interesting to compare people with and without PEM as we as with other diseases.
 

Sidereal

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http://theconversation.com/profiles/neil-harrison-103819

Dr Neil Harrison is a Consultant Neuropsychiatrist, Reader in Neuropsychiatry and Head of the Psychoneuroimmunology Lab at Brighton & Sussex Medical School. His research investigates how infection and inflammation in the body interacts with the brain to modulate emotion, motivation and cognition and contribute to common mental illnesses such as depression, chronic fatigue and Alzheimer disease.
 
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And the article he wrote for The Conversation:
https://theconversation.com/inflammation-depression-link-is-not-to-be-sneezed-at-18212

Depression: a response to sickness?
However, it’s what is happening in the brain that is so exciting. Inflammation rapidly triggers a change in the responsiveness of a critical mood-regulating network and the way that it connects to other areas of the brain. Remarkably, this is the same network that is impaired in depression. This suggests that depression - at least in some cases - could well be some type of aberrant sickness response.

Although this finding shows that mood changes induced by inflammation use the same brain network as depression, it doesn’t tell us whether inflammation could be a factor in clinical depression, which leads to more prolonged periods of feeling down.

To study this further, depression researchers teamed up with a surprising group of patients – those with chronic hepatitis-C. The disease doesn’t cause particularly high levels of inflammation but if left untreated it slowly causes liver damage that can lead to cirrhosis and ultimately liver failure. To prevent this, and to potentially cure the hepatitis-C, most people are advised to take a six to 12-month course of antivirals and an immune-system boosting drug called interferon, which helps regulate inflammation.

But interferon injections not only induce sickness symptoms but can also result in clinical depression. About one in three patients treated with interferon develop depression, typically within six to eight weeks of starting treatment. The depression presents in a similar way to other people suffering with depression, and shows a similar response to anti-depressant medication. This suggests that chronic immune stimulation can cause depression.
Wait, that sounds familiar...

Hence my concern about specificity.
 

Valentijn

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I cannot see why people are being so negative about choosing people with PEM. Edwards is a neurologist. Harrison knows all about ME classification and PEM - he is not new to the field. Why would they want to do a study on PEM without making sure they had appropriate patients?
To a patient, PEM is the delayed onset or exacerbation of neurological, immune, and muscular symptoms: ataxia, dysautonomia, cognitive dysfunction, swollen lymph nodes, sore throat, twitching/cramping muscles, pain throughout the body, etc.

On the rare occasion that psychosomatic researchers acknowledge the existence of PEM, they twist the definition of it. They basically describe it as a somewhat hysterical reaction to Delayed-Onset Muscle Soreness (DOMS), which everyone gets after a workout in the specific muscles which have been worked harder than usual. So the BPS version of PEM = DOMS + crazy.

Hence my concern is that he will select fatigue patients who report experiencing DOMS, with or without some catastrophizers thrown in.
 

Large Donner

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This is an Edwards paper too, note it defines Functional as psychogenic. Also it talks of "abnormal beliefs and expectations."

http://www.ncbi.nlm.nih.gov/pubmed/23823467


Neurobiology of functional (psychogenic) movement disorders.

Edwards MJ1, Fotopoulou A, Pareés I.
Author information

Abstract
PURPOSE OF REVIEW:
This review explores recent developments in understanding the neurobiological mechanism of functional (psychogenic) movement disorders (FMDs). This is particularly relevant given the resurgence of academic and clinical interest in patients with functional neurological symptoms and the clear shift in diagnostic and treatment approaches away from a pure psychological model of functional symptoms.

RECENT FINDINGS:
Recent research findings implicate three key processes in the neurobiology of FMD (and by extension other functional neurological symptoms): abnormal attentional focus, abnormal beliefs and expectations, and abnormalities in sense of agency. These three processes have been combined in recent neurobiological models of FMD in which abnormal predictions related to movement are triggered by self-focused attention, and the resulting movement is generated without the normal sense of agency that accompanies voluntary movement.

SUMMARY:
New understanding of the neurobiology of FMD forms an important part of reappraising the way that patients with FMD (and other functional disorders) are characterized and treated. It also provides a testable framework for further exploring the pathophysiology of these common causes of ill health.