• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

New Unger study suggests biological cause

kaffiend

Senior Member
Messages
167
Location
California
I'll be interested to see what region of the basal ganglia shows this effect. The basal ganglia are generally considered a "motor control" area of the brain. That they might be related to fatigue is interesting, given the prominent role for PEM in the disease.
 
Messages
13,774
Ignorant initial response to a media report of an unpublished study:

Could just be secondary. If patients diagnosed with CFS tend to have to work much harder to achieve things, but are thought of as only being limited by a fear of activity or deconditioning, then this could, over time, lead neurological changes in the parts of the brain related to reward mechanisms and a sense of achievement.

It would be interesting to know if these changes occur in those diagnosed with CFS who later turn out to have an exclusionary diagnosis.
 

hixxy

Senior Member
Messages
1,229
Location
Australia
Ignorant initial response to a media report of an unpublished study:

Could just be secondary. If patients diagnosed with CFS tend to have to work much harder to achieve things, but are thought of as only being limited by a fear of activity or deconditioning, then this could, over time, lead neurological changes in the parts of the brain related to reward mechanisms and a sense of achievement.

It would be interesting to know if these changes occur in those diagnosed with CFS who later turn out to have an exclusionary diagnosis.


It's studies like these that pick that 'parts' of this disease that suit their goals and discard the rest. Unfortunately the rest seems to be the most important part of the disaese. Everyone one of these seemingly psychiatric studies is so focused on fatigue that they miss some other the other often more devestating problems.

hixxy
 

FancyMyBlood

Senior Member
Messages
189
It's studies like these that pick that 'parts' of this disease that suit their goals and discard the rest. Unfortunately the rest seems to be the most important part of the disaese. Everyone one of these seemingly psychiatric studies is so focused on fatigue that they miss some other the other often more devestating problems.

hixxy

I don't think that's the case here. This research is pretty exciting because earlier studies showed involvement of the basal ganglia in interferon alpha-induced fatigue. As explained in the articles cited above the interferon-alpha induced 'sickness' symptoms share many characteristics with chronic fatigue syndrome. Of course, this begs the question what relevance this might have to us ME/CFS patients...... Well, coincidentally this issue was brought up recently in another topic discussing a MRC grant (here), which led to this quote from me:

I'm suprised nobody brought up earlier research between the established immune similarities of interferon-alpha induced symptoms and ME/CFS. For example, Andrew Miller recently demonstrated that Depression and fatigue during chronic IFN-? administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

Another interesting observation comes from Brigitte Huber, who stated in the past that both interferon-alpha and EBV are able to activate a HERV-K18 and lead to CFS symptoms. A study from her has now been completed and if I had to guess I'd say these results are positive. In a recent TWIV episode, Vincent Racaniello stated that he believes something more is at play than only EBV and 'to keep your eyes open'. My gut feeling tells me he's refering to this paper.

All in all, I'm pretty positive about this research, especially given the already established (and probably) coming literature.

This may be all conjecture, or a huge leap forward in understanding the cause(s) and pathophysiology of ME/CFS, but it sure is interesting and promising at this point in time.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Hi Kaffiend, here is a link where they discuss more than just motor control:

http://www.prohealth.com/library/showarticle.cfm?libid=16928
The basal ganglia are a constellation of interconnected areas deep in the brain. They appear to be associated with many functions, from motor activity and motivation/perceived reward to learning and habit encoding, and apparently with addictive disorders, OCD, and ADHD.)

The link this points to is: http://www.dana.org/news/brainwork/detail.aspx?id=6028

The wikipedia entry is: http://en.wikipedia.org/wiki/Basal_ganglia

http://www.scholarpedia.org/article/Basal_ganglia
This last one discusses learning - not in terms of school learning, but of the brain learning. Damage to the basal ganglia is thought to result in the brain being unable to learn how to cope with various things, and those things then degrade in function.

Bye, Alex
 

Lynne B

Senior Member
Messages
126
Location
sydney, australia
Thanks, SpecialK82, This thread is so interesting, so thanks for pointing it out.

Hi, Alex, your last link really rings a bell for me, not that I can understand most of it, but it points to three behavioural things that have caused me much pain: action selection, attention deficits and reinforcement learning.

With regard to action selectionI've been amongst family or friends and thought of a better thing to do than what I've earlier decided on but then I don't have the elasticity to change. For instance, I might think it a good idea to offer my plate of food around before I start on it (in an informal share situation) but find I don't change my earlier decision to eat it all myself based on my earlier understanding that it was only for me. That has become really awkward when I realise I don't really like it much and it would have been good to share. Also, in the early years, both my husband and I would find that when we came to the end of the newspaper we were reading we'd keep reading any part of it (even stuff we weren't interested in) because we didn't want to stop and think what to do next. Now that I'm alert to both these situations I try to keep them in mind and act on them. When reading the paper I try to break my concentration before the end and remind myself that I have to get up in a minute. That does work, so perhaps these physical difficulties are amenable to consciously-directed behavioural change.

I've noted attention deficits are a big problem too. In a lecture or talk I try to keep looking at the speaker and focusing on their ideas because if I look away I lose the thread. When I'm studying or writing at home it's very hard to go back to my thoughts after I get interrupted (so I'll have to think of a method to help there) and when I'm driving I turn off the radio if it's diverting my mind from the ever-changing traffic all around me.

I hadn't realised we also have difficulties with reinforcement learning but as motivation is such an important component of any learning I've resolved that from now on I'm going to celebrate every single incremental gain or achievement!

cheers, Lynne
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
During the experiment -- which is considered preliminary since it hasn't yet been peer-reviewed or published -- Unger and her team told participants undergoing brain scans that they'd win a small amount of money if they correctly guessed whether a pre-selected card was red or black. After choosing, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

I hope no one chews me out for this but I do wonder if this same finding would be found in a depression control group. Anyone know if they have done this same kind of study in depressed people and if they have the same finding?

(I just wonder as many with ME/CFS do have coexisting depression).
 

gu3vara

Senior Member
Messages
339
I hope no one chews me out for this but I do wonder if this same finding would be found in a depression control group. Anyone know if they have done this same kind of study in depressed people and if they have the same finding?

(I just wonder as many with ME/CFS do have coexisting depression).

I had the same question immediately after reading it, I really hope it's not seen in depression :-/
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
I wonder if they would discover this finding in any severe chronic illness group.

The headlines could easily read "Chronic Fatigue Syndrome patients unimpressed with gambling". ;)

LOL

But yeah.. maybe it could be found in chronic illness in general. Who knows. We dont know much from that study from the little info we know right now.
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
That ME/CFS patients figure out pacing suggests there is nothing wrong with reinforcement learning.

It thou often does take many ME/CFS patients a long time to learn to pace well even when they know they are doing things which make them sick. Otherwise having a push/crash cycle in our illness wouldnt be well known and so often talked about.
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
http://cfsuntied.com/blog2/2012/04/24/broken-reward-responseis-this-science/

Interesting commentary at CFS untied with a different take on things. I will make up my mind when I have seen the full paper.

Thanks for sharing that link alex, it just put so many of the thoughts I had about it into words. I personally dont trust the CDC and think it will take quite a bit till I do, I dont trust the reasons why they choose to do "this study" out of so many others they could of done.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
I thought this one was interesting:

ME/CFS Appears to Be a Disease Affecting the Basal Ganglia & Dopamine Metabolism

ProHealth.com

April 24, 2012: www.prohealth.com/library/showarticle.cfm?libid=16928

'A new study led by CDC investigator Elizabeth Unger, MD, PhD, with collaborators at Emory University, Atlanta, and the University of Modena and Reggio Emilia, Italy, has identified unique responses in the brains basal ganglia that suggest an association between a biologic functional response and chronic fatigue syndrome (ME/CFS).

In a paper presented April 24 at the Experimental Biology conference in San Diego,(1) the team reports that:

Patients with ME/CFS have decreased activation in response to reward of an area of the brain known as the basal ganglia.

(Ganglia are bundles of neurons providing relay points and interconnections. The basal ganglia are a constellation of interconnected areas deep in the brain. They appear to be associated with many functions, from motor activity and motivation/perceived reward to learning and habit encoding, and apparently with addictive disorders, OCD, and ADHD.)

Problems with the basal ganglia tend to involve fatigue.

The extent of the lowered activation in the ME/CFS patients basal ganglia is associated with the individual patients measured levels of physical and mental fatigue. (Less activation, more severe fatigue.)

How the Study Came About

Dr. Unger (chief of the CDCs Viral Diseases Branch) says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue.

Interferons are proteins that cells make to trigger immune defenses in response to pathogens such as viruses, and tumor cells. They interfere with viral replication within host cells and activate immune cells.

Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy.

Similar Symptoms

Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Dr. Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

The researchers recruited 18 patients with chronic fatigue syndrome (ME/CFS), as well as 41 healthy volunteers with no symptoms of ME/CFS.

Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward.

The participants were each told that theyd win a small amount of money if they correctly guessed whether a preselected card was red or black.

After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

This is considered a good test, as perceptions of winning or losing normally evoke strong activations of the basal ganglia.

More Muted Reaction to Stimulus = More Fatigue

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. (Stimulating activities can normally produce razzle-dazzle activity in the basal ganglia, says one leading researcher.)

When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patients fatigue was tightly tied with the change in brain activity between winning and losing.

Those with the most fatigue had the smallest change in brain activity.

Dopamine Dysfunction Involved; Inflammation Possible Cause

These findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome, Dr. Unger says.

Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness, she says. They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.

The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future.

Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. (Parkinson's disease, for example, is a movement disorder known to be tied to the death of dopamine-producing neurons in the basal ganglia.)

And in turn, the researchers speculate the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.

These results shed some important light on the riddle of ME/CFS - information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.

___

* The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC); Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia.

They discussed an abstract of their study - entitled Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue on April 24 at the Experimental Biology Conference 2012 in San Diego.

The abstract is sponsored by the American Society for Investigative Pathology (ASIP).

Source: Based on a Federation of American Societies for Experimental Biology (FASB) news release, Apr 24, 2012'

Interferon used in Hep C see MRC research funding for CFS/ME 2012: http://forums.phoenixrising.me/show...y-interferon-alpha&highlight=Interferon+alpha

Also you might find these two interesting: Chaudhuri: Proton magnetic resonance spectroscopy of basal
ganglia in chronic fatigue syndrome: 2002: http://www.cfids-cab.org/cfs-inform/Brainscans/chaudhuri.etal03.pdf

And a Lancet review of Fatigue in neurological disorders from Chaudhuri and Behan: 2004: http://www.cfids-cab.org/cfs-inform/Fatigue/chaudhuri.behan04.pdf