Mizuno et al: Low putamen activity associated with poor reward sensitivity in childhood CFS

[mango]

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

Kei Mizuno, Ph.D.a, b, c, e, , , Junko Kawatanif, Kanako Tajimaa, b, Akihiro T. Sasakia, b, d, e, Tetsuya Yonedah, Masanori Komii, j, Toshinori Hiraik, l, Akemi Tomodam, Takako Joudoig, Yasuyoshi Watanabea, b, d, e

NeuroImage: Clinical Volume 12, 2016, Pages 600–606
http://dx.doi.org/10.1016/j.nicl.2016.09.016

Highlights
• Childhood chronic fatigue syndrome (CCFS) may have low neural reward processing.
• Activity in the putamen was specifically decreased in low monetary reward.
• Reduced activity of putamen was correlated with fatigue and reward from learning.
• Low activity of the putamen is associated with poor reward sensitivity.
• Decreased neural reward processing suggests dopamine dysfunction in CCFS patients.

Abstract
Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear.

The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients.

fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires.

Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively.

We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

Keywords: Childhood chronic fatigue syndrome; Dopamine; fMRI; Motivation; Putamen; Reward sensitivity

http://www.sciencedirect.com/science/article/pii/S2213158216301747

 

[Woolie]

Sorry to say it, but another really rubbish fMRI study.

The CCFS group (kids with CFS) and a group of controls did various online card gambling tasks where you could sometimes earn money by picking the right card - in one task, they got high rewards for picking the right card, in another they got low rewards, and in a third, they got no reward.

There were no differences in CCFS and controls' response times on the tasks.

They were looking for differences in activity in various subcortical structures which have been associated with reward processing. These included the caudate nucleus, the putamen (both part of the basal ganglia) and the thalamus. There were hardly any differences at all, even on fMRI, but the authors managed to find one: for the low reward condition, the CCFS group had significantly lower activity in the putamen than controls. No differences anywhere on the other conditions.

The groups were small (14 CCFS, 13 control) and so were the differences observed. These differences also seemed to be driven by only two of the 14 CCFS kids.

There does not seem to be any attempt to discuss why only the low reward condition yielded differences (the three levels), or what sort of pattern you might predict across the three different conditions.

There's a lot of hand waving about pro-inflammatory cytokines and the possible effects of neuroinflamamtion and oxidative stress on activity in the putamen. Then some talk about how levodopa (used in Parskinson's) might alleviate our fatigue. But then it ends with this:

Cognitive behavioral therapy for CFS aims to change behavior and cognitions thought to perpetuate symptoms (including the severity of fatigue), and is effective for children and adolescents with CFS (Kawatani et al., 2011) and adults with CFS (Castell et al., 2011 and White et al., 2011). Graduated exercise therapy is also effective at reducing the severity of fatigue in adolescents with CFS (Gordon et al., 2010) and adults with CFS (White et al., 2011). In addition, combination treatments with cognitive behavioral therapy and physical training reduced mental fatigue, but did not improve motivation, in patients with cancer-related fatigue (van Weert et al., 2010). These results suggest that, in addition to dopaminergic agents, cognitive behavioral therapy, graduated exercise therapy, or a combination of these may also normalize the neural processing related to altered reward sensitivity and reward-based learning in CCFS patients.

I rest my case.

 

[Sidereal]

The recent metabolomics data suggested problems with dopamine synthesis. CBT won't do squat to normalise 'reward processing' when the enzymes needed to make the relevant neurotransmitter are underfunctioning due to low energy.

 

[Hutan]

These poor sick kids, and by extension all children with ME/CFS, have been labelled as having a reduced motivation to learn which causes reduced cognitive performance:

In addition to cognitive dysfunction, CCFS patients also exhibit severe emotional dysfunction such as reduced motivation to learn (Miike and Bell, 2008). Motivational signals influence a wide variety of cognitive processes and components of behavioral performance (Botvinick and Braver, 2015); therefore, cognitive dysfunction in CCFS patients may be closely associated with a low motivation to learn which derives from impaired neural reward processing.

This was the questionnaire the team of this paper used to measure motivation:

The balance between effort and reward was evaluated using the effort-reward imbalance for learning model questionnaire (LERI) (Fukuda et al., 2010).

Here are the results

...........................................CONTROL.........CFS...............P VALUE
LERI Effort score......................4.5 ± 1.0.............4.3 ± 0.9........0.671
Reward score..........................6.4 ± 1.1.............5.5 ± 1.2........0.075
OC score..................................3.5 ± 0.5.............3.5 ± 0.7........0.744
LERI ratio.................................0.96 ± 0.25.........1.09 ± 0.34....0.268

Looking at the P values, you can see that there really isn't any significant difference between the two groups. But they make a big deal of the different Reward Scores. So, they are saying that the healthy and CFS kids both feel that they make the same amount of learning effort but the CFS kids feel that they get less reward.

It's very interesting (appalling) to see how crude that LERI questionnaire is and how inappropriate it is for sick kids.
Here's the questions used for the Reward score:
(from this source - it may not be exactly the same as the Fukuda one which is behind a pay wall - http://successforkidswithhearingloss.com/wp-content/uploads/2011/08/Fatigue-and-Learning-Scale.pdf) ETA - it is different - it has 5 questions rather than the 4 used in this study

1. My family members or teachers let me know how much they appreciate my learning in school
2. My friends let me know (sic) regarding my learning in school
3. I am afraid that I will not be able to catch up with learning in school in the future
4. My school grades depend on my effort in learning
5. I have a promising future because of my effort and grades

A 'yes' is scored 2 points and a 'no' is scored 1 point and the points are totalled. How this is supposed to be an accurate measure of learning reward for a sick child (probably not attending school and uncertain about the future), I do not know.

Look back on the mean scores: 6.4 +-1.1 for the control group vs 5.5 +-1.2 for the CFS group. Frankly, I'm amazed there was only a difference of 0.9 between the means given those questions.

(BTW, that source where I got the questions suggested that the typical mean for boys in grades 7 to 9 is 5.7 and the mean for girls is 5.6. So, assuming the two questionnaires are the same, the CFS group's results are perfectly normal.)

Then they try to tie together this so called abnormal reward from learning with the level of activity in a bit of the brain.

In addition, putamen activity was correlated with reward from learning in CCFS patients.
The putamen is associated with reward-related learning. Putamen activity has been related to prediction error during reward learning (Schultz et al., 1997).

Tiny study, clutching at straws.

 

[trishrhymes]

Thanks everyone who has commented. I now understand better just what a crap and indeed dangerous study this is.

 

[Woolie]

@Hutan, it gets worse. The authors who published the LERI (self report effort-reward scale), used it as an independent measure. That is, they predicted that people who thought they needed to expend a lot of effort to get rewards in their school learning were more likely to have fatigue!

The questions in the LERI were:

1. Learning in school is very hard for me, and I always feel pressed for time
2. When I learn in school or during class, I must often stop my learning because of disturbing by others in class
3. I should be performing well in class or be a well-behaved child
4. I must often do extra learning (such as private tutoring school or private tutor) other than learning in school
5. I must do something that fatigues me
5. Leaning in school increases across the grades
7. Regarding learning in school, I receive appreciation from family members or teachers
8. Regarding learning in school, I receive appreciation from friends
9. Friends help me when I have some problems
10. I have no potential for good my remarks in the future
11.I fear that I will not be able to catch up with learning in school in the future
12. My marks depend on my effort in learning
13. I have a promising future because of my effort and grades
14. I feel pressure from deadlines
15. As soon as I get up, I begin to think about learning in school
16. I feel relaxed at home and forget everything about learning in school
17. My close friends tell me that I am always thinking about learning in school
18. Learning in school is always burned into my brain even when I am going to bed
19. Putting off my learning what I must do before the end of the day, I can not sleep at night

 

[Dolphin]

Free full text:
https://pdfs.semanticscholar.org/3feb/9730ed3038a938d30c76854726a0d59f4ca8.pdf

 

[dreampop]

I think the Japanese researchers, many of whom were involved in the neuroinflammation and metabolic study (watanabe was involved in this one and the metabolic one) have believed in the past CFS is psycho-social illness. Their research is a mix of crap like this and interesting biological stuff too. I wonder what they really think.

 

[Woolie]

Yes, @dreampop, that's the impression I get. They almost say something bold, then they retreat to psychosocial crap. This paper read like someone (a reviewer? co-author?) had asked them to put in something about CBT and GET at the last minute.

I don't think its useful to look at what's going on at the topmost level until we know more about what's going on downstream. Just feeling unwell and exhausted could very well affect our brain activity on all kinds of tasks, and those differences probably have little to say about mechanisms underlying MECFS.

 

[Effi]

I wonder what they really think.

I also wonder what the politics are re: ME in Japan. Does anyone know?

 

[dreampop]

I also wonder what the politics are re: ME in Japan. Does anyone know?

Or their cultural stance. Surprised we have no one from Japan on here.