Wednesday, July 30, 2008

Long live free information flow!

I am writing this post in support of PloS, the Public Library of Science. It publishes online journals with the aim to propagate free flow of information! If you are a researcher, consider publishing there whenever possible.

I am sick with the current state of publication of scientific research in bio/medico-oriented journals. Big publishers like Elsevier making money by charging high prices for journals that are composed of works by scientists who they do not pay for their work BUT THE TAXPAYERS DO, and reviewed by scientists who they do not pay either for their peer reviews. And on top, the authors loose all rights to their work, have to wait months for publication, are not allowed to submit to another journal at the same time, and have to keep their work secret until publication which means that useful research is delayed by up to two years and by consequence other scientists might go down blind alleys or commit the same mistakes. It is absolutely outrageous. And, you have to pay to get access to the research which is in 99% of cases PAID FOR BY THE TAXPAYER!

Compare this to physics, computing, and mathematics. Every researcher publishes his or her preprints (the non-peer reviewed article that is sent to a journal) on the same server and then sent it to a journal. The journals were forced to accept that the work will be online, and they add the peer-review stage to it. Now, you can read all research that any physicist, computer scientist or mathematician has done over the last decade for free on one single server.

Are kids who stutter more sensitive?

At Oxford, Per Alm showed that most research on emotional reactive / sensitivity is far from conclusive. He specifically referred to an article in the Washington Post. In response to a question Per said that the research group around Conture did not really respond to his criticism. You can see a brief episode of this debate here.

I am going to look at this in detail, too, and I'll write a few posts.  I am getting a bit bored with the statistics on the Lidcombe trials, and may be I should move to other fields. ;-) Unfortunately, two rather influential professors are deeply involved in this research... never mind.

Saturday, July 26, 2008

Biased sample fallacy in stuttering research

As I said before, I think of stuttering as a disorder coming in two phases: the dormant phase until onset of stuttering, and the reactive from onset onwards. A question of the causes of stuttering must then we split into two questions: What causes onset of stuttering? What causes recovery or non-recovery of stuttering children? In stuttering (and I would not be surprised in other disorders, too), the majority of children grow out of stuttering. Therefore, if we study the sample of persistent children, it will be a sub-sample and very likely biased, because the whole sample is the children who start stuttering.

Here is an example. Imagine, you interview 10 lottery winners, and they all tell you that they had a dream, wrote down the numbers and won! You are inclined to attribute some cause to the dreams. However, this is a fallacy, because you need to look at the whole sample, the set of all lottery participants who had a dreams and wrote down the numbers. Of course, if you look at this sample, there is no effect at all!

How could this happen in stuttering? Well, I just wrote a post on Kate Watkins' talk in Paris where she tentatively explained a reduced activity in auditory regions with a reduced input from motor regions (likely due to some bad connectivity). So one could conclude that bad connectivity causes stuttering. However, the reduced activity might just be an effect of a biased sample, because the persistent kids could not recover from stuttering due to a lower-than-average connectivity to the auditory regions. To put bluntly, if you better integrate motor and hearing data, you are more likely to develop a good compensatory system to speak (more) fluently! I am not saying that this is the case, but I am saying that it might be the case and that we must be very careful with interpretation. The 2-phase disorder framework is useful here.

Friday, July 25, 2008

Google decides

OK. I let Google decide on neurological and neurophysiological.
    6 050 hits for "neurophysiological stuttering"
125 000 hits for "neurological stuttering"
So neurological is used 20 times more often! So I will keep on using neurological for anything related to either the brain's constituents (anatomical / structural) or its primary functioning and interacting (functional).

In any way, neurophysiological is too long a word to type, and too pompous.

Neurological or neurophysiological?

Back to the debate as to the difference between neurological and neurophysiological. A friend of mine with a PhD in pychology in pain research writes:
neurological = anatomical/structural
neurophysiological = functional
I looked at the web again, and finally found someone actually describing neurological rather than refering to neurology:
neurological: Having to do with the nerves or the nervous system
But I could not find one for neurophysiological, but neurophysiology studies the functioning of the nervous system. But it seems to me that neurology should in principle include the functioning of the nervous system, because it has to do with the nervous system. And I think neurophysiologists argue that neurology is traditionally concerned with "truely anatomical and structural" deficits with clear symptomatology and not with more subtle dysfunctioning of parts of the nervous system like dyslexia for example. But I think neurologists would say that they would deal with all brain-based disorders.
Interestingly when the Society of Neuroscience talks about stuttering (here), they do not use the words "neurological" or "neurophysiological" but the word "biological" and "anatomical". However, the article is for laypeople.

Wednesday, July 23, 2008

Merci à Oliver

Oliver translates many posts from my blog into French. Let me thank him here for his efforts! You can read his blog: here.

Merci à toi, Oliver, pour tes traductions! Et bon courage pour ta grande nation au Tour de France et pour que vos cyclistes soient si vite que les coureurs du petit Luxembourg: les frères Schleck et Kim Kirchen! :-)

Better dead than half-alive!

Some argue that recovered kids actually have a bigger deficit than persistent kids, because a bigger deficit means that the right side analogue needs to completely take over! And there is also some brain imaging results that point in this direction.
I have an analogy. Think about a kingdom where the king has been wounded in battle but he hasn't died. So he is still alive but unable to perform to his best. It would have been much better if he had died and his sucessor taken over. The same often happens in politics when two key figures wrestle for power. If neither of the two is fatally wounded politically speaking, one will hold the top post but the other will keep on interfering. Such a constellation creates a constant battle for power behind the scenes and is very counter-productive. Maybe that's what is happening in us stutterers, our left side deficit is not bad enough, and interfers with attempts of the right to compensate. So maybe we need to DESTROY the left side region to become fluent. This would fit into some evidence of a few cases that became fluent after a stroke!
This stuttering brain is getting more and more complicated. I should have sticked to quantum physics, the big bang, 10 dimensional space time, and general relativity! ;-)

Kate Watkins at Paris Workshop

With some delay, I am finishing off my comments to the Paris Workshop. If you are interested in the abstracts, you can find them on this very stylish French blog but translated into French: here. I didn't publish the abstracts by request from the organisers.

Kate Watkins is a lecturer at the University of Oxford, and a very dilligent experimentalist in brain imaging of the stuttering brain. Her recent work involved scanning young people who stutter and scanning stutterers while exposed to Altered Auditory Feedback (AAF).

She started out with a review of a few theories (basal ganglia, efference copy, incomplete cerebral dominance), and referred to the meta-analysis by Brown et al. (2005). She focused on the reduced white matter integrity found by Sommer et al, Chang et al, and Watkins et al, which indicates that the region is not well connected to other regions, especially between motor and auditory cortices. Interestingly, she superimposed the locations found by the three groups, and showed that they are quite close to each other; the Chang et al's location being being the other two. She also said that we need to look for bilateral abnormalities to find causal effects. Some were skeptical. She did not elaborate in depth so it is hard for me to judge. Maybe if one side is abnormal, the other side takes over and this shows in an abnormality, too. I think she mentioned animal experiments where one side was injured and the other side compensated.

Then she talked about her current work on scanning stutterers and controls while using AAF. They found the auditory cortex less active than in controls. She offered the interpretation of reduced input from the motor regions as the cause. And again they found white matter abnormality. I didn't follow it all in detail. But I think the essence was that under AAF there was less decoupling of the motor and auditory regions in stutterers, namely activity in motor region was more correlated to activation in auditory region. Moreover, I think she speculated that a big deficit might give a better compensation than a small difference. I am looking forward to reading the published research.

Tuesday, July 22, 2008

Quality of life for stutterers

I have an idea on how to measure the impact that stuttering has on a stutterer's life. We could look at what age they die, and then compare the distribution with that of the same population. Age is probably the best indicator of quality of life overall. My guess is that there is little difference between people who stutter and fluent speakers, but it would be worth the effort to find out.

Of course, we male stutterers already know that we will unfortunately die 5 years earlier than our fellow female stutterers who according to urban myth are suffering significantly more discrimination than men and therefore by twisted feminist thinking are not actually enjoying better quality of life overall but are forced by (male) society to live much longer so that they can be discriminated much longer! ;-) However, age as the best indicator of life quality to show discrimination by race (e.g. African Americans die earlier) is of course again valid, just don't do it for sex!

Monday, July 21, 2008

Neurological or neurophysiological?

At the Oxford conference, I asked a question to Mark Onslow during the panel session. I asked how a behavioural treatment like Lidcombe could possibly be highly effective if as he agrees stuttering is driven by an underlying neurological problem.

Instead of answering the question well, he replied by saying that I did not understand terminology and that I probably mean "neurophysiological", and that there is a big difference.

Well, is there really a difference? I asked three people after the session, and no-one understood quite why one would be better than the other.

I looked up the words "neurological" and "neurophysiological".  In typical dictionary manner, I got the following very enlightening definitions: "of or relating to or used in or practicing neurology", and "of or concerned with neurophysiology"!! :-) OK, so I had to look up "neurology" and "neurophysiology".

Let's start with neurology: The medical science that deals with the nervous system and disorders affecting it.

And for neurophysiology, I got The branch of physiology that deals with the functions of the nervous system.

I cannot see any big difference. Both terms seems fine.

Relapsed kids are as severe as before

Here is an interesting observation from the follow-on paper of the Lidcombe trial. They note that those three children that had dysfluent speech recordings stuttered with a similar severity than before the treatment. First, is this observation just a statistical fluctuation or a real event? Second, can we observe the same effect in adult who relapsed after treatment? And thirdly, does it tell us something about the nature of stuttering?
I think it is a true effect for both children and adults: the relapsed have a tendency to go back to the same level of severity than before treatment. But I do not know of research that looked at this aspect. I did not consider this aspect when analyzing the outcome data of the Kassel Stuttering Therapy (KST). But I plan to re-visit the data.
Assuming it's true, can we learn a bit more about stuttering? My theory-biased interpretation is as follows: Stuttering at its core is a neurological dysfunction modulated by the response of the brain to this dysfunction. A stuttering treatment is most of all a behavioural therapy: you change some behaviours and you become fast more fluent. So going back to your old behaviours, you go back to your own severity. I cannot imagine that, especially in adults, treatment improves the underlying dysfunction and then they relapse due to a worsening of the dysfunction to before treatment. With children, new behaviours might be more easily ingrained in the brain or underlying weaknesses rectified or well compensated. But there is not a clear case for either interpretations.

Friday, July 18, 2008

Results are even worse than in abstract

I have now the full article on the follow-up of the Lidcombe trial. The abstract claims that 16% relapsed, but that's on recorded speech sample. But if you look at the parents' feedback:
... parent questionnaires indicated that eight (40%) children had stuttered at some time during the previous month and twelve (60%) children had not.
So actually 40% of the so-called recovered kids showed some stuttered speech recently according to their parents! How can this be reconciled with the magic treatment claim that Lidcombe makes all kids fluent voiced by some? It is not hard to imagine that some of these kids who had a fluent recording are actually dysfluent at others times and will unfortunately start stuttering again more severely or become covert stutterers.

And this does not even include the discussion of the natural recovery rate. Due to the small sample of 20 kids, the statistical fluctuation is huge and all results have a huge statistical error on them.

And calling the trial a random control trial is a bit dubious considering that
The majority of controls could not be contacted, possibly because many had not had regular contact with the clinic and so could not be traced.
And I haven't even read the article closely...

Thursday, July 17, 2008

Follow-up study to Lidcombe outcome study

The follow-up study of the Lidcombe random control trial is out. I do not have the full article and can only read the abstract. But the results are less than sensational: three out of 19 kids have relapsed leading to a recovery rate of 84% which is statistically close to natural recovery. What happened to the claim that Lidcombe makes all kids fluent?? And their design has failed as well as they write:
Meaningful comparison with the control group was not possible because an insufficient number of control children.
So where is the control group check then?? They are not even able to compare to a control group to see whether natural recovery is as effective. How can they claim to have done a random control trial???
I need to read the full article for more precise comments.

Extended follow-up of a randomized controlled trial of the Lidcombe Program of Early Stuttering Intervention.

Queensland Clinical Trials Centre, University of Queensland, Brisbane, QLD, Australia.
In the Lidcombe Program of Early Stuttering Intervention, parents present verbal contingencies for stutter-free and stuttered speech in everyday situations. A previous randomized controlled trial of the programme with preschool-age children from 2005, conducted in two public speech clinics in New Zealand, showed that the odds of attaining clinically minimal levels of stuttering 9 months after randomization were more than seven times greater for the treatment group than for the control group.
To follow up the children in the trial to determine extended long-term outcomes of the programme. Methods & Procedures: An experienced speech-language therapist who was not involved in the original trial talked with the children on the telephone, audio recording the conversations using a telephone recording jack. Parental reports were gathered in addition to the children's speech samples in order to obtain a balance of objective data and reports from a wide range of situations.
Outcomes & Results:
At the time of this follow-up, the children were aged 7-12 years, with a mean of 5 years post-randomization in the 2005 trial. Twenty of the 29 children in the treatment arm and eight of the 25 children in the control (no treatment) arm were able to be contacted. Of the children in the treatment group, one (5%) failed to complete treatment and 19 had completed treatment successfully and had zero or near-zero frequency of stuttering. Three of the children (16%) who had completed treatment successfully had relapsed after 2 or more years of speech that was below 1% syllables stuttered. Meaningful comparison with the control group was not possible because an insufficient number of control children were located and some of them received treatment after completing the trial.
Conclusions & Implications:
The majority of preschool children are able to complete the Lidcombe Program successfully and remain below 1% syllables stuttered for a number of years. However, a minority of children do relapse and will require their parents to reinstate the treatment procedures.
PMID: 18608610 [PubMed - as supplied by publisher]

Tuesday, July 15, 2008

If two experiments disagree...

Whenever there are two experiments and one of them gets an agreement and the other one gets disagreement [with theory], I think that it is much more likely that the experiment showing a disagreement is incorrect because it is much easier to introduce an error (any error) that destroys the agreement than to keep all things pure and accurate so that the agreement is preserved. In other words, it is unlikely to get an accurate agreement by chance.

Friday, July 11, 2008

A new blog on stuttering

Check out the interesting blog with a not-very-original title Stuttering: here. The author, Silvano Colombano, describes the theme of his blog as followed:
I am attempting to recapture a long dialogue about stuttering that I pursued on the STUTT-L list from 1994 to 1998. This dialogue was based on personal experience of my own stuttering problem and on a great deal of thinking motivated by my scientific training as a biophysicist.

I will do the editing of the list dialogue over a period of time, at the end of which I may decide to re-join the list and see what kind of progress has been made in our understanding of this affliction. I do know that no "magic bullet" has been found.
I have read a few posts, and Silvano has a good understanding of science and puts his arguments well though maybe too diplomatically thereby leaving those with muddled thinking the space to keep their opinions!

Wednesday, July 09, 2008

Surrounded by Germans at Oxford

Here is a picture of TheStutteringBrain and the Germans at Oxford. (Thx to Nicole)

From right to left: Martin Sommer (neurologist / university lecturer & researcher at Goettingen), myself, Nicole Spindler (Martin's PhD student), Beate Schwittay (German Association), Norbert Liekfeldt (British Stammering Association), and Veronika Gutmann (Martin's PhD student).

I also want to clarify that I am not German, but from Luxembourg which is a beautiful and independent country neighbouring Germany (a fact unknownst to many US Americans). :-)

Tuesday, July 08, 2008

Highlights from Oxford

I am currently in London on my way back to Luxembourg. Let me post the highlights from the conferences as I see them. I will talk details in future posts. If you have pictures of the conference, please send them to me!

1) Per Alm gave a scathing review talk on the emerging field of study that claim that certain temperamental traits are important causal components of stuttering. Specifically, he raises serious concerns about a study by the Conture group, and, on top, he said that the results of their likely-to-be flawed study have been misinterpreted and exaggerated by the Washington Post which have also found its way to the BSA (British Stammering Association) website. To summarise, the supposed evidence is evidence of bad methodology.

2) Dave Franklin from the Pagoclone group (and colleague of Stuttering Drug Tsar Jerry Maguire at Irvine) presented a poster with the results of the open label period of the Phase II Pagoclone. They claim that Pagoclone shows positive results in a subgroup and has less side effects. He handed out copies of the posters to everyone, and I am trying to get the permission to post the scanned handout here.

3) There is a widespread agreement that stuttering is a neurologically based disorder. Ann Smith pointedly asked in the final panel session whether it is not time to change from "the causes of stuttering are unknown" to "stuttering is a neurologically based disorder whose details are unknown". We all agreed.

4) Many speakers talked about very high rates of success of stutteringin early intervention, but barely mentioned the natural recovery rate. Many strongly believe that early intervention is effective above natural recovery. I can see improvements being possible but I am just not convinced that the vast majority recover fully.

5) Mark Onslow talked about a large scale longitudinal study of 1000 children starting before onset of stuttering. This should be a very interesting study, unless they mess it up statistically as they did with the BMJ study.

6) No new imaging, genetics, or theoretical developments.

7) Two talks were enlightening as they explained well concepts that I find lacking in stuttering research and therapy but are important to see the big pictures. Paul Dolan gave a good conceptually introduction to health economics, but I did not talk about specifics. Kuhn and Packman talked about complexity theory, and the complex brain with its self-regulating loops. But are these concepts applicable to help real understanding? I doubt it, and if not not by the speakers.

Tuesday, July 01, 2008

Some pics from Antwerp

Talking to Nan Rantner (co-author of the Handbook of Stuttering)

Talking to Dave Rowley (organiser of the Oxford Dysfluency Conference)

Talking to Ed Conture (well-known professor and researcher)

Talks from the Antwerp conference are on-line

The key talks of the Antwerp conference are now on-line here