Not much happening

Not much has been happening over the last months that increased our understanding of the stuttering brain. As I mentioned before, scientists are hitting the complexity barrier with the new research avenues, namely brain imaging and genetics. The easy part has been done. It is one thing to put someone in a scanner and report functional or structural differences, but it is another to devise a experimental setup that can falsify or confirm a theory on stuttering. The same is true for genetics: we now know that genes are involved in stuttering in many cases, and we even have located the chromosomes in some cases. Even if we then know the genes, we again hit the complexity wall; it's like we know the killer but not who he (or she! :-) killed and why. In fact, very few scientists (and I am talking about the professional ones and not clinicians-turned-researchers) are well equipped to handle this situation. Many are trained to work well within the experimental paradigm (i.e. how to find the genes or how to scan and interpret the findings), but stuttering is a muddy territory where you need to fine-tune your methods appropriately to the idiosyncrasies of stuttering.

Lidcombe treatment of choice? ROUND II

And again on Lidcombe trials at Kuster's ISAD site on the question/answer page of Susan Block's article. Ann Packman, co-author of the Lidcombe trials, writes:

 Hi Sue, nice article. I would like to clear up some misconceptions that have been posted about the Lidcombe Program randomised control trial. The trial was reported by Jones et al. (2005) in the British Medical Journal. There was a significant treatment effect after 9 months, compared to the no-treatment control group. The study was conducted according to CONSORT guidelines (see http://www.consort-statement.org/ which specify the appropriate methods and analyses for reporting trials in medical journals. They have been in existence for over 15 years. The study is replicable, as is the Lidcombe Program. As for the 5-year follow up study (Jones et al. 2008) of the children in this trial, it is indeed the case that three of the children were found to be stuttering again, after at least two years of fluency. This tells us that: (1) For these children the initial improvement in stuttering was apparently due to the treatment, not natural recovery (2) These children were at least spared the social penalties of stuttering for some of the early school years (3) At time of discharge from treatment, SLPs need to advise parents to be vigilant in the long term and to contact a SLP and/or re-instate treatment at the first signs of the re-appearance of stuttering (4) Further research is needed to develop better ways of maintaining Lidcombe treatment effects. Without this long-term follow up study, we would not have this important new knowledge about the nature of stuttering and about the need to work to further improve Lidcombe outcomes. Ann

 Susan Block replies:

Hello Ann, thank you for this response. Your comments show exactly how attention to scientific principles facilitate the evidence base for our profession - but also how they can frustrate some people!

Does she actually refer to me or others who are trained scientists??? Anyway, I reply:

Most people are NOT frustrated by attention to scientific principles. I am frustrated about the poor application of scientific principles to therapy outcome research like conflict of interest (proving your own treatment), passive understanding and robot-like application of statistics, leaving out subtelties, and repeating of statements and deference to authority instead of engaging in counterarguments when challenged on the strength of evidence. I will show that EVERY single of Ann's sentences (to "clear up misconceptions" according to her words) are inaccuracte. (1) "the Lidcombe Program randomised control trial". Let's be clear which kind of RCT it is. It is not a double blind RCT, the highest standard, that allows to check whether it is the treatment itself that is sucessful. It is an open-label trial with the big disadvantage that even if the treatment arm shows a higher sucess rate you cannot say whether it was the placebo effect (the fact that the kids/parents had treatment), generic feature of ALL early intervention treatments (like parent-child interaction, easing parents' stress, adaptation to the treatment setting), or actually Lidcombe-specific feature. So you are NOT actually testing Lidcombe specifically but the whole package (placebo, generic and specific)! Moreover, the randomization was broken after 9 months and was not present in the long-term data. And let's note that 9 months is from the start of the treatment and NOT from the end of the treatment. Finally, the sample size was too low for randomization to equalise the two groups: as I discuss in my rapid response to Jones 2005 in BMJ. These arguments were confirmed and mentioned by Roger Ingham's group as he told me when I met him. So calling it a Lidcombe RCT looks very scientific but is a misnomen really! (2) "The trial was reported by Jones et al. (2005) in the British Medical Journal." It is irrelevant whether it appears in BMJ or anywhere else. It does not add to the debate, and only fallaciously implies "BMJ is a really good journal so the trial must be really sound". Moreover, you are not mentioning that I wrote a rapid response in BMJ criticising the statistics or if you think I as a PhD physics have no clue you could at least mention other critical feedback. (3) "There was a significant treatment effect after 9 months, compared to the no-treatment control group." As I said the stats are wrong. And again, 9 months after the start of the treatment, but not 9 months after the end of the treatment. I just re-read the article and you are writing that the kids are still in treatment! The relevant time period is starting at the end of treatment. ANY behavioural therapy will produce gains: diets, drug, giving up smoking. The important part is the relapse. (4) "The study was conducted according to CONSORT guidelines (see http://www.consort-statement.org/ which specify the appropriate methods and analyses for reporting trials in medical journals." First, these guidelines are for standard situations, but early intervention is very different because you have the natural recovery that distorts statistics and therefore you need many more kids to create truely balanced groups via randomization. You stopped at 47 kids rather then the 100 which would have improved the statistics dramatically. In fact, you had your design at 100. Why? Second, even if the guidelines are correct, it does not imply that the implementation of the guidelines was done correctly! Kids dropped out, you gave up the control group, you changed the sample size. (5) "They have been in existence for over 15 years." That is so symptomatic of bad thinking i.e. deference to some authority. I do not care how many years something is in existence. I only care about the strength of arguments. To show you how strange this is. I could argue: Well if it is 15 years old, it is too out-dated and should not be trusted! You might convince non-scientists but you cannot conduct a debate with such pseudo arguments. (6) "As for the 5-year follow up study (Jones et al. 2008) of the children in this trial, it is indeed the case that three of the children were found to be stuttering again, after at least two years of fluency.". Again this sounds very respectable, but I have actually read the article (unlike most therapists). It is a desaster. The MAJORITY of the kids could not be contacted anymore. Why? Or did someone not contact them because they stuttered? Moreover, 3 kids relapsed is 86% recovery rate, and considering the small sample you cannot even be sure you beat the natural recovery. OK you argue that the natural recovery is much lower, but please show it to me in the control group or achieve 90% in a sample of 100 kids! "Without this long-term follow up study, we would not have this important new knowledge about the nature of stuttering and about the need to work to further improve Lidcombe outcomes. " Again, this sounds really great but your study was so poorly implemented how can we trust your results. From 134 kids referred to treatment and 47 completing it, you are left with 28 kids! So where is this important new knowledge? How can you have new knowledge on such a poor sample? The need to further improve Lidcombe? Sounds like from a spinning doctor. THE TRIAL IS NOT SET UP TO PROVE LIDCOMBE IS EFFECTIVE, so how can you say you will improve it? (7) "This tells us that:" "1. For these children the initial improvement in stuttering was apparently due to the treatment, not natural recovery (2)" NO AGAIN THE TRIAL DOES NOT EXCLUDE PLACEBO OR NON-LIDCOMBE EFFECTS. Moreover, you could even argue that those you would have recovered anyway just recovered faster in the 9 months because they have the inherent ability anyway. And we know from adult therapy, that nearly everything works for some time. Not speak about getting used to clinic environment. To summarise, I am just fed up with sloppy pseudo-scientific replies that 99% of the clinicians and stuttering community swallow happily because no-one actually sits down and looks at the trial carefully. Or she or he would find that it is a can of worms. But let me conclude by saying that at least you try to do evidence-based research. So the fact that I can criticise your research is progress in itself for I cannot criticise other approaches because they do not do any outcome research.

Hollins program

StutterTalk.com did an interview with Webster from the Hollins institute. A very large private clinic for the treatment of stuttering and they have the domain name stuttering.org! I have never looked at them very closely. I will listen to the interview and report back. Make up your own mind here.

Self-report on Abilify

A reader has sent me his self-report on the first four weeks on Abilify. I hear Abilify mentioned often. For example, Ludo Max told me that they had some very positive experience with Abilify, but they never got the money for more research, I believe. Again, we need to be careful to its real efficacy. Here is the 4-week report:

It has been 4 weeks now since I started taking Abilify and so far so good.I am 28 years old and have stuttered all my life. This is the first time I am taking medication for my stutter. I started initially on 2 mg and increased to 5 mg after 2 weeks.All secondaries like eye blinking and face contortions have gone and I feel myself a lot more in control of my speech. For the first time in my life, I have started to make eye contacts while talking.I have gone from a severe stutterer just a one month back to a mild one now.
I have started to talk a lot more at work and with my friends and family. I am not expereincing that much rush of blood and anxiety before talking.
Abilify is not a cure and I still have blocks and I still stutter. But the blocks frequency and duration have reduced substantially and I seem to apply easy onset techniques to get out of blocks more easily and frequently now than before.
I haven't had any adverse side effects so far. I haven't gained any weight, though I have been also watching my diet and working out and also I haven't experienced dizziness or restlessness. I hope that the positive effects of Abilify on my speech don't wear off after some time.

The tell-signs of flawed research

Back to John Ioannidis's work (see my post) and his tell-signs of flawed research. Let's see how much is true in stuttering research.

Corollary 1: The smaller the studies conducted in a scientific field, the less likely the research findings are to be true.

Absolutely, most samples are less than 30. He recommends 1000s!

Corollary 2: The smaller the effect sizes in a scientific field, the less likely the research findings are to be true.

Most research does not include the effect size, but only look at statistically significant differences. If they did, they would find small effect sizes.

Corollary 3: The greater the number and the lesser the selection of tested relationships in a scientific field, the less likely the research findings are to be true.

Yes, most studies look at many different variables making it more likely that some correlate by chance.

Corollary 4: The greater the flexibility in designs, definitions, outcomes, and analytical modes in a scientific field, the less likely the research findings are to be true.

Stuttering is very difficult to quantify unlike weight for example. It is a moving target, because people who stutter can fluctuate dramatically. Compare this to a weight measurement where the difference in weight between morning and evening is probably just a kg or so.

Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true.

There are great financial incentives for stuttering medication: a potential market worth 100s of million dollars. There are financial incentives in AAF (altered auditory feedback) devices, for example SpeakEasy devices. They are pushing very hard on spinning the evidence. Just have a look at their website. Regarding conventional treatments including Lidcombe, there is some money to be made but the sums involved are peanuts in comparison. It is more a matter of justifying their existence as researchers and clinicians (giving their life a meaning and purpose) than about pure financial gains.

There are certainly prejudices. This is especially true for the clinicians who test their own treatment, or you try to validate their long-held beliefs. Compare this to a geneticist who studies the genetics of stuttering (he has no prejudice on what he wants to confirm). He has no hypothesis.

Corollary 6: The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true.

The two hot areas I see are: Lidcombe treatment and emotionality/sensitivity studies... This is very different to the hot area of brain imaging or genetics where it is hot to do research but no-one knows what should be found!

If you want to do a post-doc in stuttering

Ludo Max is looking for a post-doc: check here:

The Laboratory for Speech Physiology and Motor Control in the Department of Communication Sciences at the University of Connecticut (Project P.I.: Ludo Max, Ph.D.) is seeking applications for a postdoctoral position to study various aspects of the neural systems underlying sensorimotor control of speech movements in individuals who stutter. This NIH-funded project involves both psychophysical and neuroimaging (fMRI) experiments, and the selected candidate will have opportunities to contribute to both lines of work. Facilities in the lab include, among other things, electromagnetic motion tracking for speech articulatory movements as well as for upper limb movements, real-time digital signal processors for auditory perturbations of speech and a Phantom 1.0 robot for mechanical perturbations of the jaw, tendon/muscle vibration, EEG/EP systems, and a virtual display environment for arm motor learning studies.

Candidates with a Ph.D. degree in cognitive/behavioral neuroscience, motor control, biomedical engineering, speech and hearing science, experimental psychology, and related fields are encouraged to apply. Good programming skills (Matlab and C++) are preferred. Candidates should be highly motivated and have an interest in publishing research in the area of speech motor control and stuttering.

I am sceptical he will find someone who can code well in Matlab and C, and at the same time knows something about stuttering. On the other hand, if the post-doc does not know anything about stuttering, he or she will be less biased and Ludo has the expertise anyway.

Another flawed Lidcombe study

And yet another flawed study on Lidcombe. This is especially disappointing because the group is independent of the Australian group around Mark Onslow. The co-author is Barry Guitar, university professor and the author of a well-known (and in general well written) text book on stuttering called
Stuttering: An Integrated Approach to Its Nature and Treatment . However, his research and his presentations on temperament and stuttering are suspicious to me. He might be a good clinician but a not very good science mind unfortunately. I would guess the first author is an enthusiastic and bright graduate student who has effectively wasted her or his time with research that has little relevance.

 Am J Speech Lang Pathol. 2008 Oct 9.

Long-Term Outcome of the Lidcombe Program for Early Stuttering Intervention.

Miller B, Guitar B.

University of Vermont.

PURPOSE: To report long-term outcomes of the first 15 preschool children treated with the Lidcombe Program by speech-language pathologists (SLPs) who were inexperienced with the program and independent of the program developers. Research questions were: Would the treatment have a similar outcome with inexperienced SLPs compared to outcomes when implemented by the developers? Is treatment duration associated with pre-treatment measures? Is long-term treatment outcome affected by variables associated with natural recovery? METHOD: Fifteen preschool children who completed the Lidcombe Program were assessed prior to treatment and at least 12 months following treatment. Pre-treatment data were obtained from archived files; follow-up data were obtained from interviews and recordings completed after the study had been planned. RESULTS: Measures of stuttering indicated significant changes from pre-treatment to follow-up in percent syllables stuttered (%SS) and Stuttering Severity Instrument-3 (SSI-3) scores. Pre-treatment severity was significantly correlated with treatment time. Handedness was the only client characteristic that appeared to be related long-term treatment outcome. CONCLUSIONS: The treatment produced significant long-term changes in children's speech, even when administered by SLPs newly-trained in the Lidcombe Program. Treatment results appear to be influenced by pre-treatment stuttering severity.

Without having read the article itself, I can see several flaws:

1) A sample size of 15 is much too small. Either you do at least 100 or you do not do it at all! The number is especially high because of the natural recovery rate increasing statistical fluctuations.

2) They have not controlled for natural recovery rate. It makes the results appear much more positive that they really are, because some will recover within one year naturally anyway and the stuttering severity will automatically go down. Here is a simple example. I have 20 kids. Let's assume 10 would have recovered within one year without treatment. Before, they all stutter at 5%. After one year without treatment, only 10 stutter, and the average stuttering rate is 2.5% (10 kids at 0 and 10 kids at 5%).

3) They try to find correlations in data with a very small sample size. Their finding on handedness is most likely a fluke.

But interestingly, the abstract seems to suggest that some kids are still dysfluent (I would have to read the article which costs money to access). The existence of dysfluent kids is not affected by statistics. So we can say that Lidcombe is not the cure it was claimed. In fact, I heard from many other therapists that some kids do not become fluent.

Why Most Published Research Findings Are False

John Ioannidis is saying exactly in this article what I have always believed that most published medical research is wrong. Stuttering is no except to the rule.

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

He should write a second article on what happens when others are pointing out issues in research. I tell you what happens when I point out issues: nothing, absolutely nothing. It is still being spread, and the only antitode is to shout as loud as possible: it's false. And of course I need to face up that people start to think of me as an eccentric outside who are no clue, really.

Correction on Indevus share price jump

I just realised that my post is probably not telling the whole story about Indevus' share price jump, because on the same day, they released information on another compound which this article by Anuradha Ramanathan claims has provoked the jump:

Shares of Indevus Pharmaceuticals more than doubled after the company reached a deal with U.S. health regulators to use its existing data for an early re-application seeking marketing approval for its testosterone replacement drug.

The agreement with the U.S. Food and Drug Administration removes the need for more studies and Indevus now plans to apply again for marketing approval in the first quarter of 2009, and launch the drug in the fourth quarter, the company said in a statement.

Half brain

I just saw a documentary on people who only have one half of their cortex (the high-level brain). When they spoke in front of the camera, they seem to have markable disfluencies. They did not stutter but they looked a bit like "recovered" stutterer who control themselves not to stutter but you perceive their mini-block: instead of getting out of control, they just move to the next word after a slight hesitation. Not sure whether it has a connection to stuttering.

Indevus shares jump by 50%

The shares of Indevus, the licence owner of Pagoclone, jumped by 50% in light of the announcement of a new partner Teva and the Phase IIb trial. The graph is from Yahoo!Finance.  It is a good example that you need to know both timing and impact of information to make money. I knew that the stock would jump upon such an announcement, but it did not know the timing or whether it would happen. Actually, I am an idiot. Come to think about it, I kind of knew, because in June I was told by reliable sources that there was a meeting for a new trial and that they would go ahead. I should have bought the stock and made a killing. Oh well...

Think about it, 50% higher means that the company is worth double from one day to the other. Why? Because investors believe that the future cashflows of the company are twice as high (neglecting discounting)! And it is twice as high, because 2-3 people at Teva think it is a risk worth taking. How much do they know about stuttering? Probably, very little. And I am sure they are not aware of many methodological pitfalls. But, the market trusts their judgement for the moment and so the value of Indevus goes up by 50%. I think the chances of clear success are moderate, but I also have not see the individual responsiveness of each patient.

Now everyone at Indevus who gets paid in shares for bonuses is worth twice the amount! Everyone will do everything to get Pagoclone approved. It could make or break for them as millionaires! Just imagine the other pharmaceutical companies looking at Indevus. Surely they will brainstorm on how to jump the band waggon. If any of you are such a company, you can hire me as a consultant! ;-)
 
Here is an Associated Press article, and here an extract:

Shares of Indevus Pharmaceuticals Inc. more than doubled Friday after the company said it is collaborating with Teva Pharmaceutical Industries Ltd. to develop a treatment for stuttering and could move forward with its delayed horomonal disorder drug.

Indevus' stock surged $1.78, more than doubling to close at $3.51. The Lexington, Mass.-based company's stock has traded between $1.19 and $8.22 over the past 52 weeks. Shares of Israel-based Teva, which makes both generic and branded drugs, rose 31 cents to $46.03.

100'000 visitors!!!!!!!!!!

I completely missed the 100'000 visitor celebration! Also the average number of visitors per day is 230! I have roughly 1000 unique visitors per week from all around the world; most are from the US.

Lidcombe treatment of choice?

Susan Block replied to my comments on her statement that "Lidcombe should be the treatment of choice" (see her ISAD article here):

I think we have discussed some of your comments before. It is the case, in my opinion that it has the best evidence to date for preschool children. The Franken et al study was almost impossible to replicate as their comparative treatment was not well defined. I think it is the case in the Jones et al study that the children in the Lidcombe treatment group made so much positive change that they could not justify maintaining children in a control group.

And I replied:

It is reasonable for you to say "in my opinion that it has the best evidence to date for preschool children". However. First, you actually wrote "should be the treatment of choice" implying a moral imperative i.e. it would be irresponsible for therapists not to use Lidcombe? Is it? Second, I repeat again that the trial described in Jones et al 2005 has a follow-up study Jones et al 2007 which you do not cite but in my opinion should. As I am sure you teach to your students, a treatment should be evaluated based on long-term outcome data and not short-term sucess. And the Jones et al 2007 paints a much more sober picture (apart from methodological issues). Have you read it? Regarding your comment "The Franken et al study was almost impossible to replicate as their comparitatve tretment was not well defined.", it is not relevant whether the trial is replicable or not for it to be true or not. In fact assuming the comparative treatment was completely ill-defined and chaotic, it managed to do as well as Lidcombe. This actually supports the alternative view that any treatment will be succesful. In any case, a new trial with a larger sample and extra care of defining the comparative treatment is under way. Regarding replicability, the same is true for the Lidcombe trial, because as you yourself say "it is the case in the Jones et al study that the children in the Lidcombe treatment group made so much positive change that they could not justify maintaining children in a control group.". We can never repeat it again with a control group! Would you therefore argue that it is not valid?

ISAD 2008

 

Check out Judith Kuster's online conference. With many good quality and no quality discussions on stuttering, research and treatment.

I have already posted a comment to Susan Block's article What clinicians should know to avoid the spreading of that myth Lidcombe should be used:

You are writing that "Current research indicates that the Lidcombe Program should be the treatment of choice for young children who stutter (Jones et al, 2005; Lincoln & Onslow, 1997)." This is misleading 1) It implies that Lidcombe is better than other early interventions. However, Lidcombe has never been tested against other forms of early intervention in a random control trial. It could well be that ANY intervention has a similar (or no) effect. There was only one pilot trial by Francken in the Netherlands and there was no difference with demands and capacity. She is currently conducting a large scale study between Lidcombe and DC. 2) You only cite the Jones 2005 article, but there is a follow-up paper from this year with long-term outcome. Three children have relapsed and many kids were not contactable any more. The sample is close to the natural recovery rate, not to speak 3. The study of Jones 2005 is questionable and has statistical and methodological flaws: wrong statistics, no long-term control group, and more. I think clinicians should know these facts. Evidence based practise is important but should be based on WELL ESTABLISHED evidence.

A revolution is happening.

A revolution is happening. It is the first time in the history of stuttering research that millions are being spent to test and develop a treatment for stuttering. Don't be mistaken. The stakes are dramatically increased. And do not expect some pseudo-science happening with waffling professors from the fiefdoms with no reality checks. The industry does not invest millions lightly, they know that they face reality checks, reality will hit them and they will do anything to get this working. And expect anything to include massive spinning of results in case the positive effects are there but very modest. And expect other pharmaceutical companies to at the very least do intensive brain storming to prevent them from getting a monopoly on a potential new market. We are entering the big bucks area of stuttering treatment.

I hope for the best (an effective treatment to reduce stuttering), but expect the worst (moderate efficacy in some with massive efforts of the companies to still make money but as a side effect a better understanding of stuttering).

Disclaimer to US readers: TheStutteringBrain blog specifically denies any responsibility for the wardrobe malfunction of the revolutionary Marie in the heat of the battle!

The pharmaceuticals are not sure themselves

And now the cold spin. Finally, Indevus managed to get an investor Teva in who will foot the bill for further clinical trials and thereby bets on Pagoclone being effective. Why did it take so long?

Indevus previously announced promising data from its 8-week, placebo controlled, double-blind, multi-center Phase II trial in patients with persistent stuttering which showed that pagoclone produced a statistically significant benefit in multiple primary and secondary stuttering endpoints compared to placebo. 

The text is a bit misleading in my view as it looks as if it is a significant effect. Don't confuse statistically significant with significant! Statistically significant means that with a high probability there is a difference in effect between the group that took Pagoclone and those who received a placebo. However, it does not say anything about how large this effect is! In fact, as I mentioned before. The reduction of stuttering in comparison to placebo was only about 10% in week 8. On the other hand, you can argue that you don't care about this fact, and only look at the absolute effect because it is the relevant measure for a person who stutters. However, it does show that the compound itself does not seem to be very effective at all! The open label phase (where everyone could choose to take the compound) was more successful. It is also possible that only a subgroup responds positively to Pagoclone and the other not at all, so the mean effect is not a good measure and does not show the large improvement on a sub group! Finally, it has not been published in a journal yet, as far as I know.

Under the terms of the Agreement, which is subject to applicable regulatory clearances and customary conditions, Indevus will conduct and Teva will reimburse Indevus for its expenses for a Phase IIb study. The placebo-controlled study will involve approximately 300 patients with stuttering in the U.S. treated for a period of six months and is expected to commence enrollment by Q1 2009.

I am also not exactly clear on what a Phase IIb study is. Wikipedia says: "Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. Phase II studies are sometimes divided into Phase IIA and Phase IIB. Phase IIA is specifically designed to assess dosing requirements (how much drug should be given), whereas Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose(s))." I have the suspicion that in this case Phase IIb simply means "let's do it again to be sure before doing Phase III but let's do it a bit larger, longer and fine-tune", see above.

The main difference to the last Phase II trial is probably three-fold. First, 300 instead of 132 people will participate so the statistical error will be lower. Second, they will fine-tune their methodology from the last trial. Third, they observe them for 6 months. The open label was more successful, and they probably want to collect placebo-controlled data to confirm their suspicion that the full effect comes out over several months.

But the real reason might well be, because Tera and Indevus are not 100% convinced about the efficacy of Pagoclone. Stuttering is a very tricky disorder, and they might even have read my blog! ;-) So they probably want to play it safe, and re-do the last trial but with a bigger sample size and fine-tuned methodology. And the calculation is simple: if you do a real Phase III with 1000s of people, the costs are a multiple of the 300, and probably too high a risk. Wikipedia writes on Phase III: "Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions." I may add that medication can get approved after a successful Phase IIb and Phase III runs while the medication is already on the market.

We are excited that we have partnered pagoclone with a leading pharmaceutical company with a focus on central nervous system conditions,"said Glenn L. Cooper, M.D., chief executive officer and chairman of Indevus."There are currently no approved drugs anywhere in the world for patients with stuttering. Pagoclone has tremendous potential to become a highly significant commercial product, as well as to provide a ground-breaking therapy to then early three million Americans and millions of patients around the world who are afflicted with this condition. The deal we have negotiated with Teva allows us to conduct a definitive Phase IIb trial, funded by our partner. If the trial is positive, we believe that both companies will have a unique opportunity to commercialize the first pharmaceutical product for the millions of patients who stutter.

Typical CEO-bla bla bla! He doesn't really say anything, but it sounds good! For example, "tremendous potential" but of course potential might not translate into a real medication. So it is safe to say it anyway!

Watch the phrase "to conduct a definitive Phase IIb trial". Why use "definitive"? I think it is a slip of the hand, which reveals the mood they are in: They are not really sure themselves about the "tremendous potential" but this second trial will definitively give us a clear result. And any way Teva is footing the bill. And if it works fine, we just take 50% of the profits which is still millions.

Breaking News: Pagoclone is going to Phase IIb

LEXINGTON, Mass., Sept. 26 /PRNewswire/ -- Indevus Pharmaceuticals, Inc.(Nasdaq: IDEV) today announced that it has signed a development, license and commercialization agreement with Teva Pharmaceutical Industries Ltd. for the exclusive, worldwide rights to pagoclone. Indevus previously announced promising data from its 8-week, placebo controlled, double-blind, multi-center Phase II trial in patients with persistent stuttering which showed that pagoclone produced a statistically significant benefit in multiple primary and secondary stuttering endpoints compared to placebo. Pagoclone is a novel member of the cyclopyrrolone class of compounds and acts as a gamma aminobutyric acid (GABA) selective receptor modulator.

Under the terms of the Agreement, which is subject to applicable regulatory clearances and customary conditions, Indevus will conduct and Teva will reimburse Indevus for its expenses for a Phase IIb study. The placebo-controlled study will involve approximately 300 patients with stuttering in the U.S. treated for a period of six months and is expected to commence enrollment by Q1 2009.

Following the completion of a successful Phase IIb study, the Agreement provides for Indevus to participate on a 50/50 basis with Teva in the U.S.,sharing development and marketing costs, and splitting future profits, in addition to receiving milestone payments. Under certain circumstances, either party may convert the Agreement from the 50/50 arrangement to a royalty structure where Teva will be responsible for all development and commercial costs in the U.S. and Indevus would receive royalties on net sales, in addition to milestones. In either case, if the arrangement continues, Teva will be responsible for the conduct of the Phase III program.

For territories outside of the U.S., Teva will be responsible for all future development and commercialization and Indevus will receive milestones and royalties on net sales.

Under the 50/50 participation, Indevus could receive up to $92.5 million(including the Phase IIb study expenses) in U.S. and European development milestones and R&D reimbursement. In the event of a conversion to the royalty structure, in addition to the $92.5 million of milestones and reimbursements,Indevus could receive up to $50.0 million in U.S. based sales threshold milestones.

We are excited that we have partnered pagoclone with a leading pharmaceutical company with a focus on central nervous system conditions,"said Glenn L. Cooper, M.D., chief executive officer and chairman of Indevus."There are currently no approved drugs anywhere in the world for patients with stuttering. Pagoclone has tremendous potential to become a highly significant commercial product, as well as to provide a ground-breaking therapy to then early three million Americans and millions of patients around the world who are afflicted with this condition. The deal we have negotiated with Teva allows us to conduct a definitive Phase IIb trial, funded by our partner. If the trial is positive, we believe that both companies will have a unique opportunity to commercialize the first pharmaceutical product for the millions of patients who stutter.

(Thanks to Holger!)

Can you help Connecticut scientists?

Ludo Max is looking for children and adults who stutter: see here. When I visited him last autumn, I also participated in one experiment, and I can confirm that I survived!

If you stutter or if your child stutters, you can make an important and valuable contribution to the scientific understanding of stuttering.

Researchers in the Laboratory for Speech Physiology and Motor Control in the Department of Communication Sciences at the University of Connecticut are conducting several studies that may result in new scientific knowledge about the problems involved in stuttering. Participating in any of these projects provides a wonderful opportunity to make a contribution that may benefit all individuals who stutter.

We are currently recruiting children to participate in our studies in Storrs (CT) and adults to participate in our studies in Storrs or New Haven (CT). All participants receive financial compensation and free speech, language, and hearing testing. Children also receive a small book or toy.

Children between the ages of 3 and 9, if eligible, will be invited to complete tasks such as speaking into a microphone while wearing earphones, listening to tones while wearing a cap with sensors that record the brain's responses to those tones (see top picture on the left), or pointing to visual targets with a small movement sensor taped to the finger (see middle picture on the left).

Adults between the ages of 18 and 50, if eligible, will be invited to complete tasks such as speaking into a microphone while wearing earphones, speaking with small movement sensors attached to the lips, jaw, and tongue (see bottom picture on the left), or speaking while lying in an fMRI scanner at Haskins Laboratories/Yale University.

If you want more information about any of these studies, or if you want to find out if you or your child are eligible to participate, please contact Dr. Ludo Max by e-mail (ludo.max@uconn.edu) or telephone (860-486-2630). Thank you in advance for your consideration.

Toronto and Does your child stutter?

If your child stutters (or not!) and you can make it to Toronto, please consider taking part in this research project. It is important for us to increase our understanding of stuttering, and hopefully one day your child and everyone else can profit from improved treatments resulting from such research!

Does your child stutter? The University of Toronto Speech Fluency Laboratory needs both children who stutter and children who do not stutter to participate in a research project. If your child qualifies for the study you will receive a speech, language and hearing assessment. You will be compensated for your time.

Please email d.beal@utoronto.ca if you have a child who is:

1. Between the ages of 7 and 12 years old
2. Right handed

Benefits of the study include:

1. A speech, language and hearing screening for your child
2. A free 100 page booklet on stuttering
3. Compensation for your participation and travel
4. Help advance our knowledge of the brain and the role it plays in hearing, speech and stuttering!

Back from holiday

Two major events happening in my holidays.

First, the meltdown on the investment banks. WOW! The Masters of the Universe are gone just like that. Bear Stearns (for which I worked as a risk manager, see a previous post) gone, Lehman Brothers gone, Merrill Lynch bought up, and Morgan Stanley and Goldman Sachs becoming commercial banks. They all need liquidity to work, and they could not get sufficient liquidity anymore. It will change Wall Street and finance forever, after all they were the drivers of most innovations and hired the brightest, most focused, hard-working people around.
Second, the message is going around that bilingualism is a risk factor in non-recovery of stuttering based on research done by Prof. Howell's team at University College London. The Welcome Trust has financed the research and is pushing the message: see here. Here is the summary:

Bilingual children who learn two languages in early childhood are more likely to develop stuttering than those who speak another language in the home and do not learn English until they attend school, according to research funded by the Wellcome Trust.

I will have a closer look and tell you my impression. Two immediate thoughts: bilingualism means more work for the brain but would it affect stuttering, and the sub-sample of bilingual kids is too small and induces large statistical uncertainty. But I need to read the article and do the statistical calculations.

The StutteringBrain is on holiday

I am on holiday until September 19th, but might moderate comments from time to time. Till then....

AAF not effective?

Here is a study that claims that there is no clear fluency gains when using altered auditory feedback in a real environment:

1: J Speech Lang Hear Res. 2008 Aug 11.

Effects of the SpeechEasy on objective and perceived aspects of stuttering: a six-month, Phase I clinical trial in naturalistic environments.

Pollard R, Ellis JB, Finan D, Ramig PR.

University of Colorado at Boulder.

PURPOSE: Effects of the SpeechEasy when used under extra-clinical conditions over several months were investigated. Primary purposes were to help establish Phase I level information about the therapeutic utility of the SpeechEasy and compare those results to previous findings obtained in laboratory and clinical settings. 

METHOD: Eleven adults who stutter participated. A nonrandomized, ABA group design was utilized. Speech samples were collected every two weeks in extra-clinical environments. Qualitative data was collected through weekly written logs and an exit questionnaire.

 RESULTS: Group analyses revealed a statistically significant effect of the SpeechEasy immediately post-fitting, but no treatment effect across four months' time. Individual responses varied greatly with regard to stuttering frequency and subjective impressions. Relatively more stuttering reduction occurred during oral reading than formulated speech. 

CONCLUSIONS: Based on this protocol, Phase II trials are not indicated. However, positive individual responses and self-reports suggest some clinical utility for the SpeechEasy. The use of more challenging sampling procedures strengthened external validity and captured more modest altered auditory feedback effects compared to those previously reported in laboratory settings. Device use coincided more so with positive subjective impressions than measurable fluency improvement, highlighting challenges facing clinicians when implementing principles of evidence-based practice, including client-based preferences.

My interview on StutterTalk

You can listen an interview with me on StutterTalk.

Here is a summary: (from what I remember, which is probably very biased!)

We started out having a speech goal. Mine was to speak slowly with pauses, and I was able to maintain this for about 3 seconds. 

Crackpot Award:

I explain that I want to break the code of silence and consensus by naming and shaming the most extreme offenders in ignoring scientific evidence and promising cures. I read out loud an email, where I show how crackpots are unable to engage in a constructive debate on stuttering. Greg agrees with me that no matter how nice you are or how hard you worked if your idea is wrong it is wrong and you need to be told loudly and clearly and why it is wrong. 

Measurement of sucess:

Peter complains about the excessiveness of measuring treatment sucess. I agree with him. It is like telling someone that your new car costs 17'4563 dollar and 34 cents. For all practical purposes, the car costs 17'500 dollars. There is no need for great accuracy. The false accuracy fallacy is a warning sign for pseudo-science at work. For therapy work, rough qualitative assessment by the therapist and patient is fine for me. What would you do with all this information anyway? Of course, if you want to evaluate a treatment method, you need to do it thoroughly. So my stance is: Either do it very big and very well, or don't do it at all. Greg came in with the needs for standards, and I said that the health services like to see such standard as they now need to set targets.

Lidcombe & early intervention:

I say that I am not against the treatment method per se but the way it is marketed promising a lot and based on weak and flawed research. In fact, I have no issue send my kids there. However, they have not showed long-term efficacy as they claimed. And most importantly, they have not shown that Lidcombe is better than any other treatments, because it has not been tested against others. Greg made a blatantly obvious observation that totally escaped my mind so far: They (different approaches) all talk about theory, but when you actually look at what they do, it is very similar! They all talk to parents, the kids know that it is about their speech, do speech exercises, and so on. I mention that Marie-Christen Franken from the Netherlands is currently running a trial where she compares Lidcombe with demands and capacity theory. 

Medication:

I say that medication is the only hope for improvement of ALL people who stutter on a large scale, because behavioural therapy might work for some but not for all. In the same way as diets work for few, because most are not able to stick to the new behaviours. Peter is unhappy, and explains that for two years he consistently worked on changing his behaviour. I reply with: Good on you, but many including myself were, are or will not be able to do what you have done. We are not Peters! Peter felt embarassed and somehow emotionally cannot handle the fact that he is special in this respect. I also emphasised that I am not saying that there is such medication now, or that there even will be such a medication, and that it will be a cure. My prognosis is rather than there will be better (and possibly individualised) medication within 10 years in combination with behavioural therapy that makes stuttering more or less manageable for all. It is a guess, no more. I am not fond of medication pe se also due to side-effects, but I do not see another efficient way forward unless we get some very efficient behavioural therapy.

Future:

I said that I am waiting for old professor with old ideas to retire. In physics, we say that progress is not made by old professors changing their old ideas but by them dying out! 

Joe Biden: where are his actions?

When I was a trustee at the British Stammering Association, our director Norbert Liekfeldt used to say that we do not do Politics with a big P, party politics, but definitely politics with a small p, namely lobbying for the causes of stuttering and supporting the politicians that actively support us!

Many are thrilled that the Democratic Vice-President candidate Joe Biden has been stuttering as a child and teenager, and he is one of us as he attended a conference where he spoke about his stuttering openly. But I say about a politician: Don't watch their words, watch their actions! Biden is a wealthy politician with a lot of power and networks, and direct access to any decision maker. So what has he done for the causes of stuttering? Where are his actions to help the stuttering community?

My questions are:

1) Has he proposed legislation to support our causes?
2) Lobbied for more research money into stuttering?
3) Donated money? (anyone can do that!)
4) Spoke on our behalf in the Senate or asked a member of Congress to talk about stuttering in Congress?
5) Opened up his network to connect our associations to important contacts?
6) Given us direct access to himself?
7) Invested political capital to further our causes as opposed to just gaining capital by speaking at a conference?

If many answers are NO, then I am sorry but he is not one of me!

A new treatment for stutterers?

Have a look at this interesting TED talk by Christopher deCharms. He adds a new way to change brain functions, neuroimaging therapy, to the traditional approaches of pschotherapy, pharmacology, and neuro-surgery. It is a bio-feedback mechanism: using real-time neuroimaging, the patient can see the brain activation as it happens and learn how to modify. Neuroimaging therapy is a novel concept which also promises to help people who stutter. And you heard the news first here, at TheStutteringBrain blog!

Fluency shaping therapies already use software to give stutterers feedback on their newly learned speech patterns like gentle onset. And, auditory feedback devices and recording phone calls are another biofeedback mechanism. We learn by seeing the results of our actions, and thereby learning to modify the actions.

Why not do the same with real-time neuroimaging? Imagine, you are sitting in an fMRI scanner and you are talking to your therapist at the same time. I am sure that after some practise you will see how the brain activates differently depending of whether you stutter or you speak fluently and controlling your tendency to stutter.Then, you can actively try to modify brain activation patterns. Intriguingly, you are focusing on normalised your brain function rather than normalising your speech, which must be more effective. Let me repeat: You are working on your true "internal" stuttering rather than modifying your speech caused by your "internal" stuttering.

Sure, the real-time is not as real-time as deCharms would like the method to be, and there is the noise of the scanner which might make practising difficult if not possible. However, I have no doubt that there will have silent workable real-time imaging systems, maybe in five years but definitely in ten years. Such a neuroimaging therapy is no quick-fix, but it would be much more effective way of changing behaviour, because you work on your internal issue and not use your external speech proxy as feedback.

Can a stutterer become vice-president?

A clear no! No-one with a noticeable stutter resulting in impaired communication can become vice-president or president. Can someone who stuttered as a child and is now fluent for all practical purposes? Yes! The mantra of the stuttering community is: Stutterers can do any job including being a politician or actor. And they parade in front of us Winston Churchill, Marilyn Monroe, or now Joe Biden. But have you ever heard them stutter severely in public? No, they are speaking fluently, and at best hesitantly. They are no stutterers in the eye of the public. At best, they have worked hard to minimize their stuttering so that it sounds like normal speech and does not impair communication, and at worst, they just happen to recover and attribute an event close to recovery for their recovery. But how many of us have worked hard but still stutter noticeably and have to endure the well-meaning but annoying sermons of the recovered?
Yes, stutterers can get into high power offices, but either by connections, an inherited power base or ability for background networking and dealing. And those offices are the hidden ones rather than in public view. It is a despite and not a because of.

No fluency but psychological turn around

This study confirms my suspicion and experience of stuttering therapies: no significant long-term improvement in fluency but improvements in psychological well-being:

An experimental clinical trial of a cognitive behaviour therapy package for chronic stuttering.
Menzies RG, O'Brian S, Onslow M, Packman A, St Clare T, Block S.
Australian Stuttering Research Centre, The University of Sydney.

PURPOSE: The aims of the present study were to: (1) examine the rate of Social Phobia among adults who stutter; (2) study the effects of speech restructuring treatment on social anxiety; (3) study the effects on anxiety and stuttering of a CBT package for social anxiety. METHOD: Thirty-two adults with chronic stuttering were randomly allocated to receive either: (1) speech restructuring following a CBT package for social anxiety, or; (2) speech restructuring alone. Data were obtained on a variety of speech and psychological measures at pre-treatment, post- CBT, post- speech restructuring and 12 months follow-up. RESULTS: Sixty percent of our cohort were diagnosed with Social Phobia. Speech restructuring treatment alone had no impact on the Social Phobia of our cohort at 12 months follow-up. At follow-up, participants who had received CBT showed: (1) no Social Phobia; (2) greater improvements than control subjects on a range of psychological measures of anxiety and avoidance. However, the CBT package made no difference to the speech outcomes of those with Social Phobia. CONCLUSIONS: The CBT treatment was associated with significant and sustained improvements in psychological functioning, but did not improve fluency.

Biden on video on stuttering

And here. Biden is at 0:15, 3:00 and 5:25. It is good he is open about his stuttering in childhood. For my taste, he is a bit too American: Struggling evil and overcoming it... Of course the majority struggle hard but never overcome it! Was he just the lucky one or did he do something special to help overcome it?

Joe Biden

Joe Biden, the vice presidential candidate on the democractic ticket with Obama, was once a stutterer!

WHEN Joe Biden was a youngster he had a stutter, cruelly earning him the name Bi-Bi-Biden. He conquered that affliction to become one of the Senate's great talkers and Barack Obama's pick as his vice-presidential running mate.

As a child, Biden stuttered and was teased by his classmates. He practiced reading aloud in front of a mirror and worked hard to overcome it. During law school he befriended a stutterer and worked with him regularly on his speech. Now Biden is known as a loquacious orator.

In the Biden family, children were taught to respect Catholicsm, but not necessarily the person in it. As a boy, Biden took endless ribbing from classmates for a stutter he later overcame. Much of the time, the nuns tried to help. But when a seventh-grade teacher mimicked Bu-bu-bu-bu-bu-Biden's stutter in front of the class, his mother, Jean, demanded a meeting with the principal and the offending nun. "If you ever speak to my son like that again, I'll come back and rip that bonnet off your head," she said. Later, when then-Senator Biden told her he was going to visit the pope, she said: "Don't you kiss his ring."

Check out this NSA story. I can already see the stuttering associations world-wide salivating on the prospect of a golden opportunity to spread the message!

(Thanks to Ora for the story)

No tics when alone

I just saw a documentary on tic disorders. Interestingly, a women affecting by tics said that she is symptom free when she is alone, but the tics start when her husband comes home and gets worse in public social situations. Sounds awfully familiar to stuttering. I wouldn't be surprised if a similar mechanism is behind this phenomena.

Maguire talks on medication on StutterTalk

Check out StutterTalk's interview with Jerry Maguire on medication. Jerry is the main investigator of the Pagoclone study. He introduces the field, and talks about side effects. He said that he is guinea pig amd tried several compounds. He thinks that a combination of medication and speech therapy is more effective. Greg talks about his experience on medication: he said that secondaries reduced but he had significant side effects. Then Maguire talked about Pagoclone. He says that the Phase III is going to go ahead. In Phase III, they will play around more with dosis. Pagoclone seems to be more effective with longer use. He said that Phase II showed 20 to 40% improvements, (I DO NOT AGREE BECAUSE PLACEBO DID SIMILAR. THE DIFFERENCE BETWEEN BOTH WAS ONLY ABOUT 10% REDUCTION! THE OPEN LABEL DID BETTER BUT IT IS NOT PLACEBO CONTROLLED AND NOT ALL PARTICIPATED) They then talked about fluency shaping and it's unnormal speech unlike medication. Maguire says that it is not going to be a cure with all, but he believes in a combination of different approaches is the future. Then, they talk about different cocktails that some advertise. Jerry spoke about the use of telemedicine. So whereever you are in the world, you can get a consultation with Jerry and Dave at the Stuttering Center at Irvine in California.

StutterTalk interviews TheStutteringBrain

Yesterday, I got interviewed by Greg and Peter from Stutter Talk, the second best blog on the Internet! ;-) We talked about crackpots, medication, early intervention, outlook on research and treatment, and my view on the dormant and reactive phase. I will link once it's on-line.

Side effects very often kill benefits

A reader e-mailed me on his experience of someone taking medication:

On a different subject, I discovered tonight that someone in my group has tried Zyprexa (olanzapine) on several occasions. Most recently he’s been taking it for several months. I’ve noticed that he’s been gaining weight, but I didn’t know why till tonight. He’s gained about 30 pounds (20 kg), and is hungry all the time. He also feels tired. He’s was first on 5, now 10 mg per day, but has just decided to stop it because he doesn’t like the side effects. He took it for two previous periods, and it did have a beneficial effect on the stuttering those times, but this time, he’s not seeing much benefit. He was also in the pagoclone study. He thinks he was originally in the placebo arm. He continued with pagoclone after the end of the double-blind phase, for several months only. I didn’t get a clear sense why he discontinued; I think it was simply because he wasn’t seeing much benefit. He’s also being treated for OCD and sometimes anxiety (most recently Zoloft, I think), and he says that its hard to get the balance right because Zoloft definitely exacerbates his stuttering. I think he discontinued the Zoloft when he started Zyprexa, so he could isolate the effect of the Zyprexa.

I am getting consistently such reports. Side effects are outweighting benefits, and initial gain in fluency is gradually lost. Result: all that I know have stopped taking medication with 1-2exceptions. Pagoclone is somewhat different as it is better tolerated, but I haven't received any very positive report. Except long-term fluency gains in the open label trial. So if you have taken Pagoclone or other medication and experience stable fluency gains, let me know. I want to hear of your experiences

Christian Kell at the Paris workshop

Here is the last talk of the Paris workshop: a few weeks late. Christian Kell was the last speaker. He is a post-doc at Ecole Normale, and did his PhD in Frankfurt where he collaborated with Katrin Neumann on brain imaging studies on stuttering. I have already dedicated one post to him, to recapitulate: he is famous for finding the sensory location of the male penis in the brain!

Thank God then for Christian Kell of the University of Frankfurt who stuffed eight blokes into an MRI scanner and then tickled bits of their bods with a feather while (no doubt) keeping his eyes firmly fixed on the brain activity monitor. The NS notes: "Each man's penis was represented in the same place - flanked by the areas for the toes and abdomen - Kell told the Organisation of Human Brain Mapping annual meeting in Toronto." Kell went on to lament: "The only depressing thing is that the representation is very small."

Katrin scolded me for writing about this, saying that he was shocked to read about this on my blog. I asked him at the conference, and of course it was not true but her over-reaction as always. Chris said that he was surprised by the deluge of interest, that he got used to it, because after all it will stay with him for the rest of his life. To be honest, I think he enjoys his claim for fame. Chris seems multi-talented. He asked good questions. His French for being a German is quite good. He was a driving force behind the conference. And at the end of the workhop, he played the piano supporting a singer he recruited. So if he fails to get another job in neuroscience, I am sure he can make his money in a piano bar in Pigalle!
Chris spoke about research he has done in collaboration with Katrin in Frankfurt. I haven't found the article on PubMed, so it might not be out yet. They looked at people who recovered unassisted, who improved due to a fluency shaping therapy (before, just after, and one year after), and controls. What are the brain differences? It is an interesting question. Is there a difference between unassisted recovered stutterers and controls? Is there a difference between unassisted and assisted recovered?
(It is important to say a few words on unassisted recovered. I am not sure he said something about it his talk. But, I remember someone saying that many are not really like fluent speakers, but still have hesitations at times. When you ask them about this, they say that they are fluent for all practical purposes. They do stress that fluent speech is not always automatic and that they have to work to get it. This is even more true for people who undergo therapy and become fluent. The major difference is probably that unassisted recovered have managed to have lasting improvement, whereas people who become (more) fluent through therapy are likely to relapse fully or partially.)
As with all the other talks, I do not have access to the slides, so I can only rely on the abstract and my notes. They use functional and structural MRI. Not surprisingly, they find grey matter reduction and white matter anomaly on the left side in all stutterers. I think also in unassisted recovered stutterers. So constancy across groups. However, there were clear difference in activation. Stutterers activated several regions on the right side including the activation of the right analogue of the anomalous left brain region. After therapy, the right hand side activation was normal except again activation of the right analogue. And unassisted recovered stutterers show similar activation but additionally showed activation in the anomalous right region. He refers to the Brodman area 47/12. And they conclude that: "recruitment of the left posterior orbitofrontal cortical region (BA 41/12) appeared in this study as a unique and necessary feature of long-lasting repair of stuttering.
He further states that this region is probably involved in executive control of rhythmic tension. He actually talked a lot about rhythm, but I did not follow it all. I just have written down that the right side keeps rhythm and the rhythm competence (not sure exactly what it stands for, but this is probably understanding rhythm as opposed to executing rhythmic tasks) is on the left side.
I asked him a question on methodology. They used people from a fluency shaping therapy: the Kassel Stuttering Therapy. I have also attended the intensive course plus a one-year daily practise. One striking feature is the strong rhythm and gently onset of the newly learned speech pattern. It is quite funny. If you go to Kassel, everyone speaks the same way. Though I have to say that this is on purpose and the idea is to reduce the strong rhythm gradually: over-learning. I was concerned that the stutterers were just using this way of speaking and so you should see activation in rhythm areas, after all you speak in a rhythm! He replied that they told them to try to speak as natural as possible. However, I do not completely buy this argument, because when I was in this mode of speaking and tried to speak normally, I found it hard to do. In fact, some region in my brain kept me in the other mode, and I would only gradually shift and loose the restraining power of the new speech mode. Anyway, it is an interesting study! ;-)

Facebook Group

I have created a facebook group for readers of my blog:

Readers of TheStutteringBrain Blog

I also have a facebook account: here. Become my friend! I have so few... :-)

Urban myth: more left-handed stutterers?

Check out this article on the Day of Left-handers: here. This is another urban myth.

Stuttering and dyslexia occur more often in left-handers (particularly if one is forced to change their writing hand as a child).

 Or are there more left-handers who stutter??? But I seriously doubt stuttering can be induced by changing writing hand?

Jaik Campbell

 

Well it is a bit late. The show was last week, but have a look at Jaik's comedy acts. He also stutters and is quite funny. Actually, he is already funny without teling a joke! We had some great time in Dubrovnik at the last IFA conference. He was chasing Russian girls. ;-) Check out some of his videos: here.

News from one of my crackpots

You should have a look at Steve Hill's attempt at intellectual musings on the causes of stuttering: here. He has already received a Crackpot Award, but deserves more attention.

I have a number of e-mails from people who are worried that their children might in some way "catch or copy" their stutter and therefore develop a stutter in this way. We all know how damaging our own speech impediment has been and therefore would not wish a stutter on any person let alone our children.

Other people have told me that they developed a stutter after being involved in some form of scary incident, such as a car crash. The stutter seemingly developed due to some form of shock reaction.

He clearly has no understanding of the difference between correlation and causality, is relating on anecdotes, completely disregards genetic and brain imaging work.

Stuttering is colour blind

I am wondering whether this research was necessary. They looked at whether African American kids are stuttering more or less than "European American" (poor US whites they are now labelled after us Europeans!). I guess to see whether black kids are discriminated. I would not be surprised  (but I do not know for sure) if this was a clever move by the researchers to get funding for their stuttering research by tapping into the racial equality money, and use some of the overhead for other projects. I am wondering whether we could somehow link stuttering to global warming, and we could get more money for stuttering! Or, even better for terrorism, no lets make it bioterrorism (that's closer to stuttering which is also bio) because then we can kill any criticism to our stuttering-makes-terror theory by calling  our critics unpatriotic or liberals! Seriously, the matter of the fact is that lots of money is dedicated for research that 99% of the politicians know are ineffective but politicians need to show that they care for the topic. But what really happens is that neighbouring fields jump on the bandwagon by re-writing their grant proposals to fit the political dictat. So if we want to get more money for stuttering, we need to either make us important enough to get big pots of research money or to tap others.

Actually on a second glance, this piece of research is very interesting! So I am glad it was done. Why? Well, it confirms that stuttering is roughly similar across at least two races, which fits with what we have been known anecdotally for a long time: people stutter in any culture or race. But, I am actually struck by the fact that the numbers are so similar. Yes, I would have expected that kids stutter in all races, but that the numbers are so close is interesting. It is well-known (that is a phrase I use when I have heard it somewhere but I am too lazy to look for a reference!) that different races have illnesses at different prevalence. The fact that stuttering seems to be remarkably constant might well point to the interpretation that there are many ways to start stuttering (many gene combination and no single gene) unlike for some illnesses which depend on one gene which could easily be selected out in one race. You can also argue that the same culture made them stutter in same numbers, but I do not pay this because the frequencies of illnesses is different for different races even though they live in the same culture (well do they really? There are very distinct sub-cultures in the US.)

But wait, why don't we do the same for gender and see whether one of them is discriminated! Wow, four times more boys stutter than girls! So there is a clear discrimination by society here, isn't there? But of course because the discrimination goes against the common urban myth "that women are discriminated", no-one bothers about it. Just imagine more girls had stuttered, everyone would be talking about it....

Here is the abstract:

J Speech Lang Hear Res. 2008 Jul 29. [Epub ahead of print]Links

Prevalence of Stuttering in African American Preschoolers.

Proctor A, Yairi E, Duff MC, Zhang J.

Department of Speech and Hearing Science, University of Illinois, Urbana-Champaign.

PURPOSE: This study sought to determine the prevalence of stuttering in African American (AA) two to five year olds as compared to same age European Americans (EA).

METHOD: A total of 3,164 children participated, 2,223 AAs and 941 EAs. Data were collected using a three-pronged approach that included investigators' individual interaction with each child, teacher identification, and parent identification of stuttering.

RESULTS: No statistically significant difference for stuttering was found between AA and EA children. Using the investigator and teacher method of identification, the prevalence of stuttering was 2.52% for the entire sample. For both racial groups, boys exhibited a higher prevalence of stuttering than girls. Of the three predictors (age, race, sex) of stuttering, only sex was a significant predictor.

CONCLUSIONS: AA two to five year olds are not overrepresented in the stuttering population for this age group. When data are combined for both racial groups, the prevalence of stuttering is 2.52%. More boys than girls stuttered in this sample of preschoolers.

PMID: 18664698 [PubMed - as supplied by publisher]

One of my heroes

Have a look at this interview with Richard Feynman, Noble Prize Winner and guru of theoretical physics. He is definitely one of my heroes. Here he talks about Social Sciences. He might as well have talked about the general status in stuttering research!



Also, check out his superb explanation of what science is about using chess!

Reduction of stuttering severity

I am on the mailing list of STUTT-L, and I like this post by Gunnars Neiders. Especially, the Gaining insight alone does not help strikes me fatally!

I believe that reduction of all the significant dimensions of stuttering is a valid goal of stuttering therapy. The main dimensions of stuttering are:

1) Disruption of the communication process,

2) Secondaries (eye blinks, pursing of lips, head jerks, snapping fingers, etc.,

3) Distressing emotions of anxiety, shame, etc.,

4) Avoidances of sounds, words, situations,

5) Unhelpful ... attitudes, beliefs or self-talk ("I can't stand stuttering" instead of "I don't like it, that's OK, I can stand it anyway"; "Stuttering makes a person less worthwhile as a human being" instead of "There are inconveniences associated with stuttering and sometimes I may lose out on some of the goodies of life due to stuttering, but I can unconditionally accept myself, I am just as worthy to myself, whether I stutter or not", etc.),

6) Self-limitation in social and vocational settings. (not pursuing career of choice, limiting socializing, etc.)

There are techniques to reduce all of them. Gaining insight alone does not help. There are homework assignments that help; but learning exercises does not help if one is not inclined or does not find it cost effective to do massive practice. Some techniques are more efficient than others. Six things that hold back a persons are:

a) perfectionism/all or nothing thinking (I either succeed to completely change, or it is not worth my while),

b) not knowing what type of homework exercises to do,

c) learned helplessness ("Since I have failed in the past, I will always fail),

d) not experimentally trying all types of techniques to find out what works,

e) not having persistence and

f) the self- formal therapy not being cost efficient.

If the cost in time, energy, money, etc. is too big for the effective results, it just is not worth it. It would be silly to pursue a goal in life which is too expensive, too dear.