Lack of motivation a convenient excuse?

When I talk to therapists and ask why many (most?) patients are not succeeding in therapy over the long-term. I often here things like "you are not motivated enough" or "the moment is just not right" or "there are no cures" or "we just don't know enough about stuttering" or "you need to practise more". Could I not turn this around and blame relapse on the therapist because s/he was not able to motivate the patient hard enough or made practising unnecessary difficult due to bad advice?? Have you ever heard a therapist at a conference talking about their mistakes? I haven't to this day. I only heard talks about success, enriching personal development experiences for the patient, and so on. And they also revel in showing just how sensitive, caring, bonding, holistic, intelligent, hard working, smiling, and most importantly professional (what ever that term may mean?) therapist they are; attributes that, to put it mildly, people who stutter are not that interested in, all they want are results for them!

Here is my analysis. Yes, it is true that motivation plays an important role in long-term success. You do need extraordinary motivation. For example, I was absolutely motivated at each of my therapies, though not obsessively. Even a good therapist might not be able to motivate some patients. However, this argument even though it is correct to some degree is also a very dangerous argument, because mediocre therapists can use it as an excuse for their own failure. They can hide behind it. This is also true for non-professional therapists like the crackpot award winners that I nominated. A healthy advice would be: if you are a patient and you fail, look at yourself to find points of improvements; if you are therapist and your patient failed, look at yourself to find points of improvements!

And here is a challenge to all therapists: I will buy that therapist a drink who gives a talk with the topic "The mistakes I made and why they were mistakes"! I would even offer a meal, but a meal with me might be too much punishment for the winner! :-)

The Valsalva hypothesis

Virtually all theories on stuttering from amateur (and many professional) researchers that I have seen are just wrong and void of empirical evidence. However, there is one theory where I just cannot make up my mind on whether it is a piece of the stuttering puzzle or just complete non-sense! It's Malcom Perry's Valsalva mechanism hypothesis. Claire Walker nicely summarises the hypothesis here:

So, stuttering has been linked to differing neural patterns, but why does stuttering cause different parts of the brain to be more active? One idea is called the Valsalva Mechanism, which is a natural bodily function, but it may turn the extra effort put into speech into the block that stutterers fight with everyday (3). The Valsalva Maneuver was named after an Italian anatomist, Anton Maria Valsalva and its purpose is to bring more air pressure into the lungs to help a person exert more force on an object, such as weight lifters who hold their breath when lifting large masses. (3). To create more air pressure in the lungs, the abdomen muscles contract and press against the diaphragm, which in turn presses up on the chest cavity. For this mechanism to increase the air pressure in the lungs, the larynx has to tighten around the airway so that the air cannot escape and this is called the effort closure (3). All of the muscles involved in the Valsalva mechanism are connected neurologically, so that they can all contract at the same time and with the same force (3).

The reason that this mechanism is thought to be tied to stuttering is because stutterers put a lot of force and effort into the words that they stumble over. This force causes the lips and tongue of the stutterer to press harder together, thus creating more air pressure in the lungs, but also causing speech difficulties (3). Fluent speech actually requires very little effort, so when a stutter puts a lot of effort into speaking the Valsalva Mechanism does what it is supposed to do, it is an instinctive reaction when we are trying to force something out of the body (3). This confusion between the Valsalva mechanism and the neurological components of speech can happen because there is neurological tuning involved in the motor neurons that control all the muscles involved in a movement, this includes speech (3).

What really happens during a stutterers speech is not wholly known, but if we take an example of someone stuttering on a word starting with p, say plane, then the brain remembers that p-words were difficult to say. Thus the brain ‘thinks’ that more effort has to be put into saying p-words, so the Valsalva mechanism kicks into gear and the stutterer is left squeezing their lips and trying to get any p-word to come out of their mouth (3). What makes p-words difficult for many stutterers is the fact that you have to close your lips, momentarily, to build up a little air pressure to say p-words. However if the nervous system is too excitable the brain may misinterpret this signal to mean that a Valsalva maneuver is being started and thus try and shut the air in the lungs, making speech very difficult (3).

Here is William Parry's own summary from his website:

The Valsalva Hypothesis postulates that excessively forceful closures of the mouth or larynx associated with certain types of stuttering, as well as difficulty in phonation, may involve a neurological confusion between speech and the human body's Valsalva mechanism.

Persons who stutter may have learned to activate the Valsalva mechanism in an effort to produce words, as if they were things to be forced out of the body. Such activation is most likely to occur when the stutterer anticipates difficulty or feels the need to use extra effort to speak properly. While this might instinctively feel like the right thing to do, it actually makes fluent speech impossible.

When a person who stutters prepares to exert effort in speaking, excessive neuromotor tuning of the Valsalva mechanism may occur. Such tuning may:

	render the Valsalva mechanism over-excitable to triggering stimuli, such as the increase in subglottal pressure that accompanies the start of articulation;
	interfere with normal prephonatory tuning of the vocal folds (because the larynx is instead being neurologically tuned for effort closure), thereby causing delays and difficulty in phonation; and
	contribute to abnormal laryngeal behavior, either by increasing the strength of laryngeal reflexes (the Valsalva maneuver is known to strengthen reflexes), or by interfering with the suppression of reflexes, which normally occurs during speech.

The Valsalva Hypothesis views the Valsalva mechanism as only one of many factors involved in stuttering. For example, a stutterer's anticipation of difficulty might be affected, to varying degrees, by attitudes, expectations, neurological impairments, or emotional factors.

Furthermore, a child's original disfluencies may be caused by a variety of neurological, psychological, or developmental factors not involving the Valsalva mechanism. These original causes may be different for various individuals, but their commonality is that they create the perception that speech is difficult and will require extra physical effort. The child — already accustomed to using the Valsalva maneuver when exerting effort or expelling bowel movements — may instinctively assume that words can be forced out in the same way. Continuation of this behavior during certain critical years of childhood may influence the development of nerve pathways in the brain. Over time, these behaviors become deeply rooted in the nerve pathways of the brain, making them extremely difficult to change.

For further discussion of the Valsalva Hypothesis, see Stuttering and the Valsalva Mechanism: A Key to Understanding and Controlling Stuttering.

Stuttering is cool - blog

My blog seem to become more and more popular. I receive 5 emails this week! Here is a new blog with audio comments, in case you are interested:

Hi Tom,
I'm a life long stutterer and also a regular reader of your blog. I never quite read up on the science of stuttering (you think I would have!) but your posts are fascinating. Anyway, just thought I'd send you a quick email in case you'd be interested to know that I've recently launched a podcast for stutterers. It's called "Stuttering is Cool" and it's focused around audio comments submitted by my fellow stutterers. For me, hearing other people stutter really helps me feel that I am not the only one. And it's great to meet other stutterers!

Feel free to send in your audio comments, too. The address is http://www.stutteringiscool.com

It's fun to know - blog

I discovered a new blog called It's Fun To Know. He also talks about stuttering: see here. He seems quite witty.

Twins: Little shared environmental effect

I have just re-read the 13000-twin study by Katherina Dworzynski et al and she clearly empirically confirms what I have been saying in my last posts:

Stuttering appears to be a disorder that has high heritability and little shared environment effect in early childhood and for recovered and persistent group of children by age 7.

And further,

With respect to the genetic effects throughout, it also needs to be emphasized that, even though substantial estimates of heritability were obtained, many monozygotic twin pairs were discordant for stuttering. This is further evidence for the importance of the child's unique environmental influences, in that specific stressors have unique effects when a genetic liability is present.

Again, the nature vs nurture fallacy is revealed. It is simply wrong to divide the world into nature and nurture. There are three categories: the genes (nature), unique environmental stressors (more or less random events), and shared environment effects (nurture). Think about being the CEO of a small start-up company. Unique events like you having a car accident or a virus infection, sheer bad luck, pregnancy of your most important employee, and so on can completely change the outcome of your company's success because you only have a few months of financing to hit a certain target before your bank or venture capitalist cuts financing (window of development for child). I have seen this many times. Of course, you are especially vulnerable to such events if you have a bad or weak business plan (think of this as the genes - the instructions on what to do). General market conditions are also important but not that crucial, and can increase or decrease vulnerability. I never thought that venture capital, the topic of a book I have written (see here), is relevant to stuttering! :-)

The Genain quadruplets

The Genain quadruplets are a "beautiful" experiment of nature that can teach us a lot about genetic and environmental factors. All four girls share exactly the same genes, and lived in the same family environment. Unfortunately for them but fortunately for science, they share exactly the same genetic predisposition to schizophrenia. In exchange for free treatment, the quadruplets were and still are monitored; they are now about 50 years old. Interestingly, the expression of schizophrenia was very different between the quadruplets: Myra after an initial episode was never hospitalized and is married, Nora was hospitalized repeatedly but had marginal adjustment while outside the hospital, Iris experienced more-chronic hospitalization and her symptoms range from severe catatonic withdrawal to times of marginal adjustment when she was able to leave hospital, and Hester further deteriorated and remains hospitalized! Check out this review: here.

The case study shows that the same genes for schizophrenia (and many other brain disorders like stuttering) can lead to very diverse outcomes, though all quadruplets did develop schizophrenia. The family environment including parenting skills (nurture) were the same for all four, though parents might have treated them differently. However, a difference in treatment is mostly due to the kids being different. So the parents react to the difference of the child.

So why do the Genain quadruplets develop so differently? The answer lies most likely in environmental stressors unique to a child. I would split it in pre-natal and post-natal factors. Pre-natal factors include the position of the child in the womb in relationship to the others, differences in weight due to differences in nutritional supplies, injury, and so on. And post-natal factors include illness, injury, unique random events like a traumatic experience, reactions of parents to behavior proper to one child and so on.

What's environment?

In my last posts, I spoke about onset of stuttering and about triggers. I also said that I am very skeptical that environmental factors play a leading role, especially at onset. It's the eternal debate between nature and nurture. But the more I think about this issue, the more I am convinced that I and many others have been confused and it is the really the debate between nature, events and nurture. Anything that is not attributed to genes is often called environmental. This term is strictly speaking correct, but environment is not just nurture. Rather, environment is the general environment that the child (and his siblings and friends) lives in AND unique events that happen to the child within the environment: like virus infection, head injury, traumatic experience, and so on. I would argue that, relatively speaking, events are driving divergence between siblings because they cause a large difference between the one hit by the event and the sibling which is not, as opposed to the general environment with its similar impacts on siblings.

We are definitely the product of our genes, of our events, and of the immediate environment (of family and friends) and culture that you grew up. And, even nurture is not just nurture by parents, but also by other family members and most importantly by peers. So you can see that parents actually often do not have such a big role at all. In my next post, I will talk about the Genain quadruplets (mono zygotic) and their life with a genetic predisposition to schizophrenia in order to explain my ideas with a concrete example.

Finally, as a physicist, I cannot resist pointing out to all of you that the environment is not really well-defined. Where does it start and "you" begin? You are really nothing else than a bunch of atoms! Is the air you have in your lungs part of your environment or not? and your blood? The millions of bacterias in your stomach? The 90% of atoms especially water that are completely swap every so many years and you are not even the same person physically speaking than we were 10 years ago!

Uphill struggle for the environment

I discussed the danger of associating causes to the onset of stuttering. Formulating the wrong questions is also confusing the minds of nearly all parents, and many therapists and researchers, though not all.

First, it is misleading to ask or try to answer the question: What causes stuttering? It is important to disentangle onset of stuttering and lack of recovery from stuttering. The onset of stuttering does not mean onset of life-long stuttering. An adult stutterer needs to go through both onset of stuttering and lack of recovery. If someone asks you about what causes stuttering, you should say: We must ask two questions: first what causes the onset of stuttering, and second what causes some not to recover. The two questions very likely have very different answers.

Second, it is misleading to ask what factors are to be blamed for the non-recovery of some kids. This point might be a bit more subtle. Factors, that cause some not to recover, are not really to be blamed for the non-recovery, but they are just not strong enough to overcome onset of stuttering. Think about overcoming stuttering as climbing the Mount Everest. Are you going to blame the bodies and minds of 99% of the population to cause non-ascent to Mount Everest? No, you rather say that 99% are just not good enough to climb Mount Everest as compared to the Top 1%, and you would re-assure them that they have normal bodies and minds. A better but still not perfect way to formulate the question is what causes most to recover. The question should really by: Under which (exceptional) circumstances are kids able to recover from onset of stuttering?

Let me be a bit more concrete. I will give you my big-picture guess on what is happening, and you can hopefully see why these questions are misleading us. The onset of stuttering is the failure to develop certain standard neural pathways because the construction plans are non-standard due to abnormal genes or because the construction was hampered by a neurological incident like head injury, virus infection, low birth weight. The moment of onset is the moment the system gets its first real test in the same way that your brand new but defective car engine runs smoothly until you hit high speeds on the motorway. There is no or little environmental impact like parenting skills or endured stress, except for the out-of-the-ordinary events like injury or virus infection. The onset is entirely caused by internal factors that mostly happen long time before onset like the genes or like the head injury at age 2. Your car engine has a design fault or a manufacturing problem in the factory long time before you hit the high way. Environment and outside events might make stuttering appear a bit earlier or later, but it would have appeared anyway. You could have hit the highways a week later.

At the onset, stuttering children have abnormal neural pathways which cause them to have dysfluencies to which everyone reacts someone somewhat differently in terms of stuttering symptoms. The latest brain imaging results suggest that all children (even those that later recover) have structural abnormalities. Most kids are recovering but some are not. Why? Here is how I think about it, and I use the same escalator analogy for explaining why matter cannot escape black holes! :-) Think of a downward escalator that you want to walk up. You have to overcome the downwards speed by walking up faster. The downward speed is the difficulty to create a second compensatory pathway related to the magnitude of the neurological abnormality. In order to reach the top of the escalator i.e. to recover from stuttering, you need to have an upward walking speed greater than the escalator's downward speed. The upwards speed is determined by whether the kid does the right things, which depends again on genetics like its brain plasticity, semi-genetics like temperament and purely environmental factors like good parental feedback. The key point is that the kid needs ABOVE AVERAGE compensatory skills and environment, in the same way that you need above-average walking speed to climb up a escalator with a standard speed. So those kids that only have average skills and environment to learn compensation or those who have extreme downward speeds, will fail. The majority who recovers was lucky because either the escalator had a slow downward speed which was well compensated by their average skills and environment, or the escalator had a serious downward speed but they had exceptional compensatory skills. For example, girls are more likely to recover because they have a higher ability to compensate. So finally can you really blame their average skills and their environment for stuttering? No.

The fallacious mind.

I want to talk more about the onset of stuttering and how parents, therapists and researchers often draw fallacious conclusions. They often see the onset of stuttering being related to X (be it the birth of the younger sibling, the kid being attacked by a dog, high fever, below-average language & speech capabilities, and so on), and conclude that there is a direct causal relationship. However, this is fallacious, because there are other explanations for a relationship that are not causal. The human brain has evolved to automatically search for explanations. If an event happens, you scan your environment or immediate past for explanations, and stop when you found one. This effect is especially pronounced when the event occurs suddenly like the onset of stuttering often does. We need explanations. If you cant find them, we still find them: Blame the gods.

Example: My kid starts stuttering. His brother was born a few weeks ago or I am heavily pregnant. Therefore, onset is caused by stuttering. Or, some kids that start stuttering have slower-than average language development. Therefore, slow language development causes stuttering. Or, I heard my kid stuttering the first time a day after a big dog scared her and she broke out in tears. Therefore, the dog causes stuttering. Or, my kid cried a lot and became more withdrawn, and then she started stuttering. Therefore, something cause it to be distressed which causes stuttering.

Lets be rigorous and systematic, if A is related to B, then many combinations are possible in order of likelihood:

A and B are not causally related but a pure coincidence i.e. related by chance.
A and B are not causally related because C caused A and B to happen.
A and B are not causally related (in the right order) because B caused A.
A and B are causally related.

Each of the four example can be explained by a non-causal explanations.

Example: My kid starts stuttering. His brother was born a few weeks ago or I am heavily pregnant. Therefore, onset is caused by stuttering.

Possible Non-Causal Explanation: Both onset and birth are indirectly related, i.e. they both often happen at roughly the same time due to the nature of human development and off-spring production.

Example: Some kids that start stuttering have slower-than average language development. Therefore, slow language development causes stuttering.

Possible Non-Causal Explanation: Kid had a neurological incident (head injury, virus infection, perinatal hypoxia, low birth weight) or genetic makeup that produced havoc in the developing brain leading to BOTH slow language development AND stuttering.

Example: I heard my kid stuttering the first time a day after a big dog scared her and she broke out in tears. Therefore, the dog causes stuttering.

Possible Non-Causal Explanation: Both event happen by chance at the same time. The kid like millions of others just got scared and cried, and that's it! You can always find a event to relate to onset. Kid started stuttering and something more dramatic ALWAYS happens like death of family member or friend, distressing situation like doctor's visit, thunderstorm, and so on.

Example: My kid cried a lot and became more withdrawn, and then she started stuttering. Therefore, something cause it to be distressed which caused stuttering.

Possible Non-Causal Explanation: This is a cool one. Actually stuttering caused the distress! The kid started to feel that it couldn't pronounce well in private, and it got distressed. The mother noticed this but not the dysfluency which she only noticed a few days later!!! The mother made the mistake in that she thought she had all informations on the events which she didn't have. She just saw one side of the story line!

I explicitly wrote possible non-causal explanation, because if such an explanation exists, it does not imply that it is the right one. There might be a causal explanation that is the correct one or that the effect is a combination of 2 or more explanations. It is only possible to find the right one from the many possible one by careful research. But my rule of thumb is: If there is a non-causal explanation, it will be the right one in 95% of the cases! (because most relationships in life are non-casual)

Gareth clueless on research

Gareth Gates, runner-up of Pop Idols and best-selling pop star, is definitely an inspiration for many of us on how you can really become more fluent when you work hard and are very very focused. The McGuire program is providing a good framework. However, in terms of him explaining why he stutters and why he is fluent while singing, I am sorry to say but Gareth is just a COMPLETE DISASTER. Unfortunately, he is very misinformed. So he (and the other participants) is a mixed blessing for people who stutter, because they re-enforce the message that it is just psychological or "I don't stutter when I sing because I act and I am not myself" (So who is singing, Gareth?) Success does not imply that their theory on stuttering is correct.

Gareth and McGuire people, read my blog on the latest stuttering research! Your methods are very helpful for many, but your theories are confused, fallacious and wrong.

Drayna talks on genetics at StutterTalk.com

StutterTalk.com is encroaching on my territory by content, interviewing Dennis Drayna on genetics research (download here), and overtaking me by design...

Dennis Drayna doesn't really say anything new. I think childhood stuttering is a key part of the genetics equation. It might very well be that there are genes for onset of childhood stuttering and genes for recovery of childhood stuttering, and they are not correlated!

Shut up or go to sleep!

This piece of research gives interesting insights into the learning process, which might be helpful for learning speech techniques more efficiently. Two conclusions I would draw. First, you should take a nap after an intense practise. Second, you should avoid at all costs performing conflicting behavior (like using "anti-speech techniques") after practise. For example, you practise hard and then take a break and do not focus on technique while speaking. It is probably much better to just shut up for a few hours (at least 1 hour, actually a nap would do the same thing), or practise in the evening and go to bed because then you don't speak for 9 hours!

This research shows nicely that we might be able to improve behavioural stuttering therapy not by learning about stuttering but by learning more about learning in general.

Lies, damn lies, and younger siblings

I have spoken about the danger of linking the birth of a younger sibling to the onset of stuttering before. I feel obliged to write about this again because I have read it in Barry Guitar's newly update book which is supposed to be a bible among speech therapists.

I have been looking at the empirical numbers. Unfortunately, I could only find the birth spacing of women in developing countries. The younger sibling is born

<2 years after birth of last child with a probability of 25%
2-3 years later with a probability of 25%
3-4 years later with a probability of 25%
>4 years with a probability of 25%.

Lets assume the older sibling starts to stutter at age 3, then in 50% of the cases his younger sibling is born within a year, and in 25% (50% divide by 2) within half a year.

So in 25% of the cases, parents can perceive a strong correlation between onset of stuttering and birth of younger sibling. And it's a complete illusion!!!! It is a beautiful example of the common logical fallacy of confusing correlation with causation.

Note: I am not saying that no relationship exists to exact time of onset (i.e. when it starts now or a few weeks later) or strength of onset (i.e. whether the frustration or general well-being level is higher resp lower). But the coincidence explains very well any observation... and if there is a relationship it is very weak.

My 2008 posts

I am sorry that I haven't been posting for 2 weeks. Here are a few posts that I am thinking of writing about.

- the best research published in 2007.

- my predictions for 2008.

- that small defects can lead to big effects.

- Barry Guitar's book that I am currently reading and the things I disagree with, especially on environment and temperament.

- follow-up on the Zyprexa case study.

- any new research published.

- more focus on the importance on secondary symptoms

- the relevance of the Valsava mechanism

- looking into whether I can reycle some old but relevant posts, because readers rarely read the older posts.

- more on genetics and whether they say something about environmental influences.

- my suspicion on temperament being important in childhood stuttering.

- watching out that the Lidcombe people don't oversell their approach with flawed studies.

- computing the probability that a child who just started stuttering has a younger sibling born at the same time.

- the study that will compare between Lidcombe and demand and capacities therapy approach.

Any other suggestions?

Happy Xmas!

A speech and language research blog

I just found this blog on speech and language research, but they are definitely slower in breaking the news than TheStutteringBrain though they are obviously more generalist. See here.

The history of stuttering

It is just amazing how creative people are in drawing wrong conclusions, from wikipedia:

For centuries stuttering has featured prominently in society at large. Because of the unusual-sounding speech that is produced, as well as the behaviors and attitudes that accompany a stutter, stuttering has been a subject of scientific interest, curiosity, discrimination, and ridicule. Stuttering was, and essentially still is, a riddle with a long history of interest and speculation into its causes and cures. Stutterers can be traced back centuries to the likes of Demosthenes, who tried to control his disfluency by speaking with pebbles in his mouth. The Talmud interprets Bible passages to indicate Moses was also a stutterer, and that placing a burning coal in his mouth had caused him to be "slow and hesitant of speech" (Exodus 4, v.10)
Galen's humoral theories remained influential in Europe into the Middle Ages and beyond. In this theory, stuttering was attributed to imbalances of the four bodily humors: yellow bile, blood, black bile, and phlegm. Hieronymus Mercurialis, writing in the sixteenth century, proposed methods to redress the imbalance including changes in diet, reduced lovemaking (in men only), and purging. Believing that fear aggravated stuttering, he suggested techniques to overcome this. Humoral manipulation continued to be a dominant treatment for stuttering until the eighteenth century. Partly due to a perceived lack of intelligence because of his stutter, the man who became the Roman Emperor Claudius was initially shunned from the public eye and excluded from public office.
In eighteenth and nineteeth century Europe, surgical interventions for stuttering were recommended, including cutting the tongue with scissors, removing a triangular wedge from the posterior tongue, cutting nerves, and neck and lip muscles. Others recommended shortening the uvula or removing the tonsils. All were abandoned due to the high danger of bleeding to death and their failure to stop stuttering. Less drastically, Jean Marc Gaspard Itard placed a small forked golden plate under the tongue in order to support "weak" muscles.
Italian pathologist Giovanni Morgagni attributed stuttering to deviations in the hyoid bone, a conclusion he came to via autopsy. Blessed Notker of St. Gall (ca. 840–912), called Balbulus (“The Stutterer”) and described by his biographer as being "delicate of body but not of mind, stuttering of tongue but not of intellect, pushing boldly forward in things Divine," was invoked against stammering. Other famous Englishmen who stammered were King George VI and Prime Minister Winston Churchill, who led the UK through World War II. Although George VI went through years of speech therapy for his stammer, Churchill thought that his own very mild stutter added an interesting element to his voice: "Sometimes a slight and not unpleasing stammer or impediment has been of some assistance in securing the attention of the audience…"
For centuries "cures" such as consistently drinking water from a snail shell for the rest of one's life, "hitting a stutterer in the face when the weather is cloudy", strengthening the tongue as a muscle, and various herbal remedies were used. Similarly, in the past people have subscribed to theories about the causes of stuttering which today are considered odd. Proposed causes of stuttering have included tickling an infant too much, eating improperly during breastfeeding, allowing an infant to look in the mirror, cutting a child's hair before the child spoke his or her first words, having too small a tongue, or the "work of the devil."

Trying out medication: Week 10

Here is the week 10 update from one reader who is trying out Zyprexa (Olanzapine):

It's been 10 weeks since I started on the Zyprexa and so far I am a fan. I had the blood tests at week 6 and there were no elevated levels, so that was a relief. I increased from 5mg to 10mg at week 6 and the sedation effects kicked in but are now waning again, so thats a relief. I have gained around 10 pounds in weight, however I have been less active over the last 3-4 weeks, so I am sure that if I had been more commited to an exercise plan, the weight gain would have been less (very busy at work)

With regards to the speech - most if not all of the secondaries have gone, no more twiches and facial contortions which is a relief. I find that my anxiety about speaking situations has reduced and as a result I dont worry about rearranging my words in advance. Most of the "well", "actually" and "you knows" have gone to assist with the onset of speech - things seem clearer now. I would say that my speech has improved by 80% and with any remaining blocks, I can 'plow' through them easier with less struggle.

So far, I am a fan, and according to my doctor, the full benefits will not be evident for another few months.

Gene studies more tricky

I was quite enthusiastic about genetic studies, but I now realise that it is a bit more tricky than standard genetics.

There are two ways to look for genetic influences in a disorder. First, twin studies show the strength of the genetic component by comparing the probability of both twins having the disorder for the monozygotic (share the same DNA) and heterozygotic case. Second, you can look at affected families or populations to locate responsible genes in the chromosomes. The key is to associate a trait with the disorder. For example, blue eyes or red hair are good traits.

However, stuttering is more complicated. In stuttering it is not clear what the trait is. Stuttering is not really a trait as such, but symptoms, or I think what geneticists call a state. The real trait could be a dysfunctional motor region or the failure to initiate sounds properly. And, recovered stutterers might also have this trait but they do not stutter because they compensate well. And there might be many different traits leading to the same symptoms. Therefore, overt stuttering is only roughly related to the trait, and the signal strength of any research like twin studies or family trees will be significantly reduced.

Holger visits TheStutteringBrain

Holger Stenzel is visiting me in Luxembourg over the weekend. He is very interested in stuttering medication and writes a lot about his experiences and on current medication trials and research in forums. He took Olanzapine (Zyprexa) in a self-trial for two and a half year. He said that the duration and strength of block seems to have been reduced but he didn't experience a continuous improvement of his speech. He is currently not taking any medication.

Should females treat males?

There are many more female than male therapists and most patients are male. As we all know men and women are different, though old-fashioned science-ignorant feminists and post-modernist pseudo-philosophers would argue that gender is a purely social construct. But there can be no doubt that the body is different, the brain is different, and the mind is different. Luckily, nature has given us just about enough overlap in interest and abilities to live more or less happily side by side. :-)
I think few female therapists have the ability to behave outside of their nature, and naturally put more emphasis on areas and behaviours that work for them but that do not work for most men (with some exceptions as usual). Men do not mind talking about psychological and social issues, but we have an internal timer that rings after 15 minutes. We want to move on to something else. We do not need someone to listen to us, but someone that can help us solve our problems. We don't need someone who is constantly telling us Well done, but someone who shows us what we should do and in no uncertain terms tell us when we get off course. We want to do things and not talk about things.

Why are there so many women?

Most of the speech and language therapists are female, and most people who stutter are male. The differences are most apparent in Western Europe, especially the UK. The reasons for the high proportion of female therapists in Europe is of course not sexual discrimination against men, though this fallacious argument applies for all areas where men are in a higher proportion! More women than men are interested and naturally inclined to working with children with speech and language development (and with adults to a lesser degree), though the interest and ability argument of course does not apply for any area where men are in a higher proportion!

The situation is somewhat more balanced in the US. They also call themselves speech and language pathologists, and I believe that they have a more science-based education and not just based on administrating treatments. There is also a markable difference between Western and Eastern European countries, with the Eastern European countries being more science oriented. I see it at conference all the time: they usually don't run away when I talk science or stats! There is still some respect for physicists. :-)

And the proportion of males increases with seniority and focus on research as opposed to treatment.

The European hotbed of femaleness in treatment must surely be the Michael Palin Center in London where I have yet to meet a male therapist; it's just pure estrogen. :-)

Botox your stuttering away

I never stop being surprised about the extent to which people are searching for a cure or reduction of their stuttering: walking on all four, not speaking for 3 days, remove a part of the tongue, and so on. Now I have come across articles on botox and stuttering: see here at Judy's page. As always the studies show some promising results, and as always they are deeply flawed.

Comedy or not.

YouTube classifies stuttering as comedy, and Leys is battling them. You can sign an online petition against the YouTube classifications here.

Pagoclone outlicensing negotiations

One reader, Ora from New York, called Indevus directly and asked them! Here is what he wrote to me about his re-collection of the phone call. I want to make clear that I was not part of this phone call and cannot verify any statements:

Current plan is to partner the drug with a larger firm which specializes in central nervous system drugs. Pagoclone is a legacy drug for Indevus. It went through tests for generalized anxiety disorder. They discovered in the process that it helped stutterers who participated in the trials, and that the benefit subsided after treatment was stopped. They’ve gotten some good info from the Phase II open label extension (since mid-2006).
In the meantime, Indevus' corporate focus has changed. They’ve acquired another company this year. Their corporate focus has shifted toward urology and endocrinology, and pagoclone no longer fits. Although they are still positive on pagoclone, they’ve had to make a corporate decision whether to proceed with it themselves, or devote their attention to drugs within their core focus. They decided to outlicense pagoclone to another company.
The outlicensing talks are “in late-stage discussions”, and they hope to agree with partner by end-of-year. They are in “end stage negotiations”. Timing is uncertain to a degree, but they’re hopeful that they’ll ink the agreement by end-of-year. Might extend into first quarter 2008. They recommend keeping an eye out for Indevus press releases regarding the outlicensing deal, and then closely follow the plans of the new company, including contacting their corporate communications department.
One encouraging fact is that the safety data is very good. This data has come not only from the 132 participants in the stuttering study, but also from the previous studies for anxiety and premature ejaculation, so altogether they have safety data for (I think) about 1600 people.
They have had “end of phase II meeting” with FDA. FDA has asked them to do pediatric studies or incorporate into their trial design; if not, the drug would undoubtedly be prescribed by doctors for off-label use. In the US, any FDA-approved drug can be prescribed by a doctor for any condition, not just the approved diagnoses. So the FDA wants them to design their tests to include children so they have some real data instead of guesses and extrapolations.
I asked what the Phase III study would look like. It would depend on the new company. The design of the trial would depend on discussions with the FDA, and would be adjusted as necessary “to get this through”. The FDA has already been giving them a lot of feedback.

There is nothing really new. It is important to watch their actions on the outlicensing as opposed to their words. We cannot judge the state of such negotiations and need to wait until a public announcement by both companies.

Does fever reduce stuttering?

I have just read a fascinating article: see here.

Fever can temporarily unlock autism's grip on children, a finding that could shed light on the roots of the condition and perhaps provide clues for treatment, researchers reported on Monday.
It appears that fever restores nerve cell communications in regions of the autistic brain, restoring a child's ability to interact and socialize during the fever, the study said...He said the fever effect was believed found only in children, whose brains are more "plastic" than those of adults.

Before doing the same experiment with children who stutter, let's look for anecdotal evidence. I don't really know whether I am more fluent when I have fever. I have never really paid attention as a kid, so I cannot exclude the possibility. Does anyone of you observe such an effect?

A more sophisticated look at Pagoclone

bwapplegate posted a more sophisticated and more optimistic analysis of the current state of Pagoclone than I did in my last post, here! He seems to be an analyst. Here is his analysis:

Indevus (IDEV) typically does outlicensing deals on compounds they are developing. They've outlicensed several of the ones in their pipeline, including Sanctura and Sanctura XR, which are their flagship medications.
Outlicensing essentially entails up front payments to cover the costs of the Phase III trial in return for the ability to sell the drug once it is approved. Thus, IDEV is looking for a big pharma to come in and offer XXX million for the rights to the medication. They'd give milestone payments - to initiate PIII trials, at the completion of enrollment, at the submissison of the NDA to the FDA, and on approval. After that, IDEV would typically get a royalty payment based on sales of IDEV.
This situation is interesting because:
-IDEV has a colorful past, in which it was tested as a med for GAD and panic disorder but failed. Most people think that the success of pagoclone will not be for stuttering, but for off label use for anxiety.
-Trial design and cost issues. Stuttering trials are somewhat difficult to pull off. There are hazy outcome indicators, difficulties in standardizing patient accrual, and other trial issues. the Phase II trial took something like 15 months to enroll 120 subjects over 15 sites. That's not exactly a high enrollment rate.
-The FDA wants the medication tested on children as part of the approval process. this complicates the trial design, and further complicates the trial and significantly adds to the cost.
I do think that they ultimately will partner with someone in the next quarter to 6 months and that the trial will proceed after that. My sense that IDEV is trying to get a sweetheart deal.

Bad news for Pagoclone

Unfortunately, I have bad news to report. Some time ago, I reported here on my suspicion of a delay for the Phase III trial of Pagoclone which was supposed to start in Early 2007. I speculated that Indevus might consider the risks and investment as too high. I also warned that they would not announce such a delay or stop, but that we would only know about it by absence of any news, especially in the Year End report. That's exactly what is currently happening. They have just published their Fiscal 2007 report (see here on CNN), and Pagoclone (unlike in the 2006 report) is nowhere mentioned. Except when Dr Cooper from Indevus cryptically says:

Finally, through our other business development activities, we successfully outlicensed aminocandin and IP 751 and we have discussions ongoing for the outlicensing of pagoclone, all designed to further focus our efforts in urology and endocrinology

Compare his statement in last year's report:

We are also optimistic about the positive results of our pagoclone Phase II study in stuttering and the upcoming initiation of our Phase III clinical program.

Unfortunately, my instincts tell me that the "on-going discussion" is a way of spinning bad news. Instead of saying "we are not going forward with Pagoclone and this is our third aborted attempt to find a disorder for Pagoclone", they say "we are in on-going discussion for outlicensing of Pagoclone. We are doing good because we make money by out-licensing". You can always say that you have on-going discussions, and of course they are secret so you can't reveal any details.

There was an analyst conference call today. Surely, some analyst is going to ask the question. If they are any good... If anyone has the link or transcript, please let us know.

Do bats stutter?

Have a look at this news article on bats and stuttering. That's how you sell your research. Bats seems to have simple forms of speech capabilities, but whether this leads to a better understanding or treatment of stuttering is far fetched. But it might be interesting to study whether some stutter, indeed. Here is the text:

SAN ANTONIO, Nov. 5 (UPI) -- Scientists in Texas hope the study of bat brains may eventually lead to better hearing aids or new treatments for human speech disorders like stuttering.

Using ultrasonic microphones, researchers at the University of Texas and Texas A&M have discovered bats combine sounds into a basic sort of syntax that they use to communicate and express their individuality, The San Antonio Express-News reported Monday.

"There are no animals that can kind of speak," says Michael Smotherman, a neurophysiologist at Texas A&M who is trying to identify the areas of the brain the bat uses to coordinate sounds into songs.

Smotherman hopes his research will lead to better understanding of stuttering a dysarthria, a speech disorder characterized by poor articulation.

At the University of Texas in Austin, bat researcher George Pollak is trying to understand how the bats process the social communication sounds they hear and how they recognize individual calls.

Pollak says his research could lend itself to developing hearing aids that differentiate and screen out background noise.

Recovered and persistent kids show abnormalities

I have already spoken about the important brain imaging work by Soo-Eun Chang from Christy Ludlow's group at NIH, and the department of Speech and Hearing Sciences at the University of Illinois at Urbana-Champaign. Let me put it up again as it is very important. They looked at the brain of children who do not stutter, who recovered from stuttering, and who did not recover:

Previous imaging studies in adults with persistent stuttering found left white matter deficiencies and reversed right-left asymmetries compared to fluent controls. We hypothesized that similar differences might be present indicating brain development differences in children at risk of stuttering. Optimized voxel-based morphometry compared gray matter volume (GMV) and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts in 3 groups: children with persistent stuttering, children recovered from stuttering, and fluent peers.

The results:

Both the persistent stuttering and recovered groups had reduced GMV from normal in speech-relevant regions: the left inferior frontal gyrus and bilateral temporal regions. Reduced FA was found in the left white matter tracts underlying the motor regions for face and larynx in the persistent stuttering group. Contrary to previous findings in adults who stutter, no increases were found in the right hemisphere speech regions in stuttering or recovered children and no differences in right-left asymmetries. Instead, a risk for childhood stuttering was associated with deficiencies in left gray matter volume while reduced white matter integrity in the left hemisphere speech system was associated with persistent stuttering. Anatomical increases in right hemisphere structures previously found in adults who stutter may have resulted from a lifetime of stuttering. These findings point to the importance of considering the role of neuroplasticity during development when studying persistent forms of developmental disorders in adults.

Let me rephrase in common language:

1) Brains of both recovered and persistent stuttering children show structural abnormalities.

2) Right side abnormalities in volume increases found in adults are absent in (recovered and persistent) stuttering children.

3) Stuttering in children is associated with left side abnormalities, and persistence specifically associated to white matter abnormalities.

Let me lean out of the window by saying that

1) The existence of right side abnormalities in volume increases in stuttering adults but not in children strongly suggests compensatory activities that made some right side regions grow.

2) These regions are mainly to blame for relapse in adults because they are more or less hard-wired.

How should the others behave?

I got an email from a student in speech sciences and she was asking about my opinion on what listeners should know when engaging in a conversation with someone who stutters.

1) There are no golden rules; different pws prefer different behaviour.

2) It would be good if they knew the basic facts about stuttering, e.g. high heritability, likely neurological cause, not due to nervousness, high variability of dysfluency from completely fluent to severe blocking, inability to say exactly what you want to say and so on.

3) Better understanding of stuttering itself automatically leads to better behaviour.

4) I am against rules on behaviour as they tend to make people mechanically following them.

5) The pws can do most to ease any tension and he/she has also a responsibility here. Unless you want to be the helpless victim. And after all, most have never seen someone like you before, so you should inform them that you won't bite them. :-)

6) It is practically impossible to educate the whole world.

What is your opinion?

Progress by death

In physics, we have the saying "Progress is not achieved by changing people's mind but by people with wrong ideas dying out!" or "Professors with disproved theories never change their mind, they die out." At the core of this effect is the mental bias people have for the theory they believe in. The mental bias is stronger the more you have invested. Just imagine a professor at the age of 50 spending 25 years of his or her life working a specific method or theory, and it is not working. I rarely see them give up, because they have too much at stake. There are some exceptions, but then they never had very strong beliefs.

And the same is true in stuttering. Very little people will change their mind, for example that stuttering might have a physical basis despite overwhelming evidence.

Should we go to China?

A reader wrote in response to my last post on the 2008 ISA conference in China:

Be interested on your views on China, read your blog. I am just a bit concerned about China - still seems to me to anything but a free country. I have a problem supporting an international meeting where your blog would probably be banned if you said anything critical of the government.

I agree that China is not a free and democratic country, and they would probably ban my blog if I said something critical. Especially, regarding my views on the Tibet and Taiwan issues. However, if I were the China ruler, I would probably also restrict freedom of speech and especially of movement of people around China with force if needed. China needs a smooth and slow transition from a state-planned economy and society to a more open society with a market economy. I suspect that the rulers follow this path even though they (have to) publicly endorse communism. But I could be wrong. Also, China is not a lawless dictatorship, and there is a rule of law in that you cannot easily be arrested without reason or evidence, thrown to prison and executed. Though the laws themselves obviously restrict political freedom and the people have no power to influence them. Russia is in a similar situation. I strongly believe that with the market-based economy leading to a greater exchange with other societies and improvements of quality of life the democratic forces are getting stronger and win in the long-term. So in a sense, I agree with both sides: keep on pointing out human rights abuses, and keep on controlling society to ensure a smooth transition.

Regarding support for a conference in China, politics does not play a direct role in my view. The conference is about people meeting up: stutterers, therapists, researchers, and others. It is a sign that China is opening up. (Of course, the Olympics is coming in 2008.) The conference could also have a significant impact for Chinese stutterers. It is important to talk about stuttering in the Chinese media, too. China has 1.3 billion people, 13 million stutter, and if only 1% reads my blog, I have 130'000 readers as opposed to 150 per day! :-)

To conclude, I support a conference in China but will not shy away from voicing my dissent on human right issues. What's your opinion?

北京2010 年 (Beijing 2010)

The next world conference of the International Stuttering Association is going to be in Beijing in 2010. I am convinced that they will produce a great conference. I have always been amazed by the sheer endless determination and intelligence of the Chinese people (apart from some political lapses... some of which might be understandable given the historical baggage). I wonder how traditional Chinese medicine treats stuttering. I have never been in China, but I definitely plan to go one day. So maybe the conference would be a good excuse. Here is the text from the ISA website:

It's official, the next World Conference of the International Stuttering Association will be held in Beijing, China in 2010. Yes, the newly formed Chinese Stuttering Association will host this world event in cooperation with the China Rehabilitation Research Center, Beijing Normal University and the China Medical Academy so it is sure to be a another well organised, well atttended, exciting and informative event following on from the previous ISA congress successes in Croatia, Australia, Belgium, South Africa, Sweden, Germany, USA and Japan so start planning ahead now to be part of this inspiring event. If you have any way you can assist our Chinese organising committee please contact the head of the conference organisaing committee, Zong-Shan Li at lzsh@ibcas.ac.cn. More information when it comes to hand.

Ben's brother stutters

This is a really cool song with a very cool BritPop/Rock sound. Check out Ben's brother's website and MySpace. I am wondering whether someone of them is stuttering or not. I am convinced they will hit the chart, if they haven't already. Just look at their very professional website, they are surely getting pushed by a record company.

Thx to Einar for the tip!

Wikipedia entry

I changed the Wikipedia entry on stuttering to reflect the latest empirical evidence from brain imaging.

There is little evidence of structural differences in the brains of stutterers. However, differences in auditory, linguistic and motor functions have also been proposed to account for the disorder. Research is complicated by the possibillity that differences noted between stutterers and non-stutterers are the consequences of stuttering rather than a cause.^[11]

to

"There is clear empirical evidence for structural and functional differences in the brains of stutterers. Research is complicated somewhat by the possibility that such differences could be the consequences of stuttering rather than a cause, but recent research on older children confirm structural differences thereby giving strength to the argument that at least some of the differences are not a consequence of stuttering.

I am sure someone is going to undo it again because it doesn't fit with their views. But I gave the references to the two new research articles by Watkins et al and Chang et al. I also noticed that they take out a link to my blog when I include it for further reading!!

Get a daily update on stuttering research!

If you want to get the latest research articles without reading my terrible comments and including those that I find boring, you can search "stuttering" at the PubMed website. The website has all published articles from the last decade or so.

You can even register at the website, and get an daily update for a search on stuttering. Just go to the site, register, confirm your email, do a search on "stuttering", "Save Search", and link to an email alert.

The taboos of the stuttering community

Every community has its taboo topics or words. Taboo topics are aspects out of our reality that are best not to be spoken about, certainly not to be discussed. Here are a few statements where you can get in trouble for even suggesting them for debate though they are not obviously wrong and at least debatable. In Japan: "The Japanese army is responsible for forcing Chinese women into prostitution during World War II." In Germany: "Not all Nazi policies were bad, e.g. the construction of Autobahns or the sense of community and purpose." In the US: "There is not reason why the US should have a special relationship with and blind support of Israel." In China: "The Taiwanese and Tibetan people should be allowed to decide their own destiny". Even in the no-taboo porn industry, there is a taboo topic: STDs!

Also in scientific debates we have taboos as the Watson and Larry Summers sagas show. You cannot ask the following questions without fear of being sacked. Here are a few examples: Do Blacks have on average a lower IQ and Jews on average the highest IQ among races? Are there innate differences between males and females that could help explain the high representation of male university science professors / Nobel Price winners and CEOs?

Do not expect a reasonable debate on any of these topics. The pattern is generic. First, the questioner is labeled a racist, Nazi-sympathiser, unpatriotic, sexist, or anti-semitic. Second, therefore these people are evil and stupid. Third, therefore they must be wrong. End of debate.

What are the taboos in the stuttering "community"? Let me know what your thoughts are. Here are a few candidates:

- Many stutterers prefer not to listen to people who stutter, and do not want a partner who stutters.

- Stuttering is a handicap, and stutterers cannot do every job.

- There are stutterers who did bad things. For example, we have Ben Johnson, the Canadian super sprinter who was convicted of doping. He is never mentioned as being a famous stutterers. How about criminals, serial murderers, and rapists.

- Most research in stuttering, especially those conducted by therapists, is a complete waste of time, and those low-quality researchers should be told about this rather than being congratulated for "the hard work they have done".

- Stuttering can be completely explained in scientific terms.

- Stuttering medication could well be helpful to people who stutter.

- Treatment for children is still not proven beyond doubt to be effective in the long-term.

- The majority of those who talk at conferences and claim that they cured themselves never actually stuttered severely.

- There is nothing physically wrong with *some* covert stutterers.

- The use of the word "holistic" is a reliable measure for poor quality in thinking.

- It is a good and necessary thing to take on crackpots and undertake every action possible to limit their ability to spread their message.

Taboo word No. 1: Cure, cure, cure, cure.

European Symposium on Fluency Disorders

There is a new conference coming up in Belgium in April 2008: the European Symposium on Fluency Disorders: see here for more information and a detailed program of speakers. The conference is organised by Kurt Eggers who works as a lecturer and clinician at the Lessius University College. I met him at the Oxford Dysfluency Conference in 2005, I think. He is currently doing a PhD on the role of temperament in stuttering and his PhD supervisor is Luc de Nil.

I will attend. It is only 2 and a half hours away from Luxembourg. The most interesting speakers for me are Luc de Nil with a summary of past brain research, and Nicole Ambrose on possible genetic factors for subtyping. Some talks are given via video conference link which is an interesting concept. I'll be curious how it works out!

Crackpot award for Bodehamer

I have decided to continue my crackpot awards: see here, and here. But I am now going to include anyone who proclaims theories on stuttering that are completely ignoring well-established neuroscience facts on stuttering from the last 10 years. I mainly think here about structural and functional brain differences in young and adult people who stutter, and about genetics. Bob Bodehamer is a "good" example:

The cause: There could be several causes for blocking including genetic predispositions and/or developmental problems. However, our concern is not primarily about the first cause of blocking. Our concern is with what has continued the behavior. We believe that it is the meanings placed around those early experiences of struggling to speak that have become well learned which continues the behavior. This explains how most children grow out of stuttering while some don't - it is about the meanings that the child placed around the behavior.

This statement is just plain non-sense in the light of the most recent research. He permits that these first blocks could be triggered by genetics, and these blocks are enough to learn bad habits which results in long-term stuttering. So what happens to the genes afterwards? Are they self-destructing and not play a role anymore? Also, brain scans clearly show that the brain structure of adults and young people who stutter is different than fluent speakers. There is a physical manifestation. People who stutter do not have misplaced meaning, they have misplaced brain structures. In fact, what is happening is that the physical cause STAYS THERE even for children who recover, and provokes learned behaviours for those who don't.

He should stop playing the theoretician. Science is not theology, his day job as a Southern Baptist pastor. The empirical reality informs the theory, and not the other way around. I just hope he at least does not think that the Earth was created 7000 years ago. If he wants to contribute constructively, he should acknowledge that stuttering has a clear physical component. And no-one is disputing that the effects are also learned behaviour. And here is where he can use his NLP to minimize the effects, but I doubt it is any more effective than other treatments.

Shameless advertising

This is just so bad and fits perfectly with what I alluded to in my tirade on media portrail of stuttering: see here.



I am wondering whether she is still using the device. Would be great to have her write a post on this! So if anyone knows her, let her know that I would love to hear from her.

Trial Start: DCM vs Lidcombe

Good news from Marie-Christen Franken! She has now received funding for a large-scale trial to compare the demands & capacities treatment to the Lidcombe treatment. And they have already enrolled children.

They have already published a pilot study: see here. Based on a relatively small sample and no long-term outcome measure (both are essential for a good trial!), they could not see a difference between both treatments:

This pilot study compared two treatments for stuttering in preschool-age children.Thirty children were randomly assigned to either a Lidcombe Program (LP) treatment or a Demands and Capacities Model (DCM) treatment. Stuttering frequencies and severity ratings were obtained immediately before and after treatment (12 weeks). The stuttering frequencies and severity ratings significantly decreased for both treatment groups. No differences between groups were found. Parents of children in both groups were cooperative in many respects, and there were no differences between them on scales that measured their satisfaction with the two treatments. The findings suggest that randomized controlled trials of LP versus DCM treatments are feasible, and they underline the need for experimental analyses of the two treatments. EDUCATIONAL OBJECTIVES: The reader will be able to: (1) describe the principles and methods of Lidcombe treatment for early stuttering; (2) delineate principles and methods of Demands and Capacities Model treatment; and (3) summarize results of an investigation that compared these programs' relative effects in a pilot study.

I am very curious what will come out. My guess is no big difference between both treatments. Though I am concerned that the statistics and research design like in the Lidcombe trial will be flawed. Another interesting twist would be to have a third non-treatment arm.

Meeting Marc Shell at Harvard

As you can see Marc Shell has changed a bit over the years. I guess this is what happens when you become a professor of comparative literature at Harvard University. Marc even has his own wikipedia entry, and of course he stutters. He recently wrote a book on stuttering, literature and his own experience called Stutter.
I met up with him on my East Coast stop-over from my California trip back to Europe. Boston was my first stop. The day started badly. I had arranged two meetings with two professors and they both canceled at the last minute, but then agreed to meet up upon my insistence. In the morning, I had a meeting with a professor at Harvard Business School who also wrote a book on venture capital, like myself. Mine is called Exposed to the J-curve. In the afternoon, I was supposed to meet up with Marc at 4:30. In the mean-time, I was sitting in a coffee shop at Harvard Square soaking in the atmosphere with free WiFi. And I played chess against the scrubby "chess master" outside in order to uncover him, but much to my surprise he was a true chess master with international rating and I lost all my games and money! I also have international rating and played in the World Junior Championship for Luxembourg but I am not at master level. Then I went to the English department, but Marc Shell didn't show up. I was just about to leave when the secretary run after me and called me back.

We had a good discussion on stuttering and on stuttering research. We especially talked about how more money could be channeled for stuttering research. Though I have to admit that at first it was a bit surreal to watch Marc Shell in action when the discussion turned from daily talk to intellectual. His words were chosen in such a way that my mind went blank. I mean I heard his words but didn't understand what he was saying. When science meets the arts... I noticed that his words are more loaded with specific meaning. So when I say functional I mean something that has a function, but he probably gives it a more specific meaning in the context of a given theory. He also comes up with many interesting subtle connections and ideas which make logical sense but are often not necessarily of relevance to explain the basic aspects of a phenomena.

Phase III Pagoclone trial delayed?

I know how interested every here is in stuttering medication, especially Pagoclone and its clinical trials. Some time ago, I posted a press release from Indevus about their intention to start a Phase III clinical trial in the first half of 2007: see here.

However, as of October 2007, I do not know of any evidence that the Phase III trials have already started, except the existence of waiting lists for the trial. (If you are currently part of such a trial, please let us know.) I can only speculate on this delay. First, any kind of project is often delayed by a few months for any reason. And therefore there is no reason to be concerned. Second, Indevus might have become more hesitant, and are having second thoughts. Such a re-evaluation might be in terms of efficacy, or in terms of a business decision. A re-evaluation also often happen irrespective of efficacy concerns after changes in management, the board of directors, or general strategy. For example, if Pagoclone only applies to a minority, the profit estimates might be severely affected. Such trials are very expensive, often in the tens of million dollars. On the other hand, an approved drug would have significant revenues. Indevus might also underestimate the potential market even as a "minority" drug, and therefore find the risks too high. One concern might also be their cash burn rate, i.e. they spend money without getting money back soon, and they might be looking for a partner like a venture capital fund or another pharmaceutical company to share the risks: see this intriguing conference call one year ago. As I said, I am only speculating by putting myself in their situation, based on public knowledge and based on my understanding of corporate thinking.

We will find out in the next months. However, should Indevus decide against a Phase III trial, which I hope they won't, do not expect a press release. Indevus has already stopped Pagoclone as an anti-anxiety drug and for premature ejaculation, I believe, and a third U-turn would reflect badly on them. A more likely scenario is that they postpone and delay release as long as possible, and the news appears somewhere in an annual report on page 130 in terms of a lack of provisions for Pagoclone. For example, the year-end 2007 balance sheet will be audited in March. So, the longer the trial is delayed, the higher the probability that they have indeed changed their mind.

On a side note, a detailed article on the Phase II clinical studies has not been presented at any conference or published in a peer-review journal, as far as I know. The only information comes from the Indevus press-release and conference calls to analysts: see here. However, at some point, such an academic discussion with a closer look at the data must happen.

Let's hope that this post is a storm in a teacup! Let me know when some of you are participating in a Phase III trial.

Trying out medication: Week 4

Here is the four-week report on taking Zyprexa: see here and here for earlier reports:

Four weeks into the Zyprexa Zydis and so far, so good. The first week or so was very tiring indeed, my energy levels were sapped and I was very sedated. After about 10 days my energy levels resumed and I felt fine. My facial ticks/secondaries are all but gone, as I don't have to struggle so much to get the words out. In the past my stomach used to get into knots from forcing out the words, this has also stopped as the words seem to flow better. I no longer think about speech all the time, its a refreshing change after 30+ yrs as my mind seems clearer and I can focus more. I am less anxious in speaking situations. I am still a stammerer, don't think that this drug is a "magic cure" because its not, what it enables me to do is relax and seems to make the speech timing improve as I don't have the blocks anymore when initiating speech. Weight gain has been slight - I would say about 5-6lbs, however my weight fluctuates by 2-3lbs per week up and down anyway, and I can exercise off this weight gain without any worries. To sum up....."So far so good"........ My doctor said that when he saw me after 3 weeks, he could see an improvement in my speech and my eye contact. I will be having a blood test at 6 week and may well increase the dosage to 10mg as long as the sedation effect is not too much. I imagine that this treatment works better on some sub-types than others, and its working so far. I will let you know what the blood tests show in 2 weeks.

The second brain paper

The second article is now in press at NeuroImage. The main author is Soo-Eun Chang, a post-doc in Christy Ludlow's group at NIH (National Institute of Health) in Bethesda close to Washington DC. She is a speech and language pathologist by training. I had the pleasure to meet up with her and Christy for lunch on Wednesday before I took the plane back to Old Europe. Our discussion topics included their work and stuttering medication.

Here is their abstract of Brain anatomy differences in childhood stuttering by Soo-Eun Chang, Kirk I. Erickson, Nicoline G. Ambrose, Mark A. Hasegawa-Johnson, and Christy L. Ludlow:

Previous imaging studies in adults with persistent stuttering found left white matter deficiencies and reversed right-left asymmetries compared to fluent controls. We hypothesized that similar differences might be present indicating brain development differences in children at risk of stuttering. Optimized voxel-based morphometry compared gray matter volume (GMV) and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts in 3 groups: children with persistent stuttering, children recovered from stuttering, and fluent peers. Both the persistent stuttering and recovered groups had reduced GMV from normal in speech-relevant regions: the left inferior frontal gyrus, and bilateral temporal regions. Reduced FA was found in the left white matter tracts underlying the motor regions for face and larynx in the persistent stuttering group. Contrary to previous findings in adults who stutter, no increases were found in the right hemisphere speech regions in stuttering or recovered children and no differences in right-left asymmetries. Instead, a risk for childhood stuttering was associated with deficiencies in left gray matter volume while reduced white matter integrity in the left hemisphere speech system was associated with persistent stuttering. Anatomical increases in right hemisphere structures previously found in adults who stutter may have resulted from a life-time of stuttering. These findings point to the importance of considering the role of neuroplasticity during development when studying persistent forms of developmental disorders in adults.

We'll find out whether Neanderthals stutter

Check out this interesting article: Neanderthals May Have Had Genes for Speech. The scientists have found FOXP2, a gene that in humans is known to relate to grammar/speech, in Neanderthal DNA. It is fascinating that we can now look at ancient DNA.

Once we have singled out the stuttering genes, we can also look at whether Neanderthals have these genes. Maybe they got extinct, because they were stuttering much more that modern humans!!!

Meeting the Inghams in Santa Barbara

The weekend before last I drove up North to Santa Barbara to meet up with the Inghams. They are both professors in speech science at UCLA at Santa Barbara and clearly among the leading scientists in stuttering research. They were so kind to invite me to stay at their place. They have a fantastic house in the hills of Santa Barbara. Roger Ingham showed me around in his BMW with the words "I like it much better than my Ferrari that I had before"... :-)

We had very good scientific discussions but also engaged in gossip. They were not too enthusiastic on medication to reduce stuttering due to lack of good evidence. I was questioning how this fits in with several reports (see previous blog posts) from people who stutter who took a medication and said they improved. The discrepancy might be due the existence of sub types. Or because the gains are not overt, but internal. I argued that stuttering is not just a malfunctioning of communication of the message from the person who stutteres to the listener, but that stuttering also affects the mental creation and therefore quality of the message. People who stutter either spent a lot of efforts avoiding or generating fluent speech or dealing with secondary symptoms and states of anxiety. This leaves them much less room to create good messages. I am so much better at creating messages when I stutter less and am not under time pressure. And, the medication might make this easier. Or, there were no improvements apart from placebo-enduced and due to weak methodology.


I also discussed with Roger Ingham his past, current and future research. He has a multi-million research grant and still works very closely with the brain researchers around Peter Fox in San Antonio (Texas). The Inghams go to Texas and stay there for longer periods of time, though they did not express great admiration for San Antonio's beauty. Regarding research, they are clearly moving in the direction of theory testing using methods like TMS (knocking out brain regions temporarily) to test causality, and dual tasks and fluency-enhancing setups to control the driving variables of stuttering better.