Monday, April 30, 2007

CNN talks about stuttering

Having CNN's Dr Gupta talking about stuttering is of course more authoritative than myself writing 100s of posts on my blog! So I don't want to hold back on the message, after all we learn that Jerry Maguire really wants to be Donald Duck: :-)

GERALD MAGUIRE, DR., UNIV. OF CALIFORNIA, IRVINE: I remember in kindergarten, first, second grade, I would imitate cartoon voices in class when I would be called upon. Hello, my name is Donald Duck or whatever. I haven't done them for a while, but...
GUPTA: Jerry Maguire grew up to be Dr. Maguire.
MAGUIRE:I likely stuttered the rest of my life.
GUPTA: A psychiatrist and researcher at UC Irvine, Dr. Maguire is one of the world's leading experts on stuttering. He's one of a growing number who believes stuttering is not caused by a psychological weakness, but by an anatomical problem in the brain.
MAGUIRE:We're learning that stuttering is actually a miscommunication of the brain speech centers with the mouth, throat, and tongue in getting the words out.
GUPTA:To better understand, let's take a tour through the brain. First off, this is the basil ganglea (ph), which controls speech. In people who stutter, it is believed the striatum is bombarded with too much dopamine.
MAGUIRE: We found that the medication was effective in reducing stuttering in over half, in over half the patients.
GUPTA: Pagaclone doesn't cure stuttering, but it does curb it.
MAGUIRE: I believe that the future of stuttering treatment will combine therapy and medications both.
PATIENT: Well, now, I have a free flow of thought that I've never experienced before. It's kind of weird. It's like a, kind of a revelation.

Sunday, April 29, 2007

Dysfunctional stop signalling??

In a previous post, I talked about stop and go signal.

I have to clarify my message. It is not an inability to stop movement, but the inability to start because of an inability to produce stop signals that decay properly in-time, which is a different statement. So if people who stutter are at their final syllable, they send a stop signal and that's why they stop. BUT were they to attempt one more syllable, the start signal would take a long time to become dominant due to an abnormally strong and slowly decaying stop signal. This could be due to a weak go signal OR a strong stop signal that stays too long in the system!!We can say a word when the go signal dominates the stop signal. Because of the dual nature of there being a competing go and a stop signal in a motor system, a dysfunctional go signal is not the only suspect.

And a more empirical argument.

Think about the blocks we are having. For me not being able to say a word, feels more like trying to drive with the hand brake on and not like being unable to start the car. I can feel that the syllable is "ready" in my brain, but something is holding back. And then suddenly this resistance vanishes. And on some days there is less resistance...

No shared environmental influence!!!!

At last, I can report of an interesting piece of research. The authors Dworzynski, Remington, Rijsdijk, Howell, and Plomin have used data on 1000s of twins to study genetic relationships in recovered and persistent stuttering: see Am J Speech Lang Pathol. 2007 May;16(2):169-78 or here. Remember twins can be monozygotic (the same DNA), or dizygotic (share roughly half the DNA like siblings do). If the monozygotic twins share a disorder more often than dyzygotic twins at statistical significance, then the disorder is genetic because the only difference between them are the fact that they share either all the genes or roughly half the genes. Though the interesting aspect about twin studies is that you keep the environment relatively fixed, i.e. twin grow up in the same environment. A second advantage is that technically speaking this is simple statistical computation, that even non-quantitative researchers should not be able to mess up. There are surely negatives but I am not sure, probably the inability to locate genes.

Building up a twin pool is hard work but very lucrative scientifically speaking and ensures divine reverence by other scientists. Every research field undertakes a pilgrimage to these pools, and after worshipping the holders of the holy pool are allowed access to study the genetic influence.

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

Monday, April 23, 2007

Briefer on basal ganglia

Here is a description of the basel ganglia that Rafael sent to me. Actually, it's from Per Alm and published in the proceedings for the IFA conference in Dublin 2006.

The basal ganglia circuits are organized in a direct and an indirect pathway. These two pathways are assumed to work in synergy to modulate the activity of the frontal cortex: the indirect pathway providing a diffuse inhibition of cortical activity and the direct pathway providing focused activation of the desired action. Furthermore, the two pathways are dominated by different types of dopamine receptors, D1 vs. D2, resulting in differential effects of dopamine. The cueing functions of the basal ganglia to the SMA are dependent on a clear distinction between focal activation and the surround inhibition of the cortex, in other words, a good signal-to-noise ratio. Based on this model it is easy to imagine that the cueing of the basal ganglia can be distorted in different ways. Too weak focal activation of the direct pathway would result in deficient activation of the desired action, for example difficulties in initiating speech movements. On the other hand, impaired diffuse inhibition of the cortex, provided by the indirect pathway, could result in a combination of release of unintended movements and impaired release of the intended movement. These scenarios have clear parallels with the symptoms of stuttering. Basal ganglia motor disorders are characterized by motor initiation problems, involuntary movements, and deregulated muscular tension, often with co-contraction of antagonistic muscles.

Thursday, April 19, 2007

Do we fail to stop rather than to go?

Several researchers describe stuttering as the failure to properly initiate a sound. They also talk about the disturbance in the go signal. Today, I read a very interesting article by Vanderbilt psychologists Boucher, Palmeri, Logan and Schall about how the brain decides when to start or stop movements. The graph above shows the activation of the start and stop neurons; the task is pressing a button when green and stop when red. There are really two processes in the brain battling for supremacy!

Here is the essence of the article:
"We think of people who are impulsive as acting too quickly," Logan said. "Kids with ADHD are actually slower on the 'go' task than the control kids. It's not that they go too quickly; they stop too slowly."
Take this concept to stuttering, and maybe people who stutter are actually OK on giving the go signal, but are BAD AT GIVING THE STOP SIGNAL TO THE PREVIOUS SOUND. So a block is not actually the failure to have a go signal, but a failure to initiate a stop signal to the previous sound. It is worth pointing out that every human often corrects sounds that are ready to say, but may be we cannot actually send the stop signal to this sound and therefore disturb the go signal for the next sound.

Tuesday, April 17, 2007

The 60-million dollar gamble!

You might criticize the pharmaceutical industry at times for high prices and profiteering, but they are really the only ones that are willing to take the high risk to heavily invest in pharmaceutical research.

Publicly traded companies need to disclose their quarterly financial reports. And you can access Indevus' financial report (thx for the tip, Holger!). These reports also include cashflow forecasts on the potential costs and income over the coming years. They estimate to spend about 60 million dollar on Pagaclone:
Given these uncertainties and other risks, variables and considerations related to each compound and regulatory uncertainties in general, we estimate remaining research and development costs, excluding allocation of corporate general and administrative expenses, from December 31, 2006 through the preparation of an NDA for our major compounds currently being developed as follows: approximately $9,000,000 for NEBIDO, $14,000,000 for PRO 2000, approximately $46,000,000 for IP 751 and approximately $61,000,000 for pagoclone for stuttering.

I am convinced that rival companies are currently working backstage to decide whether to join the hunt for a stuttering drug. We should be glad about such a development, as more money goes into stuttering research.

Does ADHD make it harder to become more fluent?

Lynne wrote an interesting comment:
My teen son has been diagnosed with ADHD-inattentive type and has stuttered since age 2 or 3. I have always felt that the two were tied together. He has a hard time using the techniques, and if he does, it's hard to concentrate on anything. Processing speed in class is much slower than what is expected and makes the task and speech worse if he is made to hurry.--Lynne
There are some researchers like Per Alm who see a link between the two. Lynne's son might have had some mild neurological incident around age 2-3 and therefore develop stuttering and ADHD-like symptoms. However, it might also be a pure coincidence. For example, some kids stutter and have asthma. That does not necessarily mean that both are related to each other. The kid might just have been unlucky to get both.

Nothing special here. But Lynne's observation is intriguing: ADHD-like symptoms seem to make applying speech techniques much more difficult. Based of this assumption, I can formulate the following prediction. Let's assume you have two possible casual sources of childhood dysfluencies: genetic (design flaw) and neurological incident (design implementation flaw). Kids with either or both of them start stuttering. Their brain tries to compensate to produce fluent speech. The kids with neurological incident are more likely to have ADHA-like symptoms, and are LESS ABLE to compensate. They are therefore LESS LIKELY to recover.

So I would predict that the share of stuttering kids with bad genes as opposed to neuro incident should DECREASE over time!!!

Tuesday, April 10, 2007

Looking to share room at ISA2007

After some hand-twisting from Suzana, the fabulous conference organiser, I am going to the ISA world congress in Dubrovnik in Croatia, and will give a talk on random control trials in stuttering.

I want to stay at the congress hotel itself, but a single is too expensive and therefore I am looking for someone to share a room with me.

Wednesday, April 04, 2007

Tom's oracle

Being dysfluent does not seem to be the only dysfunction we have. I have spoken about sub-standard dual tasks performance before. People who stutter are not good at learning or doing dual tasks (the details are a bit more subtle). Professor Webster from Canada was the first to study this experimentally; an excellent piece of science in the midst of the common appallingy low quality and headless research in stuttering.

Why should we be worse in some dual tasks???


We need to find out why. If we succeed, we will understand stuttering much better. And no-one can claim to understand stuttering if they cannot explain this effect.

This line of research is the key to the stuttering mystery, and a feast for a scientist:
1. it is not about speech. (but stuttering is supposed to be a speech disorder!)
2. it is a reproducable effect. (try to reproduce the same stuttering!)
3. it is a measurable and quantifiable effect. (try to quantise stuttering severity properly!)
4. it is free of psycho and behavioural noise. (try to disentangle how much of stuttering severity is bad habit, how much situational and how much fundamental!)