Passed my neuroscience course

I just finished my first neuroscience postgraduate course at the Open University on Neural networks & Cognitive Neuropsychology. (Another reason why I have not been posting as often) I passed, which might come as a shock to those who so far dismiss my arguments on the basis that I only have a PhD in physics and they have studied X, Y, Z. In fact, I got 90% in my final essay, and 75% in my assignments. I am posting my essay as evidence! I hope you enjoy. Please feel free to comment.


ECA DS 871
Author: Tom Weidig
Words: 4820 words with references


The advent of connectionist modelling represented a considerable blow to proponents of the neuropsychological approach.


Imagine you have a wrinkly dirty fatty pulp in front of you. You can study the fine microscopic details, find the nerve and glia cells, and still have only increased your fascination for the brain. This pulp is a dead fellow human's brain which analysed sensory input and listened to Chopin's nocturne, generated mental processes and deviced a plan to rob a bank, stored information and remembered childhood memory of the little creek behind their house, and controlled a body and hit his opponent a bloody nose. But you have no clue how the brain did what it did. What do you do? You might also be a doctor, and witness the diverse strange behaviour of patients with strokes or blows to the head. He comprehends speech but cannot speak any more. She can speak but not comprehend speech any more. He doesn't like his left arm any more and wants to get rid of it. Her memory span is restricted to five minutes telling you the same joke over and over again and laughing to your same joke every single time. There must be a pattern behind the functional break-downs giving clues to the organisation of the brain. You cannot look inside a living brain, but you can do a post-mortem anatomical examination looking for abnormal brain structure and relating your finding to observed deficiencies.


That's pretty much the atmosphere and constraints within which cognitive neuropsychology emerged. Clinicians were faced with a plethora of deficiencies caused by strokes, brain injury or brain disease, and the science-minded ones wanted to know what caused A to only loose speech comprehension and B only to loose speech. And with the hope that the study of these special brains sheds light on the normally functioning brain. The French physician Paul Broca's research is one of the earliest examples on how you can understand the normal brain better by looking at the damaged brain. He systematically studied aphasic patients, patients with speech production issues, post-mortem, and found lesions in the inferior frontal lobe of the left brain hemisphere - an area that is now known as Broca's area. His life work had great influence on the understanding of the brain, specifically on the lateralisation and localisation of speech functions, and he inspired others to follow and distil his approach. For example, the inspired German physician Carl Wernike looked at patients with inability to understand speech. He was able to identify more posterior regions of the left hemisphere, which were critical for language comprehension - a lack of understanding of language prevents attaching meaning to perceived speech sounds. Their prominent work in the 1860s and 1870s inspired many others to find similar relationships between physically localised lesions and functional deficiencies. The approach also reveals the interdependence of deficiencies and therefore gives information on whether the corresponding underlying processes share resources or information. A good example of double dissociation is given above: He comprehends speech but cannot speak any more. She can speak but not comprehend speech any more. Patients with pure Broca's aphasia and with pure Wernicke's aphasia suggest that speech production and language comprehension are two independent processes that do not share resources or information. Scientists started to realize the importance of searching for case studies with double dissociation.

Intensive studying of damaged brains gave rise to many interesting relationships and independences. Scientists started to order the new knowledge into flow (box and arrow) diagrams. Such frameworks are enormously helpful as they make explicit the qualitative relationships between different functions and processes. A constructive and focused debate is now possible, because a rejection of a framework cannot be categorical and vague any more. Your counterpart needs to identify the disputed box or arrow and provide solid counterarguments based on experimental findings or logical arguments. Or challenge your experimental evidence and identify flaws. A good example is the field of visual agnosia. Based on case studies, Lissauer (1890) proposed a simple framework for visual agnosia: High-level visual processing involves visual analysis first and then attribution of meaning to the perceived object. He labels a corresponding deficit in these areas as "apperceptive agnosia" (inability to create a stable percept from intact incoming low-level visual information) and "associative agnosia" (inability to associate meaning from semantic memory to the percept). Lissauer's scheme is a good first-order approximation and as such still clinically useful today. A simple copying test can distinguish between the two types of aphasia. If you are able to copy an object in drawing but unable to identify the meaning of the copied object, you will have appercetive agnosia. However, later more carefully designed and detailed studies have identified cases with different types of apperceptive agnosia: some pass the copying test but still have apperceptive agnosia. For example, Kartsounis and Warrington (1991) found that Mrs FRG was able to pass visual acuity tests but was unable to discriminate between object and background. Warrington (1985)'s model use a variety of different types of agnosia to suggest the existence of sub-stages of visual processing, and propose refinements to Lissauer’s model. Visual analysis divides up into shape coding, figure-ground segmentation, and perceptual classification. Another example of a box and arrow diagram approach is Ellis and Young (1988)'s functional architecture for hearing and speaking words. Again, the framework was developed over many years and based on sharper and sharper studies using older frameworks are guiding lights.

As with every experimental paradigm, you try to push as far and as deep as possible until you reach insurmountable limits. And limits were found. Very often the physical and functional damage is broad and fuzzy. Especially strokes can affect many regions and range from total to minor physical damage. The notable exception are purposeful lesions in animals and surgical intervention to ease severe epileptic attacks. And possibly the case of NA whose room mate's sword pierced through his nose into his brain causing a pure form of amnesia! Moreover, patients rarely show clear deficiencies but a range of deficiencies, and brain plasticity is a non-negligible factor, too. The rarity of clear case studies in lesion and dysfunction raises statistical issues, because they might have arisen by chance. Whereas if you have hundreds of cases, random fluctuations average out. Also, at least before the imaging age, anatomical studies could only be done after the patient's death when the brain would have aged and might have adapted somewhat. Finally, experiments are hard to control and all kind of biases can creep in, even for the most experienced and clever scientist. A good example is the debate on whether the brain handles living and non-living things differently. After initial excitement, other explanations emerged. First, pictures of living things are generally more complex: e.g. compare the picture of a fly to the picture of a cup. Any visual system should have more difficulties in processing a complex picture than a simple one, especially if damaged. Second, living things look similar to each other whereas non-living things do not. For example, there are many animals with four legs, a head, and a tail, but tools are all different because each tool has a different function and we would therefore expect them to look differently. A damaged visual system should have more difficulties distinguishing between similar objects. Third, familiarity could play a role. Humans see and handle tools on a daily basis, and the visual system processes pictures of familiar objects much more often. It is easy to see how a visual system tuned to familiar objects retains some abilities after damage. No doubt all of these factors can influence the performance between living and non-living, and the brain might well not think in terms of living and non-living. Therefore, Stewart et al (1992) and Funnel and de Mornay-Davies (1996) asked for more careful designs to control for these factors.

Connectionist modelling has a completely different approach. Remember. At the beginning, we found the fine microscopic details of the brain, the nerve and glia cells, but this new knowledge had only increased our fascination with the brain. Cognitive neuropsychology ignores the foundations on which brain processes must ultimately rest - the neuron: it is a top-down approach. Connectionist modelling on the other hand is a bottom-up approach. With the advance in computing power connectionist modelling was able to take the neurons seriously. Let us take a physics analogy. A gas is macroscopically well described by Boyle's perfect gas law with pressure, temperature, and volume, but microscopically a gas consists of billions of atoms colliding like fast moving gluey tennis balls. Computer simulations are now able to derive the macroscopic properties of a gas from the microscopic properties of the individual atoms. In neuroscience, the microscopic world of the individual neuron is reasonably well described, and so is the macroscopic behaviour of the brain like reading or re-calling memory. However, the holy grail of understanding is unreached: to describe the brain's macroscopic behaviour in terms of neurons. Connectionist modelling takes up this challenge: to directly simulate the interactions of neurons however difficult. No-one would doubt that all cognitive neuropsychologists when drawing their boxes and arrows knew of the ultimate incompleteness of their approach. They, especially the clinicians, would rightfully argue that theirs is a functional approach, trying to understand the broad flows of information from process to process. A first order approximation sufficient to understand and treat their case load. Surely, the neural networks would only but confirm their boxes and arrows as an emergent structure of neurons, for they have used a scientific approach to gain knowledge. However, I believe that neuropsychologists committed a forgiveable logical fallacy: If a theory fits well all known observations, it must be correct. I am not referring to the Popperian ideal of a falsifiable theory, but to the possibility that several theories (of a very different nature) could fit all known observations and how do you then decide which one is actually implemented by nature? Imagine you dance at a night club and no-one dances with you. Your theory that the girls are just too shy fits your observation, but of course there is an alternative theory, namely that you are a bad dancer or that no-one likes you! Connectionnist modelling gave birth to new insights, new and different ways of getting the same ouput but with a brainy feel. Neural networks strikingly show brain-like properties, to name a few: resistance to damage, tolerance to noisy inputs, retrieval by content, distributed memory, parallel processing, typicality effects in memory retrieval (i.e. ability to hold a prototype of a set of similar objects), ability to deal with new inputs based on experience. An amazing feat, considering that many features of neuronal activity are left out: the glia cells, the neurotransmitter levels at the synapses, the 1000s of connections, firing for no reason, non-linear effects. And now you can start asking interesting questions: Which model is correct: the box and diagram one or the neural network one? Is the box and arrow diagrams not too deterministic and computer-like? If indeed the brain is like the neural network, how can we ever model memory with box and arrow diagrams? Moreover, neural networks have brought in the quantitative area of neuroscience. It is not good enough to just run a qualitative approach with flow diagrams, but you need to quantify and explain exactly what is going on. Let's take Lissauer's model on visual processing. He assumes object identification first and then attachment of meaning to the object. It does not really help you to know this if you want to build a visual system yourself. It is like telling an overweight person to eat a bit less and do some sports. Correct, but how do you implement this strategy? Only by going through the steps, writing down an algorithm, constructing a neural network can you find out whether what looks good on paper is also implementable. Connectionist modeling is a useful tool to check whether realistic models can at least in principle be built using the current theoretical understanding about the system.

Here is an example on how connectionist modelling became a rival in love. Two very different models, one neuropsychological and one network, generate the same output: the past tense in the English language. Many verbs have regular endings of the past tense (show-> show-ed), but there are also irregular ones (go->went). How does the brain conjugate the verbs? Maybe the brain of a child has learned the rule: if you want to have the past tense of a verb, just add -ed to the end. And how do you deal with went, came, fought? Maybe the child has the exceptions to the rule learned by heart and added them to list: go -> went, come -> came, fight -> fought. Therefore for every verb, the brain might look in the exception list first, uses it if present, and applies the rule if absent. But that's a box and arrow model. How does the brain do it? Pinker (1994) argues in favour of such a dual-route model based on a double dissociation argument: in some disorders the regular form is impacted and in others the irregular one. In Pinker and Prince (1998), they suggest that there is a rule-based route (adding –ed to the ending), and a route with a list of exceptions that block the creation of a regular form for an irregular verb. (I never understood why the list has to block the rule. Is it not simpler to first look up the exception and if not found, use the rule?) In any case, the over-regularisation argument is key here. Children often make errors like goed instead of went, even though they have used the correct past tense before. The argument goes that at first children learn past tense by heart, then learn a rule on how to form past tense, and here is where they make the over-regularisation mistake until the exceptions list strengthens. Connectionist modelling challenges this neat and clear-cut computational approach to brain processes. For example Plunkett and Marchman (1996) have created a neural network that is able to conjugate the verb correctly, and most importantly without any rules or list of exceptions. It is just a neural network with many weights trained on regular verb and irregular verbs. Suddenly it is at the least feasible that a single route model with a messy structure very unlike a computer does both functions, which means that both functions share the same resources.

But why was Pinker able to argue for a dual neuropsychological model supported by a double association argument if the real thing could be a single route neural network instead? Juola and Plunkett (1998) showed that it is possible to construct a neural network that has the appearance of a double dissociation. Double dissociations can arise from nothing else but extreme cases of the natural variation of a lesioned network, and possibly amplified by the publication bias (only interesting and rare cases are published). Again, there was a network trained to conjugate verbs. The information of the irregular and regular verbs are distributed in the weights of the connections between neurons. However, by chance there are some weights which are more responsible for regular verbs and some weights are more responsible for the irregular once. If you selectively damage or remove a connection, the deterioration of the performance will not be evenly distributed between regular and irregular verbs. I saw this phenomena in my TMA02 work: depending on which weight I set to zero, a different horse's name was affected. Now assume that you have 100 people with a stroke. In the majority of cases, weights dedicated to both type of past tense will be affected. But in a few the pure weights are the only ones affected: either the weights most responsible for regular verbs are affected by chance, or the weights mostly dedicated to irregular verbs. So you can get a few patients with inability to do regular verbs and a few patients with an inability to do irregular verbs. A typical double dissociation but based on a single route. This opened up a Pandora box on neuropsychology's use of double dissociation and modularity concepts: Is the ability to perform a certain function distributed across the whole brain or an interaction of different brain regions? Or is there only one specific brain area responsible? Is a double association evidence for anatomically distinct modules or only evidence that the processes underlying the two functions do not share resources? However, we should not forget that learning the past tense in English is a cultural thing and cannot be an innate module. In Norwegian, you have two regular verb forms plus irregular verbs. So are there three routes? Today we think of the brain as composed of interacting modules shaped by evolutionary pressures. I would argue that the failure of the double dissociation argument is restricted to learned functions rather than on a wide category of related functions or at innate functions. The interesting question is what is innate: the past tense is not! But is the language ability as such an innate module or an interaction of more general purpose modules arisen from interaction with the environment especially culture?

Connectionist modelling also show interesting alternative learning paths similar to real development, and thereby highlights the inability of neuropsychological models to adequately model the development of functions in children in any detail. Neural networks are not just possible models on how a skill is generated but also on how the skill is learned. Above, we have come across the past tense. Plunkett and Marchman (1996)'s model is not just interesting as an end-product, but the training of the model can be viewed as a model of how children learn. Children learn in a U-curve. First they perform well because they learn the past tense by heart. Then they make mistakes while at the same time learning the rule of regular verbs, and finally they have mastered the past tense. Plunkett and Marchman (1996) has taught the net by feeding it with regular and irregular verbs in the same way as children encounter verbs. They compared the performance to real data from a children's study by Marcus et al (1992), and find similar results: early learning is error-free, over-regularisation errors happen but are rare for common irregular verbs, irregularisation (conjugating a regular verb irregularly) errors are rare. To conclude, a blank slate neural network is all you need to learn the past tense, no innate module is required. At least not for this task. Again we should probably make a distinction between evolutionarily recent skills and ancient skills needed for spreading the genes (like survival).

However, neural networks have an Achilles’ heel: they do not include a realistic model of learning. In a sense, neural networks do what in fact drove them away from computationalism, namely to mathematically describe a phenomena rather than show how it emerges. The weights of the connections between neurons are artificially determined by mathematical rules like the gradient descent method with the help of artificial concepts like error back propagation. How can connectionist modeling claim to build up the brain from scratch if the learning process is not well modelled? In fact, in my opinion the lack of realistic learning leaves neural networks open to a serious loophole: data mining. Neural networks have a huge number of weights that need to be trained, and there are billions of billions of billions possible constellations. In a sense it is not surprising that they can model any system with a bit of fine-tuning, trial and error, and little constrain on learning, because they have so many degrees of freedom. Let's take an analogy. This essay has about 5000 words, and in fact there are an unimaginable variety of possible texts possible; including a scence from Hamlet and the author's eulogy! I can easily train my document by adjusting the words of the essay to match those of a passage in Hamlet. Surely, we would not say that this is in any way a success of my document itself. So would we not expect neural networks to fit any system? Yes, neural networks are trained on a training set and then tested on a different set, but often the training set implicitly contains the rules. I believe, the artificial learning might well leave the system too unconstrained. On the other hand, you can argue that that's precisely the secret of the brain - it's enormous flexibility. And maybe most of its activity is indeed not real understanding but just re-coding and fitting output to expected output.



Not all is lost for cognitive neuropsychology. Sure, connectionist modelling has become a rival in love, challenges many assumptions, and provides food for thought. The neuropsychological tools are not as sharp as previously thought. However, the advent of new revolutionary tools to explore the brain has rejuvenated the field. And will keep everyone busy for many years to come. First of all, the imaging techniques have become very powerful, allowing real-time insight into the structure and functioning of the living brain. Instead of having experimental results now and a post-mortem study years later, you have experimental results and imaging data at the same time. You now have three points of reference: the task performance, the functional imaging data, and the structural data. And very importantly the resulting quantitative data allows to quantitatively compare to control brains and run proper group difference statistical tests. For example, the advent of CAT and MRI scans have made it possible to see the structure visually in vivo, and detect blood clots, squeezed brain regions, and dead tissue at high resolution. The DTI technique is also interesting, because it allows to track fibre structures in the brain and see whether there is disruption between different regions. Functional imaging tools add another twist to the study of damaged brains. You can monitor the indirect BOLD (blood oxygenation level dependency) signal and the direct electrical activity of neurons. PET and fMRI work on BOLD. The idea is that functionally active regions with plenty of firing neurons consume more blood to re-fill their battery literally - the action potential. Functional imaging data is revolutionary in the sense that you can take a time series of scans over several seconds, and see the brain at work. Or, you can scan the damaged brains over a longer period of time and monitor recovery. Of course, this can also be done for the normal brain but a damaged brain gives extra information. However, the functional BOLD methods are reaching their limits because blood flow is by nature fuzzy, not 100% correlated to neuronal activity and does not have a high time resolution. And of course because the real stuff is the electrical activity of the billions of neurons. Two techniques stand out here. EEG is more of a surface electrical activity measurement tool, whereas MEEG aims to give a 3D view of electrical activity in the brain using magnetic fields. MEEG has technical but probably solvable issues: from a 2D surface map you need to deduce a 3D activation pattern - an inverse problem. The imaging field is maturing in terms of resolution and technology (with the notable exception of MEEG which requires more work), and progress will mostly be on improved signal analysis and interpretation, using several techniques at once, lighter scanners and experimental design improvements. Very importantly, the critique on using case studies is also dramatically weakened, because we now have so much more information on a single damaged brain. Surely, a competitor in the flat screen industry only needs to look at one of your screens to be able to understand your new innovative technology, because he can take it apart.

Another area of improvements is purposeful temporary lesioning in humans without ethical concerns. The technique is called TMS, and sends out magnetic pulses that temporarily disturb the electrical activity in the targeted brain region therefore knocking out a region for a brief period of time. Experimental subjects can then be tested on tasks and their performance can be compared to a control group. For example, you ask a subject to talk and then you can aim the TMS on Broca's region. The subject will suddenly not be able to talk any more. Aiming TMS at other areas does not have this effect. However, TMS is a rather clumsy method and it is difficult to control the target area. Therefore, animal models are still very important for our understanding of the brain. Scientists are able to experimentally control the degree and area of damage with knocking out genes, well-controlled surgical lesions, targeted medication all inside a multi-technique scanner. Finally, open brain surgery inspired by Penfield's work is still done and perfected. We should also not overlook the importance of more indirect tools like genetics. Our understanding of the human genome and some gene's impact on brain function has become a powerful tool. Many genes play a crucial role in the building of the brain via protein coding. Research in many brain-based disorders have revealed a genetic component, and current research is revealing the impact of specific genes on proper brain functioning. Clearly, gene research is not relevant to patients with brain strokes and injuries, but for brains with a permanent dysfunction. A good example is the FOXP2 gene. Specific language issues, developmental verbal dyspraxia, has been linked to mutations in this gene. So the study of damaged brains can now be seen from yet another angle and tackle developmental brain disorders. The experimental tasks given to these patients are then linked to the genetic and imaging data. In fact, the impact is even wider, because evolutionary biological consideration can into play. The gene is needed for proper language, when did it evolve? Do apes have it, too? Is it just helping out other genes? The FOXP2 is an impressive example on how the study of damaged brains can open up new avenues into understanding our brain. Finally, neuropharmacology is also adding new tools to discover the damaged brain or to induce temporary damage to a region or pathway. How does cocaine impair the brain? Do dopamine-receptor blocking agents modify the functioning of a damaged brain?



To conclude, did the advent of connectionist modelling represent a considerable blow to proponents of the neuropsychological approach? Let me first be pedantic, and religiously point out that science is not about people but about statements, arguments supporting a statement, and counterarguments! So did connectionist modelling represent a considerable blow to the neuropsychological approach? No, it is more of a wake-up call. There are very different ways to model a brain. You need to explain every step quantitatively in detail. You have to be more careful with double dissociation arguments. However, the core idea of neuropsychology is still alive: you can find out a lot by studying what went wrong. No approach is better than the other, like cities: neither Paris nor London are better, they are just different ways of living. In fact, I argued above that the revolution in imaging and genetics considerably help neuropsychology to re-invent itself. You can zoom in much more into case studies. But maybe due to the genetics revolution there should be more emphasis on developmentally damaged brains like in dyslexia, stuttering, laTourette syndrome as opposed to messy damaged brains by stroke or injury. These are exciting times with so much new information from many different tools exploring each a completely different aspect of the brain. But of course there is only one brain, and at some point they all need to come together in meta-analysis. A challenging task, and maybe even impossible. I like to compare the brain to a big city with many interacting objects: factories, highways of information, objects and people, executive branches shaping the city, construction plans as genes, neurotransmitters as the weather and so on. There are many different ways to explore a city: by foot, by listening to people's stories, by buying TimeOut, by satellite pictures, by statistics. Still even though I have information on all of it, I still find it difficult to say exactly what for example London is. Where does it start where does it end? If I take Westminster away, is it still London? Whatever happens. At least the clinical side of neuropsychology will never die. The patients with damaged brains will always exist and they have specific deficiencies, and a good clinician must ask what causes these deficiencies in order to best devise a plan for the best possible recovery. But they don't care about neurons or networks, they want simple box and arrow models that are roughly right. But still I want to understand from the neuron onwards why someone doesn't like his left hand any more and wants to get rid of it.


Kartsounis, L.D. and Warrington, E.K. (1991). Failure of object recognition due to a breakdown of figure-ground discrimination in a patient with normal acuity. Neuropsychologia, 29, 969-80.
Warrington (1985). Agnosia: the impairment of object recognition. In P.J. Vinken, G.W. Bruyn, and H.L. Klawans (eds), Handbook of Clinical Neurology (vol. 45, pp. 333-49). Amsterdam: Elsevier Science Publishers.
Ellis, A.W. and Young, A. W. (1988). Human Cognitive Neuropsychology. London: Lawrence Erlbaum Associates.
Lissauer, H (1890). Ein Fall von Seelenblindheit nebst einem Beitrage zur Theorie derselben, Archiv für Psychatrie und Nervernkrankheiten, 21, 222-70
Stewart, F., Parkin, A. J., and Hunkin, N. M. (1992). Naming impairments following recovery from Herpes Simplex Encephalitis: Category-specific? The Quarterly Journal of Experimental Psychology, 44A, 261-84.
Funnel, E, and de Mornay-Davies, P.D. (1996). JBR: A re-assessment of concept familiarity and a category-specific disorder for living things. Neurocase, 2, 135-153.
Pinker, S. (1994). The language instinct: how the mind creates language. William Morrow, New York.
Pinker, S. and Prince, A. (1998). On language and connectionism: Analysis of a parallel distributed processing model of language acquisition. Cognition, 28, 73-193.
Plunkett, K. and Marchman, V. A. (1996). Learning from a connectionist model of the acquisition of the English past tense. Cognition, 61, 299-308.
Farah and McClelland (1991) in Cohen,G., Johnston, R. and Plunkett, K. (eds) 2000 Exploring Cognition: Damaged Brains and Neural Nets, Hove, Psychology Press (Taylor & Francis).
Devlin in Cohen,G., Johnston, R. and Plunkett, K. (eds) 2000 Exploring Cognition: Damaged Brains and Neural Nets, Hove, Psychology Press (Taylor & Francis).

From an evolutionary perspective

Stuttering has a genetic component. First, homozygotic twins are more likely to stutter both than heterozygotic twins. Second, several locations on chromosomes are correlated to stuttering. These two sources of evidence in combination with research from other disorders allow two conclusions. First, there is not a single gene for stuttering, but many different ones or combinations of. (For example, deafness is associated to tens of different genes.) Second, genes are not a sufficient condition to develop stuttering in all people: if you have the genes, you could be fluent. And if you dont have the genes, you could develop stuttering. However, the likelihood of being in the stuttering group is influenced by the genes. For the non-genetics group, it is likely that a neurological incident (possibly enhanced by environmental stress) kickstarts stuttering. Examples would be an infection or a brain trauma, whose likelihood could also be related to non-speech related genes. Such genes would probably not show up in correlation studies as their signals are too weak and multi-factorial.

Due to its genetic component, stuttering is a candidate for evolutionary adaptation. About 1% of the population stutters, and did not recover naturally from the sample of 3-5% of children who temporarily stutter. It is interesting to look at the past history of stuttering, and ask whether this ratio was stable throughout the evolution of speech in humans, or whether in fact the proportion of the stuttering population was greater in early humans. If the proportion was indeed greater, there must have been evolutionary pressure that reduced the proportion to the 1% of today. (A gender perspective would be even more interesting, as women are 4 times less likely to develop stuttering. This could suggest that they were under greater evolutionary pressure, however this might not be directly linked to speech but more general pressure that favours stable and fast maturity of females for the survival of tribes.) The question is whether this scenario makes sense theoretically and fits all known data, and if it makes sense, whether nature took this course, and whether experiments can be devised to check predictions.

The mechanism of exactly how and why evolutionary pressures made humans evolve speech unlike in their closest relatives the apes is not clear. It is reasonable to assume that humans started out like the apes of today in that they used different sounds with different intonation to communicate mental states. The crucial aspect that gave advantages to early humans is probably the emergence of rudimentary grammar that allowed early humans to combine those tens of sounds representing general concepts into thousands of different sentence combinations. However, grammar requires extra brain resources/modules. So instead of a mental concept being associated to one sound and going to the motor cortex, it now took a detour to a new region that combines words into sentences to better represent and communicate a mental concept. This ability to create sentences imposed great pressure on the brain and at the same time more greater fine motor control of the muscles is needed. A reasonble guess is that the brain divided up the pathway of making sounds into two: one old for sounds (how we speak), and one more recent for automatic speech where the early human could focus on what to say (and also on how to combine words) as opposed to how (intonation) he would say it. The social and natural smile might be an analogy.

It is reasonable to assume that nature favours fluent speakers. This is especially true as early humans became more and more organised in tribes, and social skills and communication skills became important, and a lack thereof a distinguishing feature from others. The evolutionary pressure only started when fkuency became important. So it might well correlate with emergence of culture. (Another example would be genes for dyslexia, that could only have been exposed to evolutionary pressure when writing became important, unless dyslexic have other defficiencies.)

It is possible to at least in principle falsify the theory. My theory is that early humans had more genes creating unstable speech, stuttering,and these are being selected out by evolutionary pressures. So the theory predicts that a higher proportion of early humans carry stuttering genes. So a comparison between a sample of modern humans and early humans would reveal sample differences. In practise, such a test is not possible yet as old DNA degrades relatively fast, unless preserved under special conditions. The promising news is that new techniques are being developed to extract ancient DNA. For example, such techniques have been used in Neanderthals with an age of tens of thousands of years. So there will probably be a DNA bank at some point in the future on ancient DNA which could be used.

Leys persists

Leys persists with his campaign to get Google change their policy regarding stuttering cures:

Tom, I thought you and your readers might be interested in this story.

Following the BSA’s complaints, the Advertising Standards Authority has just made adjudications against five more ads from two organisations, HowToStopStutter.com and StopStutteringSecrets.com The adjudications have been published today at http://www.asa.orguk/asa/adjudications/public/

These adjudications have been made because the organisations in question did not respond to the ASA’s requests for data which might have supported their claims.

An additional benefit of these adjudications is that Google, who ran these ads, are deemed to be affiliate marketers, and thus bear responsibility for accepting ads which infringe the advertising codes.

So we have written to Matt Brittin, the Country Director of Google UK, pointing out that, once again, Google has been found to be taking money for ads, without taking responsibility for their content We also reminded him that, in addition to the British Stammering Association, many other authoritative people and organisations – including the Royal College of Speech and Language Therapists and the Stuttering Foundation of America – have already advised Google that stammering cannot be ‘cured’. That is why we have all asked that stuttering/stammering should be included in the Google ‘Miracle Cures’ policy, so that ads of this kind will no longer be accepted by Google.

We will carry on reporting ads to the ASA which feature misleading claims about stammering treatments. Google, we hope, will reconsider their position.

Exam Stress

I have the CFA Level II exam on Saturday with 3000 pages that I had to study. I only finished reading last week, and now I revise, and guess what, I can't remember anything. Oh God. Only 4 days left...

After the exam, I will have more time for the blog...

I did a recording with StutterTalk and its hosts Peter and Eric. We talked on the neurological basis of stuttering. I am not 100% happy with my performance; too many ideas. I need to focus on an idea at a time, talk less and stutter less! :-)

Anyway, Peter was asking an excellent question regarding my position that stuttering is mostly learned behaviour from an unstable and sensitive speech system most likely due to neurological connectivity issues: I often see kids that started starting a few days ago and they often have already full-blown stuttering symptoms. How can this be learned behaviour? Here is my answer:

a. His experience is consistent with a large scale survey on early childhood stuttering that shows sudden onset of stuttering to be typical. And therefore, it seems unlikely to be just learned behaviours, even though learned behaviours can be learned within days, I guess?

b. I did not actually mean what I said that stuttering is mostly learned behaviour from an unstable and sensitive speech system. I really mean: automatic response and learned behaviours. If you observe stutterers, there are two kinds of behaviours: shared by most stutterers and not shared by most stutters. (In fact it would be interesting to do a study of this. Which symptoms are most shared?) Behaviours shared by most stutterers is mostly likely an automatic response due delayed speech initiation like a long pause, a block, repetition. And then there is learned behaviour like looking down, moving your arm etc. Think of holding your breath: we all react in identical ways, but at the same time we also handle it differently.

Here is what I really mean: there are three types of activities. The internal activity of the brain, the overt automatic response to delayed speech initiation, and learned behaviour associated to stuttering and triggered by events, words, situations, people, etc.

At least one courageous clinician

Watch this video blog by Chamonix Olsen, where she refers to her negative experience with SpeechEasy and talks about a research/review article on the device. Note I talked about this article a year ago, and as you can imagine, it is nowhere found on the Speech Easy website. I congratulate Chamonix for making clear statements (untainted by the bla bla bla consensus talk and I-have-to-be-careful-not-to-hurt-someone's-feelings approach) in contrast to many (but not all) of her colleagues that are too coward to speak out their true mind clearly and publicly or make any controversial statement or just too lazy or not qualified enough to actually read the research articles in detail. I just hope she will not start her own blog... that would be too much competition. The next thing she should talk about is the Lidcombe treatment approach.. ;-)

(Thx to Ora for the tip)

Abnormalities a consequence of stuttering?

Here is an often made argument that is getting more and more difficult to defend.

Comparing a stutter's brain with a non-stutter's brain leads to a dead end because the very fact that a person stutters for years and years has an affect on the brain. Just like a person who plays the piano for years has a different brain structure than a person who doesn't. But it doesn't mean that the piano player was born with that brain structure

Here are the arguments against:

a. Scans on older kids also show structural brain abnormalities thereby making it less likely to be a consequence of stuttering.

b. Scans on adults who recovered from childhood stuttering also show structural brain abnormalities.

c. Genes either cause (e.g. stuttering families) or significantly contribute to stuttering in many but by far not all stutterers. They are physical objects that code proteins that are used to build part of the brain. So the brains of these stutterers are definitely physically different from the very start, because they have genes that are abnormal.

d. The fact that genes can cause or contribute towards stuttering shows that physical stuff can cause or contribute towards stuttering and is a strong indication that other physical events like brain injury or virus infection might lead to similar physical deficiencies.

e. The magic brain plasticity is a feel-good myth. The brain virtually never goes back to normal after a stroke or a development disorder like stuttering. If the kid is lucky, the brain will find a different way to do the same task, but very likely at the cost of inferior performance.

f. Surely there are adaptations, but this does not able that it is all adaptations.

g. One Japanese researcher, Dr Mori, has found abnormalities in infants before they start stuttering using a technique called light spectroscopy, I believe.

More on Rex and genes

Some more on my debate with Rex. He has already moved towards admitting that genetics does play a role, but still thinks that the non-genetics part must be social environment. So lets move him a bit further away from this stance.

>>>The figures suggest that genetics plays a role, but identical twins are (as the name suggests) identical, so their parents treat them in identical ways, and their environments are usually identical. However, the figures also indicate that environmental factors play a very significant role. If stuttering were purely genetic, there would be 100% concordance among identical twin stutterers ... but there isn't!

No no no.

First, if genes can cause or contribute to stuttering, that means that physical stuff can cause or contribute to stuttering. And therefore, it is very likely that non-genetic physical stuff like brain trauma or virus infection striking in the same functional regions as the genes, will also cause or contribute to stuttering. So the proof of genetical influence very often indicate that other physical may also cause or contributors! You cannot say: Oh genes is 40% so social environment is 60%. Only that "other physical causes" and "social environment" equals 60%! Where social environment can run from 0 to 60%!

Second, the twin studies do not show that environmental factors play a significant role. It only shows that non-genetics factors play a role. It is a commonly made mistake to attribute non-genetics factors to parental skills (the nurture part) exclusively.This attitude comes from the flawed nature-nurture view. A vast majority of non-genetic influences do not come from parents or social environment, but from random events like pre-natal events, accidents, illnesses, trauma. Then most impact from their social environment come  from the influence of their peers and from school. Kids spent the vast majority of their time with their peers, their school teachers. Relatively little with their parents. And even parental influence is not uniform for both twins. Kids can react very differently to parents. I am not saying parents play no role, but with increasing age less and less, and at very early age kids are not social beings but more like animals.


>>> The scientific literature that you cite is just a rehash of what has been done for decades. Nothing new has been found. The same questions that were asked 30 years ago are still being asked today ... zero progress.

I gave links to review articles for laypeople. There has been a lot of progress on empirical findings but the full picture will be quite complex.

And there is recent research. For example, I also cited the very recent and large scale (1000s of twins):

Am J Speech Lang Pathol. 2007 May;16(2):169-78. Genetic etiology in cases of recovered and persistent stuttering in an unselected, longitudinal sample of young twins. Dworzynski K, et al.

But here are others:

Am J Hum Genet. 2006 Apr;78(4):554-63. Epub 2006 Feb 1. New complexities in the genetics of stuttering: significant sex-specific linkage signals. Suresh R, Ambrose et al.

J Fluency Disord. 2007;32(1):33-50. Epub 2006 Dec 30. Genetic studies of stuttering in a founder population. Wittke-Thompson JK, Ambrose N, et al.



>>>> My understanding is that the stuttering researchers are of an embarrassingly poor standard ... and something tells me that you agree with me.

I agree with you, but not for genetics and brain imaging. ALL the scientists who work in these areas are professional scientists. Most of them are not outstanding scientists, but they apply the standards of their fields well.

Selection bias in trial?

>> I was not allowed to participate because I didn't stutter enough during the videotaped speaking portion. 

Some readers are telling me that they were not allowed to register because they did not stutter at the evaluation session. How will this affect the trial?

First of all, I speculate that there are two types here. The one who stutter very mildly even when they stutter, but the impact might be mostly on the psychological pain side. No issue to the outside world but only to themselves. The other type stutter or block in some situations but were just very fluent. Outside world classifies them as stutterers in these situations.

I am concerned by the following statisticall bias. Lets assume Type II is fluctuating in fluency a lot. Lets say they stutter 20% of the time and don't 80% of the time. So the trial will drop 80% of them. OK lets change the numbers to 50% and 50%. It is easier to compute. So Type II-accepted will stutter at registration and in 50% of the time at evaluation after trial and 50% not. So 50% have gains in fluency not coming from the medication. But because we have a control/placebo arm, both arms will see the gains. So more sucess in placebo arm and treatment arm. The other 50% have no gains from this effect. This effect is balanced out if we include the Type II-not-accepted, because 50% might stutter giving a loss in fluency in both arms and the other 50% do not stutter with no effect. So to conclude by dropping the fluent stutterers, they increase the placebo and treatment effect.

Shouldn't severe stuttering be weeded out?

>> Based on the theory of Evolutions and survival of the fittest...shouldn't severe stutterers be weeded out with Time (thousands of years). So Stuttering might have some evolutionary advantages? Care to speculate? Some people subconsciously choose to stutter. Like self-mutilation (brains of self-mutilators)

 Good question. Here is my answer and I start with some genetics. First of all, the theory of evolution is not about the survival of the fittest but about sexual selection. The gene pool (organism made up of the genes) that is able to spread their genes most effectively via mating will survive. Think of the peacock. The bigger the tail the less fit for survival, but the better for mating because females go for males with bigger tails (god knows why! :-) So it is important to view everything in terms of sexual selection.

Second, only the bad stuff is likely to be selected out. This implies that some features might stay for a very long time in the gene pool, because they do not really hurt the gene pool's chance of reproduction. For example, a gene defect leading to infertility is immediately selected out, but a bigger nose might not because it does not really harm in reproduction. Third, sometimes a genes provokes a bad thing and a good thing. So this big-nose gene might also lead to bigger hands which is an advantage in surviving the environment and thereby increasing chances for sexual reproduction.

Fourth, highly relevant to stuttering, selection takes a long time to select out bad genes. So when you still see the bad genes in the gene pool it might well be that there was not enough time for them to be selected out. In fact, it might be selected out right now, and the proportion of the bad gene in the population might already have decreased. So when you see people stutter, being dyslexic, or genetic heart issues, it might well lead to less reproductive success, but the selection pressure might not be too high or the gene mutation happened not long ago and the people with these conditions might be the remnants of a much bigger population.

Fifth, some conditions cannot be selected out, because it is physically impossible to further improve the organism. Like humans, nature has a limited amount of ressources. Think of health care, you can tak 10 million to improve cancer treatment or 10 million to improve Alzheimer, but you cannot do both at the same time. Same here, some gene might improve things in one part of the brain but make it worse in another. So when conditions are at a very low precentage it might be impossible to further select them out.

Sixth, some conditions like stuttering are not strongly genetic, so it takes much longer to select them out. Also, it is not a single gene most likely, making it even more difficult.

Fifth, some genes only lead to condition in the appropriate environment. So maybe some of our fluent human beings carry the genes but did not develop stuttering or recovered from it. This makes selecting out the genes more complicated.

To summarise, you are making the assumption that the proportion of stutterers has NOT been declining about the last few thousands of years, thereby saying: OK it has been stable and it must be bad, and therefore there must be a counterforce. I would argue that the most likely scenario is that the proportion of stuttering is still declining, being selected out, and that stuttering might be less critical for reproduction sucess in our ancestors where hunting skills were much more important. And I also believe that nature might well not be able to optimize the brain much more so selecting out might take a very long time. Of course, it might be that some stuttering genes might give some benefit to the carrier; maybe it protects against a disease at the expense of stuttering. And again, stuttering is not strongly genetic, so selection will take longer.

Einar's question

Einar asked a question to me:

“How much stuttering is socially acceptable?”

I know this is not a “politically correct” question. It not a scientific question, but rather a psychological or sociological one. I know stuttering is a disability, so nobody should be discriminated because of his stutter. But doesn’t the freedom of oneself end where the freedom of others starts? Let’s take a couple of examples: A group of people is having a discussion, one of those folks has a stutter. Do the other participants in the group have to wait each time he adds to the discussion? Or should the stutterer remain silent at times in order not to disrupt the flow of the discussion? Would it be rude or understandable if one of the other participants cuts his sentences off?

Or another example, a speaker at a conference stutters. Do the listeners have to sit and wait patiently for him to get his message across? (bearing the consequences: lost time, patience…). Up to what degree? How long can a block be to be "socially acceptable"? Would it be rude or understandable if one of the listeners loses his patience and walks out?

 As you wrote your question is not a scientific one, so different people will give different answers. I can only say that I cannot stand listening to my own stuttering for too long! For me, it clearly depends on the severity; if it is mild or just a few soft blocks, I don't care. So to be honest, I do not want to work with a colleague who stutters alot or have a girlfriend that stutters a lot. But then again, I also prefer my colleagues to be intelligent, funny, good-looking, fit, interesting, and honest!

Your question on how long a block is not be socially acceptable. I would go back to the science of stuttering, and say the following. Our neurology causes a long delay in speech initiation in every so many syllables: the exact frequency varying enormously depending on many factors. The reason why we develop stuttering symptoms as opposed to just delayed speech initiation is because this delay is not acceptable anymore and we try to counteract. I would be surprised if this research hasn't been done before. I believe it is about 2-3 seconds of silence when the listener starts to direct its attention to the lack of speech. After 3 seconds of silence where speech is expected, the abnormal territory starts and social pressure from ourselves and the listener is created, and mounting with further delay. It might even be possible to define real stuttering as silence of more than 3 seconds where speech was expected, and learned stuttering as dysfluent speech per se.

Read the articles, Rex

I have to post on Rex's reply to me pointing out that everyone with a stuttering-is-learned-behaviour theory needs to tell me why genetics influences stuttering and why we have abnormal brains. I say it loud and clear. THE TIME IS OVER WHERE YOU COULD JUST WAFFLE ALONG WITH RANDOM LOGICAL THOUGHTS. YOU ACTUALLY NEED TO READ THE SCIENTIFIC LITERATURE BECAUSE GENE AND BRAIN EVIDENCE IS CONSTRAINING AND RULING OUT ALL KINDS OF THEORIES!

Here is Re's response highlighting my point exquisitely.

How come stuttering is strongly influenced by genes?

Is it? How has this been proven? Have they discovered the genes responsible? No they haven't. Have they done tests on twins *reared apart*? I don't know, but I doubt it. What is the contribution of genes and what is the contribution of environment? Lets face it - after all these years of research, nobody has a clue.

Yes, they have shown this. A quick 5 minute search would tell you. Go to PubMedline archive and search for "stuttering genetics". Or check out tese review articles: here, and here.

Here is the evidence:


a. There are whole families where nearly everyone stutters. They are in Cameroon, Kansas, and Pakistan. Read Drayna's review article or

See Drayna, D. "Newly discovered families give impetus to genetic research," Stuttering Foundation of America newsletter, Fall 2005, page 1. Viswanath, N., H.S. Lee, R. Chakraborty. "Evidence for a Major Gene Influence on Persistance Developmental Stuttering," Human Biology, June 2004, 76:3, 401-412.


b. One-egg twins are much more likely to both stutter at the same time than two-egg twins.

See Am J Speech Lang Pathol. 2007 May;16(2):169-78. Genetic etiology in cases of recovered and persistent stuttering in an unselected, longitudinal sample of young twins. Dworzynski K, Remington A, Rijsdijk F, Howell P, Plomin R.

c. Currently, studies are underway to locate the genes: see work by Drayna and by Ambrose.


And the same for brain imaging.

These structural differences: are they congenital, or are they caused by the fact that a stutterer has been stuttering all his/her life? Remember, years of stuttering behaviour can change the brain ... plasticity, and all that. Nobody can answer this with certainty.

No, they have now done studies on older kids which shows the similar kids, and you still have the genes which are the physical objects that build up the brain.

One thing about stuttering which has been largely been ignored by researchers and commentators is that there may well be more than one variant of it - even though they may manifest themselves as the same behaviours.

I agree with your statement, but that doesn't mean that anything that looks feasible as a cause is a cause.

Big day for humanity

My blog is about stuttering, but I can't help blogging about my excitement on the launch of two revolutionary satellites that will change our understanding of the universe, especially its origin, structure and future. If all goes according to plan, of course! I am talking about Herschel and Planck from the European Space Agency. Herschel is the biggest ever telescope sent into orbit and will exceed Hubble's capacities, which have already awed us with amazing pictures and the age of the universe (13.7 billion years). (Hubble is currently being repaired, and will provide even more detailed pictures.) Planck is even more exciting as it studies the remnants of the big bang, the micro-wave background radition from 380'000 years after the inflation of the universe started. By its unprecedingly precise measurements, candidate models for the unification of all laws of physics will fall or survive. A great day for European science. And we should not forget that the Large Hardon Collider is going on-line in a few months giving us an even finer view on the structure of matter.

Pagoclone trial (registration) ended?

A reader sent me the following email:

...I went in for the trials. I'm on X and they told me I could not join the trials till I was 4 weeks from my last dose. ... They told me the trials would continue for several more months so I could go off it slowly. ... Two weeks in slowly going off it, they told me the trials have prematurely ended, and I should get back on my medication. I asked them when it will be available on the market, and they said they would get the head guy to call me and tell me but he never did. They basically said the trials were 'going so well' that is the reason they were discontinuing them early.

I am puzzled at what this means. It is most likely that they have a record number of participants and don't need any more participants. I would not be surprised. Or may they just closed one site? But I doubt they stopped registration because it was so sucessful in efficacy.

Did others experience similar?

(I just listened to a podcast on StutterTalk.com and Jerry Maguire said that enrollment has stopped on most sites as numbers have been reached. The blind trial goes for 8 months with intermediate measurement points. So assuming the last patient was enrolled on May 1st. The last measurement should be in 7 months (in November) plus 2 more months evaluating speech samples plus 2 months stats. So the final results should be there in about a year. Of course internally they will know the analysis of the intermediate measurements probably after the summer. So maybe we can expect preliminary public results in November.)

Your question: Pagoclone

A reader asked:

Is pagoclone an anti-anxiety drug? Is pagoclone a good medication for the treatment of stuttering? It seems like pagoclone reduces anxiety, which would seem to reduce stuttering (theoretically). So do you like pagoclone as a treatment for stuttering. Take it once daily for the rest of your life and forget about it (vs. other stuff you can do) It this correct: pagoclone reduces anxiety and therefore reduce stuttering, NOT pagoclone reduces stuttering directly... also, side effects like weight gain?

Side effects: The side effects for Pagoclone seem to be mild compared to older medication. I have often read that second-generation medication is not more effective than first-generation medication but it is much more tolerable with mild side effects. Not sure how true it is.

Anti-anxiety: Pagoclone was tested for anti-anxiety disorder but the trials were stopped, likely it was not effective enough. But it might have helped reducing the general anxiety level of normal brain rather than countering anxiety attacks.

Stuttering: We do not know yet, but the current Phase IIb trial will tell us much more. What is already clear is a) it is not going to be a miracle fluency pill b) it will not work for everyone if it works.

pagoclone reduces anxiety and therefore reduce stuttering, NOT pagoclone reduces stuttering directly... We do not know. I tend to think that Pagoclone (if effective) calms the brain and puts it more into a "at home alone" mode which facilitates fluency. But Jerry Maguire disagrees with me and believes that it acts directly on issue. The jury is out there.

So do you like pagoclone as a treatment for stuttering. Take it once daily for the rest of your life and forget about it (vs. other stuff you can do): Here is my view.

The first German on blogosphere

A stuttering friend of mine, Blanka Koffer, has started her blog. She writes history as a profession and in that her blog is the first German blog. It is called Stottern usw. (which means Stuttering etc.). I suggested she adds a picture of her, and she promised to do so. And I told her not to fear speaking out her mind. Unfortunately, that is exactly what she did, and she started off by disagreeing with me! How unloyal can you be? :-) If you can understand German, I recommened her blog.

Ask me any questions!

I invite you to submit questions about stuttering. I will answer them all! ;-)

I just got an email from saying that someone else said that "if you stutter when you are alone, you have brain damage". Unfortunately, I do not have access to the newsgroup. But here is my answer.

The fact that you even stutter when alone indicates that your emergence of stuttering is relatively independent on social speaking situations. And indeed suggests a neurological cause rather than a socially or behaviourally conditioned cause.  However, if you are a person who does not stutter when alone, you cannot use this argument and then say that therefore your stuttering is purely psychological. Think of your old car with an old battery, it works fine in dry and warm weather but it won't work in wet or cold weather. You won't notice the deficiency (stuttering) in dry and warm (when alone) weather! You might very well also have neurological issues (maybe less than those who stutter when alone) that get revealed when your brain has to worked at full speed and demanding conditions! However, I am not denying that social situations can strongly modulate the severity of stuttering. But we need to distinguish between two types of causes: a) much greater neurological demand on brain b) triggers to learned behaviour. Social situations always create greater neurological demands leading to a higher chance of jams leading to stuttering behaviour, and depending on the situation learned behaviour might additionally be triggered leading to stuttering behaviour (avoidance of eye contacts, fillers, tension, and so on).

IFA Program

Here is the program for the IFA conference in Rio in August. Click on the week days to get the name of the speakers.

As I said before, not too impressed by the key speakers. NOTE THE LIDCOMBE PEOPLE GIVE TALKS ABOUT ALL KIND OF THINGS BUT NOT ON THEIR OWN FOLLOW-UP STUDY OF THEIR FAMOUS PSEUDO RANDOM CONTROL TRIAL. WHY? EVEN THEIR FLAWED SETUP SHOWS THAT THE RATE WAS NOT CLEARLY BETTER THAN NATURAL RECOVERY. That's how research is done. If you don't like your results, you don't spend the effort to promote it! Instead they talk about refinements like time to treat, individual differences, technical aids, and so on. Needless to say that it is all completely useless given that it is already tricky to properly do overall sucess rate due to statistical erros from high natural recovery rate: they search in the haystack when in fact it is not even possible to locate the haystack! But of course if you do not understand stats well and are not trained in hard science, you just don't see the issues and your brain gives great meaning to a research that is meaningless.

Here are the talks I would consider going to. And of course all the posters. I often find that posters contain more interesting research, and by grad students who are still clear thinking and not corrupted by bad role models. But often overly impressed by authority.

Recovery from stuttering
Howell Peter, Davis Stephen

A longitudinal study of syntax, prosody and recovery from stuttering
Rusbridge Sarah, Howell Peter

Stuttering and the ICD 9/10: A debate within our profession
Bernstein Ratner Nan, Maguire Gerald

Dysfluency levels in various speaking conditions in acquired neurogenic stuttering
Balasubramanian Venu, Cronin Kristine, Max Ludo

Comparing sequence learning and retention in stuttering and Parkinson’s disease
Smits-Bandstra Sarah, Gracco Vince, De Nil Luc

peech and nonspeech sensorimotor learning in individuals who stutter
Max Ludo, Baldwin Caitlin J., Cronin Kristine L., Flanagan J. Randall

Genetic epidemiological relations between Stuttering, Cluttering and Specific Language Impairment
Fibiger Steen, von Bornemann Hjelmborg Jacob, Fagnani Corrado, Skytthe Axel

Multiple facets of stuttering: Insights from brain and behavioural research
Luc De Nil

Neurobiological explanations of developmental stuttering: Contributions from brain imaging studies
Watkins Kate, Ward David

Association Studies of chromosome 18 microsatellites and Familial Persistent Stuttering n
Domingues Carlos Eduardo

Parent-child interaction after the Lidcombe Program and the DCM-based treatment
Oonk Leonoor, Franken Marie-Christine, Koedoot Caroline

Another neuroscience article from China

Here is another article from the same Chinese group Lu et al in another good journal. Again, sounds interesting. And they look like serious professional scientists. They have another article out in Neuroscience; I need to compare to see what is different. Here they seem to look into Per's hypothesis that the pathway involving the basal ganglia is affected in stuttering people. And they find all kind of anatomically and connective differences. I need to look at the complete article in detail. But I keep on promising that I look at articles carefully and report back. But I never do... :-(

1: Cortex. 2009 Mar 13.

Altered effective connectivity and anomalous anatomy in the basal ganglia-thalamocortical circuit of stuttering speakers.

Lu C, Peng D, Chen C, Ning N, Ding G, Li K, Yang Y, Lin C.

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.

Combining structural equation modeling (SEM) and voxel-based morphometry (VBM), this study investigated the interactions among neural structures in the basal ganglia-thalamocortical circuit (BGTC) in the left hemisphere of stuttering and non-stuttering speakers. Stuttering speakers (n=12) and non-stuttering controls (n=12) were scanned while performing a picture-naming task and a passive-viewing (baseline) task. Results showed significant differences between stuttering and non-stuttering speakers in both effective connectivity and anatomical structures in the BGTC in the left brain. Specifically, compared to non-stuttering speakers, stuttering speakers showed weaker negative connectivity from the left posterior middle temporal gyrus (PMTG) to the putamen, but stronger positive connectivity from the putamen to the thalamus, from the thalamus to the PMTG and anterior supplementary motor area (preSMA), and from the anterior superior temporal gyrus (ASTG) to the preSMA. Accompanying such altered connectivity were anatomical differences: compared to non-stuttering controls, stuttering speakers showed more grey matter (GM) volume concentration in the left putamen, less GM volume concentration in the left medial frontal gyrus and ASTG, and less white matter volume concentration underlying the left posterior superior temporal gyrus inside the BGTC. These results shed significant light on the neural mechanisms (in terms of both functional connectivity and neural anatomy) of stuttering.

Back from Paris

I was in Paris this weekend competing in the Toastmaster's division International Speech contest after I won my club and area contests. There were six contestants from each area covering the Benelux countries and France. Unfortunately, I didn't make it into the Top3; only the first three are announced. But it was a great experience, and the delivery of my speech my best so far. And many people came up to me after the talk, and congratulates me: Best talk I have heard for ages, Very inspiring, My No1. And so on... So why did I not make it into the Top3? God knows what the judges were thinking. But seriously, I really enjoyed my presentation, they laughed at all my jokes, and everyone was listening... The only one who did not congratulate me was a person who also stutters, sorry who is a recovering stutterer from the McGuire course! ;-)

The speech was recorded, so I will try to post it. Try out Toastmaster!

Hollins Institute in trouble

Ley Geddes/BSA has reported the Hollins Institue for exaggerated and unconfirmed success claims to the UK Advertising Standards Authority (http://www.asa.org.uk) who can act internationally.

I got hold of the official complaint:

'Hollins claims for the efficacy of their programme are featured in their mailing pack (jpeg attached). As a charity and a leading authority on stammering/stuttering, the BSA asked for supporting evidence. Our areas of concern are as follows:

1. It is possible that 90% of people who stutter could achieve normal fluency by the end of an in-house program, but it would be useful to know how ‘normal fluency’ was defined and judged.

2. As I am sure all SLPs (speech therapists) know, the difficulty normally comes in finding ways to transfer the high level of fluency which can be achieved on a program (particularly, an in-house program) to normal life and then to maintain it. Thus it would be unusual for 75% of people who have attended an in-house program to be speaking with normal levels of fluency two years after a course had ended. So it would be very useful to know how this level of ‘normal fluency’ was defined, achieved and judged. It is highly debatable whether John Stossel's researcher (Stossel is a reporter on ABC News and a graduate of HCRI) had the necessary independence, experience or expertise to enable you to describe his phone interviews as independent verification of the efficacy of the program. And, incidentally, it would be useful to know how long ago these phone interviews were carried out.

3. It is not clear if the term ‘program graduates’ means everyone who was on the program or simply a select group. If, for example, it excludes those people who did not complete the program, or who were not judged to have graduated, then it would be useful to know what proportion of people who started the program are being defined as graduates.'

We explained again to HCRI that unless these claims can be substantiated we believe they will continue to give false hope to those who stammer and give people who do not stammer the false impression that stammering can be overcome in the vast majority of cases.'

As ASHA supports our campaign against misleading ads, and the HCRI Clinical Supervisor is ASHA certified, we have advised Arlene Pietranton of this action. HCRI have been told about this too.

I am personally sorry that it has come to this as we felt that HCRI could - or should - have been able to provide support, on a confidential basis if necessary, because these claims are a key element in the HCRI marketing proposition.

Neuroscience report from China

In another sign that China is catching up with Western dominated science, I found this article published in Neuroscience, a renowned journal. I cannot really find out from the abstract what is going on, and why they gave them a covert picture-naming task to do. Structural equation modeling is a statistical method combining quantitative data and qualitative causal assumptions, but that does not help me much. My guess is that they put some in a scanner and gave them a task and monitored the brain processes and used this structural equation modeling to gain information. But I never heard of this method before, but Neuroscience is a good journal so they don't just accept everything.

They claim functional disconnection from the left IFG to the left motor areas, and altered connectivity in the basal ganglia-thalamus-cortical circuit, and abnormal integration of supramodal information across the cerebellum and several frontal-parietal regions. From the words, it fits past neuroscience research, but really I would need to look at this in more depth!

Here is the abstract. Please send me the paper if you have access:

Neuroscience. 2009 Apr 10.
The Role of Large-Scale Neural Interactions for Developmental Stuttering.

Lu C, Ning N, Peng D, Ding G, Li K, Yang Y, Lin C.
State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, P. R. China.

Using structural equation modeling (SEM) method, the present study examined the role of large-scale neural interactions in developmental stuttering while ten stuttering and nine non-stuttering subjects performed a covert picture-naming task. Results indicated that the connection patterns were significantly different between stuttering and non-stuttering speakers in both omnibus connection pattern and individual connection path coefficient. Specifically, stuttering speakers showed functional disconnection from the left IFG to the left motor areas, and altered connectivity in the basal ganglia-thalamus-cortical circuit, and abnormal integration of supramodal information across the cerebellum and several frontal-parietal regions. These results indicate that the large-scale dysfunctional neural interactions may be involved in stuttering speakers' difficulties in planning, execution, and self-monitoring of speech motor sequence during word production.

PMID: 19364522 [PubMed - as supplied by publisher]

Oprah Winfrey should be ashamed

I am utterly shocked by the Oprah Winfrey show on the Speech Easy device. I had never actually seen it. It is just so so bad. I have been critical of the Lidcombe trials and claims of efficacy, but this is a different league. The Lidcombe trials were just sloppy research done with good intentions but not so good scientific rigor. But the Oprah Winfrey show is about dumbing down realities, misleading, sloppy research, promising miracles, abusing the emotions of people, and getting the science wrong. They showed Ratstatter and Kalinowski as inventors of the device. That's a joke. Many people were thinking along similar lines. The worse was when Joe Kalinowski took out the device and stuttered severely. I can do that, too. And God made him suffer terribly to help others???? Wow!

I would love to know what has happened with the two guys who were on the show. We need to find out their contact details and speak to them. One is called Mark Babcock. And the others Wesley Cock?

Let us know if you have more details!

Analysis of latest "research"

Greg Snyder at stuttering.me did a good job in commenting on the latest research. In fact, he did a better job than I am going to do here, because I am quite busy. Here is how scientists usually read articles. Remember time is very valuable.


A life-time of stuttering: How emotional reactions to stuttering impact activities and participation in older people? Bricker-Katz G, Lincoln M, McCabe P. Disabil Rehabil. 2009 Apr 3:1-11.

ok. might be a bit interesting as i have never heard anything about older stuttering people and how they handle stuttering. is of course dead-end research and will do nothing for better understanding of stuttering. but might be interesting to know more about this age group and one can use it to exert political pressure for more ressources.


Speech skill learning of persons who stutter and fluent speakers under single and dual task conditions. Smits-Bandstra S, De Nil L. Clin Linguist Phon. 2009 Jan;23(1):38-57.

Good scientists. They really seem to be obsessed with the single/dual task performances. Not necessarily a bad thing. If you find a difference, you should zoom into it as much as possible. Will try to read, but i am nearly convinced it is like the other papers. not very clear what is really going on and no very clear effects. But will read abstract and probably ask for paper.


Peer Responses to Stuttering in the Preschool Setting. Langevin M, Packman A, Onslow M. Am J Speech Lang Pathol. 2009 Mar 30.

dead-end research. seems plainly obvious. complete waste of time. i can tell you what is happening. either i ask a few speech therapists of their experiences. that takes me 4 emails to write and within a week i am done. or i guess: some kids will notice, either asking why do you stutter or they might laugh. but most will just accept it. so what have we learned. NOTHING. NOTHING. NOTHING AT ALL.


Social anxiety and the severity and typography of stuttering in adolescents. Mulcahy K, Hennessey N, Beilby J, Byrnes M. J Fluency Disord. 2008 Dec;33(4):306-19. Epub 2009 Jan 6.

dead-end and stamp collecting research. why do we need research to find out what all adolescents and adult stutters tell us. it is not easy in school and many of us experienced severe social anxiety.


Delayed auditory feedback effects during reading and conversation tasks: Gender differences in fluent adults. Corey DM, Cuddapah VA. J Fluency Disord. 2008 Dec;33(4):291-305. Epub 2009 Jan 3.

stamp collecting research. you make some observations and then? And I am never a friend of looking at speech data. way too down stream of the real issue.


Effects of altered auditory feedback (AAF) on stuttering frequency during monologue speech production. Antipova EA, Purdy SC, Blakeley M, Williams S. J Fluency Disord. 2008 Dec;33(4):274-90. Epub 2008 Oct 14.

also stamp collecting research. same as last one.


Non-linguistic auditory processing in stuttering: Evidence from behavior and event-related brain potentials. Hampton A, Weber-Fox C. J Fluency Disord. 2008 Dec;33(4):253-73. Epub 2008 Aug 30.

good scientists. might be interesting. will read abstract and might ask for paper.

Stuttering Hub interviews The Stuttering Brain

Hiten at Stuttering Hub posted an interview with me: check here. He did the interview a long time ago with me, but I still agree with me, which is not always the case!

Candy for kids?

I know I haven't been active for a few days. Too much work. I am writing my final essay in the neuroscience Master course on Cognitive Neuropsychology (Damaged Brains) and Connectionist Modelling (Neural Networks). And I have the CFA (chartered financial analyst) level II exam with 3000 pages beginning of June! I am way way behind schedule... Why do I do all these exams? Is PhD not enough?

As I said, I have no time. So I just listened to StutterTalk's interview with Barry Guitar. He is using voluntary stuttering with kids. If they voluntarily stutter, they get candy. Interesting idea... You instil positive or overwrite negative associations about stuttering into kids. Does this mean that they are more relaxed about their stuttering and therefore will stutter less or at the very least handle stuttering better? Or do they now stutter more because they have positive associations? It might well be more effective that the Lidcombe approach of just praising the kids or giving neutral feedback.

I am also amazed at his turn-around. I witnessed him praising a lot research on temperament and reactivity of stuttering kids and how it can explain non-recovery. And now I hear him talking about the great progress in brain imaging on stuttering kids, and how a bad neurology is really at the core of the problem! Is he starting to read my blog or what?? To be honest, he seems to be really getting into it. Now I am even concerned he is pushing the neuro stuff too far and ignoring the behavioural issues that come into existence due to the neurology and take on a life of its own!

In general, I am getting more concerned that the wave is splashing to the other extreme: from purely behavioural to purely neurological. I firmly believe that you need both. Sure, the source of stuttering is clearly neurological, but I also believe that most stuttering behaviour is independent of a neurological momentary delay and is behavioural: a natural reaction to delays in speech initiation which got associated to words, settings and situations.

Stuttering a brain disorder?

I just listened to an interview on StutterTalk with Jerry Maguire, and everyone seemed to agree that stuttering is a brain disorder.

I am going to shock my readers now, but I believe that stuttering is not just a brain disorder but also a behavioural disorder. The underlying cause is a brain abnormality leading to instable speech which then leads to association between stuttering and words, situations or people. And these associations can trigger stuttering without there being a neurological issue at that very instance. So 90% of your stuttering events might well NOT be of a neurological cause but you stutter because one of your associations have been triggered by a word, event or situation leading the brain to execute stuttering. I believe more and more that stuttering is a hybrid disorder.

Compare to Tourette syndrome for example. The urge for the tics are always there but sometimes they are suppressed longer and other times there are not. (Unless I misunderstand the disorder...) But with stuttering, the neurological stuttering is not always there...

Patent application for stuttering medication

A reader dug out this patent application for a stuttering medication: (I couldn't get the line breaks working...)

Treatment of stuttering and other communication disorders with norepinephrine re-uptake inhibitors

USPTO Application #: 20070032554
Title: Treatment of stuttering and other communication disorders with norepinephrine reuptake inhibitors
Abstract: Provided are methods and medicaments for treating stuttering or another communication disorder, comprising administering to a patient in need of such treatment an effective amount of a selective norepinephrine reuptake inhibitor. (end of abstract)

Agent: Eli Lilly & Company - Indianapolis, IN, US
Inventor: Douglas Kenneth Kelsey
USPTO Applicaton #: 20070032554 - Class: 514651000 (USPTO)

Treatment of stuttering and other communication disorders with norepinephrine reuptake inhibitors description/claims


The Patent Description & Claims data below is from USPTO Patent Application 20070032554, Treatment of stuttering and other communication disorders with norepinephrine reuptake inhibitors.

Brief Patent Description - Full Patent Description - Patent Application Claims


BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates to the fields of pharmaceutical chemistry and central nervous system medicine. More specifically, the present invention relates to methods of treating communication disorders, such as stuttering, in children, adolescents, and adults by administering selective norepinephrine reuptake inhibitors to patients in need of such treatment.

[0003] 2. Description of Related Art

[0004] The Diagnostic and Statistical Manual ofMental Disorders, Fourth Edition (DSM-IV) (1994), American Psychiatric Association, Washington, D.C., pp. 55-65, describes a number of communication disorders usually first diagnosed in infancy, childhood, or adolescence. These include stuttering, expressive language disorder, mixed receptive-expressive language disorder, phonological disorder, and communication disorder not otherwise specified. Stuttering is perhaps the most well known of these disorders.

[0005] Stuttering is a speech disorder in which the normal flow of speech is disrupted by frequent repetitions or prolongations of speech sounds, syllables, or words, or by an individual's inability to start a word. The speech disruptions may be accompanied by rapid eye blinks, tremors of the lips and/or jaw, or other struggle behaviors of the face or upper body that a person who stutters may use in an attempt to speak. Certain situations, such as speaking before a group of people or talking on the telephone, tend to make stuttering more severe, whereas other situations, such as singing or speaking alone, often improve fluency. Stuttering is also referred to as stammering, especially in England, and by a broader term, dysfluent speech.

[0006] Characteristics of stuttering are described in Section 307.0 of the DSM-IV at pp. 63-65. While all individuals are dysfluent at times, the person who stutters is differentiated from someone with normal speech disfluencies by the kind and amount of dysfluencies.

[0007] Characteristics of stuttering include: [0008] Repetition of sounds, syllables, parts of words, whole words, and phrases [0009] Prolongation, or stretching, of sounds or syllables [0010] Tense pauses, hesitations, and/or no sound between words [0011] Speech that occurs in spurts, as the client tries to initiate or maintain voice [0012] Related behaviors, for example reactions that accompany stuttering such as tense muscles in the lips, jaw, and/or neck; tremor of the lips, jaw, and/or tongue during attempts to speak; foot tapping, eye blinks, head turns, etc. (to try to escape from the stuttering); etc. There are many related behaviors that can occur and vary from person to person. [0013] Variability in stuttering behavior, depending on the speaking situation, the communication partner(s), and the speaking task. A person who stutters may experience more fluency in the speech-language pathologist's office than in a classroom or workplace. There may be no difficulty making a special dinner request at home, but extreme difficulty ordering a meal in a restaurant. Conversation with a spouse may be easier, and more fluent, than that with a boss. A person may be completely fluent when singing, but experience significant stuttering when talking on the telephone. [0014] A feeling of loss of control. The person who stutters may experience sound and word fears, situational fears, anticipation of stuttering, embarrassment, and a sense of shame. Certain sounds or words may be avoided. One word may be substituted for another that is thought to be harder to say. Or, certain speaking situations may be avoided altogether. For example, a person who stutters may always wait for someone else to answer the phone. Or, he or she may walk around a store for an hour rather than ask sales staff where an item can be found. These reactions to stuttering occur in more advanced stages.

[0015] Repetitions and prolongations are essential features of stuttering. The presence of the other listed behaviors varies from person to person.

[0016] Developmental stuttering (DS), with or without associated psychiatric illness, is the most common form, and includes all cases with gradual onset in childhood that are not the result of acquired brain damage. Persistent developmental stuttering (PDS) is DS that has not undergone spontaneous or speech therapy-induced remission. Acquired stuttering, which is much rarer than DS, may occur in previously fluent individuals. This form may be neurogenic, resulting from brain damage associated with, for example, stroke, traumatic brain injury, Alzheimer's disease, renal dialysis, Parkinson's disease, and progressive supranuclear palsy (Heuer et al. (1996) Ear Nose Throat J. 75:161-168; Brazis et al. (1996) Localization in Clinical Neurology, Third Ed., Little, Brown and Company, Boston, Mass., p.515).

[0017] Based on neuroimaging research data and the effectiveness of dopamine receptor antagonists in DS, this form of stuttering appears to have a hyperdopaminergic origin.

[0018] It is estimated that over three million Americans stutter. Stuttering affects individuals of all ages, but occurs most frequently in young children between the ages of 2 and 6 who are developing language. The prevalence of stuttering in prepubertal children is 1%, and drops to 0.8% in adolescence. The male-to-female ratio is approximately 3: 1. Most children outgrow their stuttering, and it is estimated that less than 1 percent of adults stutter.

[0019] Family and twin studies strongly suggest a genetic factor in the etiology of stuttering. The risk of stuttering among first-degree biological relatives is more than three times that in the general population. About 10% of daughters, and 20% of sons, of men who stutter will also stutter.

[0020] There is at present no cure for stuttering. However, a variety of treatments are available that may improve stuttering to some degree. These include speech therapy to improve fluency and success in communication; parent education to restructure the child's speaking environment to reduce episodes of stuttering; and the use of interventions such as electronic devices or medications. Electronic devices which help an individual control fluency may be more of a bother than a help in most speaking situations, and are often abandoned by individuals who stutter. Medications that affect brain function often have side effects that make them difficult to use for long-term treatment.

[0021] Many medications have been studied for use in treating stuttering. Evidence suggests that persons who stutter exhibit hypometabolism of the striatum and increased dopamine activity (Wu et al. (1995) Neuroreport 6:501-5; Wu et al. (1997) Neuroreport 8:767-70; Wu et al. (1997) In: Hulstijn W, Peters HRM, van Lieshout PHHM, eds. Speech production: motor control, brain research and fluency disorders. International Congress Series 1146. Amsterdam: Excerpta Medica 339-41). Drugs that boost dopamine levels exacerbate stuttering. Ritalin has a similar effect. Tricyclic antidepressants have proved ineffective, and in fact stuttering has been reported as an adverse event with the use of these compounds.

[0022] In contrast, the dopamine antagonist haloperidol has been shown in replicated, double-blind trials to reduce the symptoms of stuttering, leading to the hypothesis that D.sub.2 receptor antagonists may be important in the treatment of developmental stuttering (J. P. Brady (1991) Am. J. Psychiatry 148:1309-16). Unfortunately, as this drug is not well tolerated by this patient population and carries substantial risk of extrapyramidal symptoms and tardive dyskinesia, it is not recommended for the treatment of stuttering.

[0023] In a recent small study, Maguire et al. ((2000) J. Clin. Psychopharmacology 20:479-482) demonstrated that the serotonin-dopamine antagonist risperidone may be effective in the treatment of developmental stuttering, and recommended further investigations of risperidone for this purpose. While extrapyramidal symptoms and akathisia were not found with the use of risperidone, sedation was common, and some participants developed transient sexual and menstrual cycle side effects that resolved with discontinuance of the medication, or with a reduction in dose. These side effects are thought to be due to the elevation of the hormone prolactin by risperidone (haloperidol also raises prolactin levels in some patients).

[0024] Paroxetine and Sertraline, selective serotonin reuptake inhibitors, are also used for the treatment of stuttering, but cause a number of undesirable side effects.

[0025] Newer medications more narrowly target dopamine receptors. Olanzapine (Zyprexa), has been used successfully to treat developmental and acquired stuttering in children, adolescents, and adults (Lavid et al. (1999) Annals of Clinical Psychiatry 11(4): 233-236; Lavid et al. (2000) Presented at the annual meeting of the American Psychiatric Association, Chicago III., 2000). Side effects were mostly limited to slight weight gain and drowsiness.

[0026] The present invention addresses the need in the art for improved treatments for stuttering that are both safe and effective.

SUMMARY OF THE INVENTION

[0027] Accordingly, in a first aspect, the present invention provides a method of treating stuttering or another communication disorder, comprising administering to a patient in need of such treatment an effective amount of a selective norepinephrine reuptake inhibitor. The selective norepinephrine reuptake inhibitor can be, but is not limited to, any of the compounds disclosed herein.

[0028] In another aspect, the present invention provides the use of a selective norepinephrine reuptake inhibitor, such as any of the compounds disclosed herein, or other selective norepinephrine reuptake inhibitors, for the manufacture of a medicament for the treatment of stuttering or another communication disorder.

[0029] Further scope of the applicability of the present invention will become apparent from the detailed description provided below. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the present invention, are given by way of illustration only since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

Genes located?

Look at this intriguing article from China. They seem to have found a genetic relationship between dopamine and stuttering. However, I am not geneticist, so I do not know exactly what the result means and whether the results are reliable or not. Maybe a reader can help us out?

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Mar;29(3):375-80.

[Single nucleotide polymorphisms of DAT and DRD2 genes in Han Chinese population and their association with stuttering.]

Pan CH, Song LP, DU J, Lan J, Wu CM, Wu LJ, Lin L, Wang W.

Graduate School of Chinese Academy of Sciences, Beijing 100049, China.

OBJECTIVE:

To explore the correlations of dopamine transporter gene (DAT) and dopamine D(2) receptor gene (DRD2) to stuttering. METHODS: To examine the correlations of the 5 single nucleotide polymorphisms (SNPs) in dopaminergic gene (C252T, C1804T, and C1820T in DAT gene, and T1054C and C1072T in DRD(2) gene) to stuttering in Han Chinese individuals, a case-control study involving 112 patients with stuttering and 112 gender-matched controls was carried out. Genotyping was performed by a combined approach using polymerase chain reaction (PCR) and pyrosequencing.

RESULTS:

C1804T showed no polymorphism in either the patients or the control subjects and was therefore excluded from the following analysis. The C allele frequency at C1072T site was significantly higher, but T allele frequency significantly lower in the stuttering group than in the control group. The patients had significantly higher CC and lower CT genotype frequencies than the control group. There were no significant differences in the allelic frequencies of C252T, C1820T and T1054C between the patients and the controls, suggesting a Hardy-Weinberg equilibrium at these 3 loci. CONCLUSION: The presence of the C allele at C1072T in DRD(2) gene is associated with increased susceptibility to stuttering in Han Chinese, whereas the T allele provides protection against the onset of stuttering.