Dopamine and Stuttering

From: Jonathan Bashor
Date: 10/3/99
Time: 10:01:15 AM
Remote Name: 207.174.156.17

Comments

Has anyone noticed if the effect of the dopamine uptake drugs diminishes over time ? I remember reading
about Dr. Sacks work with post-encephalitis patients. They exhibited Parkinson-like symptoms. For a while,
giving them dopamine produced a dramatic change in their condition. 

Re: Dopamine and Stuttering

From: Larry Molt
Date: 10/8/99
Time: 3:05:42 PM
Remote Name: 131.204.63.26

Comments

Hi Jonathan 

I'm assuming that you're referring to such an effect in the use of dopaminergic neuropharmaceuticals in
treating stuttering, and there never has been an effect like what was noted with Sachs post-encephalic patients.
That doesn't mean that a reduction in effectiveness isn't noted for some patients. The response to
neuropharmaceurticals varys widely among individuals. What is a therapeutic dosage for one individual may
produce devastating results in others, and yield no discernible results in yet others. Some individuals adapt
over time, and dosages must be increased to maintain effectiveness, and yet limited enough to prevent
unwanted side effects. Many of the dopaminergic drugs may create may create additional unwanted
behaviors/movements, called tardive dyskinesias, especially as dosages increase, however, there is also a wide
variation in susceptibility to this. All usage needs to monitored very carefully. 

Hope that answers your question - thanks for your interest! 

Larry Molt

Genetic basis of Tourette's, stuttering, ADHD, and OCD

From: Thomas David Kehoe
Date: 10/3/99
Time: 1:22:29 PM
Remote Name: 216.160.168.244

Comments

Comings et al. (1996) correlated the three genes that control dopamine levels with ADHD, stuttering,
Tourette's, and obsessive-compulsive disorder. While this may answer the question of whether stuttering has
a genetic basis, it opens another question: why do some people with these genes develop stuttering, while
other develop Tourette's, ADHD, or OCD, and still other individuals with these genes develop none of these
diseases? (Comings, D., et al., "Polygenic Inheritance of Tourette Syndrome, Stuttering, Attention Deficit
Hyperactivity, Conduct, and Oppositional Defiant Disorder," American Journal of Medical Genetics
67:264-288, 1996) 

Singer et al. ("Neurology", June 1998) found that Tourette's was triggered by a childhood autoimmune
disorder. I've talked to parents whose children suddenly started stuttering after a fever, suggesting an
antineuronal antibody attack on the child's speech motor control area. But other parents say that the onset of
stuttering was not associated with a fever or infection. -- 

Stuttering Science & Therapy Website http://www.fluencydevices.com 

Thomas David Kehoe Casa Futura Technologies (888) FLU-ENCY

Re: Genetic basis - Question 1: why different manifestations in
different individuals

From: Larry Molt
Date: 10/8/99
Time: 6:08:26 PM
Remote Name: 131.204.63.26

Comments

Hi Tom 

Thank you for your comments. I apologize for the delay in responding, but your questions deserve a lengthy
response rather than a quick one, so I waited until I could give them the attention they deserve. I have no
pretensions towards being a genetics expert, and thatÕs what your questions deal with (and I did not include
genetics in my paper because IÕm not particularly knowledgeable in that area); however, you asked, so IÕm
willing to take a stab at them. Because IÕve got several items to discuss in relation to your posting, IÕve broken
it into 2 responses. This first one deals with your report of the Comings et al. (1996) article and your question
"why do some people with these genes develop stuttering, while others develop TS, ADHD, or OCD, and still
other individuals with these genes develop none of these diseases?" 

First, IÕd like to caution you concerning your conclusions of what the Comings, Wu, Chiu, Ring, Gade, Ahn,
MacMurray, Dietz, & Muhleman (1996) article "Polygenetic inheritance of Tourette syndrome, stuttering,
attention deficit hyperactivity, conduct, and oppositional defiant disorder" indicates. The study examined
individuals with TS, and via an extensive questionaire, identified a variety of behaviors (e.g., school
performance, learning disorders, panic attacks, reading problems, stuttering, general anxiety, somatization,
sleep, sexual obsession, schizoid, tics, phobias, alcohol abuse, substance abuse, sleep disorders, oppositional
defiant, manic, etc.) and correlated the occurrence of those behaviors with polymorphic disruptions in three
different gene alleles associated with dopamine function (DRD2 polymorphism, DbetaH polymorophism, and
DAT1 polymorphism, and by the way, these 3 are by no means the only alleles that are associated with the
regulation of dopamine function and so could interfere with dopaminergic function if genetically disordered).
For one allele there was a high occurrence of stuttering in the individuals with TS, for the second there was a
much smaller but still statistically significant occurrence, and for the third allele, the occurrence was not
statistically significant. The authors then examined occurrences of the accompanying disorders when all three
alleles were present. Stuttering was one of the accompanying disorders most frequently present when all three
polymorphic variants of the alleles were present (ADHD was the most common, and oppositional defiant
disorders, tics, OCD, mania, alcohol abuse, and general anxiety were also statistically significant, and several
other behaviors demonstrated similar trends but were not significant). As you know, statistical significance
simply means that the frequency of occurrence observed/measured appears to be an accurate value, based on
probability tables. It doesnÕt mean stuttering was present for all, in fact in can be present in a relatively small
number of individuals and still be statistically significant, and this is the case in some of the genotypes (e. g.,
present in 21% of the TS individuals). 

There is an inherent problem with how stuttering was dealt with in the study. Participants responded to a
single question in the questionaire Š and it read: "have you ever had problems with stuttering?". No indication
if stuttering was actively present, if they had it at one time but had recovered (which would seem to weaken the
genetic linkage) or even if they actually had developmental stuttering). There is a risk, I would argue, in
believing their numbers for stuttering. Nonetheless, I would agree that stuttering was likely present in many of
the individuals. 

The article dealt with individuals with TS. As you know, TS is diagnosed by having a variety of behaviors
present, not just the presence of motor or vocal tics. While there was a concordance between the three
polymorphic allele genotypes that affect dopaminergic systems and many of the behaviors, it is not clear cause
and effect Š there could be (and almost certainly are) many other polymorphic (or other disruptions) alleles in
these individuals with TS. While personally my own thoughts about stuttering in some individuals fit with
their linkage of dopaminergic genetic irregularites, I would in no way extrapolate that these results, done on
individuals with clear neurogenic pathology, have direct implications for the majority of individuals who
stutter, and I would hope that you would not either! The study talks about links to stuttering (poorly defined)
in individuals with TS. Most people who stutter do not share the same symptom pattern that TS individuals
do. Further, while I agree there is some reasonableness in including stuttering in the behaviors examined
because of a possible dopaminergic link, the study in NO way implies these allele patterns are the sole genetic
bases for stuttering (and IÕm very reasonably confident that they are not). 

While this has certainly been an indirect way to do it, I hope it has proposed an answer to your question "why
do some people with these genes develop stuttering, while others develop TS, ADHD, or OCD, and still other
individuals with these genes develop none of these diseases?" Š there were different symptom patterns for each
polymorphic allele, not all individuals possessed all 3, and there was variability of symptoms even within
individuals with all 3. In other words, there certainly is not a 1:1 correspondance between presence of a
genetic anomaly and presence of symptoms, and especially in the case of polygenetic disorders like TS it is the
interaction of multiple gene abnormalities that is the key (and that interaction includes many other genes than
just the ones examined in the Comings, et al. study, and must not preclude environmental interactions either Š
as Comings also pointed out). 

I have no expectation that finding a genetic base for stuttering will be easy. While some neuromotor disorders
like HuntingtonÕs disease have been linked to a clearly identifiable gene disorder and a clearly identified
transmission pattern, stuttering doesnÕt appear to follow such a pattern. The strong diversity of the population,
the wide diversity of stuttering symptoms across individuals, and the inability, despite good research attempts,
to describe a clear genetic transmission pattern lead me to believe that the disorder follows a polygenetic pattern
like TS and many other disorders. It stems from the disruption in the interactions among several genes, and
between genes and the environment. 

Whew! There it is, for whatever its worth. I commend you for your interest an efforts to explore stuttering. IÕll
tackle your second question, concerning antineuronal antibody attack of the speech motor system, in a second
posting. 

Warmest Regards, Larry Molt 

Re: Genetic basis of Tourette's - Question 2: Antineuronal
antibodies from strep infection

From: Larry Molt
Date: 10/19/99
Time: 2:54:32 AM
Remote Name: 131.204.63.26

Comments

Hello again Tom 

The Singer, Giuliano, Hansen, Hallett, Laurino, Benson, & Kiessling (1998) article was certainly intriguing,
wasn't it! However, I hope that wasnÕt the only article you read on the issue, for the evidence seems to be
weighted against such a model. Research by Kiessling, et al, (1993); Kiessling, Marcotte, & Culpepper
(1994); Allen, Leonard & Swedo (1995); and Singer, et al. (1997) have failed to demonstrate such antibodies
in a substantial number of patients with TS. 

The concept of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection
(PANDAS) is a fairly new idea, and in the case of TS came about from some serendipitous emergence of TS
in previously asymptomatic children. First reported for a single case in Japan in 1978 by Kondo & Kabasawa,
followed by a report of 2 cases by Matarazzo (1992), it follows similar findings for another childhood
neuromotor disorder, SydenhamÕs Chorea (SC). There were some important differences, however. In both
reports, the children did not respond to typical TS treatment paradigms using neuroleptic pharmaceuticals, but
instead responded to treatment by anti-inflammatory and anti-bacterial agents. In only one case was
exacerbation of TS symptoms noted during times of recurrent bacterial infections. The lack of response to
traditionally effective TS treatments leaves open the question of whether we are seeing the manifestation of
different disorders with similar symptoms. 

This has sparked a great deal of interest in PANDAS as a possible etiological source in at least some TS
patients, with it viewed by some as an induced autoimmune disease. Some of the natural characteristics of TS
lend themselves well to such a model: the waxing and waning of symptoms might be linked to reoccurrence of
additional strep infections, the gradual disappearance of symptoms as the child grows into adulthood in about
1/3 of patients; the later life reoccurrence in some cases. Additionally, in the case of SydenhamÕs Chorea,
which has a much better documented link to PANDAS, there are reports of appearance or worsening of tics
and/or OCD in children with recent strep infections, and which responded well to prednisone or plasma
exchange therapy. Some SC patients demonstrate enlargement of the caudate nucleus of the basal ganglia
under MRI scans. 

How does this fit in with the genetic models of TS? One possible link might be that cellular immunity may play
a role in these disorders. Some families show a predisposition to the development of rheumatic fever following
streptococcal infections. 

There are, however, quite a few shortcomings to the autoimmune hypotheses of TS. Kurlan (1998) has
pointed out that in TS tics generally worsen during periods of stress or illness, so exacerbations concomitant
with strep infections may only represent a nonspecific response to stress. IÕve already mentioned that several
other studies have reported the existence of many TS patients who donÕt exhibit the antibodies reported in the
Singer et al. (1998) article. Additionally, strep is a rather common occurrence of childhood, and many "normal
children" demonstrate similar patterns of antibody response without any TS (or any other) symptoms.
PRESENCE DOES NOT EQUATE TO CAUSE AND EFFECT. 

I would encourage you to read "TouretteÕs Syndrome and PANDAS: Will the relation bear out?" by R. Kurlan
(Neurology, 1998; 50: 1530-1534) (its the same issue as the Singer, et al. article that you cited). The article
cites several additional factors mediating against the PANDAS theory for TS. Kurlan concludes that its
possible that postinfectious, immune-mediated mechanisms are active for a small subgroup of TS cases, but
also proposes that symptoms resembling TS (what they term "developmental basal ganglia syndrome") may be
caused by a variety of different conditions and that immune processes may be one of a number of possible
mechanisms. 

One parting comment, for itÕs certainly apropos for your question concerning stuttering and PANDAS: Kurlan
discusses why there may appear to be serendipitous links between infection and initial diagnosis of TS
symptoms. He proposes that the symptoms were already present, but the exacerbation brought on by the
infection is what made somebody suddenly view the symptoms as tics and led to the Dx of TS. Does that
sound like what weÕve often said about stuttering and trying to link its appearance to traumatic events and/or
illnesses? 

Warmest Regards, 

Larry Molt 

Questions concerning Basal Ganglia

From: Stefanie Thibodaux Prothro
Date: 10/10/99
Time: 5:35:34 PM
Remote Name: 32.100.25.103

Comments

Dear Sir: I am sorry for list of questions that I am presenting to you. In reading your article, my brain was
consumed with questions. As being a graduate student (as you remember) my brain is filled with theories and
questions. I am trying hard to understand the possible etiology of stuttering. If you could answer just one of
my questions or even give me references on what to research, it would be greatly appreciated. Thank you,
Stefanie 

1. If the basal ganglia is involved in stuttering, are there any specific treatment options to remediate stuttering? 

2. Would surgery or medication be involved in the remediation of stuttering? 

3. Is there a specific difference between an adult male/female or child male/female if the basal ganglion is the
cause of the stuttering? 

4. Is there a specific cultural difference among the various ethnic groups? 

5. What types of treatment or therapy options are available to a school based speech language pathologist? 

6. Is there any specific intervention strategies, in your opinion, that would benefit a classroom teacher who has
a student who stutters? 

7. What are some future topics for research? 

8. Is cerebral dominance the cause for language based stuttering? Why or why not? 

9. If language based stuttering is influenced by the cerebral dominance theory would treatments differ? 

Re: Questions concerning Basal Ganglia (reply to questions
1-4)

From: Larry Molt
Date: 10/13/99
Time: 9:12:44 AM
Remote Name: 131.204.63.26

Comments

Hi Stephanie! 

First, never apologize for asking questions Š thatÕs part of the purpose of a conference like this, and its what
we need Š the next generation of SLPs continuing to question and explore. IÕll tackle the first few of your
questions with this posting, and reply to the remainder in a few more postings. 

1. If the basal ganglia is involved in stuttering, are there any specific treatment options to remediate stuttering? 

It certainly opens up a number of options that might not be considered in traditional SLP therapeutic
approaches. This includes viewing stuttering from a different paradigm and changing therapeutic emphasis, or
such things as the use of neuropharmaceutical adjuncts to therapy/management 

2. Would surgery or medication be involved in the remediation of stuttering? 

I certainly donÕt see surgery as an option; the majority of basal gangliar disorders are not dealt with surgically,
and there have been few successes with the surgical attempts. There has been some limited speculation about
surgery in light of the transcranial magnetic stimulation research on PWS currently being carried out by Drs.
Peter Fox, Roger Ingham, and Janice Costello Ingham. This technique can be used to temporarily disrupt
neural activity within specific regions of the brain, and the researchers are investigating its effects on several
regions identified in previous PET studies as showing aberrant function in (some) PWS. The outcome of their
research may have many different implications for treatment, and surgery has been hypothesized as one (i. e.,
if electromagnetically "knocking out" a certain area results in normal fluency with no other observable negative
side effects, then surgical ablation of that area might be considered an option). Personally I have doubts that
will be the outcome Š the majority of attempts to deal with neurological dysfunction seem to carry a price tag of
unwanted side effects that is often too high to pay. 

Medication is currently being considered as an option, although its important to point out that no medication
has yet to be found 100% effective for ameliorating stuttering, and all have noticeable side effects. I wrote an
article for last yearÕs ISAD Conference on the use of neuropharmaceutical agents, and its still accessible via
The Stuttering Home Page (ISAD98 Online Conference) Š IÕd encourage you to check it out if youÕre
interested in this area, and especially the writings of Dr. John Brady: Brady, J. P. (1991). The pharmacology
of stuttering: A critical review. American Journal of Psychiatry, 148, 1309-1316. Brady, J. P. (1998).
Drug-induced stuttering: A review of the literature. Journal of Clinical Psychopharmacology, 18, 50-54. 

3. Is there a specific difference between an adult male/female or child male/female if the basal ganglion is the
cause of the stuttering? 

IÕm a little bit unsure of your question. There are differences in male-female ratio patterns for many of the
basal gangliar disorders, and also evidence of differences in recovery rate between the sexes. Tourette
syndrome is a good example of this, with a male-female ratio pattern that looks similar to that reported for
stuttering. 

4. Is there a specific cultural difference among the various ethnic groups? 

The research hasnÕt held this out to be noticeably true in stuttering. One of the areas of research explored in
attempts to support Wendall JohnsonÕs Diagnosogenic theory was that as attitudes to communication (and
success/competition) varied among cultures, so would the prevalence of stuttering Š yet the research results
generally support a prevalence figure fairly close to 1% across all cultures. IÕd encourage you to look at a copy
of Oliver BloodsteinÕs "Handbook of Stuttering" which should be available at your university library for a nice
summary of the research in this area. 

If it turns out that some cases of stuttering are caused by basal ganglia involvement that is hereditary, it is
possible that there would be ethnic differences (but there doesnÕt have to be differences). For example, several
years ago there was some speculation that sickle cell anemia, a hereditary disorder that is more prevalent in the
African/African-American population might put children with it at slightly higher at risk for stuttering. 

Great questions, Stephanie! IÕll tackle the rest in my next posting. 

Warmest Regards, 

Larry Molt 

Re: Questions concerning Basal Ganglia (reply to questions
5-9)

From: Larry Molt
Date: 10/14/99
Time: 9:11:00 AM
Remote Name: 131.204.63.26

Comments

5. What types of treatment or therapy options are available to a school based speech language pathologist? 

I assume youÕre referring to the possibility of a basal gangliar link, and what options that would leave the
school-based SLP. First, if for some individuals medication might alleviate some of the symptoms, then the
relationship between the SLP and the prescribing physician would be a vital one Š with the SLP providing
feedback to the physician to help with getting blood levels set correctly Š reporting on symptoms Š both how
well the stuttering is being addressed as well as the presence of side effects Š to achieve the best therapeutic
dosage. But I would expect much more would be needed from the SLP. Currently, none of the dopaminergic
drugs totally alleviate stuttering symptoms, and the SLP would be vital in dealing with the remaining
symptoms. (as has been suggested by Dr. Gerry Maguire, at Univ. California-Irvine, in his research with
risperidone). ThereÕs a second point to be made, however, and that is that the presence of a BG link need not
mean that the SLP may have to make many changes in the therapeutic approach. Many of the therapeutic
techniques currently in use are ones that have positive effects on BG disorders. The psychological/counseling
approaches aimed at alleviating fear would help to reduce triggering by the limbic/BG links; motor
simplification techniques taught in fluency shaping approaches attack some of the neuromotor components.
These techniques have shown great success in reducing stuttering symptoms in a large percentage of the
population; they just havenÕt been effective at removing all stuttering (possibly because of the underlying
neural function abnormalities that still remain, at least in some PWS). 

6. Is there any specific intervention strategies, in your opinion, that would benefit a classroom teacher who has
a student who stutters? 

As I mentioned in the previous answer, what has worked well in the past still works well today, even if our
etiological models may shift for some PWS. Techniques aimed at reducing fear towards stuttering and towards
speaking situations, and techniques aimed at changing and simplifying speech production are still vital and
useful strategies. 

7. What are some future topics for research? 

Great question! ItÕs always fun to prognosticate. Continuing the research into genetic links is vitally important,
for it should give us much greater insight into the disorder. Further brain imaging studies during speech
production are also vital Š weÕve learned so much already, and weÕre just seeing the tip of the iceberg. Another
key component is doing more research in very young children Š examining what is going on as stuttering first
starts to appear Š weÕve got lots of great researchers examining this right now Š Ehud Yarii, and Nan Ratner,
and Scott Yaruss come immediately to mind but there are plenty more. This is particularly vital information.
And we need much more research examining physiological and neurophysiological components in these young
children Š Tony Caruso has been emphasizing that for more than a decade. But there are other important
research areas that need emphasis that donÕt directly involve etiology. These include systematic investigation of
therapeutic techniques and continuing the search for new and innovative techniques. Lots of people are
attempting to apply new approaches to therapy Š for example, Woody Starkweather and Janet GivensÕ use of
gestalt approaches; and similarly, the use of REBT, talked about by Gardner Gately about a decade ago and
now being pushed vociferously by Gunars Neiders; and even other cognitive psychotherapies. 

8. Is cerebral dominance the cause for language based stuttering? Why or why not? 

Well, IÕve got to admit youÕve got me nervous in your choice of words, both with "cerebral dominance" "
language based stuttering". IÕm not comfortable with the latter Š for it implies we are confident of the etiology,
and I donÕt think we are at all. I would agree that in some PWS language adeptness, or rather a degree of
ineptness, plays a vital role Š but is that the sole source of the stuttering? Lots of kids have much worse
language disorders or delay - but they donÕt stutter Š what makes the difference? Its got to be more than just
language. As to your use of the former term, cerebral dominance implies that it works the same way for
everybody, and I donÕt think thatÕs necessarily true at all. As a brain imaging researcher Š IÕll tell you that
language appears to be all over the brain, both in left and right hemispheres, subcortically, even cerebellar,
with brainstem, and even corticospinal components. We can talk about a predominant hemisphere for
language, where damage or disorders result in more easily seen symptomotology, but there are activities going
on everywhere, and disorders anywhere have the potential for disrupting the exquisite temporal demands of
such an incredibly complex system of systems that is language, and thus impairing fluency. 

The imaging research does demonstrate altered patterns of activation across myriad levels of neurological
function in PWS when stuttering, some of which donÕt exist when they speak under fluent conditions. I still
feel we donÕt have enough information to determine what is really important, and whatÕs not, in trying to make
a determination about altered hemispheric dominance in PWS. 

9. If language based stuttering is influenced by the cerebral dominance theory would treatments differ? 

Returning to my answer to question 8, above, I really donÕt think we have enough information on whatÕs
wrong or different in PWS, or what the "correct" pattern is, to think about changing treatment approaches. 

Thanks for your interest, Stephanie. Southern University is lucky to have a student with such a bright,
inquisitive mind. Keep asking questions! 

Warmest Regards, 

Larry Molt 

food supplement

From: Gabriele Scaiola
Date: 10/16/99
Time: 4:51:36 PM
Remote Name: 195.191.76.97

Comments

(Sorry for my bad English) Can i reduct stuttering with amminoacid like taurine,gluammine,triptofane or other
supplements ?Often i noticed that my fluency went better(for a while)after a choccolat bar (who is full of
triptofane) or a energy drink based on taurine.

Re: food supplement

From: Larry Molt
Date: 10/20/99
Time: 12:04:38 AM
Remote Name: 131.204.63.26

Comments

Hi Gabriele 

Another very good question, unfortunately you're probably asking the wrong person this question, for I'm not
a pharmacology expert by any means. However, I do have a few thoughts as to your question. 

First, by triptofane, IÕm guessing you mean tryptophan. Tryptophan is one of the metobolic precursor
elements for the production of serotonin. I briefly mention a little in the article about the effects of serotoinergic
agents and possible effects on basal gangliar function, but I know of no study examining the effectiveness of
tryptophan in controlling basal gangliar dysfunction. YouÕre a step or two too advanced for me in trying to talk
about self-dosing using candy bars. Could it have an effect? Possibly, but as I said, I know of no empirical
evidence, and candy bars are a relatively uncontrolled delivery system! 

You mentioned taurine. There are limited reports that it may serve as an anti-epileptic agent. Anti-epileptics
have been used in the treatment of stuttering with limited or no results. It does have an effect on potassium
levels and could be considered a neuroinhibition neuromodulator working alongside GABA and glycine.
Again, maybe there is a link there, however, it doesnÕt fit strongly with current models or neuropharmaceutical
agents known to be effective in at least some individuals who stutter. 

By gluammine IÕm guessing youÕre talking about the nonessential amino acid glutamine. It is linked in the
body to GABA, an important chemical in basal gangliar regulation. As in the other two, theoretically there
could be links to a possible effect on stuttering, but at least for now, they remain tenuous. 

Its fun to experiment, and see what effects are observed. One must be cautious, however, because the
"placebo effect" is very strong in self-administered supplements. Thank you for your interesting question, and
good luck in your explorations. 

Warmest Regards, 

Larry Molt 

Similarity ParkinsonŹ Stuttering

From: Lieven Grommen
Date: 10/18/99
Time: 5:01:18 AM
Remote Name: 212.190.18.184

Comments

As a general practioner I have met some impressive cases of Parkinson disease. The most congruent symptom
seems to be the blocking. No stutterer can block for hours like some terminal Parkinson patients. My question
is: are there data about the immediate ( I am quite aware of the nocive tardive effects of the substance) effect of
L-DOPA on stuttering?

Re: Similarity ParkinsonŹ Stuttering

From: Larry Molt
Date: 10/19/99
Time: 3:24:59 AM
Remote Name: 131.204.63.26

Comments

Hi Lieven (BTW, I really enjoyed your article on covert stuttering!): 

You ask a very good question. One of the things I did not discuss in my paper was the similarities between
Parkinson disease and stuttering in many areas of basal ganglia symptomotology, and your example of
"freezing" (blocking) is very apt, and there are several others, aren't there!. I stayed away from PD in the
paper both for interests of brevity with the limited space available, and also because I see more differences in
symptoms between PD & stuttering than I see similarities, suggesting a greater difference in manifestation of
basal gangliar dysfunction. As to your question about immediate effects of L-DOPA on stuttering, I am
currently unaware of any such data. I wouldn't necessarily expect L-DOPA to be as effective as some of the
other dopaminergic agents, at least at the low dosages associated with risperidone or olanzapine, because my
impression is that we're talking about possibly a different receptor mechanism function between the disorders.
You've got my interest piqued, however, and I will do a more thorough search, and I'll get e-mail you if I find
anything. 

Warmest Regards, 

Larry

A fool can ask more questions than a wise man answer

From: Gunars K. Neiders
Date: 10/18/99
Time: 6:03:14 PM
Remote Name: 12.13.226.16

Comments

ISAD Larry Molt 

A job extremely well done, both in writing the paper and answering the questions. I pose some questions
which I am really curious to know answers to. I am willing to investigate them myself, if you can only point
me in the right direction. (Although I am no longer a graduate student, your paper really aroused my
curiosity.) 

Firstly, some questions about learning aids and references: 

1. Is there a textbook or paper that maps the Central Nervous System with all the regions and the associated
functions? 2. Have the brain researchers evolved a language [such as mathematics is in physics, and flow
charts in medical diagnosis and computer system modeling] for describing the interactions between the various
regions of brain to hypothesize the feed forward and feedback signals between various regions? 3. Have you
heard of any computer models of the Central Nervous System? 4. What dictionary or book would you suggest
that would give me good definitions of all the terms that you have used in your paper? 

Secondly, having come to your paper after an exchange with Joe Kalinowski and Andy Stuart that involved
paradigms in science, and especially in the study of stuttering, as well as Kuhn and Popper (the philosophers
of science) can you answer the following: 

5. Do you think there would be an advantage to separate etiology as to the original cause of onset of stuttering
(onset etiology) and what causes the propagation of stuttering (propagation etiology). To me it appears that
once the process of stuttering is set into motion, if we had a clear "snapshot" of the CNS this would provide
enough information to optimally manage the stuttering. The onset etiology would be useful in possibly
preventing the stuttering from becoming chronic. The advantage would be that complexity of the models or
paradigms could be reduced. 6. Based on your extensive knowledge have you formulated a model using flow
charts about what propagates stuttering? 

Thirdly, questions dealing I have some questions of trying to find references: 

7. In your paper you quote Erenberg, Cruse, & Rothner (1987) long term follow up study of individuals of
TS. Where can I find some of the best long term follow up studies of people who stutter? 8. In your paper you
quote the Tourette Syndrome Classification Study Group (1993)...The study group went on to include a list of
associated behavioral characteristics seen in individuals with TS: obsessive-compulsive behavior (OCB),
attention deficit hyperactivity disorder (ADD), impulsivity, aggressiveness, anxiety, phobias, depression,
self-injury, low frustration tolerance, poor socialization, and low self esteem. You continue Abwender et al
(1998) that observed both ADD and OCB in some of the children and adults who stutter. Also in answer to
Thomas Kehoe you stated... Comings, Wu, Chiu, Ring, Gade, Ahn, MacMurray, Dietz, &Muhleman (1996)
article "Polygenetic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and
oppositionaldefiant disorder" indicates. The study examined individuals with TS, and via an extensive
questionaire, identified a variety of behaviors (e.g.,school performance, learning disorders, panic attacks,
reading problems, stuttering, general anxiety, somatization, sleep, sexual obsession,schizoid, tics, phobias,
alcohol abuse, substance abuse, sleep disorders, oppositional defiant, manic, etc. My question to you is where
can I find analogous modern studies of using extensive questionnaires used with people who stutter to
determine if they also have these identified behaviors? 

The rest of the questions I have we can discuss sometime over a social beer. 

Thanking you in advance, 

Gunars 

Re: A fool can ask more questions than a wise man answer
(answers to questions 1-4)

From: Larry Molt
Date: 10/20/99
Time: 12:55:49 AM
Remote Name: 131.204.63.26

Comments

Gunars, my friend, hello 

I'll take a stab at your questions. 

1. A recommendation of a good book mapping/describing the CNS? A good one, extremely comprehensive, is
"Principles of Neural Science" Kandell, Schwartz, and Jessell, published by Elsevier Science. The med school
bookstore at UW should have it, or there is always Amazon. If you order through Amazon, besure to enter
through Judy Kuster's link, so she gets even more money! 

2. A "language" utilized by brain researchers? Neuroscience researchers come from all kinds of different
disciplines, including the ones you mentioned in your question (physics, medicine, and CE) and so
consequently a wide variety of modeling and descriptive devices are used. 

3. Have I heard of computer models of the CNS? Yes - just do a search using any of the search robots on the
web and you'll come across dozens, of varying degrees of sophistication. 

4. What dictionary would I reccommend to cover the terms used in neural science? Any good medical
dictionary would have them. I use Steadman's, primarily because I got it free. Taber's, Dorland's, there's lots
of good ones out there. 

more to come. that's one beer you owe me. more to come ;) 

Larry

"Modeling and descriptive devices" ... Please POINT, I'll
fetch :-)

From: Eternal student Gunars K. Neiders
Date: 10/20/99
Time: 11:57:59 AM
Remote Name: 12.13.226.15

Comments

Larry, 

Sorry to be a pest. 

Can you get me started on what do I search on (key words), what magazines do I go to, which books, what
authors, ANYTHING to get me on the right road to get at least SOME models as examples to see if I can put
together a model of stuttering that is more unambiguous than the English language. 

Again, sorry for the imposition. Even a few vague phrases like, flow charts, etc. could get me started. 

Gunars 

Re: "Modeling and descriptive devices" ... Please POINT, I'll
fet...

From: Larry Molt
Date: 10/25/99
Time: 1:04:55 AM
Remote Name: 131.204.63.26

Comments

Hi Gunars 

I wish I had better news for you, for I know where you're heading with this. Unfortunately, the news is bad.
We do not, in my opinion, have any truly realistic models that take in the depth and breadth of complexity
inherent in language formulation and motor production of spoken language. 

If you want to try some key word searches for models, I'd suggest looking at the executive order/executive
function area combined with vocal/verbal language, but the research is in its very infancy - the diversity and
complexity of all that goes into language production is not well understood, not reflected in the models (they
tend to center on specific functions/paths) and the empirical support for the models is lacking. 

You're too soon on this, my friend. 

Warmest Regards, 

Larry 

Re: A fool can ask more questions than a wise man answer
(reply to questions 5-8)

From: Larry Molt
Date: 10/25/99
Time: 2:00:51 AM
Remote Name: 131.204.63.26

Comments

Hi again Gunars! 

IÕll resume my attempts to answer your questions. 

Question 5: any advantage to separating etiology by onset etiology vs. propagation etiology? First off, IÕm
much more comfortable using slightly different terminology. The discipline often differentiates between
"predisposing" causes, "precipitating" causes, and "maintaining" causes. In answer to your question, I feel
such a framework may be very useful for explaining inter-individual differences we see among people who
stutter, and even some of the intra-individual differences (e.g. why different situations have differing effects
on amount/severity of stuttering). Personally, IÕd argue your statement about such a strategy reducing the
complexity of models or paradigms: while we could say weÕve reduced the NUMBER of models, that model
would of necessity have to be very complex to deal with the diversity of symptomotology across the
population. 

Question 6: have I formulated a model about what propagates stuttering? Easy to answer: No (and have no
plans to in the near future Š call me in about 5-10 years). We just donÕt know, Gunars. We donÕt know how
the basal ganglia precisely works for any particular movement, let alone the scores of muscles simultaneously
involved in any 20 milliseconds of verbal language production. We donÕt know how semantic intent is turned
into grammatical form. We donÕt know how words are stored. We donÕt know how they are recalled. We
donÕt know how grammar is generated. We donÕt know how this moves into the motor production aspect. We
donÕt know how motor programs are pulled up, nor how they are modulated. We donÕt know how language
functions in the brain and so thereÕs no way to build meaningful models of disorders when we donÕt know
how normal language production functions. 

Question 7: where to find long term follow up studies of PWS? Not much to find. The Newcastle studies
come to mind (Andrews & Harris Š check in your copy of BloodsteinÕs handbook). You could always call
Webster at Hollins College ;-). 

Question 8. Where to find studies where extensive questionnaires looking at diverse symptomotology such as
TS, ADHD, OCD, etc have been used in stuttering? First, as I tried to point out in response to Tom KehoeÕs
question, the questionnaire used by Comings was sorely lacking in complexity. There hasnÕt been research
that systematically looked at such a diversity of disorders in stuttering Š Gordon Blood & Robin Seider (Story)
did a nice study of 1060 school aged stuttering children with a limited look at concomitant problems in 1981
(JSHD). 

WeÕve been trying to put together just such a questionnaire here at Auburn for over a year, and I have 3
comments to make: first, thereÕs a great deal of diversity in instruments that are currently available looking at
any one disorder, and many disorders are diagnosed on the basis of several questionnaires/checklists, making
it difficult to decide what to include. Second, thereÕs a question about who can answer the questions; some
need to be answered by the parents, others by teachers, other items are best determined by a psychologist or
pediatric neurologist. Third, the more I look at the questionnaires for these other disorders, and based on my
own experience with over 1000 people who stutter, the less I think that weÕll see much of the symptomotology
in kids who stutter. Just take a gander at the OCD checklists posted on the internet to see what IÕm referring to
Š I donÕt know many PWS who will come up positive on more than 1 or 2 items on those checklists (as would
most nonstutterers). WeÕre continuing to work on it, and hope to have an alpha version ready for limited
administration next spring, but IÕm not optimistic weÕll find much. 

Wll, there you go. My attempts at your questions. Hope they help. BTW, I know a good pub in Charleston
where I can collect on those beers you now owe me. 

Warmest Regards, 

Larry Molt 

Basal Ganglia's Possible Role in Stuttering...

From: Karen Rockwell, Fontbonne College, St. Louis, MO
Date: 10/19/99
Time: 10:39:49 PM
Remote Name: 209.96.5.66

Comments

I see that in your bio (at beginning of article) that you are involved in EEG topographic mapping of brain
activity--have you personally observed, through PET, SPECT, EEG, MRI, etc., any of the chemical or
blood-flow differences observed by the researchers you have cited? Are other researchers also leaning toward
the theory that stuttering is somehow related to other basal ganglia disorders of movement, or is this
hypothesis still in its beginning stages? I find this type of research fascinating, and I hope it continues, as
technology provides us with more advanced equipment. Thanks for your very interesting article!

Re: Basal Ganglia's Possible Role in Stuttering...

From: Larry Molt
Date: 10/20/99
Time: 12:27:39 AM
Remote Name: 131.204.63.26

Comments

Hi Karen! 

The EEG research we've been doing has examined hemispheric function in people who stutter from several
different perspectives, including motor, auditory, and linguistic variables. We're noted differences in
hemispheric activation patterns for each of those variables in at least some people who stutter, but not all. In
the motor domain we've used the movement related brain potential paradigms to map motor preparation for
brief laryngeal vocalizations and noted differences in timing that one could hypothetically link to BG
dysfunction, however you could also speculate on a wide variety of other influencers also. 

EEG mapping gives excellent temporal resolution, on the order of microseconds, but little or no direct
evidence of blood flow or chemical patterning and weak spatial resolution unless paired with MRI. PET,
SPECT, and fMRI all are much better at spatial resolution, but they sacrifice temporal resolution. 

The basal ganglia is currently an area of interest to many researchers, both within SLP as well as other
disciplines, but there is much interest in several other neural areas also, and all these theories are in their
infancy, for its only recently that the equipment to closely scrutinize neurologic function has become available
(and affordable). I'm with you - this type of research is fascinating, and its great to hear of your interest - we
need new young blood continuing the quest. 

Warmest Regards, 

Larry Molt 

Spasmodic Dysphonia and Stuttering

From: Meghan Culey
Date: 10/20/99
Time: 8:37:39 PM
Remote Name: 208.156.164.210

Comments

Hello, My name is Meghan and I am a graduate student at Minnesota State University, Mankato. I found your
article extremely interesting. A question that I have is about the relationship between spasmodic dysphonia and
stuttering. Do they generally co-occur or does one tend to precede another? Thank you for any comments you
may have. 

Re: Spasmodic Dysphonia and Stuttering

From: Larry Molt
Date: 10/25/99
Time: 12:04:51 AM
Remote Name: 131.204.63.26

Comments

Hi Meghan! 

I'll make a deal with you. I'll answer your question if you promise to tell Judy Kuster what a great job she did
with the ISAD'99 Online Conference (and tell the chairperson at MSU that she deserves a raise)! 

Seriously, you asked an excellent question, and it sounds like I didn't do a good job of explaining the results
of the Kiziltan & Akalin article I quoted in the paper. There is little or no co-occurrence of spasmodic
dysphonia and stuttering, nor does one follow the other. Most individuals with SD will have few or no
stuttering symptoms, although there are some similarities in the symptoms that probably prompted Kiziltan and
Akalin to propose their theory. When I mentioned that they had reported a co-occurrence of stuttering, the
co-occurrence was in patients with torsional dystonia (a form of dystonia that affects other body parts rather
than the larynx), not SD. That was certainly a vital part of their theory, for if you see individuals with known
basal ganglia dysfunction (the dystonia) with a much higher than normal prevalence of stuttering, one might
speculate they share an underlying cause. This is also similar to what has been reported for Tourette syndrome
(another basal gangliar based disorder), with a much higher than normal prevalence of stuttering. 

One could easily ask why the converse wouldnÕt be true Š that we should see a much higher incidence of
concomitant basal ganglia disorders in stutterers; the literature, however, has not demonstrated that so far. My
guess is that the explanation would go something like this: stuttering may result from a weaker level of
dysfunction, and so other basal gangliar disorders would not be expected. The other disorders result from
more serious disturbances. But thatÕs why they are accompanied by stuttering in a number of cases Š the
dysfunction is way more than adequate enough to result in stuttering co-occurring. 

Thanks for your interest. Be sure to ask Judy lots and lots of great questions like this in the clinic at Mankato
(it keeps her on her toes)! 

Warmest Regards, 

Larry Molt 

THANK YOU!

From: Stefanie Thibodaux Prothro
Date: 10/22/99
Time: 6:31:58 AM
Remote Name: 166.72.156.201

Comments

Dr. Molt, I have been thinking of ways to tell you how grateful I am that you responded to my questions.
Your patience in answering my questions the way that you did was overwhelming. I am very appreciative of
your generosity. Your responses triggered more questions which in turn triggered more, I have generated a list
that will keep me busy for quite some time. I just wanted to let you know just how impressed I was with you
for taking the time to answer each question with sincerity and REFERENCES! I am looking forward to
reading more of your articles especially involving the basal ganglia. Do you think there could be a relationship
between stuttering and dysarthria (hypokinetic)? Sorry, you don't have to answer that until next year's
conference. Thank you again for time and effort, it IS greatly appreciated. 

Warmest regards, Stefanie

Re: THANK YOU/Hypokinetic dysarthria and stuttering - any
relationship?

From: Larry Molt
Date: 10/25/99
Time: 12:49:44 AM
Remote Name: 131.204.63.26

Comments

Hi Stefanie! 

Actually, the thank you should be coming from me to you - thank you for interest, your curiosity, and your
enthusiasm. It's wonderful to see! 

On to your question about hypokinetic dysarthria. The classic example of this form of dysarthria is of course
Parkinson disease (PD). Lieven Grommen asked me in an earlier question about similarities between PD and
stuttering, and IÕll refer you to that answer. Basically, there are some similarities, such as the classic freezing,
the possibility of sub-clinical tremor activity in speech structures in stutterers, the fact that PD symptoms are
often markedly reduced or absent under strong emotional experiences or when caught off-guard, much like the
PWS who is fluent when responding spontaneously without thinking about his or her reply or responding in a
crisis or emergency. One might speculate that the fact that some PWS speed up their speaking rate noticeably
may be similar to the dramatically increased rate of movement seen in PD, but one could also easily argue that
the rate increase in stuttering is a learned secondary symptom (the results of research into speaking rate in
people with PD has shown mixed results). Dr. Joe Kalinowski, in a posting on the Stutt-L list-serve about 2
months ago, mentioned that the effect of choral reading in PWS was similar to people with PD experiencing a
greater range of movement and a more natural gait when following the movements of another individual. 

Unfortunately, the differences between the two far outweigh the similarities, and that is why I mentioned
transient tic disorders, dystonia, and TS in my paper, which share a much greater number of similarities with
stuttering. One might argue that some forms of the hyperkinetic dysarthrias might show more similarity with
stuttering (for that includes TS, myoclonus and tics, and dystonia). By the way, this doesnÕt exclude some
type of a realtionship between hypokinetic dysarthria and stuttering Š they may share an underlying
neurochemical relationship (e. g. dopaminergic dysfunction) but based on our current knowledge IÕd guess
weÕre looking at very different manifestations/different forms of dysfunction and even different basal gangliar
sites. 

Once again Stefanie, thank you for your interest! Feel free to contact me via e-mail if you have more questions
(moltlaw@auburn.edu), and I hope to see a great thesis dealing with stuttering coming out of Southern
University with your name on it! 

Warmest Regards, 

Larry Molt