Monday, June 06, 2005

More on basal ganglia

Per Alm has posted a long comment on my last post on whether the basal ganglia is involved in PDS. Click on "Comments" at the bottom of my previous post, or go directly using this link.

Let me summarise what (I think) he said.

1) The basal ganglia could well NOT be dysfunctional and still be involved in PDS as part of a wider system often called the basal ganglia-thalamocortical circuit, which would show dysfunction.

2) The fluency-inducing effects provide the strongest argument in favour.

3) Brain anomaly studies by Foundas et al, Sommer et al, and Jaencke et al. are interesting but too preliminary for final judgment.

4) But their findings could fit: "the basal ganglia generates go-signals based on the input from widespread cortical regions, but the input from the sensorimotor cortex can be assumed to be especially important. If the signals from the sensorimotor cortex to the basal ganglia are disrupted, distorted, or weak, the basal ganglia will not be able to do their part of the job. The result will be distorted output from the basal ganglia to the SMA, which will make it difficult for SMA to generate the final go-signals for the speech segments."

5) "Stuttering with adult onset has been reported after lesions in various parts of this circuit, like the basal ganglia, the thalamus, and the SMA. However, the characteristics of the disorder can be expected to be somewhat different depending on location and nature of the dysfunction. "

6) There is a lack of CLEAR experimental evidence as experiments have not been specifically set up to study basal ganglia effects and brain imaging studies have weaknesses.

7) But, "In fact, the meta-analysis by Brown, Ingham et al. did find differences in basal ganglia activation between stuttering persons and controls. The controls showed a weak left globus pallidus activation, which was not shown by the stuttering persons."

8) Per goes and gives an possible explanation for 7). [please refer to his comments for the details]

9) Factors within the basal ganglia might well increase or decrease the risk for stuttering in the proposed model like the number of dopamine receptors.

I still have to digest all his comments. Especially on brain anatomy, where I need to learn more about. I am also a bit reluctant to go into too detailed discussion as I don't want to loose every reader of my blog. But please feel free to post detailed comments.

But here are some challenges to Per, which might be hard to overcome:

1) Devise experiments that can unambiguously test aspects of the theory. For example, which experiments could be made that can FALSIFY the basal ganglia theory?

2) Show that the possible dysfunctions, that you state, of the basal ganglia circuit (which not only caters for aspects of speech that PDS affects) does not have any effects on other brain functions. This circuit seems to be rather distributed and entertaining many regions, and I find it hard to imagine a dysfunction not having more widespread effects. And I also find it hard to see why so many different factors result in basically the same symptoms.

3) Avoid arguments that are prone to logical fallacies. For example, I am a bit uncomfortable with Per referring to arguments like "different types of stuttering", "also other factors can influence", "the wider circuit", "several potential problems when studying stuttering by means of functional brain imaging". It might be true that many factors influence PDS or that there are different types, but then how can your theory be (or how can you make your theory) testable / falsifiable? It might be true that, as you state, there are several potential problems with brain imaging, but then how can you use brain imaging results to defend/falsify your theory?


Tom

3 comments:

Per Alm said...

Hi Tom,

Thanks for your comments. You put forward some important points with address to me. I'll start with point 1 and 3 which are related:

>But here are some challenges to Per, which might be hard to overcome:

>1) Devise experiments that can unambiguously test aspects of the theory. For example, which experiments could be made that can FALSIFY the basal ganglia theory?

>3) Avoid arguments that are prone to logical fallacies. For example, I am a bit uncomfortable with Per referring to arguments like "different types of stuttering", "also other factors can influence", "the wider circuit", "several potential problems when studying stuttering by means of functional brain imaging". It might be true that many factors influence PDS or that there are different types, but then how can your theory be (or how can you make your theory) testable / falsifiable?

I do not agree that the examples you mention reflect "logical fallacies". From your questions I assume that your reasoning in these matters to a large extent is based on Karl Poppers criteria for a scientific theory: that it should be possible to falsify. In this context my vague expression of "different types of stuttering" will make falsification impossible. I like Popper, especially his focus on the importance of building hypotheses. However, his strict criterion regarding falsification is often difficult to apply in scientific practice. In order to refresh my memory regarding the philosophy of science I looked in Encyclopedia Britannica. I agree with the views expressed in their articles:

"Criterion for scientific theory. ... The philosopher Karl Popper's widely accepted criterion for a scientific theory is that it ... must be formulated in such a way that falsification is in principle possible. For all its value as a test of scientific pretensions, however, it must not be supposed that the experimenter normally proceeds with Popper's criterion in mind. ... If a succession of tests agrees with (or fails to falsify) a hypothesis, it is regarded as reasonable to treat the hypothesis as true, at all events until it is discredited by a subsequent test. The scientist is not concerned with providing a guarantee of his conclusion, since, however many tests support it, there remains the possibility that the next one will not. His concern is to convince himself and his critical colleagues that a hypothesis has passed enough tests to make it worth accepting until a better one presents itself." (Encyclopædia Britannica Online)

"Scientific theory. Systematic ideational structure of broad scope, conceived by the human imagination, that encompasses a family of empirical (experiential) laws regarding regularities existing in objects and events ... A scientific theory is a structure suggested by these laws and is devised to explain them in a scientifically rational manner.
In attempting to explain things and events, the scientist employs (1) careful observation or experiments, (2) reports of regularities [laws], and (3) systematic explanatory schemes (theories). ...
Empirical laws and scientific theories differ in several ways. In a law, reasonably clear observational rules are available for determining the meaning of each of its terms; thus, a law can be tested by carefully observing the things and properties referred to by these terms. ... In the case of scientific theories, however, some of the terms commonly refer to things that are not observed. Thus, it is evident that theories are imaginative constructions of the human mind—the results of philosophical and aesthetic judgments as well as of observation ... Moreover, theories cannot ordinarily be tested and accepted on the same grounds as laws. ... scientific theories have much greater scope, explaining a variety of such laws and predicting others as yet undiscovered." (Encyclopædia Britannica Online)

So you are right, I'm not able, for the moment, to formulate experiments that would falsify the basal ganglia theory. However, I think we can and have to live with this state of affairs, for the time being. We have to gather more observations and gradually build more and more solid models. We are still trying to get a first rough picture of what it's all about. I think we need to develop tentative hypotheses, which are open to revision when new pieces of the puzzle are found.

Tom also asks: "It might be true that, as you state, there are several potential problems with [functional] brain imaging, but then how can you use [functional] brain imaging results to defend/falsify your theory?"

I think functional brain imaging is and will be very important in research on stuttering, but it is a challenge. In my last posting I discussed how existing functional brain imaging data may elucidate the basal ganglia hypothesis. It sure is a complex question, and it would lead to far to develop this issue further here.

Point number 2 from Tom was:
>2) Show that the possible dysfunctions, that you state, of the basal ganglia circuit (which not only caters for aspects of speech that PDS affects) does not have any effects on other brain functions. This circuit seems to be rather distributed and entertaining many regions, and I find it hard to imagine a dysfunction not having more widespread effects. And I also find it hard to see why so many different factors result in basically the same symptoms.

When examining for example finger tapping, differences has been found (on a group average level) between stuttering and nonstuttering persons. There are also reports of a an increased number of gross motor impairments in stuttering groups. So, the dysfunction does not only affect speech. Also, dysfunctions with a high degree of specificity is also seen in dystonia, a disorder with involuntary muscular contractions of various parts of the body, sometimes specific for a certain activity such as writing, walking, or playing an instrument. It seems to be generally agreed that dystonia is a disorder involving the basal ganglia-thalamocortical circuits, but there are still disagreement regarding the exact roles of the sensorimotor cortex vs. the basal ganglia. Again, the existence of subgroups with differing pathology is very likely. Another point is that there are several characteristics of speech that differ from most other human activities: It is a fast, sequential, highly automated, motor behavior. It is learnt and guided by a combination of somatosensory and auditory feedback. The motor expression is modulated by emotional influence. It is normally produced solely based on internal cues, without guidance of external cues. In summary, I think the specificity of the symptoms does not falsify the model.

Best regards,

Per Alm

Tom Weidig said...

Hi Per,

I didnt intend to imply that your examples are logical fallacies. It was just that when I was reading your arguments I sometimes was asking myself "Is this a logical fallacy or not?". I was just trying to emphasise that the basial ganglia theory contains a lot of flexibility that can be used to explain away problems.

I am aware that science does not really go the way described by Poppper. It is a complicated mix between deduction and induction. But I do think that a "final" theory must reflect Popper's criteria of falsiability. Because if it is not falsiable, i cannot test it. Why did so many theories of PDS survive for so long??

I agree with you that the current state is still messy and more observations are needed and need to be replicated, and it is hard to be much more precise. That's why I have put it as a challenge to you to come up with a falsiable theory.

But maybe the nature of PDS is very multi-factoral and then theory building and testing becomes extremely difficult.

I am aware of the finger tapping stuff by Webster. De Nil and Bosshardt have also done some work. But they did not identify subtypes of PDS. Does this mean that there is one only specific dysfunction? So why are there differences for finger tapping? What does it say about a possible dsyfunction in the basal ganglia circuit? Can it identify the dysfunction or rule out some options?

I still think that these difference seems to be quite subtle (nearly not observable) (I have PDS but I never noticed that my finger tapping was bad!!! :-), far more subtle that in dystonia. Does this not put constraints of the possible dysfunctions and its strength?

Thx for a good debate!
Tom

Per Alm said...

Hi Tom

I agree that it is a problem if a theory is too flexible, so that it can incorporate any finding. I thought a bit about possible findings that would not be possible to incorporate in the basal ganglia model. One such finding might be if it could be shown that lesions of the cerebellum has a causal relation to stuttering. Cerebellum is not a part of the basal ganglia-thalamocortical circuits. However, occasional reports of onset of stuttering after lesions to the cerebellum would not falsify the model: it can not be excluded that also other parts of the brain was damaged, for example diffuse lesions of axons in the upper part of the brain stem. So, strict falsification is not easy... (Right now I'm not sure if there are any reports of stuttering with onset after lesions to the cerebellum. Are you updated? Anyhow, if reports exist I think they are very rare. In contrast, a large portion of reports of stuttering after lesions involve structures in the basal ganglia-thalamocortical motor circuit.)

What I think it boils down to is that science is a matter of arguments. If you got a theory that is possible to falsify, but it withstands the tests, then you have a very strong argument. However, that is not the only type of valid arguments for a theory.

> Thx for a good debate!

Thank you! It is important. Hope to meet you in Oxford.

Best wishes,
Per