Saturday, February 22, 2014

Freaky speaking- what we know about stuttering

Review of "Out with it", by Katherine Preston, with supplementary data.

Yes, I stutter. And it is a royal drag. Preston's book memoir about tells her story of the trials and travails of not being able to face the world with normal ease and confidence. Stuttering is specially odd because speech is such a rich medium, conveying emotion and status and so much else along with the explicit information. All that gets garbled up if one is fighting to get every other syllable out.

The first half of Preston's book is outstanding, portraying her trials in very affecting and articulate terms. The second half is where I (and she, until she drastically rewrote the project), was expecting to learn the most up-to-date science about stuttering, and branch out to the stories of other people. But unfortunately, it kept being about her, bringing the reader pretty much up to the very moment of Preston's life in the midst of manuscript writing.

Anyhow, let me fill in here with some of what the book should have conveyed. Stuttering is, as Preston relates, a maddeningly protean condition, coming in a wide spectrum of forms and severity. It is affected by emotional tenor, and remits after pretty much any novel therapy, but then returns again, afflicting the subject with guilt as well as disfluency. Is it caused by mean parents? Is it strictly a genetic and brain development condition? Well, some of each, but mostly the latter. Preston cites the most supportive and healthy parents possible, but one gets the sense that other cases get contributions at least in part from the family dynamic.

At base, stuttering won't happen without a biological predisposition, which is known to be highly heritable (as well as male-biased). 82% heritable in a recent twin study, in fact. Unlike other disorders whose genetics have been vague, full of false turns and bad statistics, a few genes have successfully been linked to stuttering, including GNPTAB, GNPTG, and NAGPA, which all function in a pathway important to lysosomes, the cell's recycling centers. They encode enzymes needed to tag the roughly 40-50 lysosomal enzymes, which collectively break down fats, proteins, and other molecules so that the cell can get rid of its waste. Lack of the tag leads to the enzymes end up mis-addressed, secreted outside, and thus to lysosomes that can't do their jobs. The stuttering mutations and their effects are only partial, though. Far more severe diseases are caused by more severe mutations- the type II mucolipidoses, which are fatal.

How all this leads to brain-specific issues, let alone speech-specific issues, is quite unkown. But the genetics is not going to lie, so there must be some mechanism by which, say, some neurons, at some stage of development, might be more sensitive to this internal deficiency than the rest of the cells of the body.. etc. etc. Perhaps enough lysosomal proteins leak out of the cell by the external secretion pathway (which is the default, when proteins are incorrectly targetted) that they mess up neuronal pathfinding or myelination during development. One can fill in the tech-talk ad libitum at the moment.

But these three genes only account for about 10% of the genetic ingredients of stuttering, so others, a few of which are known, may be more informative as to the mechanism. One is FOXP2, a transcription regulator which is known to be responsible for other, far more severe, speech deficits when more heavily damaged, and to be a target of evolutionary change in the recent human lineage, perhaps relating to speech acquisition among other things. Another is CNTNAP2, which operates just downstream of FOXP2 in the same pathway. But it has to be said that, in light of the general theory that stuttering is a developmental brain deficit, there is little liklihood that any of these genes / molecules will lead to some chemical cure. They had their effect back during development, and that cake is baked, so to speak. Incidentally, one paper maintains that "... a mouse model of stuttering may be possible.", which sort of boggles the mind!

Proceeding to the anatomical level, there has been quite a bit of brain scanning work on stutterers recently, with a wide range of targets and findings. The networks in play are speech recognition, in the auditory cortex, then Broca's area more related to speech production, and of course the general motor system, which comprises the cerebral motor cortex running over the midline of the brain surface from ear to ear, and its outputs through the spinal cord, plus important modulatory motor systems like the basal ganglia and the cerebellum.

Basic surface brain map, including auditory speech area (Wernicke's area) and the speech production area (Broca's area), which are heavily tied to each other, before leading to later motor areas in the motor cortex, cerebellum, brain stem, larynx, etc. Broca's area is heavily lateralized, being larger on the left than the right. Broca's area can also be referred to as Brodman area 44/45, the inferior frontal gyrus of the cortex, and as the pars triangularis / pars opicularis.

The most frequent finding is that the left side of the cortex, where Broca's area is notoriously lateralized, is short-changed a bit, and that the right side takes over somewhat more physical gray matter and speech functions. This leads to a hypothesis that reduced lateral dominance leads to a sort of speech train wreck, where both sides of the brain are trying to run one mouth, as it were, and not doing very good job of it.

Example of differential scanning of the brain's anatomy, in this case tensor imaging of white matter tracts connecting to or from Broca's area. The significant density difference indicates that the conduits between Broca's area and others are deficient in stutterers. Connection to the incoming auditory areas is particularly deficient.

But many studies have been done, finding variations in many of the various areas involved in speech, and disagreeing in certain respects. One gets the sense that the natural variability of people's brains, combined with the low numbers of subjects one can use for this kind of study, and perhaps the relatively small effects, makes it difficult to reach definite conclusions, though the field is still young. A brief bibliography:
  • Evidence of Left Inferior Frontal–Premotor Structural and Functional Connectivity Deficits in Adults Who Stutter.
  • Atypical brain torque in boys with developmental stuttering.
  • Resting-state brain activity in adult males who stutter.
  • Functional brain activation differences in stuttering identified with a rapid fMRI sequence.
  • Motor excitability evaluation in developmental stuttering: a transcranial magnetic stimulation study.
  • Brain activity in adults who stutter: Similarities across speaking tasks and correlations with stuttering frequency and speaking rate.
  • Atypical caudate anatomy in children who stutter.
  • Using Brain Imaging to Unravel the Mysteries of Stuttering.
  • Corpus callosum differences associated with persistent stuttering in adults.
  • Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation.
  • Stuttering: a dynamic motor control disorder

On the bright side, treatment for Parkinson's disease in people who happened to also have stuttering, by the novel methods of deep brain stimulation in the thalamus has led to alleviation of stuttering, according to a couple of papers (though it also made it worse in others). What is the ventral intermediate nucleus of the thalamus? It seems to sit between cortical imputs and the cortical motor system, so it is involved in learning and regulation of motor behavior.

Given its negative effects, why is stuttering as prevalent as it is, for as long as it has been, from the earliest historical records? I think, like with many other conditions, it is a matter of balancing selection, whereby some of its genetic ingredients, when not all concentrated in a fully stuttering phenotype, correlate generally with high reactivity and fast reflexes. Which can have positive aspects, in a past world if not this one.

It is also worth noting how stuttering is one more example of the absence of a soul. Pending more thorough research, all signs point to it being a circuitry problem where developmental deficiencies cause some lack of coordination. No demon, soul, or higher power need be, or can be, invoked.

  • Synanon and stuttering.
  • Post-Christian, with a little nostalgia.
  • The anthropocene will be (or has already been) distinguished by the death of most other large life forms. And countless not so large ones.
  • The IRS- another GOP whipping boy, starved to fail. Just like the post office.
  • Public libraries totally rock!
  • Gains slipping away in Afghanistan.
  • Money, meaning, and happiness.
  • Billionaires are not, typically, your friend. There is a class war, and they are winning.
  • Social security, on the other hand, is, and helped enormously in the recession.
  • Fracking for thee, but not for me.
  • How do banks work? Still a matter of some controversy.
  • What, exactly, is "public" about Facebook's corporate structure? Z-berg gets to spend the public's money.
  • This week in the WSJ "A taxpayer needed a taxable income of $307,000 to enter the top 1%, a figure that hardly qualifies as "rich" today, especially in cities like New York, Chicago, Los Angeles or San Francisco."

2 comments:

  1. As a devotee of E.O. Wilson I was drawn to your blog because of its name. In general I like it very much, but how you come to view the neuroscience of stuttering as "one more example of the absence of a soul" is quite beyond me. For another view check out the Neither Black Nor White posting on my blog at Cereflections.wordpress.com.

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  2. Hi, rpeter-

    Thank you very much for your comment. And you are right.. I overstepped reason there, expressing my beliefs, not any logical conclusion from the existing data. But the trajectory of the field is pretty clear, that step by step, each aspect of cognition and mental activity as we understand them are finding their correlates in the physical brain. We'll see just how far that goes.

    I enjoyed your linked column. But there again, it is not clear that you stand on logic. Why is one or either side of this (religion) debate an intellectual desert? Which side is making false claims? Which side makes more false claims? Your portrayal of naturalists as claiming that the laws of physics explain "everything" doesn't seem accurate. They have their outstanding problem of dark matter, not to mention the origin of the universe. Then there are all the other fields of human understanding, from chemistry to painting, which, while they may in some ultimate way rest on physics, have their own (what some call emergent) rules and concepts.

    The issue is not really which side is able to explain "everything", but which side can explain "anything" in any effective way. Religious concepts are psychological and archetypal. They create an atmosphere of social (even tribal) cohesion by invoking magical thinking- that we may live forever, that a super-father figure instructs us, loves us, or punishes us, and that our nature is in some part something supernatural rather than mundane and material. It is all very psychologically congenial, even explanatory on some therapeutic level. But has it ever explained anything on a concrete, scientific basis? No, not even once.

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