White matter days: Dyslexia, OCD and Williams’ Syndrome may all involve white matter growth irregularities

Edward Degas, Woman Ironing 1887 courtesy National Gallery of Art

More on white matter month — What happens when one part of the brain is “unplugged”?

Dyslexia, Williams Syndrome, and OCD all involve cognitive processes that seem to go awry. It’s not as though something is necessarily lacking — but rather a particular trait is distorted.

It may be that white matter tracts — the fibers that connect one brain are to another — somehow didn’t grow properly during brain development. Sometimes if the white matter is damaged or grows in the wrong direction or is weakened — areas of the brain act as though they are “unplugged”.

White matter is like a highway — connecting areas of gray matter, having direction, sometimes 8 lanes, sometimes just a two lane dirt road, sometimes full of potholes. (So to speak, I suppose). For instance, multiple sclerosis is improper white matter myelination — the coating 0r paving, if you will, of the white matter.

People with Williams Syndrome often have problems catching a ball or jumping over something — poor visual-spatial skills. Two papers (( citations below) show white matter structure and position differ in Williams Syndrome from nons. I thought this was interesting because the genetic defect that causes Williams Syndrome causes improper neuron-cytoskeleton — in other words, the “white matter highway” nerve cells don’t grow in the right direction, firing from one area of gray matter to the other, or else, the “highway” is weak in some areas.

Dyslexia involves trouble understanding writing — the same symptoms seen in a particular disease where gray matter clumps disrupt white matter tracts. Chang et al., (abstract below) studied that and then propose a way to study similar symptoms of dyslexia — viewing it as a white matter wiring problem.

And then there’s OCD . OCD has been studied for a really long time, and if you just look at the titles of the abstracts, there are different sub-species. Like hoarders, and those who apparently can’t recognize facial expressions of disgust. Are these two things connected? I mean, aren’t hoarders usually living in atrocious conditions? Do they not feel social stigma because they can’t recognize facial expressions of disgust?

More later but it is interesting to consider empathy: Empathy is a two sided coin. You can feel empathy and have compassion. Or you can empathize and use it to hurt, or to do nothing.

If the empathy region is “unplugged” — then it is arbitrary how that empathy is used. Hmm. Here’s a review paper that I’m looking at now.

Here’s the abstracts discussed above:

1: Chang BS, Katzir T, Liu T, Corriveau K, Barzillai M, Apse KA, Bodell A,
Hackney D, Alsop D, Wong S, Walsh CA.
A structural basis for reading fluency: white matter defects in a genetic brain malformation. Neurology. 2007 Dec 4;69(23):2146-54.
PMID: 18056578[PubMed - indexed for MEDLINE]

2: Hoeft F, Barnea-Goraly N, Haas BW, Golarai G, Ng D, Mills D, Korenberg J,
Bellugi U, Galaburda A, Reiss AL.
More is not always better: increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams Syndrome. Neurosci. 2007 Oct 31;27(44):11960-5.

PMID: 17978036 [PubMed - indexed for MEDLINE]

3: Marenco S, Siuta MA, Kippenhan JS, Grodofsky S, Chang WL, Kohn P, Mervis CB,
Morris CA, Weinberger DR, Meyer-Lindenberg A, Pierpaoli C, Berman KF.
Genetic contributions to white matter architecture revealed by diffusion tensor imaging in Williams syndrome. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15117-22. Epub 2007 Sep 7. PMID: 17827280 [PubMed - indexed for MEDLINE]

4: Yoo SY, Jang JH, Shin YW, Kim DJ, Park HJ, Moon WJ, Chung EC, Lee JM, Kim IY,
Kim SI, Kwon JS. White matter abnormalities in drug-naïve patients with obsessive-compulsive disorder: a diffusion tensor study before and after citalopram treatment. Acta Psychiatr Scand. 2007 Sep;116(3):211-9.
PMID: 17655563 [PubMed - indexed for MEDLINE]

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1. (full abstract) Neurology. 2007 Dec 4;69(23):2146-54.

A structural basis for reading fluency: white matter defects in a genetic brain malformation.

Chang BS, Katzir T, Liu T, Corriveau K, Barzillai M, Apse KA, Bodell A, Hackney D, Alsop D, Wong S, Walsh CA.

Comprehensive Epilepsy Center, KS-457, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. bchang@bidmc.harvard.edu

BACKGROUND: Multiple lines of evidence have suggested that developmental dyslexia may be associated with abnormalities of neuronal migration or axonal connectivity. In patients with periventricular nodular heterotopia–a rare genetic brain malformation characterized by misplaced nodules of gray matter along the lateral ventricles–a specific and unexpected reading disability is present, despite normal intelligence. We sought to investigate the cognitive and structural brain bases of this phenomenon. METHODS: Ten adult subjects with heterotopia, 10 with dyslexia, and 10 normal controls were evaluated, using a battery of neuropsychometric measures. White matter integrity and fiber tract organization were examined in six heterotopia subjects, using diffusion tensor imaging methods. RESULTS: Subjects with heterotopia and those with developmental dyslexia shared a common behavioral profile, with specific deficits in reading fluency. Individuals with dyslexia seemed to have a more prominent phonological impairment than heterotopia subjects. Periventricular nodular heterotopia was associated with specific, focal disruptions in white matter microstructure and organization in the vicinity of gray matter nodules. The degree of white matter integrity correlated with reading fluency in this population. CONCLUSIONS: We demonstrate that a genetic disorder of gray matter heterotopia shares behavioral characteristics with developmental dyslexia, and that focal white matter defects in this disorder may serve as the structural brain basis of this phenomenon. Our findings represent a potential model for the use of developmental brain malformations in the investigation of abnormal cognitive function.

PMID: 18056578 [PubMed - indexed for MEDLINE]