Early ReportMetabolic abnormalities in developmental dyslexia detected by 1H magnetic resonance spectroscopy
Introduction
There is now substantial evidence to suggest that developmental dyslexia is a disorder of neurobiological origin. In addition to the well-known deficit in phonological processing,1 dyslexic individuals have altered lateral cerebral symmetry,2 impaired visual3 and auditory processing,4 disordered magnocells,5 and altered patterns of cerebral activation on verbal, visual, and auditory tasks.6, 7, 8 The area of the brain most frequently implicated is the temporo-parietal cortex2, 9 and, more recently, the cerebellum.10
Magnetic resonance spectroscopy has been used extensively to characterise the biochemical profiles of brain disorders in vivo—most typically in its application to traumatic events in which some gross physical or metabolic insult has occurred (such as head injury or stroke) or in its application to disorders such as epilepsy, multiple sclerosis, inherited metabolic deficits, or mental disorders (such as schizophrenia). In 1996, investigators showed that magnetic resonance spectroscopy is capable of resolving more subtle differences in normal brain—eg, the variation in brain pH with cognitive ability in boys.11 The non-invasive nature of magnetic resonance spectroscopy makes it particularly suited to investigation of a disorder such as developmental dyslexia, when concurrent assessment of the individual's performance is desirable.
To find out whether the neurological and physiological deficits in dyslexia also manifested as biochemical changes in the brain, we obtained localised 1H magnetic resonance spectra bilaterally from the temporo-parietal lobe and cerebellum of 14 well-defined dyslexic men and 15 non-dyslexic control men of similar age. The relative concentrations of choline-containing compounds (Cho; a marker of overall cellular density), creatine-containing compounds (Cre; a marker of cellular energetics) and N-acetylaspartate (NA; a marker of neuronal density) were assessed.
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Patients and methods
We recruited, with informed consent, 29 adult male volunteers aged 20–41 years. 15 were normal readers and 14 were dyslexic. All the dyslexic individuals had been formally diagnosed by educational psychologists either as adults or as children, most within the previous 2 years. They were identified as dyslexic owing to an unexpected and large discrepancy between reading and spelling achievement and expected achievement based on age-defined and intelligence-defined norms. We confirmed their
Results
In the left temporo-parietal lobe, the ratio of Cho to NA was significantly decreased in dyslexic individuals compared with controls (Mann-Whitney U test; p=0·005; table). We found no difference in the ratio of Cre/NA, whereas the Cho/Cre ratio was lower in dyslexic men (non-significant), which suggests that the decrease in the Cho/NA ratio resulted from a decrease in Cho. The temporo-parietal lobe ratio of Cho/NA was also lower in developmental dyslexia on the left side compared with the right
Discussion
Histochemical and cell-culture studies have shown that brain cell-types, or structures, or both, have characteristic magnetic resonance spectroscopy metabolite profiles. For example, the Cho resonance (δ=3·2 ppm) is a marker of overall cell density and total membrane content.17 The concentration of Cho is higher in white matter than in grey matter, and higher in glial cells than in neurons. The NA resonance (δ=2·1 ppm) occurs only in neuronal cells and is a marker of neuronal-cell density and
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