Converging evidence for triple word form theory in children with dyslexia.

This article has 3 parts. The 1st part provides an overview of the family genetics, brain imaging, and treatment research in the University of Washington Multidisciplinary Learning Disabilities Center (UWLDC) over the past decade that points to a probable genetic basis for the unusual difficulty that individuals with dyslexia encounter in learning to read and spell. Phenotyping studies have found evidence that phonological, orthographic, and morphological word forms and their parts may contribute uniquely to this difficulty. At the same time, reviews of treatment studies in the UWLDC (which focused on children in Grades 4 to 6) and other research centers provide evidence for the plasticity of the brain in individuals with dyslexia. The 2nd part reports 4 sets of results that extend previously published findings based on group analyses to those based on analyses of individual brains and that support triple word form awareness and mapping theory: (a) distinct brain signatures for the phonological, morphological, and orthographic word forms; (b) crossover effects between phonological and morphological treatments and functional magentic resonance imaging (fMRI) tasks in response to instruction, suggestive of cross-word form computational and mapping processes; (c) crossover effects between behavioral measures of phonology or morphology and changes in fMRI activation following treatment; and (d) change in the relationship between structural MRI and functional magnetic resonance spectroscopy (fMRS) lactate activation in right and left inferior frontal gyri following treatment emphasizing the phonological, morphological, and orthographic word forms. In the 3rd part we discuss the next steps in this programmatic research to move beyond word form alone.

Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla.

Proton magnetic resonance spectroscopy ((1)H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. Proton MRS measures of brain lactate responses have been used to study regional brain metabolism in clinical populations. This study examined whether variations in blood glucose influence the lactate response to visual stimulation in the visual cortex. Six subjects were scanned twice, receiving either saline or 21% glucose intravenously. Using (1)H-MRS at 1.5 Tesla with a long echo time (TE=288 ms), the lactate doublet was visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased significantly from resting to visual stimulation. Hyperglycemia had no effect on this increase. The order of the slice-selective gradients for defining the spectroscopy voxel had a pronounced effect on the extent of contamination by signal originating outside the voxel. The results of this preliminary study demonstrate a method for observing a consistent activity-stimulated increase in brain lactate at 1.5 T and show that variations in blood glucose across the normal range have little effect on this response.

Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI.

This study investigated the neural correlates of virtual reality analgesia. Virtual reality significantly reduced subjective pain ratings (i.e. analgesia). Using fMRI, pain-related brain activity was measured for each participant during conditions of no virtual reality and during virtual reality (order randomized). As predicted, virtual reality significantly reduced pain-related brain activity in all five regions of interest; the anterior cingulate cortex, primary and secondary somatosensory cortex, insula, and thalamus (p<0.002, corrected). Results showed direct modulation of human brain pain responses by virtual reality distraction.

Reproducibility of proton MR spectroscopic imaging (PEPSI): comparison of dyslexic and normal-reading children and effects of treatment on brain lactate levels during language tasks.

BACKGROUND AND PURPOSE: We repeated a proton echo-planar spectroscopic imaging (PEPSI) study to test the hypothesis that children with dyslexia and good readers differ in brain lactate activation during a phonologic judgment task before but not after instructional treatment. METHODS: We measured PEPSI brain lactate activation (TR/TE, 4000/144; 1.5 T) at two points 1-2 months apart during two language tasks (phonologic and lexical) and a control task (passive listening). Dyslexic participants (n = 10) and control participants (n = 8) (boys and girls aged 9-12 years) were matched in age, verbal intelligence quotients, and valid PEPSI voxels. In contrast to patients in past studies who received combined treatment, our patients were randomly assigned to either phonologic or morphologic (meaning-based) intervention between the scanning sessions. RESULTS: Before treatment, the patients showed significantly greater lactate elevation in the left frontal regions (including the inferior frontal gyrus) during the phonologic task. Both patients and control subjects differed significantly in the right parietal and occipital regions during both tasks. After treatment, the two groups did not significantly differ in any brain region during either task, but individuals given morphologic treatment were significantly more likely to have reduced left frontal lactate activation during the phonologic task. CONCLUSION: The previous finding of greater left frontal lactate elevation in children with dyslexia during a phonologic judgment task was replicated, and brain activation changed as a result of treatment. However, the treatment effect was due to the morphologic component rather than the phonologic component.

Midlife memory improvement predicts preservation of hippocampal volume in old age.

This study examines whether midlife change in episodic memory predicts hippocampal volume in old age. From the Seattle Longitudinal Study we retrospectively identified 84 healthy, cognitively normal individuals, age 52 to 87, whose episodic memory had reliably declined (n = 33), improved (n = 28) or remained stable (n = 23) over a 14-year period in midlife (age 43-63). Midlife memory improvement was associated with 13% larger hippocampal volume (p < 0.01) in old age (age 66-87), compared with old age individuals whose midlife episodic memory had either declined or remained stable during midlife. Midlife memory change did not predict total hippocampal volume for those currently in late middle age (age 52-65). The pattern of findings was not modified by gender, apolipoprotein ε4 status, education or current memory performance. Change in midlife memory scores over 14 years, but not any single assessment, predicted hippocampal volumes in old age, emphasizing the importance of longitudinal data in examining brain-cognition relationships. These findings suggest that improvement in memory in midlife is associated with sparing of hippocampal volume in later life.