Alexandra J. Richardson

Sensitivity to dynamic auditory and visual stimuli predicts nonword reading ability in both dyslexic and normal readers

BACKGROUND Developmental dyslexia is a specific disorder of reading and spelling that affects 3-9% of school-age children and adults. Contrary to the view that it results solely from deficits in processes specific to linguistic analysis, current research has shown that deficits in more basic auditory or visual skills may contribute to the reading difficulties of dyslexic individuals. These might also have a crucial role in the development of normal reading skills. Evidence for visual deficits in dyslexia is usually found only with dynamic and not static stimuli, implicating the magnocellular pathway or dorsal visual stream as the cellular locus responsible. Studies of such a dissociation between the processing of dynamic and static auditory stimuli have not been reported previously. RESULTS We show that dyslexic individuals are less sensitive both to particular rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to dynamic visual-motion stimuli. There were high correlations, for both dyslexic and normal readers, between their sensitivity to the dynamic auditory and visual stimuli. Nonword reading, a measure of phonological awareness believed crucial to reading development, was also found to be related to these sensory measures. CONCLUSIONS These results further implicate neuronal mechanisms that are specialised for detecting stimulus timing and change as being dysfunctional in many dyslexic individuals. The dissociation observed in the performance of dyslexic individuals on different auditory tasks suggests a sub-modality division similar to that already described in the visual system. These dynamic tests may provide a non-linguistic means of identifying children at risk of reading failure.

The Oxford-Durham Study: A Randomized, Controlled Trial of Dietary Supplementation With Fatty Acids in Children With Developmental Coordination Disorder

Background. Developmental coordination disorder (DCD) affects ∼5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood. Mounting evidence suggests that a relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. Given the current lack of effective, evidence-based treatment options for DCD, the use of fatty acid supplements merits investigation. Methods. A randomized, controlled trial of dietary supplementation with ω-3 and ω-6 fatty acids, compared with placebo, was conducted with 117 children with DCD (5–12 years of age). Treatment for 3 months in parallel groups was followed by a 1-way crossover from placebo to active treatment for an additional 3 months. Results. No effect of treatment on motor skills was apparent, but significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups. After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress. Conclusions. Fatty acid supplementation may offer a safe efficacious treatment option for educational and behavioral problems among children with DCD. Additional work is needed to investigate whether our inability to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress.

A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties.

(1) The authors tested the prediction that relative deficiencies in highly unsaturated fatty acids (HUFAs) may underlie some of the behavioral and learning problems associated with attention-deficit/hyperactivity disorder (ADHD) by studying the effects of HUFA supplementation on ADHD-related symptoms in children with specific learning difficulties (mainly dyslexia) who also showed ADHD features. (2) Forty-one children aged 8-12 years with both specific learning difficulties and above-average ADHD ratings were randomly allocated to HUFA supplementation or placebo for 12 weeks. (3) At both baseline and follow-up, a range of behavioral and learning problems associated with ADHD was assessed using standardized parent rating scales. (4) At baseline, the groups did not differ, but after 12 weeks mean scores for cognitive problems and general behavior problems were significantly lower for the group treated with HUFA than for the placebo group; there were significant improvements from baseline on 7 out of 14 scales for active treatment, compared with none for placebo. Group differences in change scores all favored HUFA, reaching conventional significance levels for 3 out of 14 scales. (5) HUFA supplementation appears to reduce ADHD-related symptoms in children with specific learning difficulties. Given the safety and tolerability of this simple treatment, results from this pilot study strongly support the case for further investigations.

Omega-3 fatty acids in ADHD and related neurodevelopmental disorders.

Summary Omega-3 fatty acids are dietary essentials, and are critical to brain development and function. Increasing evidence suggests that a relative lack of omega-3 may contribute to many psychiatric and neurodevelopmental disorders. This review focuses on the possible role of omega-3 in attention-deficit/hyperactivity disorder (ADHD) and related childhood developmental disorders, evaluating the existing evidence from both research and clinical perspectives. Theory and experimental evidence support a role for omega-3 in ADHD, dyslexia, developmental coordination disorder (DCD) and autism. Results from controlled treatment trials are mixed, but the few studies in this area have involved different populations and treatment formulations. Dietary supplementation with fish oils (providing EPA and DHA) appears to alleviate ADHD-related symptoms in at least some children, and one study of DCD children also found benefits for academic achievement. Larger trials are now needed to confirm these findings, and to establish the specificity and durability of any treatment effects as well as optimal formulations and dosages. Omega-3 is not supported by current evidence as a primary treatment for ADHD or related conditions, but further research in this area is clearly warranted. Given their relative safety and general health benefits, omega-3 fatty acids offer a promising complementary approach to standard treatments.

Metabolic abnormalities in developmental dyslexia detected by 1H magnetic resonance spectroscopy

BACKGROUND Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain. METHODS We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age. FINDINGS We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or =0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men. INTERPRETATION We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.

Docosahexaenoic Acid for Reading, Cognition and Behavior in Children Aged 7–9 Years: A Randomized, Controlled Trial (The DOLAB Study)

Background Omega-3 fatty acids are dietary essentials, and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems. Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning, although most previous trials have involved children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) or developmental coordination disorder (DCD). Here we investigated whether such benefits might extend to the general child population. Objectives To determine the effects of dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA) on the reading, working memory, and behavior of healthy schoolchildren. Design Parallel group, fixed-dose, randomized, double-blind, placebo-controlled trial (RCT). Setting Mainstream primary schools in Oxfordshire, UK (n = 74). Participants Healthy children aged 7–9 years initially underperforming in reading (≤33rd centile). 1376 invited, 362 met study criteria. Intervention 600 mg/day DHA (from algal oil), or taste/color matched corn/soybean oil placebo. Main Outcome Measures Age-standardized measures of reading, working memory, and parent- and teacher-rated behavior. Results ITT analyses showed no effect of DHA on reading in the full sample, but significant effects in the pre-planned subgroup of 224 children whose initial reading performance was ≤20th centile (the target population in our original study design). Parent-rated behavior problems (ADHD-type symptoms) were significantly reduced by active treatment, but little or no effects were seen for either teacher-rated behaviour or working memory. Conclusions DHA supplementation appears to offer a safe and effective way to improve reading and behavior in healthy but underperforming children from mainstream schools. Replication studies are clearly warranted, as such children are known to be at risk of low educational and occupational outcomes in later life. Trial Registration ClinicalTrials.gov NCT01066182 and Controlled-Trials.com ISRCTN99771026

MRI and neuropsychological improvement in Huntington disease following ethyl-EPA treatment.

A 6-month randomized, placebo-controlled pilot study of the ethyl-ester of eicosapentaenoic acid (ethyl-EPA) was carried out in seven in-patients with advanced (stage III) Huntingtons disease (three on ethyl-EPA, four on placebo; no significant difference in age or sex between the groups). After 6 months all the patients treated with ethyl-EPA improved on the orofacial component of the Unified Huntingtons Disease Rating Scale while all the patients on placebo deteriorated on this scale (p <0.03). Following subvoxel registration of follow-up 3D MRI brain scans with baseline scans, subtraction images showed that while the placebo was associated with progressive cerebral atrophy, the ethyl-EPA was associated with a reverse process. We conclude that treatment with ethyl-EPA is associated with beneficial motor and MRI changes.

Abnormal cerebral phospholipid metabolism in dyslexia indicated by phosphorus-31 magnetic resonance spectroscopy

It has recently been suggested that many of the features of dyslexia may be explicable in terms of an abnormality of membrane phospholipid metabolism. To investigate this we studied 12 dyslexic and 10 non‐dyslexic adults using in vivo cerebral phosphorus‐31 magnetic resonance spectroscopy (31P MRS), as the phosphomonoester (PME) and phosphodiester (PDE) peaks include indices of membrane phospholipid turnover. Spectral localization was achieved using four‐dimensional chemical shift imaging methods. The PME peak area was significantly elevated in the dyslexic group, as evidenced by higher ratios of PME/total phosphorus (F=9.5, p<0.006), PME/NTP (F=17.5, p<0.001) and PME/PDE (F=6.9, p<0.02). No other spectral measurements differed significantly between the groups. These findings are consistent with the hypothesis that membrane phospholipid metabolism is abnormal in dyslexia. The PME peak is multicomponent, but predominantly consists of phosphoethanolamine (PE) and phosphocholine (PC), which are precursors of membrane phospholipids. Our finding of raised PME in dyslexia could therefore reflect reduced incorporation of phospholipids into cell membranes, although definitive interpretation must await further evidence.

Two Visual Motion Processing Deficits in Developmental Dyslexia Associated with Different Reading Skills Deficits

Developmental dyslexia is associated with deficits in the processing of visual motion stimuli, and some evidence suggests that these motion processing deficits are related to various reading subskills deficits. However, little is known about the mechanisms underlying such associations. This study lays a richer groundwork for exploration of such mechanisms by more comprehensively and rigorously characterizing the relationship between motion processing deficits and reading subskills deficits. Thirty-six adult participants, 19 of whom had a history of developmental dyslexia, completed a battery of visual, cognitive, and reading tests. This battery combined motion processing and reading subskills measures used across previous studies and added carefully matched visual processing control tasks. Results suggest that there are in fact two distinct motion processing deficits in developmental dyslexia, rather than one as assumed by previous research, and that each of these deficits is associated with a different type of reading subskills deficit. A deficit in detecting coherent motion is selectively associated with low accuracy on reading subskills tests, and a deficit in discriminating velocities is selectively associated with slow performance on these same tests. In addition, evidence from visual processing control tasks as well as self-reports of ADHD symptoms suggests that these motion processing deficits are specific to the domain of visual motion, and result neither from a broader visual deficit, nor from the sort of generalized attention deficit commonly comorbid with developmental dyslexia. Finally, dissociation between these two motion processing deficits suggests that they may have distinct neural and functional underpinnings. The two distinct patterns of motion processing and reading deficits demonstrated by this study may reflect separable underlying neurocognitive mechanisms of developmental dyslexia.

Low Blood Long Chain Omega-3 Fatty Acids in UK Children Are Associated with Poor Cognitive Performance and Behavior: A Cross-Sectional Analysis from the DOLAB Study

Background Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA), especially DHA (docosahexaenonic acid) are essential for brain development and physical health. Low blood Omega-3 LC-PUFA have been reported in children with ADHD and related behavior/learning difficulties, as have benefits from dietary supplementation. Little is known, however, about blood fatty acid status in the general child population. We therefore investigated this in relation to age-standardized measures of behavior and cognition in a representative sample of children from mainstream schools. Participants 493 schoolchildren aged 7–9 years from mainstream Oxfordshire schools, selected for below average reading performance in national assessments at age seven. Method Whole blood fatty acids were obtained via fingerstick samples. Reading and working memory were assessed using the British Ability Scales (II). Behaviour (ADHD-type symptoms) was rated using the revised Conners’ rating scales (long parent and teacher versions). Associations were examined and adjusted for relevant demographic variables. Results DHA and eicosapentaenoic acid (EPA), accounted for only 1.9% and 0.55% respectively of total blood fatty acids, with DHA showing more individual variation. Controlling for sex and socio-economic status, lower DHA concentrations were associated with poorer reading ability (std. OLS coeff. = 0.09, p = <.042) and working memory performance (0.14, p = <.001). Lower DHA was also associated with higher levels of parent rated oppositional behavior and emotional lability (−0.175, p = <.0001 and −0.178, p = <.0001). Conclusions In these healthy UK children with below average reading ability, concentrations of DHA and other Omega-3 LC-PUFA were low relative to adult cardiovascular health recommendations, and directly related to measures of cognition and behavior. These findings require confirmation, but suggest that the benefits from dietary supplementation with Omega-3 LC-PUFA found for ADHD, Dyspraxia, Dyslexia, and related conditions might extend to the general school population.