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Increasing evidence implicates functional deficiencies or imbalances of omega-3 and omega-6 fatty acids in dyslexia. The associations between literacy skills and omega-3 and omega-6 fatty acid status were examined. 32 dyslexics and 20 controls completed standardised tests of reading and spelling and gave venous blood samples for analysis of the polar lipid fatty acid composition of red blood cell (RBC) membranes. Relationships between literacy skills and omega-3 and omega-6 concentrations were examined using rank-order correlations. Better word reading was associated with higher total omega-3 concentrations in both dyslexic and control groups. In dyslexic subjects only, reading performance was negatively associated with the ratio of arachidonic acid/eicosapentaenoic acid (ARA/EPA) and with total omega-6 concentrations. There were no significant differences in membrane fatty acid levels between the dyslexic and control subjects. However, the finding that omega-3 status was directly related to reading performance irrespective of dyslexia supports a dimensional view of this condition, and our results also suggest that it is the omega-3/omega-6 balance that is particularly relevant to dyslexia.

Objective To determine if the available data support the use of omega-3 essential fatty acids (EFA) for clinical use in the prevention and/or treatment of psychiatric disorders. Participants The authors of this article were invited participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA). Evidence Published literature and data presented at scientific meetings were reviewed. Specific disorders reviewed included major depressive disorder, bipolar disorder, schizophrenia, dementia, borderline personality disorder and impulsivity, and attention-deficit/hyperactivity disorder. Meta-analyses were conducted in major depressive and bipolar disorders and schizophrenia, as sufficient data were available to conduct such analyses in these areas of interest. Consensus process The subcommittee prepared the manuscript, which was reviewed and approved by the following APA committees: the Committee on Research on Psychiatric Treatments, the Council on Research, and the Joint Reference Committee. Conclusions The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood disorders. Meta-analyses of randomized controlled trials demonstrate a statistically significant benefit in unipolar and bipolar depression (p = .02). The results were highly heterogeneous, indicating that it is important to examine the characteristics of each individual study to note the differences in design and execution. There is less evidence of benefit in schizophrenia. EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry. Treatment recommendations and directions for future research are described. Health benefits of omega-3 EFA may be especially important in patients with psychiatric disorders, due to high prevalence rates of smoking and obesity and the metabolic side effects of some psychotropic medications.

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.

(1) It is possible to investigate aspects of phospholipid-related signal transduction in humans noninvasively using the niacin skin flush test. (2) Patients with schizophrenia have previously been reported to show a reduced flushing response. (3) The aim of this study was to devise a comprehensive index of cutaneous response to the niacin test, incorporating aqueous methyl nicotinate concentration and time, and to test this index in schizophrenia. (4) A discrete approximation to a continuous volumetric index, which we have named the volumetric niacin response (VNR), was devised. Its value was measured in 27 patients with DSM-IV schizophrenia and 26 age- and sex-matched normal controls. (5) The mean value of the VNR in the patients with schizophrenia (16.26) was significantly smaller than that of 26.77 in the normal controls (P

Sleep problems in children are associated with poor health, behavioural and cognitive problems, as are deficiencies of long-chain omega-3 fatty acids such as docosahexaenoic acid. Theory and some evidence support a role for these fatty acids in sleep regulation, but this issue has received little formal investigation. We examined associations between blood fatty acid concentrations (from fingerstick blood samples) and subjective sleep (using an age-standardized parent questionnaire) in a large epidemiological sample of healthy children aged 7-9 years (n = 395) from mainstream UK schools. In a randomized controlled trial, we then explored whether 16-week supplementation (600 mg day(-1) ) with algal docosahexaenoic acid versus placebo might improve sleep in a subset of those children (n = 362) who were underperforming in reading. In a randomly selected subsample (n = 43), sleep was also assessed objectively via actigraphy. In 40% of the epidemiological sample, Child Sleep Habits Questionnaire scores indicated clinical-level sleep problems. Furthermore, poorer total sleep disturbance scores were associated weakly but significantly with lower blood docosahexaenoic acid (std coeff. -0.105*) and a lower docosahexaenoic acid : arachidonic acid ratio (std coeff. -0.119**). The treatment trial showed no significant effects on subjective sleep measures. However, in the small actigraphy subsample, docosahexaenoic acid supplementation led on average to seven fewer wake episodes and 58 min more sleep per night. Cautiously, we conclude that higher blood levels of docosahexaenoic acid may relate to better child sleep, as rated by parents. Exploratory pilot objective evidence from actigraphy suggests that docosahexaenoic acid supplementation may improve children's sleep, but further investigations are needed.

1. Abnormal neuronal membrane phospholipid metabolism is increasingly recognized as being of central importance to a number of neuropsychiatric disorders. Currently, two important indices of membrane phospholipid metabolism tend to be measured: the ratio of the areas of the phosphomonoester (PME) and phosphodiester (PDE) peaks from in vivo cerebral phosphorus magnetic resonance spectroscopy (31P MRS) studies; and erythrocyte membrane fatty acid concentrations. Thus far, there have been no studies comparing these two indices to ascertain the extent to which they agree. 2. The authors measured these indices in nine normal adults. Spectral localization was achieved using four-dimensional chemical shift imaging methods and erythrocyte membrane fatty acid concentrations (from blood samples taken at the time of scanning) were measured using gas liquid chromatography. 3. Levels of PDE (an index of phospholipid catabolism), measured using cerebral 31P MRS, were significantly correlated with reduced concentrations of the highly unsaturated fatty acids docosahexaenoic acid (DHA) (r = -0.68, p < 0.05) and eicosapentaenoic acid (EPA) (r -0.78, p < 0.02). No significant correlations were found between peripheral concentrations of any highly unsaturated fatty acids and PME levels, nor between their essential fatty acid precursors and either PDE or PME levels. Other 31-phosphorus metabolites also showed no significant correlations with the blood fatty acid measures. 4. The correlations between central measures of PDE and peripheral measures of DHA and EPA provide validation of cerebral 31P MRS as a non-invasive technique for the study of membrane phospholipid metabolism in vivo.

Developmental dyslexia is a complex syndrome whose exact cause remains unknown. It has been suggested that a problem with fatty acid metabolism may play a role, particularly in relation to the visual symptoms exhibited by many dyslexics. We explored this possibility using two self-report questionnaires, designed on the basis of clinical experience, to assess (1) clinical signs of fatty acid deficiency; and (2) symptoms associated with dyslexia in known dyslexic and non-dyslexic subjects. Dyslexic signs and symptoms included the auditory-linguistic and spoken language difficulties traditionally associated with the disorder, as well as visual problems (both with reading and more generally) and motor problems. Fatty acid deficiency signs were significantly elevated in dyslexic subjects relative to controls, particularly within males (P

There is mounting evidence that developmental dyslexia is a neurodevelopmental disorder which involves abnormalities of fatty acid metabolism, particularly with respect to certain long-chain highly unsaturated fatty acids (HUFAs). Psychophysical evidence also strongly suggests that dyslexics may have visual deficits as well as phonological problems. Specifically, these visual deficits appear to be related to the magnocellular pathway, which is specialized for processing fast, rapidly-changing information about the visual scene. It remains unclear how these two aspects of dyslexia – fatty acid processing and visual magnocellular function – could be related. We propose some hypotheses – necessarily speculative, given the paucity of biochemical research in this field to date – which address this question.

Introduction: A patient with severe intractable symptoms of schizophrenia was treated for 6 months with a fatty acid supplement, primarily as a test of the hypothesis that membrane phospholipid metabolism is abnormal in schizophrenia. His symptomatology was predominantly positive, consistent with an ‘Active’ syndrome thought to reflect a relative imbalance of left over right hemispheric activation. Longitudinal studies have previously shown changes in functional lateralisation with symptom remission in schizophrenia, hence this was examined at intervals over the 6-month period. Method: The subject was a 30-year-old male with DSM-IV schizophrenia. For 2 years prior to this study his clinical profile had not changed and he had remained free of neuroleptic medication. Treatment with 30 ml/day of emulsion rich in eicosapentaenoic acid was started, and clinical ratings were made at monthly intervals for 6 months. Motor laterality had been assessed using Annett’s handedness scale and pegboard task 1 year pre-baseline, and this was repeated at 0, 3 and 6 months from the start of treatment. Results: As measured by the Schedules for the Assessment of Positive Symptoms and Negative Symptoms, a marked reduction in his symptoms was first apparent at 2-month follow-up; further improvement followed, so that at the 6-month point few symptoms remained. Corresponding to his clinical improvement, the patient’s performance on the pegboard task at 3-month follow-up had shifted from a strong right-hand advantage to near symmetry, owing to a marked improvement in his left-hand scores. On retest at 6 months this change in asymmetry was also maintained. Conclusions: These findings suggest that treatment with certain fatty acids may have significant benefits in the management of schizophrenia. They are also consistent with existing evidence that an Active syndrome of schizophrenia reflects a left over right hemispheric imbalance which is functional in nature, and can therefore change with symptom remission.

In schizophrenia syndrome-related recognition memory impairments have been demonstrated to be dependent on hemispheric specialisation — word deficits (left hemisphere) in a Withdrawn syndrome and face deficits (right hemisphere) in an Active syndrome. Deficits were largely absent in recovered patients. Here the in state/trait nature was examined through longitudinal investigation of 33 patients. In 19 patients who were tested when psychotic and when symptoms remitted (with order randomised) memory improved with recovery, particularly word memory in Withdrawn patients and face memory in Active patients. In patients who presented with different syndromes on separate admissions there was evidence that cognitive asymmetry patterns reversed with syndrome changes. In nine patients in whom the retest reliability of syndrome–asymmetry relations was examined across repeat admissions or periods or recovery, the asymmetries were stable. In sum, further evidence was disclosed of reliable associations between left vs. right preferential hemispheric impairment and syndromes based on activity vs. withdrawal. Acknowledgement of the importance of this individual difference may assist in elucidating heterogeneity of cognitive function in schizophrenia. Reversals of asymmetry support a functional component to recognition memory deficits in schizophrenia with possible relevance to the recovery process.

In schizophrenia reduction of the P300 amplitude is a robust statistical finding but with inconsistent evidence of symptom correlates and of lateral asymmetry. Here relations were examined with active and withdrawn syndromes which in other cognitive and electrophysiological measurement modalities have been associated with opposite functional asymmetries. A standard oddball detection task was used to elicit auditory evoked potentials from dextral DSM-IV schizophrenic patients. On clinical ratings blind to the psychophysiology, eight were classified as withdrawn and 12 had a predominance of active syndrome features. Both patient groups had congruent P300 maxima at Pz or P4, attesting to their application to the detection task. Syndromes were differentiated by opposite asymmetries in P300, N200-P300 and N100 amplitudes at the posterior temporal sites: a reduction in P300 and N200-P300 amplitudes on the left in the active patients, and a reduction on the right in the withdrawn patients, with the opposite asymmetries in N100 amplitudes. The syndrome-related asymmetries in P300, also manifested in earlier attentional (N100) components are interpreted in terms of thalamo-cortical arousal systems having generalised, internalised influences, rather than in terms of later cognitive processes underpinning the P300. The findings endorse a syndromal approach to laterality research in schizophrenia.

Summary 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≤0·01) and right cerebellum (Cho/NA, p≤0·01; creatine [Cre] to NA p≤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≤0·01; Cre/NA in cerebellum, left vs right, p≤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.

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/beta 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.

Background: \ud 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.\ud \ud Participants: \ud 493 schoolchildren aged 7–9 years from mainstream Oxfordshire schools, selected for below average reading performance in national assessments at age seven.\ud \ud Method: \ud 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.\ud \ud Results: \ud 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 =

Background: \ud 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.\ud \ud Objectives: \ud 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.\ud \ud Design: \ud Parallel group, fixed-dose, randomized, double-blind, placebo-controlled trial (RCT).\ud \ud Setting: \ud Mainstream primary schools in Oxfordshire, UK (n = 74).\ud \ud Participants: \ud Healthy children aged 7–9 years initially underperforming in reading (≤33rd centile). 1376 invited, 362 met study criteria.\ud \ud Intervention: \ud 600 mg/day DHA (from algal oil), or taste/color matched corn/soybean oil placebo.\ud \ud Main Outcome Measures: \ud Age-standardized measures of reading, working memory, and parent- and teacher-rated behavior.\ud \ud Results: \ud 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.\ud \ud Conclusions: \ud 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.\ud \ud Trial Registration: \ud ClinicalTrials.gov NCT01066182 and Controlled-Trials.com ISRCTN99771026.

We previously reported evidence in university students of three syndromes of schizotypy which have strong affinities with three-syndrome models of schizophrenia. As in schizophrenia two of the syndromes were associated with opposite hemispheric asymmetry patterns: an Active syndrome with a left > right asymmetry, and a Withdrawn syndrome with a right > left asymmetry. The third Unreality syndrome bore no consistent relation to pattern of asymmetry. Cognitive asymmetry was measured by comparing recognition memory for unfamiliar faces using a neuropsychological test which assesses temporoparietal functions. Here the same approach was extended to the broader concept of psychosis proneness with a new inventory with four subscales: Introvertive Anhedonia, Impulsive Nonconformity, Unusual Experiences, and Cognitive Disorganisation. In support of the relevance of an activation dimension to cognitive asymmetry, Impulsive Nonconformity was associated with word > face superiority, as was a self report measure of Energy. Introvertive Anhedonia was associated with face > word superiority. As in schizophrenia these predicted asymmetry relations were significant in males only. Neither the Unusual Experiences nor Cognitive Disorganisation subscales were associated with cognitive asymmetry.

A recent study indicates that schizophrenia patients are prone to auditory hallucinations because they have difficulty recognising their ‘inner speech' as their own, and consequently tend to misattribute it to an external source.

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.

Background. Developmental coordina- tion 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 psychiat- ric disorders such as dyslexia and attention-deficit/hyper- activity 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 -3 and -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 treat- ment 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 be- havioral problems among children with DCD. Addi- tional work is needed to investigate whether our inabil- ity to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress. Pediatrics 2005;115:1360-1366; developmental coordination disorder, fish oil, supplementation, RCT, reading, spelling, behavior, omega-3 fatty acids, dyspraxia.

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) Huntington's 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 Huntington's 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.

Functional neuroimaging techniques such as single-positron emission computed tomography (SPECT) and positron emission tomography (PET) offer considerable scope for investigating disturbances of brain activity in psychiatric disorders. However, the heterogeneous nature of disorders such as schizophrenia limits the value of studies that group patients under this global label. Some have addressed this problem by considering schizophrenia at a syndromal level, but so far, few have focussed at the level of individual symptoms. We describe the first neuroimaging study of the specific symptom of religious delusions in schizophrenia. 99mTc HMPAO high-resolution SPECT neuroimaging showed an association of religious delusions with left temporal overactivation and reduced occipital uptake, particularly on the left.

There is increasing evidence that abnormalities of fatty acid and membrane phospholipid metabolism play a part in a wide range of neurodevelopmental and psychiatric disorders. This proposal is discussed here in relation to attention-deficit/hyperactivity disorder (ADHD), dyslexia, developmental coordination disorder (dyspraxia) and the autistic spectrum. These are among the most common neurodevelopmental disorders of childhood, with significant implications for society as well as for those directly affected. However, controversy still surrounds both the identification and management of these conditions, and while their aetiology is recognized as being complex and multifactorial, little progress has yet been made in elucidating predisposing factors at the biological level. An overview is provided here of the contents of this Special Issue, which contains a selection of reports from a unique multidisciplinary workshop involving both researchers and clinicians. Its purpose was to explore the possibility that ADHD, dyslexia, dyspraxia and autism fall within a phospholipid spectrum of disorders. This proposal could explain the high degree of co-morbidity between these conditions, their aggregation within families and relation to other psychiatric disorders, and a range of associated features that are already well known at a clinical level. The existing evidence for fatty acid abnormalities in these disorders is summarized, and new approaches are outlined that have the potential to improve both the identification and the management of these and related neurodevelopmental and psychiatric conditions.

Deficits in phonological skills appear to be at the heart of reading disability; however, the nature of this impairment is not yet known. The hypothesis that dyslexic subjects are impaired in auditory frequency discrimination was tested by using an attention-independent auditory brain potential, termed mismatch negativity (MMN) while subjects performed a visual distractor task. In separate blocks, MMN responses to graded changes in tone frequency or tone duration were recorded in 10 dyslexic and matched control subjects. MMN potentials to changes in tone frequency but not to changes in tone duration were abnormal in dyslexic subjects. This physiological deficit was corroborated by a similarly specific impairment in discriminating tone frequency, but not tone duration, which was assessed separately. Furthermore, the pitch discrimination and MMN deficit was correlated with the degree of impairment in phonological skills, as reflected in reading errors of regular words and nonwords. It is possible that in dyslexia a persistent sensory deficit in monitoring the frequency of incoming sound may impair the feedback control necessary for the normal development of phonological skills.

BK Puri,’ AJ Richardson,’ JM Allsop,’ CJ Higgins,3 CM Calvin3 N Saeed4 ‘MRI Unit, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 OHS, *University Department of Physiology, Parks Road, Oxford OX1 3PT, ‘Charing Cross Campus, Imperial College School of Medicine, London W6 SRP, 4Picker Research Group, MRI Unit, Hammersmith Hospital, Du Cane Road, London W12 OHS