A.J. Richardson

Impaired Auditory Frequency Discrimination in Dyslexia Detected with Mismatch Evoked Potentials

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. Ann Neurol 1999;45:495–503

A volumetric biochemical niacin flush-based index that noninvasively detects fatty acid deficiency in schizophrenia

(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<.0004). (6) With a threshold value for the VNR of 21, the test differentiated well between schizophrenia and normal controls (P=.002) with a sensitivity of 78% and a specificity of 65%. (7) The present results confirm that the flushing response is reduced in schizophrenia, and show that calculation of the VNR is an effective means of allowing the total response in different patients or patient groups to be readily compared.

Associations between central and peripheral measures of phospholipid breakdown revealed by cerebral 31-phosphorus magnetic resonance spectroscopy and fatty acid composition of erythrocyte membranes

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.

Cognitive asymmetry patterns in schizophrenia: retest reliability and modification with recovery

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.

Laterality changes accompanying symptom remission in schizophrenia following treatment with eicosapentaenoic acid.

INTRODUCTIONnA 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.nnnMETHODnThe 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 Annetts handedness scale and pegboard task 1 year pre-baseline, and this was repeated at 0, 3 and 6 months from the start of treatment.nnnRESULTSnAs 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 patients 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.nnnCONCLUSIONSnThese 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.

Opposite patterns of P300 asymmetry in schizophrenia are syndrome related.

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.

Schizotypal traits in relation to cerebellar volume and asymmetry: A high-resolution 3D magnetic resonance imaging study

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