Separate influences of acoustic AM and FM sensitivity on the phonological decoding skills of impaired and normal readers

Developmental dyslexia is associated with deficits in the processing of basic auditory stimuli. Yet it is unclear how these sensory impairments might contribute to poor reading skills. This study better characterizes the relationship between phonological decoding skills, the lack of which is generally accepted to comprise the core deficit in reading disabilities, and auditory sensitivity to amplitude modulation (AM) and frequency modulation (FM). Thirty-eight adult subjects, 17 of whom had a history of developmental dyslexia, completed a battery, of psychophysical measures of sensitivity to FM and AM at different modulation rates, along with a measure of pseudoword reading accuracy and standardized assessments of literacy and cognitive skills. The subjects with a history of dyslexia were significantly less sensitive than controls to 2-Hz FM and 20-Hz AM only. The absence of a significant group difference for 2-Hz AM shows that the dyslexics do not have a general deficit in detecting all slow modulations. Thresholds for detecting 2-Hz and 240-Hz FM and 20-Hz AM correlated significantly with pseudoword reading accuracy. After accounting for various cognitive skills, however, multiple regression analyses showed that detection thresholds for both 2-Hz FM and 20-Hz AM were significant and independent predictors of pseudoword reading ability in the entire sample. Thresholds for 2-Hz AM and 240-Hz FM did not explain significant additional variance in pseudoword reading skill, it is therefore possible that certain components of auditory processing of modulations are related to phonological decoding skills, whereas others are not.

Development of a passive MEG stimulus for measurement of the binaural masking level difference

The ability to hear a target signal over background noise is an important aspect of efficient hearing in everyday situations. This mechanism depends on binaural hearing whenever there are differences in the inter-aural timing of inputs from the noise and the signal. Impairments in binaural hearing may underlie some auditory processing disorders, for example temporal-lobe epilepsies. The binaural masking level difference (BMLD) measures the advantage in detecting a tone whose inter-aural phase differs from that of the masking noise. BMLD’s are typically estimated psychophysically, but this is challenging in children or those with cognitive impairments. The aim of this doctorate is to design a passive measure of BMLD using magnetoencephalography (MEG) and test this in adults, children and patients with different types of epilepsy. The stimulus consists of Gaussian background noise with 500-Hz tones presented binaurally either in-phase or 180° out-of-phase between the ears. Source modelling provides the N1m amplitude for the in-phase and out-of-phase tones, representing the extent of signal perception over background noise. The passive BMLD stimulus is successfully used as a measure of binaural hearing capabilities in participants who would otherwise be unable to undertake a psychophysical task.

Predicting dyslexia using prereading skills:the role of sensorimotor and cognitive abilities

Background: It is well established that phonological awareness, print knowledge and rapid naming predict later reading difficulties. However, additional auditory, visual and motor difficulties have also been observed in dyslexic children. It is examined to what extent these difficulties can be used to predict later literacy difficulties. Method: An unselected sample of 267 children at school entry completed a wide battery of tasks associated with dyslexia. Their reading was tested 2, 3 and 4 years later and poor readers were identified (n = 42). Logistic regression and multiple case study approaches were used to examine the predictive validity of different tasks. Results: As expected, print knowledge, verbal short-term memory, phonological awareness and rapid naming were good predictors of later poor reading. Deficits in visual search and in auditory processing were also present in a large minority of the poor readers. Almost all poor readers showed deficits in at least one area at school entry, but there was no single deficit that characterised the majority of poor readers. Conclusions: Results are in line with Pennington’s (2006) multiple deficits view of dyslexia. They indicate that the causes of poor reading outcome are multiple, interacting and probabilistic, rather than deterministic. Keywords: Dyslexia; educational attainment; longitudinal studies; prediction; phonological processing.

Pre-attentive auditory sensory processing in autistic spectrum disorder:are electromagnetic measurements telling us a coherent story?

Sensory processing is a crucial underpinning of the development of social cognition, a function which is compromised in variable degree in patients with pervasive developmental disorders (PDD). In this manuscript, we review some of the most recent and relevant contributions, which have looked at auditory sensory processing derangement in PDD. The variability in the clinical characteristics of the samples studied so far, in terms of severity of the associated cognitive deficits and associated limited compliance, underlying aetiology and demographic features makes a univocal interpretation arduous. We hypothesise that, in patients with severe mental deficits, the presence of impaired auditory sensory memory as expressed by the mismatch negativity could be a non-specific indicator of more diffuse cortical deficits rather than causally related to the clinical symptomatology. More consistent findings seem to emerge from studies on less severely impaired patients, in whom increased pitch perception has been interpreted as an indicator of increased local processing, probably as compensatory mechanism for the lack of global processing (central coherence). This latter hypothesis seems extremely attractive and future trials in larger cohorts of patients, possibly standardising the characteristics of the stimuli are a much-needed development. Finally, specificity of the role of the auditory derangement as opposed to other sensory channels needs to be assessed more systematically using multimodal stimuli in the same patient group. (c) 2006 Elsevier B.V. All rights reserved.

Morphology in autism spectrum disorders:local processing bias and language

We conducted a detailed study of a case of linguistic talent in the context of autism spectrum disorder, specifically Asperger syndrome. I.A. displays language strengths at the level of morphology and syntax. Yet, despite this grammar advantage, processing of figurative language and inferencing based on context presents a problem for him. The morphology advantage for I.A. is consistent with the weak central coherence (WCC) account of autism. From this account, the presence of a local processing bias is evident in the ways in which autistic individuals solve common problems, such as assessing similarities between objects and finding common patterns, and may therefore provide an advantage in some cognitive tasks compared to typical individuals. We extend the WCC account to language and provide evidence for a connection between the local processing bias and the acquisition of morphology and grammar.

Interval timing in children:effects of auditory and visual pacing stimuli and relationships with reading and attention variables

Motor timing tasks have been employed in studies of neurodevelopmental disorders such as developmental dyslexia and ADHD, where they provide an index of temporal processing ability. Investigations of these disorders have used different stimulus parameters within the motor timing tasks which are likely to affect performance measures. Here we assessed the effect of auditory and visual pacing stimuli on synchronised motor timing performance and its relationship with cognitive and behavioural predictors that are commonly used in the diagnosis of these highly prevalent developmental disorders. Twenty- one children (mean age 9.6 years) completed a finger tapping task in two stimulus conditions, together with additional psychometric measures. As anticipated, synchronisation to the beat (ISI 329 ms) was less accurate in the visually paced condition. Decomposition of timing variance indicated that this effect resulted from differences in the way that visual and auditory paced tasks are processed by central timekeeping and associated peripheral implementation systems. The ability to utilise an efficient processing strategy on the visual task correlated with both reading and sustained attention skills. Dissociations between these patterns of relationship across task modality suggest that not all timing tasks are equivalent.

Independent modulation of engagement and connectivity of the facial network during affect processing by CACNA1C and ANK3 risk genes for bipolar disorder

IMPORTANCE Genome-wide association studies (GWASs) indicate that single-nucleotide polymorphisms in the CACNA1C and ANK3 genes increase the risk for bipolar disorder (BD). The genes influence neuronal firing by modulating calcium and sodium channel functions, respectively. Both genes modulate ?-aminobutyric acid-transmitting interneuron function and can thus affect brain regional activation and interregional connectivity. OBJECTIVE To determine whether the genetic risk for BD associated with 2 GWAS-supported risk single-nucleotide polymorphisms at CACNA1C rs1006737 and ANK3 rs10994336 is mediated through changes in regional activation and interregional connectivity of the facial affect-processing network. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional functional magnetic resonance imaging study at a research institute of 41 euthymic patients with BD and 46 healthy participants, all of British white descent. MAIN OUTCOMES AND MEASURES Blood oxygen level-dependent signal and effective connectivity measures during the facial affect-processing task. RESULTS In healthy carriers, both genetic risk variants were independently associated with increased regional engagement throughout the facial affect-processing network and increased effective connectivity between the visual and ventral prefrontal cortical regions. In contrast, BD carriers of either genetic risk variant exhibited pronounced reduction in ventral prefrontal cortical activation and visual-prefrontal effective connectivity. CONCLUSIONS AND RELEVANCE Our data demonstrate that the effect of CACNA1C rs1006737 and ANK3 rs10994336 (or genetic variants in linkage disequilibrium) on the brain converges on the neural circuitry involved in affect processing and provides a mechanism linking BD to genome-wide genetic risk variants.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

Background - The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. Method - We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. Results - Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. Conclusions - Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity. © 2010 Cambridge University Press.

Experiments in time:exploring the components of motor timing behaviour in dyslexia

This investigation aimed to pinpoint the elements of motor timing control that are responsible for the increased variability commonly found in children with developmental dyslexia on paced or unpaced motor timing tasks (Chapter 3). Such temporal processing abilities are thought to be important for developing the appropriate phonological representations required for the development of literacy skills. Similar temporal processing difficulties arise in other developmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD). Motor timing behaviour in developmental populations was examined in the context of models of typical human timing behaviour, in particular the Wing-Kristofferson model, allowing estimation of the contribution of different timing control systems, namely timekeeper and implementation systems (Chapter 2 and Methods Chapters 4 and 5). Research examining timing in populations with dyslexia and ADHD has been inconsistent in the application of stimulus parameters and so the first investigation compared motor timing behaviour across different stimulus conditions (Chapter 6). The results question the suitability of visual timing tasks which produced greater performance variability than auditory or bimodal tasks. Following an examination of the validity of the Wing-Kristofferson model (Chapter 7) the model was applied to time series data from an auditory timing task completed by children with reading difficulties and matched control groups (Chapter 8). Expected group differences in timing performance were not found, however, associations between performance and measures of literacy and attention were present. Results also indicated that measures of attention and literacy dissociated in their relationships with components of timing, with literacy ability being correlated with timekeeper variance and attentional control with implementation variance. It is proposed that these timing deficits associated with reading difficulties are attributable to central timekeeping processes and so the contribution of error correction to timing performance was also investigated (Chapter 9). Children with lower scores on measures of literacy and attention were found to have a slower or failed correction response to phase errors in timing behaviour. Results from the series of studies suggest that the motor timing difficulty in poor reading children may stem from failures in the judgement of synchrony due to greater tolerance of uncertainty in the temporal processing system.

The influence of variations in eating disorder-related symptoms on processing of emotional faces in a non-clinical female sample:an eye-tracking study

This study aimed to: i) determine if the attention bias towards angry faces reported in eating disorders generalises to a non-clinical sample varying in eating disorder-related symptoms; ii) examine if the bias occurs during initial orientation or later strategic processing; and iii) confirm previous findings of impaired facial emotion recognition in non-clinical disordered eating. Fifty-two females viewed a series of face-pairs (happy or angry paired with neutral) whilst their attentional deployment was continuously monitored using an eye-tracker. They subsequently identified the emotion portrayed in a separate series of faces. The highest (n=18) and lowest scorers (n=17) on the Eating Disorders Inventory (EDI) were compared on the attention and facial emotion recognition tasks. Those with relatively high scores exhibited impaired facial emotion recognition, confirming previous findings in similar non-clinical samples. They also displayed biased attention away from emotional faces during later strategic processing, which is consistent with previously observed impairments in clinical samples. These differences were related to drive-for-thinness. Although we found no evidence of a bias towards angry faces, it is plausible that the observed impairments in emotion recognition and avoidance of emotional faces could disrupt social functioning and act as a risk factor for the development of eating disorders.

Facial affect processing inbipolar disorder:a magnetoencephalography study

Background: Identifying biological markers to aid diagnosis of bipolar disorder (BD) is critically important. To be considered a possible biological marker, neural patterns in BD should be discriminant from those in healthy individuals (HI). We examined patterns of neuromagnetic responses revealed by magnetoencephalography (MEG) during implicit emotion-processing using emotional (happy, fearful, sad) and neutral facial expressions, in sixteen BD and sixteen age- and gender-matched healthy individuals. Methods: Neuromagnetic data were recorded using a 306-channel whole-head MEG ELEKTA Neuromag System, and preprocessed using Signal Space Separation as implemented in MaxFilter (ELEKTA). Custom Matlab programs removed EOG and ECG signals from filtered MEG data, and computed means of epoched data (0-250ms, 250-500ms, 500-750ms). A generalized linear model with three factors (individual, emotion intensity and time) compared BD and HI. A principal component analysis of normalized mean channel data in selected brain regions identified principal components that explained 95% of data variation. These components were used in a quadratic support vector machine (SVM) pattern classifier. SVM classifier performance was assessed using the leave-one-out approach. Results: BD and HI showed significantly different patterns of activation for 0-250ms within both left occipital and temporal regions, specifically for neutral facial expressions. PCA analysis revealed significant differences between BD and HI for mild fearful, happy, and sad facial expressions within 250-500ms. SVM quadratic classifier showed greatest accuracy (84%) and sensitivity (92%) for neutral faces, in left occipital regions within 500-750ms. Conclusions: MEG responses may be used in the search for disease specific neural markers.

Does cochlear implantation improve speech recognition in children with auditory neuropathy spectrum disorder? A systematic review

OBJECTIVE: Cochlear implantation (CI) is a standard treatment for severe-profound sensorineural hearing loss (SNHL). However, consensus has yet to be reached on its effectiveness for hearing loss caused by auditory neuropathy spectrum disorder (ANSD). This review aims to summarize and synthesize current evidence of the effectiveness of CI in improving speech recognition in children with ANSD. DESIGN: Systematic review. STUDY SAMPLE: A total of 27 studies from an initial selection of 237. RESULTS: All selected studies were observational in design, including case studies, cohort studies, and comparisons between children with ANSD and SNHL. Most children with ANSD achieved open-set speech recognition with their CI. Speech recognition ability was found to be equivalent in CI users (who previously performed poorly with hearing aids) and hearing-aid users. Outcomes following CI generally appeared similar in children with ANSD and SNHL. Assessment of study quality, however, suggested substantial methodological concerns, particularly in relation to issues of bias and confounding, limiting the robustness of any conclusions around effectiveness. CONCLUSIONS: Currently available evidence is compatible with favourable outcomes from CI in children with ANSD. However, this evidence is weak. Stronger evidence is needed to support cost-effective clinical policy and practice in this area.

Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease?

Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease.

Changes in brain activation during working memory and facial recognition tasks in patients with bipolar disorder with Lamotrigine monotherapy

Verbal working memory and emotional self-regulation are impaired in Bipolar Disorder (BD). Our aim was to investigate the effect of Lamotrigine (LTG), which is effective in the clinical management of BD, on the neural circuits subserving working memory and emotional processing. Functional Magnetic Resonance Imaging data from 12 stable BD patients was used to detect LTG-induced changes as the differences in brain activity between drug-free and post-LTG monotherapy conditions during a verbal working memory (N-back sequential letter task) and an angry facial affect recognition task. For both tasks, LGT monotherapy compared to baseline was associated with increased activation mostly within the prefrontal cortex and cingulate gyrus, in regions normally engaged in verbal working memory and emotional processing. Therefore, LTG monotherapy in BD patients may enhance cortical function within neural circuits involved in memory and emotional self-regulation. © 2007 Elsevier B.V. and ECNP.