A magnetoencephalographic study of low-level auditory processing in developmental dyslexia

The possibility that developmental dyslexia results from low-level sensory processing deficits has received renewed interest in recent years. Opponents of such sensory-based explanations argue that dyslexia arises primarily from phonological impairments. However, many behavioural correlates of dyslexia cannot be explained sufficiently by cognitive-level accounts and there is anatomical, psychometric and physiological evidence of sensory deficits in the dyslexic population. This thesis aims to determine whether the low-level (pre-attentive) processing of simple auditory stimuli is disrupted in compensated adult dyslexics. Using psychometric and neurophysiological measures, the nature of auditory processing abnormalities is investigated. Group comparisons are supported by analysis of individual data in order to address the issue of heterogeneity in dyslexia. The participant pool consisted of seven compensated dyslexic adults and seven age and IQ matched controls. The dyslexic group were impaired, relative to the control group, on measures of literacy, phonological awareness, working memory and processing speed. Magnetoencephalographic recordings were conducted during processing of simple, non-speech, auditory stimuli. Results confirm that low-level auditory processing deficits are present in compensated dyslexic adults. The amplitude of N1m responses to tone pair stimuli were reduced in the dyslexic group. However, there was no evidence that manipulating either the silent interval or the frequency separation between the tones had a greater detrimental effect on dyslexic participants specifically. Abnormal MMNm responses were recorded in response to frequency deviant stimuli in the dyslexic group. In addition, complete stimulus omissions, which evoked MMNm responses in all control participants, failed to elicit significant MMNm responses in all but one of the dyslexic individuals. The data indicate both a deficit of frequency resolution at a local level of auditory processing and a higher-level deficit relating to the grouping of auditory stimuli, relevant for auditory scene analysis. Implications and directions for future research are outlined.

Experiments and observations on the behaviour and brain of the aging female mouse with special reference to dementia of the Alzheimer type

The objective of this research was to investigate the effects of normal aging and the additional effects of chronic exposure to two experimental diets, one enriched in aluminium, the other enriched in lecithin, on aspects of the behaviour and brain histology of the female mouse. The aluminium diet was administered in an attempt to develop a rodent model of Dementia of the Alzheimer Type (DAT). With normal aging, almost all assessed aspects of behaviour were found to be impaired. As regards cognition, selective impairments of single-trial passive avoidance and Morris place learning were observed. While all aspects of open-field behaviour were impaired, the degree of impairment was directly related to the degree of motoric complexity. Deficits were also observed on non-visual sensorimotor coordination tasks and in olfactory discrimination. Histologically, neuron loss, gliosis, vacuolation and congophilic angiopathy were observed in several of the brain regions/fibre tracts believed to contribute to the control of some of the assessed behaviours. The aluminium treatment had very selective effects on both behaviour and brain histology, inducing several features observed in DAT. Behaviourally, the treatment induced impaired spatial reference memory; reduced ambulation; disturbed olfactory function and induced the premature development of the senile pattern of swimming. Histologically, significant neuron loss and gliosis were observed in the hippocampus, entorhinal cortex, amygdala, medial septum, pyriform and pr-frontal cortex. In addition, the brain distribution of congophilic angiopathy was significantly increased by the treatment. The lecithin treatment had effects on both non-cognitive and cognitive aspects of behaviour. The effects of aging on open-field ambulation and rearing were partially ameliorated by the treatment. A similar effect was observed for single-trial passive avoidance performance. Age-dependent improvements in acquisition/retention were observed in 17-23 month mice and Morris place task performance was improved in 11 and 17 month mice. Histologically, a partial sparing of neurons in the cerebellum, hippocampus, entorhinal cortex and subiculum was observed.

Changing faces

News & Comment. Many influential models of prefrontal cortex function suggest that activity within this area is often associated with additional activity in posterior regions of the cortex that support perception. The purpose of this cortical ‘coupling’ is to ensure that a perceptual representation is generated and then maintained within the working memory system. Areas in the right ventrolateral prefrontal cortex (vlPFC) and the fusiform gyrus have been implicated as associate areas involved in face processing. In an interesting case study by Vignal, Chauvel and Halgren the functional relationship between these two areas was tested1. In order to confirm the epileptogenic foci prior to resective surgery in a 30-year-old male patient, depth electrodes were implanted into sites around prefrontal, anterior temporal and premotor cortices. While the patient was looking at a blank screen, 50-Hz electrical stimulation of two probes implanted into the right anterior frontal gyrus resulted in the patient’s reporting the perception of a series of colourful faces. These facial hallucinations were described as being ‘…like passing slides, one after the after, linked together’. When asked to look at an actual face during stimulation at the same sites the patient reported transformation of that face (such as appearing without spectacles or with a hat). These findings were related to activity of a cortical network involving the vlPFC and the fusiform gyrus. This paper thus suggests a role in face processing for the vlPFC, evoking working memory processes to maintain facial representations.

Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia

Context: Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction and abnormalities at the nodes of Ranvier (NOR) interface where myelin and axons interact. Objective: To identify abnormalities in the expression of oligodendroglial genes and proteins that participate in the formation, maintenance, and integrity of the NOR in SZ. Design: The messenger RNA (mRNA) expression levels of multiple NOR genes were quantified in 2 independent postmortem brain cohorts of individuals with SZ, and generalizability to protein expression was confirmed. The effect of the ANK3 genotype on the mRNA expression level was tested in postmortem human brain. Case-control analysis tested the association of the ANK3 genotype with SZ. The ANK3 genotype's influence on cognitive task performance and functional magnetic resonance imaging activation was tested in 2 independent cohorts of healthy individuals. Setting: Research hospital. Patients: Postmortem samples from patients with SZ and healthy controls were used for the brain expression study (n=46) and the case-control analysis (n=272). Healthy white men and women participated in the cognitive (n=513) and neuroimaging (n=52) studies. Main Outcome Measures: The mRNA and protein levels in postmortem brain samples, genetic association with schizophrenia, cognitive performance, and blood oxygenation level-dependent functional magnetic resonance imaging. Results: The mRNA expression of multiple NOR genes was decreased in schizophrenia. The ANK3 rs9804190 C allele was associated with lower ANK3 mRNA expression levels, higher risk for SZ in the case-control cohort, and poorer working memory and executive function performance and increased prefrontal activation during a working memory task in healthy individuals. Conclusions: These results point to abnormalities in the expression of genes and protein associated with the integrity of the NOR and suggest them as substrates for the disconnectivity syndrome in SZ. The association of ANK3 with lower brain mRNA expression levels implicates a molecular mechanism for its genetic, clinical, and cognitive associations with SZ. ©2012 American Medical Association. All rights reserved.

Sex differences in bipolar disorder:a review of neuroimaging findings and new evidence

Objectives: The sex of an individual is known to modulate the clinical presentation of bipolar disorder (BD), but little is known as to whether there are significant sex-by-diagnosis interactions on the brain structural and functional correlates of BD. Methods: We conducted a literature review of magnetic resonance imaging (MRI) studies in BD, published between January 1990 and December 2010, reporting on the effects of sex and diagnosis. In the absence of any functional MRI (fMRI) studies, this review was supplemented by original data analyses focusing on sex-by-diagnosis interactions on patterns of brain activation obtained during tasks of working memory, incentive decision-making, and facial affect processing. Results: We found no support for a sex-by-diagnosis interaction in global gray or white matter volume. Evidence regarding regional volumetric measures is limited, but points to complex interactions between sex and diagnosis with developmental and temperamental factors within limbic and prefrontal regions. Sex-by-diagnosis interactions were noted in the pattern of activation within the basal ganglia during incentive decision-making and within ventral prefrontal regions during facial affect processing. Conclusions: Potential sex-by-diagnosis interactions influencing the brain structural and functional correlates of disease expression in BD have received limited attention. Our data suggest that the sex of an individual modulates structure and function within subcortical and cortical regions implicated in disease expression. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Cognitive systems associated with the hippocampus of the human brain and their role in behaviour and neurodegenerative disease

Cognitive systems research involves the synthesis of ideas from natural and artificial systems in the analysis, understanding, and design of all intelligent systems. This chapter discusses the cognitive systems associated with the hippocampus (HC) of the human brain and their possible role in behaviour and neurodegenerative disease. The hippocampus (HC) is concerned with the analysis of highly abstract data derived from all sensory systems but its specific role remains controversial. Hence, there have been three major theories concerning its function, viz., the memory theory, the spatial theory, and the behavioral inhibition theory. The memory theory has its origin in the surgical destruction of the HC, which results in severe anterograde and partial retrograde amnesia. The spatial theory has its origin in the observation that neurons in the HC of animals show activity related to their location within the environment. By contrast, the behavioral inhibition theory suggests that the HC acts as a ‘comparator’, i.e., it compares current sensory events with expected or predicted events. If a set of expectations continues to be verified then no alteration of behavior occurs. If, however, a ‘mismatch’ is detected then the HC intervenes by initiating appropriate action by active inhibition of current motor programs and initiation of new data gathering. Understanding the cognitive systems of the hippocampus in humans may aid in the design of intelligent systems involved in spatial mapping, memory, and decision making. In addition, this information may lead to a greater understanding of the course of clinical dementia in the various neurodegenerative diseases in which there is significant damage to the HC.

Target consolidation under high temporal processing demands as revealed by MEG

We investigated the nature of resource limitations during visual target processing by imposing high temporal processing demands on the cognitive system. This was achieved by embedding target stimuli into rapid-serial-visual-presentation-streams (RSVP). In RSVP streams, it is difficult to report the second of two targets (T2) if the second follows the first (T1) within 500 ms. This effect is known as the attentional blink (AB). For the AB to occur, it is essential that T1 is followed by a mask, as without such a stimulus, the AB is significantly attenuated. Usually, it is thought that T1 processing is delayed by the mask, which in turn delays T2 processing, increasing the likelihood for T2 failures (AB). Predictions regarding amplitudes and latencies of cortical responses (M300, the magnetic counterpart to the P300) to targets were tested by investigating the neurophysiological effects of the post-T1 item (mask) by means of magnetoencephalography (MEG). Cortical M300 responses to targets drawn from prefrontal sources – areas associated with working memory – revealed accelerated T1 yet delayed T2 processing with an intervening mask. The explanation we are proposing assumes that “protection” of ongoing T1 processing necessitated by the occurrence of the mask suppresses other activation patterns, which boosts T1 yet also hinders further processing. Our data shed light on the mechanisms employed by the human brain for ensuring visual target processing under high temporal processing demands, which is hypothesized to occur at the expense of subsequently presented information.

Nutritional influences on cognitive function:mechanisms of susceptibility

The impact of nutritional variation, within populations not overtly malnourished, on cognitive function and arousal is considered. The emphasis is on susceptibility to acute effects of meals and glucose loads, and chronic effects of dieting, on mental performance, and effects of cholesterol and vitamin levels on cognitive impairment. New developments in understanding dietary influences on neurohormonal systems, and their implications for cognition and affect, allow reinterpretation of both earlier and recent findings. Evidence for a detrimental effect of omitting a meal on cognitive performance remains equivocal: from the outset, idiosyncrasy has prevailed. Yet, for young and nutritionally vulnerable children, breakfast is more likely to benefit than hinder performance. For nutrient composition, despite inconsistencies, some cautious predictions can be made. Acutely, carbohydrate-rich–protein-poor meals can be sedating and anxiolytic; by comparison, protein-rich meals may be arousing, improving reaction time but also increasing unfocused vigilance. Fat-rich meals can lead to a decline in alertness, especially where they differ from habitual fat intake. These acute effects may vary with time of day and nutritional status. Chronically, protein-rich diets have been associated with decreased positive and increased negative affect relative to carbohydrate-rich diets. Probable mechanisms include diet-induced changes in monoamine, especially serotoninergic neurotransmitter activity, and functioning of the hypothalamic pituitary adrenal axis. Effects are interpreted in the context of individual traits and susceptibility to challenging, even stressful, tests of performance. Preoccupation with dieting may impair cognition by interfering with working memory capacity, independently of nutritional status. The change in cognitive performance after administration of glucose, and other foods, may depend on the level of sympathetic activation, glucocorticoid secretion, and pancreatic β-cell function, rather than simple fuelling of neural activity. Thus, outcomes can be predicted by vulnerability in coping with stressful challenges, interacting with nutritional history and neuroendocrine status. Functioning of such systems may be susceptible to dietary influences on neural membrane fluidity, and vitamin-dependent cerebrovascular health, with cognitive vulnerability increasing with age.

Functional neuroanatomy and behavioural correlates of the basal ganglia:evidence from lesion studies

Introduction: The basal ganglia are interconnected with cortical areas involved in behavioural, cognitive and emotional processes, in addition to movement regulation. Little is known about which of these functions are associated with individual basal ganglia substructures. Methods: Pubmed was searched for literature related to behavioural, cognitive and emotional symptoms associated with focal lesions to basal ganglia structures in humans. Results: Six case-control studies and two case reports were identified as relevant. Lesion sites included the caudate nucleus, putamen and globus pallidus. These were associated with a spectrum of behavioural and cognitive symptoms, including abulia, poor working memory and deficits in emotional recognition. Discussion: It is often difficult to precisely map associations between cognitive, emotional or behavioural functions and particular basal ganglia substructures, due to the non-specific nature of the lesions. However, evidence from lesion studies shows that most symptoms correspond with established non-motor frontal-subcortical circuits. © 2013-IOS Press and the authors. All rights reserved.

The impact of ageing and gender on visual mental imagery processes:a study of performance on tasks from the Complete Visual Mental Imagery Battery (CVMIB)

In this study we aim to evaluate the impact of ageing and gender on different visual mental imagery processes. Two hundred and fifty-one participants (130 women and 121 men; age range = 18–77 years) were given an extensive neuropsychological battery including tasks probing the generation, maintenance, inspection, and transformation of visual mental images (Complete Visual Mental Imagery Battery, CVMIB). Our results show that all mental imagery processes with the exception of the maintenance are affected by ageing, suggesting that other deficits, such as working memory deficits, could account for this effect. However, the analysis of the transformation process, investigated in terms of mental rotation and mental folding skills, shows a steeper decline in mental rotation, suggesting that age could affect rigid transformations of objects and spare non-rigid transformations. Our study also adds to previous ones in showing gender differences favoring men across the lifespan in the transformation process, and, interestingly, it shows a steeper decline in men than in women in inspecting mental images, which could partially account for the mixed results about the effect of ageing on this specific process. We also discuss the possibility to introduce the CVMIB in clinical assessment in the context of theoretical models of mental imagery.

Analysis and interpretation of serial position data

The representation of serial position in sequences is an important topic in a variety of cognitive areas including the domains of language, memory, and motor control. In the neuropsychological literature, serial position data have often been normalized across different lengths, and an improved procedure for this has recently been reported by Machtynger and Shallice (2009). Effects of length and a U-shaped normalized serial position curve have been criteria for identifying working memory deficits. We present simulations and analyses to illustrate some of the issues that arise when relating serial position data to specific theories. We show that critical distinctions are often difficult to make based on normalized data. We suggest that curves for different lengths are best presented in their raw form and that binomial regression can be used to answer specific questions about the effects of length, position, and linear or nonlinear shape that are critical to making theoretical distinctions. © 2010 Psychology Press.

On-line puzzle game based assessment & training for ADHD

Attention-deficit hyperactivity disorder (ADHD) is the most prevalent and impairing neurodevelopmental disorder, with worldwide estimates of 5.29%. ADHD is clinically characterized by hyperactivity-impulsivity and inattention, with neuropsychological deficits in executive functions, attention, working memory and inhibition. These cognitive processes rely on prefrontal cortex function; cognitive training programs enhance performance of ADHD participants supporting the idea of neuronal plasticity. Here we propose the development of an on-line puzzle game based assessment and training tool in which participants must deduce the ‘winning symbol’ out of N distracters. To increase ecological validity of assessments strategically triggered Twitter/Facebook notifications will challenge the ability to ignore distracters. In the UK, significant cost for the disorder on health, social and education services, stand at £23m a year. Thus the potential impact of neuropsychological assessment and training to improve our understanding of the pathophysiology of ADHD, and hence our treatment interventions and patient outcomes, cannot be overstated.

Towards person-centered neuroimaging markers for resilience and vulnerability in Bipolar Disorder

Improved clinical care for Bipolar Disorder (BD) relies on the identification of diagnostic markers that can reliably detect disease-related signals in clinically heterogeneous populations. At the very least, diagnostic markers should be able to differentiate patients with BD from healthy individuals and from individuals at familial risk for BD who either remain well or develop other psychopathology, most commonly Major Depressive Disorder (MDD). These issues are particularly pertinent to the development of translational applications of neuroimaging as they represent challenges for which clinical observation alone is insufficient. We therefore applied pattern classification to task-based functional magnetic resonance imaging (fMRI) data of the n-back working memory task, to test their predictive value in differentiating patients with BD (n=30) from healthy individuals (n=30) and from patients' relatives who were either diagnosed with MDD (n=30) or were free of any personal lifetime history of psychopathology (n=30). Diagnostic stability in these groups was confirmed with 4-year prospective follow-up. Task-based activation patterns from the fMRI data were analyzed with Gaussian Process Classifiers (GPC), a machine learning approach to detecting multivariate patterns in neuroimaging datasets. Consistent significant classification results were only obtained using data from the 3-back versus 0-back contrast. Using contrast, patients with BD were correctly classified compared to unrelated healthy individuals with an accuracy of 83.5%, sensitivity of 84.6% and specificity of 92.3%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their relatives with MDD, were respectively 73.1%, 53.9% and 94.5%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their healthy relatives were respectively 81.8%, 72.7% and 90.9%. We show that significant individual classification can be achieved using whole brain pattern analysis of task-based working memory fMRI data. The high accuracy and specificity achieved by all three classifiers suggest that multivariate pattern recognition analyses can aid clinicians in the clinical care of BD in situations of true clinical uncertainty regarding the diagnosis and prognosis.

Pleasure, pain and procrastination:reflections on the experience of doing memory-work research

The focus of this article is the process of doing memory-work research. We tell the story of our experience of what it was like to use this approach. We were enthused to work collectively on a "discovery" project to explore a method with which we were unfamiliar. We hoped to build working relationships based on mutual respect and the desire to focus on methodology and its place in our psychological understanding. The empirical activities highlighted methodological and experiential challenges, which tested our adherence to the social constructionist premise of Haug's original description of memory work. Combined with practical difficulties of living across Europe, writing and analyzing the memories became contentious. We found ourselves having to address a number of tensions emanating from the work and our approach to it. We discuss some of these tensions alongside examples that illustrate the research process and the ways we negotiated the collective nature of the memory-work approach. © 2012 Copyright Taylor and Francis Group, LLC.

Spatial-spectral flexible optical networking:enabling switching solutions for a simplified and efficient SDM network platform

The traffic carried by core optical networks grows at a steady but remarkable pace of 30-40% year-over-year. Optical transmissions and networking advancements continue to satisfy the traffic requirements by delivering the content over the network infrastructure in a cost and energy efficient manner. Such core optical networks serve the information traffic demands in a dynamic way, in response to requirements for shifting of traffics demands, both temporally (day/night) and spatially (business district/residential). However as we are approaching fundamental spectral efficiency limits of singlemode fibers, the scientific community is pursuing recently the development of an innovative, all-optical network architecture introducing the spatial degree of freedom when designing/operating future transport networks. Spacedivision- multiplexing through the use of bundled single mode fibers, and/or multi-core fibers and/or few-mode fibers can offer up to 100-fold capacity increase in future optical networks. The EU INSPACE project is working on the development of a complete spatial-spectral flexible optical networking solution, offering the network ultra-high capacity, flexibility and energy efficiency required to meet the challenges of delivering exponentially growing traffic demands in the internet over the next twenty years. In this paper we will present the motivation and main research activities of the INSPACE consortium towards the realization of the overall project solution. © 2014 Copyright SPIE.