Temporal and spatial attention in dyslexia

It was hypothesized that the deficits underlying reading impairment may arise from supra-modal deficits in temporal and spatial attention, disrupting, on the one hand, the ability to segment the temporally ordered phonemes of language and thus the acquisition of decoding skills, and, on the other, the ability to integrate spatially and temporally ordered orthographic information acquired from the fluent visual scanning of written text. Temporal and spatial attentional deficits in dyslexia were investigated using a lateralized visual temporal order judgment (TOJ) paradigm that allowed both sensitivity to temporal order and spatial attentional bias to be measured. Dyslexic and non-dyslexic participants were required to report the temporal order of two simple visual stimuli presented in either the same or different lateral hemifields. Findings indicated that dyslexic participants showed markedly impaired sensitivity to temporal order, and that the degree of impairment was correlated with the severity of their dyslexia. Furthermore, the findings suggested that at least three partially dissociated deficits may underlie both impaired TOJ task performance and reading disorder. One is a deficit associated with difficulty in reporting the temporal order of two visual stimuli, particularly when the first is presented in right hemifield; with slow word recognition and non-word reading; and with deficits in spelling and phonological skill. This constellation of deficits was interpreted as reflecting deficits in networks in left cerebral hemisphere implicated in phoneme-grapheme mapping and visual orienting. The second is a deficit that is associated with a rightward attentional bias; with inaccurate non-word reading that is worse than predicted by phonological skill or by word recognition; and with poor sustained attention. This constellation of impairments was interpreted as evidence of a deficit in right-lateralised networks implicated in the modulation of arousal, and possibly reflecting a “developmental left-neglect” syndrome. A third deficit was associated with impaired temporal order sensitivity, regardless of hemifield presentation; with symptoms of Attentional Deficit and Hyperactivity Disorder (ADHD); and with increased interference from distractor stimuli. This constellation of deficits suggests that the impaired network is implicated in executive control of attention, including conflict resolution and working memory. The results of the investigation as a whole suggests that the reading impairments of dyslexia may arise from attentional deficits that have with substantial overlap with those of ADHD, and include deficits in attentional networks implicated in orienting attention to temporally presented stimuli

Temporal and spatial attention in dyslexia

It was hypothesized that the deficits underlying reading impairment may arise from supra-modal deficits in temporal and spatial attention, disrupting, on the one hand, the ability to segment the temporally ordered phonemes of language and thus the acquisition of decoding skills, and, on the other, the ability to integrate spatially and temporally ordered orthographic information acquired from the fluent visual scanning of written text. Temporal and spatial attentional deficits in dyslexia were investigated using a lateralized visual temporal order judgment (TOJ) paradigm that allowed both sensitivity to temporal order and spatial attentional bias to be measured. Dyslexic and non-dyslexic participants were required to report the temporal order of two simple visual stimuli presented in either the same or different lateral hemifields. Findings indicated that dyslexic participants showed markedly impaired sensitivity to temporal order, and that the degree of impairment was correlated with the severity of their dyslexia. Furthermore, the findings suggested that at least three partially dissociated deficits may underlie both impaired TOJ task performance and reading disorder. One is a deficit associated with difficulty in reporting the temporal order of two visual stimuli, particularly when the first is presented in right hemifield; with slow word recognition and non-word reading; and with deficits in spelling and phonological skill. This constellation of deficits was interpreted as reflecting deficits in networks in left cerebral hemisphere implicated in phoneme-grapheme mapping and visual orienting. The second is a deficit that is associated with a rightward attentional bias; with inaccurate non-word reading that is worse than predicted by phonological skill or by word recognition; and with poor sustained attention. This constellation of impairments was interpreted as evidence of a deficit in right-lateralised networks implicated in the modulation of arousal, and possibly reflecting a “developmental left-neglect” syndrome. A third deficit was associated with impaired temporal order sensitivity, regardless of hemifield presentation; with symptoms of Attentional Deficit and Hyperactivity Disorder (ADHD); and with increased interference from distractor stimuli. This constellation of deficits suggests that the impaired network is implicated in executive control of attention, including conflict resolution and working memory. The results of the investigation as a whole suggests that the reading impairments of dyslexia may arise from attentional deficits that have with substantial overlap with those of ADHD, and include deficits in attentional networks implicated in orienting attention to temporally presented stimuli

Biological Maturation Status Variation Within Chronological Age Groups and the Impact on Injury

This Study investigated the variation of biological maturation status within chronological age groups in a football academy and its impact on injury. The injury factors of type, incidence, severity, and burden were used. What is more, the timing and status of PHV were identified as well as biological to draw comparisons and identify differences within the injury patterns. An injury audit was kept throughout the season to attain this data for the 72 participants in the chronological age groups (under 12, 13, 14, 15, 16) along with the player's measurements being taken pre-, mid-, and post-season. Descriptive statistics and a between-groups ANOVA were completed for data analysis. The results found that the range of biological maturation within the chronological age groups increased up to under 15s, while under 16s although they had a variance it was not as much as those in under 15s. Injury incidence peaked in those who were chronologically U12. With no distinctive pattern for the rest of the age-grouped teams Injury burden and days lost were both highest in the U15s. While circa-PHV had the most association with all injury factors. Once further broken down into their PHV status timing, on-time maturers were found to have the greatest injury association. Overall, the results from this study do not directly align with those already found and more research is needed particularly into the players PHV timing

Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate

Background: Deficits characteristic of Attention Deficit/Hyperactivity Disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the Default Mode Network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation. Method: We obtained functional magnetic resonance images from eighteen methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate. Results: When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off- methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition. Conclusions: During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children

Quantifying the core deficit in classical schizophrenia

In the classical descriptions of schizophrenia, Kraepelin and Bleuler recognised disorganization and impoverishment of mental activity as fundamental symptoms. Their classical descriptions also included a tendency to persisting disability. The psychopathological processes underlying persisting disability in schizophrenia remain poorly understood. The delineation of a core deficit underlying persisting disability would be of value in predicting outcome and enhancing treatment. We tested the hypothesis that mental disorganization and impoverishment are associated with persisting impairments of cognition and role-function, and together reflect a latent core deficit that is discernible in cases diagnosed by modern criteria. We used Confirmatory Factor Analysis to determine whether measures of disorganisation, mental impoverishment, impaired cognition and role functioning in 40 patients with schizophrenia represent a single latent variable. Disorganization scores were computed from the variance shared between disorganization measures from three commonly used symptom scales. Mental impoverishment scores were computed similarly. A single factor model exhibited a good fit, supporting the hypothesis that these measures reflect a core deficit.Persisting brain disorders are associated with a reduction in Post Motor Beta Rebound (PMBR), the characteristic increase in electrophysiological beta amplitude that follows a motor response. Patients had significantly reduced PMBR compared with healthy controls. PMBR was negatively correlated with core deficit score.While the symptoms constituting impoverished and disorganised mental activity are dissociable in schizophrenia, nonetheless, the variance that these two symptom domains share with impaired cognition and role function, appears to reflect a pathophysiological process that might be described as the core deficit of classical schizophrenia

Human cardiac mesenchymal stem cell like cells, a novel cell population with therapeutic potential.

Cardiac stem/progenitors are being used in the clinic to treat patients with a range of cardiac pathologies. However, improvements in heart function following treatment have been reported to be variable, with some showing no response. This discrepancy in response remains unresolved. MSCs have been highlighted as a regenerative tool as these cells display both immunomodulatory and pro-regenerative activity. The purpose of this study was to derive a cardiac MSC population to provide an alternative/support to current therapies. We derived human cardiac-mesenchymal-stem-cell-like-cells (CMSCLC) so named as they share some MSC characteristics. However, CMSCLC lack the MSC tri-lineage differentiation capacity, being capable of only rare adipogenic differentiation and demonstrating low/no osteogenic or chondrogenic potential, a phenotype that may have advantages following transplantation. Further, CMSCLC expressed low levels of p16, high levels of MHCI and low levels of MHCII. A lack of senescent cells would also be advantageous for cells to be used therapeutically, as would the ability to modulate the immune response. Crucially, CMSCLC display a transcriptional profile which includes genes associated with cardio-protective/cardio-beneficial effects. CMSCLC are also secretory and multipotent, giving rise to cardiomyocytes and endothelial cells. Our findings support CMSCLC as a novel cell population suitable for use for transplantation

Glutathione and glutamate in schizophrenia: a 7T MRS study

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with “residual schizophrenia”, in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione–glutamate component; an insula-visual glutathione–glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione–glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness

Reduced Prefrontal Gyrification in Carriers of the Dopamine D4 Receptor 7-Repeat Allele With Attention Deficit/Hyperactivity Disorder: A Preliminary Report

Objective: Structural and functional abnormalities have been noted in the prefrontal cortex of individuals with neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD). Cortical thickness and gyrification, both of which have been reported as abnormal in the prefrontal cortex in ADHD, are thought to be modulated by genetic influences during neural development. This study aimed to investigate the effects of a polymorphism of the dopamine DRD4 gene (the 7-repeat (7R) “risk” allele) on thickness and gyrification as distinct parameters of prefrontal cortical structure in children with ADHD.Method: Structural images and genetic samples were obtained from 49 children aged 9–15 years (25 with ADHD and 24 matched controls), and measures of cortical thickness and gyrification for inferior, middle, and superior frontal cortex were calculated.Results: A significant interaction between diagnosis and genotype on prefrontal gyrification was observed, largely driven by reduced inferior frontal gyrification in patients who carried the DRD4 7R allele. Furthermore, inferior frontal gyrification—but not thickness—related to everyday executive functioning in 7R allele carriers across groups.Conclusions: Prefrontal gyrification is reduced in children with ADHD who also carry the DRD4 7R allele, and it relates to critical functional skills in the executive domain in carriers of the risk allele. More broadly, these effects highlight the importance of considering precise neurodevelopmental mechanisms through which risk alleles influence cortical neurogenesis and migration

A multi-layer network approach to MEG connectivity analysis

Recent years have shown the critical importance of inter-regional neural network connectivity in supporting healthy brain function. Such connectivity is measurable using neuroimaging techniques such as MEG, however the richness of the electrophysiological signal makes gaining a complete picture challenging. Specifically, connectivity can be calculated as statistical interdependencies between neural oscillations within a large range of different frequency bands. Further, connectivity can be computed between frequency bands. This pan-spectral network hierarchy likely helps to mediate simultaneous formation of multiple brain networks, which support ongoing task demand. However, to date it has been largely overlooked, with many electrophysiological functional connectivity studies treating individual frequency bands in isolation. Here, we combine oscillatory envelope based functional connectivity metrics with a multi-layer network framework in order to derive a more complete picture of connectivity within and between frequencies. We test this methodology using MEG data recorded during a visuomotor task, highlighting simultaneous and transient formation of motor networks in the beta band, visual networks in the gamma band and a beta to gamma interaction. Having tested our method, we use it to demonstrate differences in occipital alpha band connectivity in patients with schizophrenia compared to healthy controls. We further show that these connectivity differences are predictive of the severity of persistent symptoms of the disease, highlighting their clinical relevance. Our findings demonstrate the unique potential of MEG to characterise neural network formation and dissolution. Further, we add weight to the argument that dysconnectivity is a core feature of the neuropathology underlying schizophrenia