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Background/Objective: White matter tractography is a non-invasive method, which reconstructs three-dimensional trajectories of the brain tracts using diffusion-tensor imaging (DTI) data. Due to the partial volume effect of DTI data, some of tractography algorithms are unable to follow the correct pathways after the crossing and branching regions. The main challenge for tractography methods has been the ability to detect these regions. Fast marching techniques are capable of tracking the fibers with wide spreading. Materials and Methods: In order to detect true fibers, an adaptive functional anisotropy (FA) weighted function is proposed to modify the speed function of these algorithms. The performance of the proposed tractography method is assessed using synthetic data and its feasibility is showed by extracting some well-known tracts using healthy human DTI datasets. Result: The percentage of the length of whole tracts extracted by our proposed method is above 85% even for a signal to noise ratio (SNR) level equal to 16. The ability of this method to detect the fiber crossing in simulation data is above 90%. Furthermore, the tractography results of some well-known tracts demonstrate the ability of the proposed methods to extract the correct pathways from the anatomical point of view. Conclusion: This method has led to great impact on the fast-marching fiber-tracking method in propagating the tractography front in an adaptive manner. The suggested speed function can make the speed of front propagation adapted to the type of brain's environments such as isotropic and anisotropic regions. [ABSTRACT FROM AUTHOR]

A novel azo-linked porous organic polymer (AL-POP) was synthesized from caffeic acid and benzidine via an azo-coupling reaction and characterized by FTIR, SEM-EDS, BET, TGA, XRD and zeta potential analysis. AL-POPs were incorporated into melamine sponges and used for pipette tip micro solid-phase extraction (PT-MSPE) of six types of B vitamins (including thiamine, riboflavin, nicotinamide, pyridoxine, folic acid, and cyanocobalamin). After extraction, the samples were analyzed using high performance liquid chromatography-diode array detection (HPLC-DAD) system. The effect of AL-POP composition on the extraction efficiency (EE) of vitamins was investigated and benzidine to caffeic acid mol ratio of 1.5, 3.35 mmol of NaNO 2, and reaction time of 8 h were selected as optimum conditions. The efficiency of the extraction process was improved by optimizing various parameters such as the amount of sorbent, pH and ionic strength of the sample, sample volume, number of sorption and desorption cycles, type of wash solvent, and type and volume of eluent solvent. Linearity (R 2 ≥0.9987), Limit of detection (LOD) (11.88-18.97 ng/mL), limit of quantification (LOQ) (39.62-63.23 ng/mL), and enrichment factor (EF) (1.27-4.31) were obtained using calibration curves plotted under optimum conditions. Recovery values of these six B vitamins in the spiked multivitamin syrup samples varied from 80.01% to 108.35%, with a relative standard deviation (RSD) below 5.44%. Eventually, the optimized method was successfully used to extract and quantify the B vitamins in multivitamin syrup and non-alcoholic beer., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prolonged sensory deprivation has repeatedly been linked to cortical reorganization. We recently demonstrated that individuals with congenital anosmia (CA, complete olfactory deprivation since birth) have seemingly normal morphology in piriform (olfactory) cortex despite profound morphological deviations in the orbitofrontal cortex (OFC), a finding contradictory to both the known effects of blindness on visual cortex and to the sparse literature on brain morphology in anosmia. To establish whether these unexpected findings reflect the true brain morphology in CA, we first performed a direct replication of our previous study to determine if lack of results was due to a deviant control group, a confound in cross sectional studies. Individuals with CA (n = 30) were compared to age and sex matched controls (n = 30) using voxel- and surface-based morphometry. The replication results were near identical to the original study: bilateral clusters of group differences in the OFC, including CA atrophy around the olfactory sulci and volume increases in the medial orbital gyri. Importantly, no group differences in piriform cortex were detected. Subsequently, to assess any subtle patterns of group differences not detectable by our mass-univariate analysis, we explored the data from a multivariate perspective. Combining the newly collected data with data from the replicated study (CA = 49, control = 49), we performed support vector machine classification based on gray matter volume. In line with the mass-univariate analyses, the multivariate analysis could accurately differentiate between the groups in bilateral OFC, whereas the classification accuracy in piriform cortex was at chance level. Our results suggest that despite lifelong olfactory deprivation, piriform (olfactory) cortex is morphologically unaltered and the morphological deviations in CA are confined to the OFC., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Ambiguous sensory information can lead to spontaneous alternations between perceptual states, recently shown to extend to tactile perception. The authors recently proposed a simplified form of tactile rivalry which evokes two competing percepts for a fixed difference in input amplitudes across antiphase, pulsatile stimulation of the left and right fingers. This study addresses the need for a tactile rivalry model that captures the dynamics of perceptual alternations and that incorporates the structure of the somatosensory system. The model features hierarchical processing with two stages. The first and the second stages of model could be located at the secondary somatosensory cortex (area S2), or in higher areas driven by S2. The model captures dynamical features specific to the tactile rivalry percepts and produces general characteristics of perceptual rivalry: input strength dependence of dominance times (Levelt's proposition II), short-tailed skewness of dominance time distributions and the ratio of distribution moments. The presented modelling work leads to experimentally testable predictions. The same hierarchical model could generalise to account for percept formation, competition and alternations for bistable stimuli that involve pulsatile inputs from the visual and auditory domains., (© 2023. The Author(s).)

In perceptual rivalry, ambiguous sensory information leads to dynamic changes in the perceptual interpretation of fixed stimuli. This phenomenon occurs when participants receive sensory stimuli that support two or more distinct interpretations; this results in spontaneous alternations between possible perceptual interpretations. Perceptual rivalry has been widely studied across different sensory modalities including vision, audition, and to a limited extent, in the tactile domain. Common features of perceptual rivalry across various ambiguous visual and auditory paradigms characterize the randomness of switching times and their dependence on input strength manipulations (Levelt's propositions). It is still unclear whether the general characteristics of perceptual rivalry are preserved with tactile stimuli. This study aims to introduce a simple tactile stimulus capable of generating perceptual rivalry and explores whether general features of perceptual rivalry from other modalities extend to the tactile domain. Our results confirm that Levelt's proposition II extends to tactile bistability, and that the stochastic characteristics of irregular perceptual alternations agree with non-tactile modalities. An analysis of correlations between subsequent perceptual phases reveals a significant positive correlation at lag 1 (as found in visual bistability), and a negative correlation for lag 2 (in contrast with visual bistability)., (© 2021. Crown.)

Identifying structural measures that capture early brain development and are sensitive to individual differences in behavior is a priority in developmental neuroscience, with potential implications for our understanding of both typical and atypical populations. T1-weighted/T2-weighted (T1w/T2w) ratio mapping, which previously has been linked to myelination, represents an interesting candidate measure in this respect, as an accessible measure from standard magnetic resonance imaging (MRI) sequences. Yet, its value as an early infancy measure remains largely unexplored. Here, we compared T1w/T2w ratio in 5-month-old infants at familial risk (n = 27) for autism spectrum disorder (ASD) to those without elevated autism risk (n = 16). We found lower T1w/T2w ratio in infants at high risk for ASD within widely distributed regions, spanning both white and gray matter. In regions differing between groups, higher T1w/T2w ratio was robustly associated with higher age at scan (range: ~ 4-6.5 months), implying sensitivity to maturation at short developmental timescales. Further, higher T1w/T2w ratio within these regions was associated with higher scores on measures of concurrent developmental level. These findings suggest that T1w/T2w ratio is a developmentally sensitive measure that should be explored further in future studies of both typical and atypical infant populations., (© The Author(s) 2021. Published by Oxford University Press.)

Research indicates that individuals with autism spectrum disorder (ASD) are superior at local processing while the integration of local features to global percepts is reduced. Here, we compared infants at familiar risk for ASD to typically developing infants in terms of global coherence processing at 5 months of age, using steady state visually evoked potentials (SSVEP). We found a different topographical organization for global form and motion processing in infants at risk (n = 50) than in controls (n = 23). In contrast, activation patterns for local visual change were strikingly similar between groups. Although preliminary, the results represent the first neurophysiological evidence supporting the view that basic atypicalities in perception may play a role in the developmental pathways leading to ASD.

Premature ovarian insufficiency (POI) is a clinically and etiologically heterogeneous disorder characterized by menstrual irregularities and elevated levels of FSH before age of 40 years. Genetic anomalies are among the recognized causes of POI. Here, we aimed to identify the genetic cause of POI in an inbred pedigree with nine POI and two ichthyosis-affected members. Inheritance of POI and ichthyosis were, respectively, dominant and recessive. Reproduction-related information and measurements of relevant hormones were obtained. Genetic studies included homozygosity mapping, linkage analysis, exome sequencing, and screening of candidate variants. A mutation within ALOX12B, which is a known ichthyosis causing gene, was identified as cause of ichthyosis. ALOX12B encodes a protein involved in steroidogenesis and lipid metabolism. Considering the importance of steroidogenesis in reproduction functions, the possibility that the ALOX12B mutation is also cause of POI was considered. Screenings showed that the mutation segregated with POI status. Linkage analysis with respect to POI identified a single strongly linked locus (LOD > 3) that includes ALOX12B. Exome sequencing on POI-affected females identified the mutation in ALOX12B and also a sequence variation in SPNS2 within the linked locus. A possible contribution of the SPNS2 variation to POI was not strictly ruled out, but various data presented in the text including reported association of variations in related gene ALOX12 with menopause-age and role of ALOX12B in atretic bovine follicle formation argue in favor of ALOX12B. It is, therefore, concluded that the mutation in ALOX12B is the likely cause of POI in the pedigree.

Binocular rivalry occurs when the two eyes are presented with incompatible stimuli and perception alternates between these two stimuli. This phenomenon has been investigated in two types of experiments: (1) Traditional experiments where the stimulus is fixed, (2) eye-swap experiments in which the stimulus periodically swaps between eyes many times per second (Logothetis et al. in Nature 380(6575):621-624, 1996). In spite of the rapid swapping between eyes, perception can be stable for many seconds with specific stimulus parameter configurations. Wilson introduced a two-stage, hierarchical model to explain both types of experiments (Wilson in Proc. Natl. Acad. Sci. 100(24):14499-14503, 2003). Wilson's model and other rivalry models have been only studied with bifurcation analysis for fixed inputs and different types of dynamical behavior that can occur with periodically forcing inputs have not been investigated. Here we report (1) a more complete description of the complex dynamics in the unforced Wilson model, (2) a bifurcation analysis with periodic forcing. Previously, bifurcation analysis of the Wilson model with fixed inputs has revealed three main types of dynamical behaviors: Winner-takes-all (WTA), Rivalry oscillations (RIV), Simultaneous activity (SIM). Our results have revealed richer dynamics including mixed-mode oscillations (MMOs) and a period-doubling cascade, which corresponds to low-amplitude WTA (LAWTA) oscillations. On the other hand, studying rivalry models with numerical continuation shows that periodic forcing with high frequency (e.g. 18 Hz, known as flicker) modulates the three main types of behaviors that occur with fixed inputs with forcing frequency (WTA-Mod, RIV-Mod, SIM-Mod). However, dynamical behavior will be different with low frequency periodic forcing (around 1.5 Hz, so-called swap). In addition to WTA-Mod and SIM-Mod, cycle skipping, multi-cycle skipping and chaotic dynamics are found. This research provides a framework for either assessing binocular rivalry models to check consistency with empirical results, or for better understanding neural dynamics and mechanisms necessary to implement a minimal binocular rivalry model.

The striatum has long been associated with cognitive functions, but the mechanisms behind this are still unclear. Here we tested a new hypothesis that the striatum contributes to executive function (EF) by strengthening cortico-cortical connections. Striatal connectivity was evaluated by measuring the resting-state functional connectivity between ventral and dorsal striatum in 570 individuals, aged 3-20 years. Using structural equation modeling, we found that inter-individual differences in striatal connectivity had an indirect effect (via fronto-parietal functional connectivity) and a direct effect on a compound EF measure of working memory, inhibition, and set-shifting/flexibility. The effect of fronto-parietal connectivity on cognition did not depend on age: the influence was as strong in older as younger children. In contrast, striatal connectivity was closely related to changes in cognitive ability during childhood development, suggesting a specific role of the striatum in cognitive plasticity. These results support a new principle for striatal functioning, according to which striatum promotes cognitive development by strengthening of cortico-cortical connectivity., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose: To report the genetic analysis of an Iranian Bietti crystalline dystrophy (BCD)-affected family, and to review previously reported mutations in the gene and assess the distribution of affected amino acids in the encoded protein., Methods: The eleven exons of CYP4V2 were sequenced in the DNA of the proband of the Iranian BCD family. The putative disease-causing variation was screened in all affected and non-affected members. BCD causing CYP4V2 mutations previously reported in the literature were compiled, and positions of amino acids affected by nonsense and missense mutations were mapped onto the primary structure of the CYP4V2 protein., Results: C.1219G > T in CYP4V2 that causes p.Glu407* was identified as cause of BCD in the Iranian family. The mutation segregated with disease status. Clinical presentations were similar among affected members, except that one patient presented with retinal macular hole. Twelve nonsense and 47 missense mutations in CYP4V2 were compiled. Inspection of distribution of amino acids affected by the mutations suggested non-random distribution and clustering of affected amino acids in nine regions of the protein, including regions that contain the heme binding site, the metal binding site, and a region between these binding sites. The most C-terminus proximal nonsense mutation affected position 482., Conclusions: This study presents results of the genetic analysis of an Iranian BCD family. Protein regions affected by mutations within the nine mutation clusters include regions well conserved among orthologous proteins and human CYP4 proteins, some of which are associated with known functions. The findings may serve to identify reasonable candidate gene region targets for gene editing therapy approaches.

Most cortical areas send projections to the striatum. In some parts of the striatum, the connections converge from several cortical areas. It is unknown whether the convergence and non-convergence zones of the striatum differ functionally. Here, we used diffusion-weighted magnetic resonance imaging and probabilistic fiber tracking to parcellate the striatum based on its connections to dorsolateral prefrontal, parietal and orbitofrontal cortices in two different datasets (children aged 6-7 years and adults). In both samples, quantitative susceptibility mapping (QSM) values were significantly correlated with working memory (WM) in convergence zones, but not in non-convergence zones. In children, this was also true for mean diffusivity, MD. The association of MD to WM specifically in the convergent zone was replicated in the Pediatric Imaging, Neurocognition, and Genetics (PING) dataset for 135 children aged 6-9 years. QSM data was not available in the PING dataset, and the association to QSM still needs to be replicated. These results suggest that connectivity-based segments of the striatum exhibit functionally different characteristics. The association between convergence zones and WM performance might relate to a role in integrating and coordinating activity in different cortical areas., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G > A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0.8) with that of the previously suggested DD susceptibility genes KIAA0319, CTNND2, CNTNAP2 and GRIN2B. We investigated the association of common variation in NCAN to brain structures in two data sets: young adults (Brainchild study, Sweden) and infants (FinnBrain study, Finland). In young adults, we found associations between a common genetic variant in NCAN, rs1064395, and white matter volume in the left and right temporoparietal as well as the left inferior frontal brain regions. In infants, this same variant was found to be associated with cingulate and prefrontal grey matter volumes. Our results suggest NCAN as a new candidate gene for DD and indicate that NCAN variants affect brain structure.

The axon guidance receptor, Robo1, controls the pathfinding of callosal axons in mice. To determine whether the orthologous ROBO1 gene is involved in callosal development also in humans, we studied polymorphisms in the ROBO1 gene and variation in the white matter structure in the corpus callosum using both structural magnetic resonance imaging and diffusion tensor magnetic resonance imaging. We found that five polymorphisms in the regulatory region of ROBO1 were associated with white matter density in the posterior part of the corpus callosum pathways. One of the polymorphisms, rs7631357, was also significantly associated with the probability of connections to the parietal cortical regions. Our results demonstrate that human ROBO1 may be involved in the regulation of the structure and connectivity of posterior part of corpus callosum.

Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique in which the magnetic susceptibility characteristic of molecular and cellular components, including iron and myelin, is quantified. Rapid iron accumulation in subcortical nuclei and myelination of the white matter tracts are two important developmental processes that contribute to cognitive functions. Both also contribute to the magnetic susceptibility of the brain tissues. Here, we used the QSM as indirect measures of iron in subcortical nuclei and myelin in caudo-frontal white matter pathways. We included two groups of participants; 21 children aged 6-7years and 25 adults aged 21-40years. All subjects also performed tests estimating their visuo-spatial working memory capacity. Adults had higher magnetic susceptibility in all subcortical nuclei, compared to children. The magnetic susceptibility of these nuclei highly correlated with their previously reported iron content. Moreover, working memory performance correlated significantly with the magnetic susceptibility in caudate nucleus in both children and adults, while the correlation was not significant for gray matter density. QSM of white matter in the caudo-frontal tract also differed between children and adults, but did not correlate with working memory scores. These results indicate that QSM is a feasible technique to measure developmental aspects of changes in the striatum, possibly related to iron content that is relevant to cognition., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Developmental dyslexia is the most common learning disorder in children. Problems in reading and writing are likely due to a complex interaction of genetic and environmental factors, resulting in reduced power of studies of the genetic factors underlying developmental dyslexia. Our approach in the current study was to perform exome sequencing of affected and unaffected individuals within an extended pedigree with a familial form of developmental dyslexia. We identified a two-base mutation, causing a p.R229L amino acid substitution in the centrosomal protein 63 kDa (CEP63), co-segregating with developmental dyslexia in this pedigree. This mutation is novel, and predicted to be highly damaging for the function of the protein. 3D modelling suggested a distinct conformational change caused by the mutation. CEP63 is localised to the centrosome in eukaryotic cells and is required for maintaining normal centriole duplication and control of cell cycle progression. We found that a common polymorphism in the CEP63 gene had a significant association with brain white matter volume. The brain regions were partly overlapping with the previously reported region influenced by polymorphisms in the dyslexia susceptibility genes DYX1C1 and KIAA0319. We hypothesise that CEP63 is particularly important for brain development and might control the proliferation and migration of cells when those two events need to be highly coordinated.

The increase in working memory (WM) capacity is an important part of cognitive development during childhood and adolescence. Cross-sectional analyses have associated this development with higher activity, thinner cortex, and white matter maturation in fronto-parietal networks. However, there is still a lack of longitudinal data showing the dynamics of this development and the role of subcortical structures. We included 89 individuals, aged 6-25 years, who were scanned 1-3 times at 2-year intervals. Functional magnetic resonance imaging (fMRI) was used to identify activated areas in superior frontal, intraparietal cortices, and caudate nucleus during performance on a visuo-spatial WM task. Probabilistic tractography determined the anatomical pathways between these regions. In the cross-sectional analysis, WM capacity correlated with activity in frontal and parietal regions, cortical thickness in parietal cortex, and white matter structure [both fractional anisotropy (FA) and white matter volume] of fronto-parietal and fronto-striatal tracts. However, in the longitudinal analysis, FA in white matter tracts and activity in caudate predicted future WM capacity. The results show a dynamic of neural networks underlying WM development in which cortical activity and structure relate to current capacity, while white matter tracts and caudate activity predict future WM capacity., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Cytogenetically visible chromosomal translocations are highly informative as they can pinpoint strong effect genes even in complex genetic disorders., Methods and Results: Here, we report a mother and daughter, both with borderline intelligence and learning problems within the dyslexia spectrum, and two apparently balanced reciprocal translocations: t(1;8)(p22;q24) and t(5;18)(p15;q11). By low coverage mate-pair whole-genome sequencing, we were able to pinpoint the genomic breakpoints to 2 kb intervals. By direct sequencing, we then located the chromosome 5p breakpoint to intron 9 of CTNND2. An additional case with a 163 kb microdeletion exclusively involving CTNND2 was identified with genome-wide array comparative genomic hybridisation. This microdeletion at 5p15.2 is also present in mosaic state in the patient's mother but absent from the healthy siblings. We then investigated the effect of CTNND2 polymorphisms on normal variability and identified a polymorphism (rs2561622) with significant effect on phonological ability and white matter volume in the left frontal lobe, close to cortical regions previously associated with phonological processing. Finally, given the potential role of CTNND2 in neuron motility, we used morpholino knockdown in zebrafish embryos to assess its effects on neuronal migration in vivo. Analysis of the zebrafish forebrain revealed a subpopulation of neurons misplaced between the diencephalon and telencephalon., Conclusions: Taken together, our human genetic and in vivo data suggest that defective migration of subpopulations of neuronal cells due to haploinsufficiency of CTNND2 contribute to the cognitive dysfunction in our patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Practicing a musical instrument is associated with cognitive benefits and structural brain changes in correlational and interventional trials; however, the effect of musical training on cognition during childhood is still unclear. In this longitudinal study of child development we analyzed the association between musical practice and performance on reasoning, processing speed and working memory (WM) during development. Subjects (n = 352) between the ages of 6 and 25 years participated in neuropsychological assessments and neuroimaging investigations (n = 64) on two or three occasions, 2 years apart. Mixed model regression showed that musical practice had an overall positive association with WM capacity (visuo-spatial WM, F = 4.59, p = 0.033, verbal WM, F = 9.69, p = 0.002), processing speed, (F = 4.91, p = 0.027) and reasoning (Raven's progressive matrices, F = 28.34, p < 0.001) across all three time points, after correcting for the effect of parental education and other after school activities. Music players also had larger gray matter volume in the temporo-occipital and insular cortex (p = 0.008), areas previously reported to be related to musical notation reading. The change in WM between the time points was proportional to the weekly hours spent on music practice for both WM tests (VSWM, β = 0.351, p = 0.003, verbal WM, β = 0.261, p = 0.006) but this was not significant for reasoning ability (β = 0.021, p = 0.090). These effects remained when controlling for parental education and other after school activities. In conclusion, these results indicate that music practice positively affects WM development and support the importance of practice for the development of WM during childhood and adolescence.

Functional magnetic resonance imaging (fMRI) is an effective tool for the measurement of brain neuronal activities. To date, several statistical methods have been proposed for analyzing fMRI datasets to select true active voxels among all the voxels appear to be positively activated. Finding a reliable and valid activation map is very important and becomes more crucial in clinical and neurosurgical investigations of single fMRI data, especially when pre-surgical planning requires accurate lateralization index as well as a precise localization of activation map. Defining a proper threshold to determine true activated regions, using common statistical processes, is a challenging task. This is due to a number of variation sources such as noise, artifacts, and physiological fluctuations in time series of fMRI data which affect spatial distribution of noise in an expected uniform activated region. Spatial smoothing methods are frequently used as a preprocessing step to reduce the effect of noise and artifacts. The smoothing may lead to a shift and enlargement of activation regions, and in some extend, unification of distinct regions. In this article, we propose a bootstrap resampling technique for analyzing single fMRI dataset with the aim of finding more accurate and reliable activated regions. This method can remove false positive voxels and present high localization accuracy in activation map without any spatial smoothing and statistical threshold setting., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Volume and integrity of white matter correlate with reading ability, but the underlying factors contributing to this variability are unknown., Methods: We investigated single nucleotide polymorphisms in three genes previously associated with dyslexia and implicated in neuronal migration (DYX1C1, DCDC2, KIAA0319) and white matter volume in a cohort of 76 children and young adults from the general population., Results: We found that all three genes contained polymorphisms that were significantly associated with white matter volume in the left temporo-parietal region and that white matter volume influenced reading ability., Conclusions: The identified region contained white matter pathways connecting the middle temporal gyrus with the inferior parietal lobe. The finding links previous neuroimaging and genetic results and proposes a mechanism underlying variability in reading ability in both normal and impaired readers., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.

Functional magnetic resonance imaging (fMRI) is an effective method for measuring the brain neuronal activities. Numerous statistical methods are used for fMRI analyzing. However, determining the true activated regions among the whole apparent activated voxels is a vital but challenging task. The activation pattern of fMRI data analysis is affected under the presence of source of variations such as noise, artifacts, and physiological fluctuations. Finding an accurate and reliable activation map from a single data analysis is essential for true interpretation of an individual data especially when it should be used in neurosurgical planning. We introduced a resampling process (called Bootstrapping) through the original EPI data, with the aim of evaluating the reproducibility of the activation changes throughout a task-related signal variation.