Evidence for the late MMN as a neurophysiological endophenotype for dyslexia.

Dyslexia affects 5-10% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore "unaffected" despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/-/ba/contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300-700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia

Reproducibility of Brain Responses: High for Speech Perception, Low for Reading Difficulties

Neuroscience findings have recently received critique on the lack of replications. To examine the reproducibility of brain indices of speech sound discrimination and their role in dyslexia, a specific reading difficulty, brain event-related potentials using EEG were measured using the same cross-linguistic passive oddball paradigm in about 200 dyslexics and 200 typically reading 8-12-year-old children from four countries with different native languages. Brain responses indexing speech and non-speech sound discrimination were extremely reproducible, supporting the validity and reliability of cognitive neuroscience methods. Significant differences between typical and dyslexic readers were found when examined separately in different country and language samples. However, reading group differences occurred at different time windows and for different stimulus types between the four countries. This finding draws attention to the limited generalizability of atypical brain response findings in children with dyslexia across language environments and raises questions about a common neurobiological factor for dyslexia. Our results thus show the robustness of neuroscience methods in general while highlighting the need for multi-sample studies in the brain research of language disorders

Language and reading impairments are associated with increased prevalence of non-right handedness

Funding: Royal Society - UF150663, RGF\EA\180141; Wellcome Trust - 217065/Z/19/Z; H2020 European Research Council - 694189; NWO - 451-15-017; National Health and Medical Research Council - 1173896; Canadian Institute for Health Research - MOP-133440.Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6–19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06–1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.Publisher PDFPeer reviewe

Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways

Profilins are prominent regulators of actin dynamics. While most mammalian cells express only one profilin, two isoforms, PFN1 and PFN2a are present in the CNS. To challenge the hypothesis that the expression of two profilin isoforms is linked to the complex shape of neurons and to the activity-dependent structural plasticity, we analysed how PFN1 and PFN2a respond to changes of neuronal activity. Simultaneous labelling of rodent embryonic neurons with isoform-specific monoclonal antibodies revealed both isoforms in the same synapse. Immunoelectron microscopy on brain sections demonstrated both profilins in synapses of the mature rodent cortex, hippocampus and cerebellum. Both isoforms were significantly more abundant in postsynaptic than in presynaptic structures. Immunofluorescence showed PFN2a associated with gephyrin clusters of the postsynaptic active zone in inhibitory synapses of embryonic neurons. When cultures were stimulated in order to change their activity level, active synapses that were identified by the uptake of synaptotagmin antibodies, displayed significantly higher amounts of both isoforms than non-stimulated controls. Specific inhibition of NMDA receptors by the antagonist APV in cultured rat hippocampal neurons resulted in a decrease of PFN2a but left PFN1 unaffected. Stimulation by the brain derived neurotrophic factor (BDNF), on the other hand, led to a significant increase in both synaptic PFN1 and PFN2a. Analogous results were obtained for neuronal nuclei: both isoforms were localized in the same nucleus, and their levels rose significantly in response to KCl stimulation, whereas BDNF caused here a higher increase in PFN1 than in PFN2a. Our results strongly support the notion of an isoform specific role for profilins as regulators of actin dynamics in different signalling pathways, in excitatory as well as in inhibitory synapses. Furthermore, they suggest a functional role for both profilins in neuronal nuclei

Language and reading impairments are associated with increased prevalence of non‐right‐handedness

Handedness has been studied for association with language‐related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non‐right‐handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex‐matched controls identified from 10 distinct cohorts (age range 6–19 years old; European ethnicity) using a priori set criteria. A meta‐analysis (Ncases = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06–1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions

Specific learning disorder: prevalence and gender differences.

Comprehensive models of learning disorders have to consider both isolated learning disorders that affect one learning domain only, as well as comorbidity between learning disorders. However, empirical evidence on comorbidity rates including all three learning disorders as defined by DSM-5 (deficits in reading, writing, and mathematics) is scarce. The current study assessed prevalence rates and gender ratios for isolated as well as comorbid learning disorders in a representative sample of 1633 German speaking children in 3rd and 4th Grade. Prevalence rates were analysed for isolated as well as combined learning disorders and for different deficit criteria, including a criterion for normal performance. Comorbid learning disorders occurred as frequently as isolated learning disorders, even when stricter cutoff criteria were applied. The relative proportion of isolated and combined disorders did not change when including a criterion for normal performance. Reading and spelling deficits differed with respect to their association with arithmetic problems: Deficits in arithmetic co-occurred more often with deficits in spelling than with deficits in reading. In addition, comorbidity rates for arithmetic and reading decreased when applying stricter deficit criteria, but stayed high for arithmetic and spelling irrespective of the chosen deficit criterion. These findings suggest that the processes underlying the relationship between arithmetic and reading might differ from those underlying the relationship between arithmetic and spelling. With respect to gender ratios, more boys than girls showed spelling deficits, while more girls were impaired in arithmetic. No gender differences were observed for isolated reading problems and for the combination of all three learning disorders. Implications of these findings for assessment and intervention of learning disorders are discussed

Expected and observed number of comorbid cases for the three cutoff criteria.

<p>Expected and observed number of comorbid cases for the three cutoff criteria.</p

Prevalence rates (N = 1633) for specific learning disorders: isolated and combined deficits in reading, spelling, and arithmetic skills.

<p><i>Note:</i> sd = standard deviation; CI = confidence interval; RD = Reading Deficit; SD = Spelling Deficit; AD = Arithmetic Deficit; RSD/SRD = Reading and spelling Deficit; RAD/ARD = Reading and arithmetic Deficit; SAD/ASD = Spelling and Arithmetic Deficit; RSAD/SRAD/ARSD = Reading, spelling and arithmetic Deficit.</p

Prevalence rates (N = 1633) for specific learning disorders including cutoff for normal performance.

<p><i>Note:</i> Between = children who fulfill deficit criteria for the relevant domain (RD, SD or AD), but score between the deficit criterion and the criterion for normal performance on at least one other measure.</p