Electrophysiological signatures of spelling sensitivity development from primary school age to adulthood.

Recognizing spelling errors is important for correct writing and reading, and develops over an extended period. The neural bases of the development of orthographic sensitivity remain poorly understood. We investigated event-related potentials (ERPs) associated with spelling error recognition when performing the orthographic decision task with correctly spelled and misspelled words in children aged 8-10 years old, early adolescents aged 11-14 years old, and adults. Spelling processing in adults included an early stage associated with the initial recognition of conflict between orthography and phonology (reflected in the N400 time window) and a later stage (reflected in the P600 time window) related to re-checking the spelling. In children 8-10 years old, there were no differences in ERPs to correct and misspelled words; in addition, their behavioral scores were worse than those of early adolescents, implying that the ability to quickly recognize the correct spelling is just beginning to develop at this age. In early adolescents, spelling recognition was reflected only at the later stage, corresponding to the P600 component. At the behavioral level, they were worse than adults at recognizing misspelled words. Our data suggest that orthographic sensitivity can develop beyond 14 years.

Effect of presentation rate on auditory processing in Rett syndrome: event-related potential study.

BACKGROUND: Rett syndrome (RS) is a rare neurodevelopmental disorder characterized by mutations in the MECP2 gene. Patients with RS have severe motor abnormalities and are often unable to walk, use hands and speak. The preservation of perceptual and cognitive functions is hard to assess, while clinicians and care-givers point out that these patients need more time to process information than typically developing peers. Neurophysiological correlates of auditory processing have been also found to be distorted in RS, but sound presentation rates were relatively quick in these studies (stimulus onset asynchrony, SOA < 1000 ms). As auditory event-related potential (ERP) is typically increased with prolongation of SOA we aim to study if SOA prolongation might compensate for observed abnormalities. METHODS: We presented a repetitive stimulus (1000 Hz) at three different SOAs of 900 ms, 1800 ms, and 3600 ms in children with RS (N = 24, Mean age = 9.0 ± 3.1) and their typical development (TD) peers (N = 27, Mean age = 9.7 ± 3.4) while recording 28-channels electroencephalogram, EEG. Some RS participants (n = 10) did not show clear ERP and were excluded from the analysis. RESULTS: Major ERP components (here assessed as N1P1 and P2N1 peak-to-peak values) were smaller at SOA 900 than at longer SOAs in both groups, pointing out that the basic mechanism of adaptation in the auditory system is preserved in at least in RS patients with evident ERPs. At the same time the latencies of these components were significantly delayed in the RS than in TD. Moreover, late components (P2N1 and N2P2) were drastically reduced in Rett syndrome irrespective of the SOA, suggesting a largely affected mechanism of integration of upcoming sensory input with memory. Moreover, developmental stagnation of auditory ERP characterized patients with RS: absence of typical P2N1 enlargement and P1 and N1 shortening with age at least for shortest SOA. LIMITATIONS: We could not figure out the cause for the high percentage of no-evident ERP RS participants and our final sample of the RS group was rather small. Also, our study did not include a control clinical group. CONCLUSIONS: Thus, auditory ERPs inform us about abnormalities within auditory processing that cannot be fully overcomed by slowing presentation rate.

Opposite effects of rapid auditory stimulation on tetanized and non-tetanized tone of adjacent frequency: Mismatch negativity study.

Our study describes the effects of sensory tetanization on neurophysiological and behavioral measures in humans linking cellular studies of long-term potentiation with high-level brain processes. Rapid (every 75ms) presentation of pure tone (1020 Hz, 50ms) for 2 minutes was preceded and followed by oddball blocks that contained the same stimulus presented as deviant (probability of 5-10%) interspersed with standard (80-90%) and deviant tones (5-10%) of adjacent frequencies (1000 and 980Hz, respectively). Mismatch negativity (MMN) component in response to tetanized tone (1020Hz), while being similar to MMN for non-tetanized tone before tetanization, became larger than that after tetanization, pointing to the increase in cortical differentiation of these tones. However, this differentiation was partially due to the MMN decrease after tetanization for tones adjacent to tetanized frequency, suggesting the influence of lateral inhibition to this effect. Although MMN correlated with tone discriminability in a psychophysical task, the behavioral improvement after tetanization was not statistically detectable. To conclude, short-term auditory tetanization affects cortical representation of tones that are not limited to the tetanized stimuli.

An inclusive paradigm to study mu-rhythm properties.

Studying mu-rhythm in developmental disorders is crucial for identifying the origin of motor and social malfunctioning. However, the commonly used mu-rhythm experimental protocol, that requires following instructions, is challenging for children with motor and cognitive deficits. Here we present an inclusive experimental procedure that contains passive hand movement, closed and open eyes and hand movement observation and examine properties of EEG mu-rhythm obtained in this paradigm in 51 typically developing children and adults aged from 4 to 31 years. The independent component analysis (ICA) was used to separate occipital alpha- and mu-rhythm components and showed better performance than the channel-wise analysis. The identified mu-rhythm ICA components were localized above the left and right sensorimotor cortex, demonstrating suppression both to passive hand movement and hand movement observation and no difference in power between closed- and open-eye conditions. No interhemispheric differences were observed. The alpha-rhythm ICA components were localized in occipital regions and demonstrate characteristic suppression to open-eye conditions. The mu-rhythm frequency of peak suppression to passive hand movement as well as the amount of suppression increased with age. The beta-band mu-rhythm activity, while being less pronounced, was also suppressed both during passive hand movement and hand movement observation, while to a lesser degree than alpha-band mu during passive hand movement. Thus, we confirmed the classical properties of mu-rhythm and for the first time showed the developmental trajectory of mu-rhythm properties obtained during passive hand movement. The proposed experimental protocol and pipeline can be used further in studies of the mu-rhythm in challenging populations.

Electrophysiological and Behavioral Evidence for Hyper- and Hyposensitivity in Rare Genetic Syndromes Associated with Autism.

Our study reviewed abnormalities in spontaneous, as well as event-related, brain activity in syndromes with a known genetic underpinning that are associated with autistic symptomatology. Based on behavioral and neurophysiological evidence, we tentatively subdivided the syndromes on primarily hyper-sensitive (Fragile X, Angelman) and hypo-sensitive (Phelan-McDermid, Rett, Tuberous Sclerosis, Neurofibromatosis 1), pointing to the way of segregation of heterogeneous idiopathic ASD, that includes both hyper-sensitive and hypo-sensitive individuals. This segmentation links abnormalities in different genes, such as FMR1, UBE3A, GABRB3, GABRA5, GABRG3, SHANK3, MECP2, TSC1, TSC2, and NF1, that are causative to the above-mentioned syndromes and associated with synaptic transmission and cell growth, as well as with translational and transcriptional regulation and with sensory sensitivity. Excitation/inhibition imbalance related to GABAergic signaling, and the interplay of tonic and phasic inhibition in different brain regions might underlie this relationship. However, more research is needed. As most genetic syndromes are very rare, future investigations in this field will benefit from multi-site collaboration with a common protocol for electrophysiological and event-related potential (EEG/ERP) research that should include an investigation into all modalities and stages of sensory processing, as well as potential biomarkers of GABAergic signaling (such as 40-Hz ASSR).

Generalization of sustained neurophysiological effects of short-term auditory 13-Hz stimulation to neighbouring frequency representation in humans.

A fuller understanding of the effects of auditory tetanization in humans would inform better language and sensory learning paradigms; however, there are still unanswered questions. Here, we probe sustained changes in the event-related potentials (ERPs) to 1020- and 980-Hz tones following a rapid presentation of 1020-Hz tone (every 75 ms, 13.3 Hz, tetanization). Consistent with some previous studies, we revealed the increase in the P2 ERP component after tetanization. Contrary to some other studies, we did not observe the expected N1 increase after tetanization even in the identical experimental sequence. We detected a significant N1 decrease after tetanization. Expanding previous research, we showed that P2 increase and N1 decrease are not specific to the stimulus type (tetanized 1020 Hz and non-tetanized 980 Hz), suggesting the generalizability of tetanization effect to the not-stimulated auditory tones, at least to those of the neighbouring frequency. The ERPs' tetanization effects were observed for at least 30 min-the most prolonged interval examined, consistent with the duration of long-term potentiation, LTP. In addition, the tetanization effects were detectable in the blocks where the participants watched muted videos, an experimental setting that can be easily used in children and other challenging groups. Thus, auditory 13-Hz stimulation affects brain processing of tones including those of neighbouring frequencies.

The ages of zone of proximal development for retrospective time assessment and anticipation of time event.

From childhood to adulthood, an individual's ability to estimate and anticipate the timing of events changes continuously. This study investigated the ability of 287 children aged 5-14 years to estimate the duration of prior events and anticipate the timing of future events for determination of the age at which children improve their timing skills. The Luria neuropsychological assessment battery and the Wechsler Intelligence Scale for Children (WISC-IV) were applied to find correlations between timing skills and the development of cognitive functions. The findings demonstrated that retrospective estimation of duration has a zone of proximal development in children between the ages of six to eight; in these children, the accuracy of time assessment significantly improved after receiving the prompt. However, improvement in time estimation was significantly lower in those children who achieved lower results in the attention and memory tests and demonstrated reduced spatial and verbal reasoning skills. The zone of proximal development for the ability to anticipate the timing of future events was demonstrated in children between the ages of nine to eleven years. The improvement of time anticipation was negatively correlated with the number of mistakes made during the dynamic praxis test.

A Toolbox and Crowdsourcing Platform for Automatic Labeling of Independent Components in Electroencephalography.

Independent Component Analysis (ICA) is a conventional approach to exclude non-brain signals such as eye movements and muscle artifacts from electroencephalography (EEG). A rejection of independent components (ICs) is usually performed in semiautomatic mode and requires experts' involvement. As also revealed by our study, experts' opinions about the nature of a component often disagree, highlighting the need to develop a robust and sustainable automatic system for EEG ICs classification. The current article presents a toolbox and crowdsourcing platform for Automatic Labeling of Independent Components in Electroencephalography (ALICE) available via link http://alice.adase.org/. The ALICE toolbox aims to build a sustainable algorithm to remove artifacts and find specific patterns in EEG signals using ICA decomposition based on accumulated experts' knowledge. The difference from previous toolboxes is that the ALICE project will accumulate different benchmarks based on crowdsourced visual labeling of ICs collected from publicly available and in-house EEG recordings. The choice of labeling is based on the estimation of IC time-series, IC amplitude topography, and spectral power distribution. The platform allows supervised machine learning (ML) model training and re-training on available data subsamples for better performance in specific tasks (i.e., movement artifact detection in healthy or autistic children). Also, current research implements the novel strategy for consentient labeling of ICs by several experts. The provided baseline model could detect noisy IC and components related to the functional brain oscillations such as alpha and mu rhythm. The ALICE project implies the creation and constant replenishment of the IC database, which will improve ML algorithms for automatic labeling and extraction of non-brain signals from EEG. The toolbox and current dataset are open-source and freely available to the researcher community.

40-Hz Auditory Steady-State Response (ASSR) as a Biomarker of Genetic Defects in the SHANK3 Gene: A Case Report of 15-Year-Old Girl with a Rare Partial SHANK3 Duplication.

SHANK3 encodes a scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+ inhibitory neurons-the key players in the generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response (ASSR). However, 40-Hz ASSR was not studied in relation to SHANK3 functioning. Here, we present a 15-year-old girl (SH01) with previously unreported duplication of the first seven exons of the SHANK3 gene (22q13.33). SH01's electroencephalogram (EEG) during 40-Hz click trains of 500 ms duration binaurally presented with inter-trial intervals of 500-800 ms were compared with those from typically developing children (n = 32). SH01 was diagnosed with mild mental retardation and learning disabilities (F70.88), dysgraphia, dyslexia, and smaller vocabulary than typically developing (TD) peers. Her clinical phenotype resembled the phenotype of previously described patients with 22q13.33 microduplications (≈30 reported so far). SH01 had mild autistic symptoms but below the threshold for ASD diagnosis and microcephaly. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential (ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD's ASSR. The absence of 40-Hz ASSR in patients with microduplication, which affected the SHANK3 gene, indicates deficient temporal resolution of the auditory system, which might underlie language problems and represent a neurophysiological biomarker of SHANK3 abnormalities.