Left hemispheric deficit in the sustained neuromagnetic response to periodic click trains in children with ASD.

BACKGROUND: Deficits in perception and production of vocal pitch are often observed in people with autism spectrum disorder (ASD), but the neural basis of these deficits is unknown. In magnetoencephalogram (MEG), spectrally complex periodic sounds trigger two continuous neural responses-the auditory steady state response (ASSR) and the sustained field (SF). It has been shown that the SF in neurotypical individuals is associated with low-level analysis of pitch in the 'pitch processing center' of the Heschl's gyrus. Therefore, alternations in this auditory response may reflect atypical processing of vocal pitch. The SF, however, has never been studied in people with ASD. METHODS: We used MEG and individual brain models to investigate the ASSR and SF evoked by monaural 40 Hz click trains in boys with ASD (N = 35) and neurotypical (NT) boys (N = 35) aged 7-12-years. RESULTS: In agreement with the previous research in adults, the cortical sources of the SF in children were located in the left and right Heschl's gyri, anterolateral to those of the ASSR. In both groups, the SF and ASSR dominated in the right hemisphere and were higher in the hemisphere contralateral to the stimulated ear. The ASSR increased with age in both NT and ASD children and did not differ between the groups. The SF amplitude did not significantly change between the ages of 7 and 12 years. It was moderately attenuated in both hemispheres and was markedly delayed and displaced in the left hemisphere in boys with ASD. The SF delay in participants with ASD was present irrespective of their intelligence level and severity of autism symptoms. LIMITATIONS: We did not test the language abilities of our participants. Therefore, the link between SF and processing of vocal pitch in children with ASD remains speculative. CONCLUSION: Children with ASD demonstrate atypical processing of spectrally complex periodic sound at the level of the core auditory cortex of the left-hemisphere. The observed neural deficit may contribute to speech perception difficulties experienced by children with ASD, including their poor perception and production of linguistic prosody.

[Lateralized brain language semantic network demonstrated by word repetition suppression effect in MEG].

We studied auditory word repetition suppression effect using magnetoencephalography while subjects listened to "new" and "old" words whose familiarity they had to judge upon presentation. The lateralization of brain magnetic activity during processing of "new" and "old" words were estimated by computing RMS measure of whole-brain magnetic response within time window of semantic N400 (350-450 ms). A magnetic N400 was significantly stronger in the left than in the right hemisphere for the "new" words only. Repetition of "new" words led to sharp decrease of N400 response RMS in the left hemisphere but did not change right-hemispheric N400 RMS. The asymmetry index of this repetition suppression effect was lateralized to the left hemisphere for the majority of the participants and its magnitude was related to memory task performance. The findings point to a strong left-hemispheric dominance of word repetition suppression effect within the brain semantic networks at the level of whole-network response.

[Functional dissociation of parts of the "sensorimotor complex" in the human cortex with the method of magnetoencephalography].

A method of non-invasive human primary motor cortex mapping has been developed. In 18 healthy right-handed subjects magnetic brain responses caused by repeated voluntary left or right index finger movements were studied. Movement onsets were derived from the accelerometer signal. Recordings of magnetic activity throughout whole experimental sessions in all subjects were concatenated into a single sequence, which was separated into independent components using independent component analysis and ranked according to the amount of mutual information with the modified accelerometer signal. Independent components that demonstrated maximum relation to the finger movement were averaged relative to the movement onset. The results of the distributed brain source modeling of the two independent components that manifested maximum amount of mutual information has demonstrated that their sources localize in the cortical areas corresponding to anatomical markers of hand representation in the primary motor and the primary sensory cortices contralateral to the movement. The method developed has demonstrated the fundamental possibility of localizing the M1 area in healthy subjects.

[Magnetoencephalography in the presurgical evaluation of patients with drug-resistant epilepsy].

Magnetoencephalography (MEG) in combination with structural MRI (magnetic source imaging, MSI) plays an increasingly important role as one of the tools for presurgical evaluation of medically intractable focal epilepsy. The aim of the study was to compare the MSI and commonly used video EEG monitoring method (vEEG) in their sensitivity to interictal epileptic discharges (IED) in 22 patients with drug resistant epilepsy. Furthermore, the detection and localization results obtained by both methods were verified using the data of electrocorticography (ECoG) and postsurgical outcome in 13 patients who underwent invasive EEG monitoring and surgery. The results showed that MSI was superior to vEEC in terms of sensitivity to IED with difference in sensitivity of 22%. The data also suggested that MSI superiority to vEEG in detecting epileptic discharges might, at least partly, arise from better MEG responsiveness to epileptic events coming from the medial, opercular and basal aspects of cortical lobes. MSI localization estimates were in the same cortical lobe and at the same lobar aspects as the epileptic foci detected by ECoG in all patients. Thus, magnetic source imaging can provide critical localization information that is not available when other noninvasive methods, such as vEEG and MRI, are used.

[Localization of cortical motor areas in humans by magnetoencephalography].

Movement-related MEG activity initiated by voluntary unilateral index finger movement was studied in 16 normal volunteers. Evoked motor field response was obtained by averaging with respect to movement onset detected by the actogram. Group averaging of single dipole solutions for the peak of the readiness field (Bereitschaftspotential) revealed activation of the cortical area corresponding to typical motor representation of the hand. Individual data showed strong individual differences in dipole localization, which may be associated with simultaneous activation of sensorimotor cortical areas. Readiness field obtained from each individual was localized either in the pre- or post-central gyrus. Individual differences in the localization may be related to simultaneous activation of the cortical areas incorporated in the sensorimotor complex. The study demonstrates that single dipole modeling may be used for the localization of the sensorimotor complex, but it is insufficient to separate the activity components of this complex.

[Adaptive method for EEG spectrum component decomposition].

A new computerized method for EEG rhythms extraction is proposed as a development of the idea of adjustable boundaries of frequency components that was put forward in previous investigations. Principle component analysis of the correlation matrix of EEG spectra with subsequent rotation of factor solutions was used for decomposition of a spectrum into physically meaningful spectral components. The method was tested on EEG of 14 healthy subjects recorded in 17 functional waking states. Fourteen independent spectral components in the spectral range from 0 to 100 Hz were extracted and their frequency boundaries were consistent with the current knowledge on frequency components of EEG oscillations. Main advantage of the described method is the adjustable estimation of EEG frequency oscillators taking into account characteristic properties of individual EEGs. Possible area of application might be the correct evaluation of spectral power of the EEG rhythms, EEG coherence and other spectral characteristics in clinical and experimental research, studies of the frequency characteristics of the EEG rhythms in different human functional states, changes in frequency characteristics of the EEG rhythms during maturation and in mental pathology.

[Developmental continuity of working memory from infancy to preschool age].

The objective of the paper was to study the developmental continuity of working memory function from infancy to preschool age. At the age of 10 to 11 months 44 participants completed delayed response task (A-not-B) that measures working memory function. Between 5 and 7 years of age the same participants performed three tasks assessing working memory for temporal order in auditory and visual modalities and a control task measuring short-term visuospatial memory. The dependence of temporal-order memory at preschool age on individual level of infant working memory was found for all methods of measurement despite the differences in way of presentation and reproducing of the stimuli order. Results indicate direct continuity in the development of working memory function from infancy to preschool age.

[Phase-locked alpha oscillations evoked by illusory contour perception in normal and autistic preschool boys].

We examined temporal dynamics of EEG phase-locked alpha oscillations during perception of illusory (Kanizsa square) and non-illusory images in boys with autism and age-matched typically developing boys. In typically developing boys the illusory contour (IC) as compared to the control stimulus provoked an increased alpha response at the parietal scalp areas. This IC effect demonstrated continuity within the time window of 133-267 ms after the stimulus onset. Although boys with autism did not display this effect at the group level, part of the sample showed an atypical two-stage pattern of illusory contour effect. The first early stage of IC effect (50-133 ms) was pronounced at the midline occipital electrode localized in the vicinity of the primary visual cortex. The localization and the early onset time suggest that this early IC effect is related to abnormally enhanced "low-level" locally-oriented processes of contour completion in autism. The second stage of IC effect (267-400 ms) was observed at the left parietal region only, and was delayed comparatively to that in healthy boys, suggesting the deficit of "intermediate" processes of perceptual grouping linked to the higher-order visual areas.

The right hemisphere fails to respond to temporal novelty in autism: evidence from an ERP study.

OBJECTIVE: This study aimed to investigate electrophysiological correlates of initial attention orienting to temporally novel sound in children with autism (CWA). METHODS: Twenty-one CWA (4-8 years) and 21 age-matched typically developing children (TDC) were presented with pairs of clicks separated by a 0.5s intra-pair interval, with longer (7-9s) intervals between pairs. Children watched a silent movie during click presentation. We assessed EEG perturbations and event-related potentials (ERP) in response to sounds of different temporal novelty - first (S1) and second (S2) clicks in the pair. RESULTS: In TDC, the early attention-modulated midtemporal N1c wave evoked by S1 and corresponding EEG phase locking and power increase were right-lateralized and were bilaterally higher than those evoked by S2. CWA demonstrated abnormal S1 responses, characterized by reduced N1c amplitude and EEG phase locking in the right midtemporal region, reversed leftward lateralization of the phase locking, and diminished later frontal N2 wave. Their brain responses to S2 were essentially normal. CONCLUSIONS: The impaired right hemispheric processing of temporary and contextually novel information and suboptimal lateralization of normally right-lateralized attention networks may be important features of autistic disorder. SIGNIFICANCE: Results of this study contribute to the understanding of autism neurobiology.

[Alpha oscillations of human brain elicited by illusory contour perception].

We examined the changes in the phase-locked and total alpha oscillations of EEG during perception of illusory (Kanizsa square) and non-illusory images in 16 healthy adults. We applied a wavelet-based time-frequency analysis to compute alpha band power, statistical evaluation was performed using repeated-measures ANOVA and the non-parametric multi-way analysis. Results showed that both stimuli provoked an initial increase of total alpha power emerging not later than in 100 ms after the stimulus onset. The increase was caused by the phase-locked alpha response, and the illusory contour was systematically followed by a higher level of alpha power than the non-illusory one. Further suppression of total alpha power occurred within the time window of 200-500 ms after the stimulus onset and did not depend on the stimulus type. Both stages of the total alpha response were more prominent over the parieto-occipito-temporal scalp areas. We hypothesize that the first stage of alpha response is related to the modulation of the activity of neural circuits participating in processing of a coherent pattern whereas a later suppression of total alpha power links to the orienting processes.

EEG theta rhythm in infants and preschool children.

OBJECTIVE: To study behavioral correlates of theta oscillations in infants and preschool children. METHODS: EEG was recorded during baseline (visual attention) and two test conditions--exploration of toys and attention to 'social' stimulation. Age specific frequency boundaries of theta and mu rhythms were assessed using narrow bin analysis of EEG spectra. RESULTS: Theta spectral power increased whereas mu power decreased under test conditions in both age groups. In preschoolers theta rhythm increased predominantly over anterior regions during exploratory behavior and over posterior regions during attention to social stimulation. Theta frequency range changed with age from 3.6 to 5.6 Hz in infants to 4-8 Hz in children, and mu range from 6.4-8.4 Hz to 8.4-10.4 Hz. CONCLUSIONS: In early life, theta oscillations are strongly related to behavioral states with substantial attentional and emotional load. The scalp distribution of theta spectral power depends on age and behavioral condition and may reflect engagement of different brain networks in control of behavior. SIGNIFICANCE: The findings contribute to the scanty knowledge about the developmental course of theta rhythm. Data on behavioral correlates of theta rhythm in early life may improve our understanding of cognitive and mental processes in healthy and neuropsychiatrically diseased children.

Age-related and individual differences in the performance of a delayed response task (the A-not-B task) in infant twins aged 7-12 months.

The aim of the present work was to analyze the age-related dynamics and nature of interindividual differences in performing the A-not-B task, which addresses working memory in children aged 7-12 months. The cohort consisted of 150 children aged 7-12 months from mono- and dizygotic twin pairs. Working memory was assessed in terms of the maximum delay which the children could tolerate in a delayed response test (the A-not-B task). Performance of the task improved with age, such that a sharp change in the ability to tolerate the delay occurred between nine and ten months of age. Mental development as assessed using the Bayley scale showed a significant correlation with the duration of the delay in the task only after a threshold period (9-10 months of age) in the development of working memory. Analysis of intrapair correlations in mono- and dizygotic twins showed that interindividual differences in the A-not-B task delay at age 7-9 months were completely determined by individual environmental factors (including measurement errors), while at age 10-12 months the leading role in the interindividual variability in this measure was taken by the systematic environment. These results show that the abilities to tolerate delays at the beginning and end of the second six months of life are based on different mechanisms.

[Developmental and individual differences in delayed response task performance (A-not-B task) in 7- to 12-month-old infant twins]. / Vozrastnye i individual'nye razlichiia v vypolnenii zadachi na otstrochennyi otvet (proba A-not-B) u detei bliznetsov 7-12 mesiatsev zhizni.

The purpose of the study was to explore developmental and individual differences in the working memory that was assessed by performance of the A-not-B task in 7- to 12-month-old infant twins. The sample included 150 infant twins participating in genetic project, 18 of them were tested at 8 and 11 months of age. Information concerning birth weight and gestational age was collected from birth records. All infants were tested using Bayley Scales of Mental and Psychomotor Development. The infant's working memory (WM) was tested during A-not-B task performance, which was shown to depend on the maturity of the prefrontal cortex. The behavioral data were analyzed off-line using videotape records. The one-way ANOVA revealed that the AB performance improves with age. A highly significant improvement of the ability to tolerate the delay in A-not-B task was observed between 9 and 10 months of life. There was no longitudinal stability in individual infant performance of A-not-B across the period of 7-12 months of age. The AB delay was significantly correlated with psychomotor and mental development only after the crucial period of the rapid increase in the AB delay (9-10 months). The analysis of intraclass mono- and dizygotic correlations showed that individual differences in the WM (tolerance to AB delay) at 7-9 months and at 10-12 months are of different nature. There was a significant effect of shared environment on AB delay variance in 10-12-month-old group, whereas down to this age no systematic influence on individual variability was observed. These findings suggest that the ability to tolerate the AB delay can be provided by different brain mechanisms in 7-9 and 10-12-month-old infants.