Long-range temporal correlations in resting state alpha oscillations in major depressive disorder and obsessive-compulsive disorder.

Introduction: Mental disorders are a significant concern in contemporary society, with a pressing need to identify biological markers. Long-range temporal correlations (LRTC) of brain rhythms have been widespread in clinical cohort studies, especially in major depressive disorder (MDD). However, research on LRTC in obsessive-compulsive disorder (OCD) is severely limited. Given the high co-occurrence of OCD and MDD, we conducted a comparative LRTC investigation. We assumed that the LRTC patterns will allow us to compare measures of brain cortical balance of excitation and inhibition in OCD and MDD, which will be useful in the area of differential diagnosis. Methods: In this study, we used the 64-channel resting state EEG of 29 MDD participants, 26 OCD participants, and a control group of 37 volunteers. Detrended fluctuation analyzes was used to assess LRTC. Results: Our results indicate that all scaling exponents of the three subject groups exhibited persistent LRTC of EEG oscillations. There was a tendency for LRTC to be higher in disorders than in controls, but statistically significant differences were found between the OCD and control groups in the entire frontal and left parietal occipital areas, and between the MDD and OCD groups in the middle and right frontal areas. Discussion: We believe that these results indicate abnormalities in the inhibitory and excitatory neurotransmitter systems, predominantly affecting areas related to executive functions.

Atypical brain responses to 40-Hz click trains in girls with Rett syndrome: Auditory steady-state response and sustained wave.

AIM: The current study aimed to infer neurophysiological mechanisms of auditory processing in children with Rett syndrome (RTT)-rare neurodevelopmental disorders caused by MECP2 mutations. We examined two brain responses elicited by 40-Hz click trains: auditory steady-state response (ASSR), which reflects fine temporal analysis of auditory input, and sustained wave (SW), which is associated with integral processing of the auditory signal. METHODS: We recorded electroencephalogram findings in 43 patients with RTT (aged 2.92-17.1 years) and 43 typically developing children of the same age during 40-Hz click train auditory stimulation, which lasted for 500 ms and was presented with interstimulus intervals of 500 to 800 ms. Mixed-model ancova with age as a covariate was used to compare amplitude of ASSR and SW between groups, taking into account the temporal dynamics and topography of the responses. RESULTS: Amplitude of SW was atypically small in children with RTT starting from early childhood, with the difference from typically developing children decreasing with age. ASSR showed a different pattern of developmental changes: the between-group difference was negligible in early childhood but increased with age as ASSR increased in the typically developing group, but not in those with RTT. Moreover, ASSR was associated with expressive speech development in patients, so that children who could use words had more pronounced ASSR. CONCLUSION: ASSR and SW show promise as noninvasive electrophysiological biomarkers of auditory processing that have clinical relevance and can shed light onto the link between genetic impairment and the RTT phenotype.

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.

Lower loss rate of serotonergically modulated neuronal accumulator for time in patients with major depressive disorder.

Major depressive disorder (MDD) is characterized by dramatic and persistent worsening of mood, as well as a subjective feeling of time slowing. However, experimental data on time perception are inconsistent. As serotonergic dysfunction implicated in MDD etiology, we aim to examine time perception in MDD through the framework of lossy temporal integration model, previously also related to serotonergic transmission. Thirty-one patients with recurrent depressive disorder in partial remission and thirty control participants, without a history of psychiatric and neurological disorders, performed duration discrimination of visual stimuli (duration ranges from 3.2 to 6.4 s) and subjective minute production tasks. To infer about central serotonergic transmission, an electroencephalogram in response to the 1000 Hz tone of different intensity (50, 60, 70 and 80 dB SPL) was recorded. Patients with MDD shorten the past durations in the duration discrimination task significantly less than controls, thus being more objective. No difference in the subjective minute production was recorded. Patients with MDD have also exhibited larger auditory evoked potentials in response to the tones of high intensity (70 and 80 dB SPL) when compared with the controls. This resulted in a steeper slope of auditory evoked potentials by intensity function. These converging findings suggest a lower loss rate of neuronal temporal accumulator modulated by serotonergic transmission in patients with MDD.

Abnormal spectral and scale-free properties of resting-state EEG in girls with Rett syndrome.

Spontaneous EEG contains important information about neuronal network properties that is valuable for understanding different neurological and psychiatric conditions. Rett syndrome (RTT) is a rare neurodevelopmental disorder, caused by mutation in the MECP2 gene. RTT is characterized by severe motor impairments that prevent adequate assessment of cognitive functions. Here we probe EEG parameters obtained in no visual input condition from a 28-channels system in 23 patients with Rett Syndrome and 38 their typically developing peers aged 3-17 years old. Confirming previous results, RTT showed a fronto-central theta power (4-6.25 Hz) increase that correlates with a progression of the disease. Alpha power (6.75-11.75 Hz) across multiple regions was, on the contrary, decreased in RTT, also corresponding to general background slowing reported previously. Among novel results we found an increase in gamma power (31-39.5 Hz) across frontal, central and temporal electrodes, suggesting elevated excitation/inhibition ratio. Long-range temporal correlation measured by detrended fluctuation analysis within 6-13 Hz was also increased, pointing to a more predictable oscillation pattern in RTT. Overall measured EEG parameters allow to differentiate groups with high accuracy, ROC AUC value of 0.92 ± 0.08, indicating clinical relevance.

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.

Does the Potocki-Lupski Syndrome Convey the Autism Spectrum Disorder Phenotype? Case Report and Scoping Review.

Potocki-Lupski Syndrome (PTLS) is a rare condition associated with a duplication of 17p11.2 that may underlie a wide range of congenital abnormalities and heterogeneous behavioral phenotypes. Along with developmental delay and intellectual disability, autism-specific traits are often reported to be the most common among patients with PTLS. To contribute to the discussion of the role of autism spectrum disorder (ASD) in the PTLS phenotype, we present a case of a female adolescent with a de novo dup(17) (p11.2p11.2) without ASD features, focusing on in-depth clinical, behavioral, and electrophysiological (EEG) evaluations. Among EEG features, we found the atypical peak-slow wave patterns and a unique saw-like sharp wave of 13 Hz that was not previously described in any other patient. The power spectral density of the resting state EEG was typical in our patient with only the values of non-linear EEG dynamics: Hjorth complexity and fractal dimension were drastically attenuated compared with the patient's neurotypical peers. Here we also summarize results from previously published reports of PTLS that point to the approximately 21% occurrence of ASD in PTLS that might be biased, taking into account methodological limitations. More consistent among PTLS patients were intellectual disability and speech and language disorders.

Clinical EEG of Rett Syndrome: Group Analysis Supplemented with Longitudinal Case Report.

Rett syndrome (RTT), a severe neurodevelopmental disorder caused by MECP2 gene abnormalities, is characterized by atypical EEG activity, and its detailed examination is lacking. We combined the comparison of one-time eyes open EEG resting state activity from 32 girls with RTT and their 41 typically developing peers (age 2-16 years old) with longitudinal following of one girl with RTT to reveal EEG parameters which correspond to the RTT progression. Traditional measures, such as epileptiform abnormalities, generalized background activity, beta activity and the sensorimotor rhythm, were supplemented by a new frequency rate index measured as the ratio between high- and low-frequency power of sensorimotor rhythm. Almost all studied EEG parameters differentiated the groups; however, only the elevated generalized background slowing and decrease in our newly introduced frequency rate index which reflects attenuation in the proportion of the upper band of sensorimotor rhythm in RTT showed significant relation with RTT progression both in longitudinal case and group analysis. Moreover, only this novel index was linked to the breathing irregularities RTT symptom. The percentage of epileptiform activity was unrelated to RTT severity, confirming previous studies. Thus, resting EEG can provide information about the pathophysiological changes caused by MECP2 abnormalities and disease progression.

Social Behavioral Deficits in Krushinsky-Molodkina Rats, an Animal Model of Audiogenic Epilepsy.

In clinical practice, epilepsy is often comorbid with the autism spectrum disorders (ASDs). This warrants a search of animal models to uncover putative overlapping neuronal mechanisms. The Krushinsky-Molodkina (KM) rat strain is one of the oldest inbred animal models for human convulsive epilepsies. We analyzed the behavioral response of adult seizure-naive KM males in three-chambered tests for social preference. We found that a presence of social stimuli (encaged unfamiliar Wistar rats of the same age and sex) evoked a reduced or reversed exploratory response in freely moving KM individuals. The epilepsy-prone rats demonstrated remarkably shortened bouts of social contacts and displayed less locomotion around the stranger rat-containing boxes, together with a pronounced freezing response. The decrease in social preference was not due to a general decrease in activity, since relative measures of activity, the index of sociability, were decreased, too. The susceptibility to audiogenic seizures was verified in the KM cohort but not seen in the control Wistar group. We propose the KM rat strain as a new animal model for comorbid ASD and epilepsy.

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.

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.

Reviewing Evidence for the Relationship of EEG Abnormalities and RTT Phenotype Paralleled by Insights from Animal Studies.

Rett syndrome (RTT) is a rare neurodevelopmental disorder that is usually caused by mutations of the MECP2 gene. Patients with RTT suffer from severe deficits in motor, perceptual and cognitive domains. Electroencephalogram (EEG) has provided useful information to clinicians and scientists, from the very first descriptions of RTT, and yet no reliable neurophysiological biomarkers related to the pathophysiology of the disorder or symptom severity have been identified to date. To identify consistently observed and potentially informative EEG characteristics of RTT pathophysiology, and ascertain areas most worthy of further systematic investigation, here we review the literature for EEG abnormalities reported in patients with RTT and in its disease models. While pointing to some promising potential EEG biomarkers of RTT, our review identify areas of need to realize the potential of EEG including (1) quantitative investigation of promising clinical-EEG observations in RTT, e.g., shift of mu rhythm frequency and EEG during sleep; (2) closer alignment of approaches between patients with RTT and its animal models to strengthen the translational significance of the work (e.g., EEG measurements and behavioral states); (3) establishment of large-scale consortium research, to provide adequate Ns to investigate age and genotype effects.

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.

Atypical processing of tones and phonemes in Rett Syndrome as biomarkers of disease progression.

Due to severe motor impairments and the lack of expressive language abilities seen in most patients with Rett Syndrome (RTT), it has proven extremely difficult to obtain accurate measures of auditory processing capabilities in this population. Here, we examined early auditory cortical processing of pure tones and more complex phonemes in females with Rett Syndrome (RTT), by recording high-density auditory evoked potentials (AEP), which allow for objective evaluation of the timing and severity of processing deficits along the auditory processing hierarchy. We compared AEPs of 12 females with RTT to those of 21 typically developing (TD) peers aged 4-21 years, interrogating the first four major components of the AEP (P1: 60-90 ms; N1: 100-130 ms; P2: 135-165 ms; and N2: 245-275 ms). Atypicalities were evident in RTT at the initial stage of processing. Whereas the P1 showed increased amplitude to phonemic inputs relative to tones in TD participants, this modulation by stimulus complexity was absent in RTT. Interestingly, the subsequent N1 did not differ between groups, whereas the following P2 was hugely diminished in RTT, regardless of stimulus complexity. The N2 was similarly smaller in RTT and did not differ as a function of stimulus type. The P2 effect was remarkably robust in differentiating between groups with near perfect separation between the two groups despite the wide age range of our samples. Given this robustness, along with the observation that P2 amplitude was significantly associated with RTT symptom severity, the P2 has the potential to serve as a monitoring, treatment response, or even surrogate endpoint biomarker. Compellingly, the reduction of P2 in patients with RTT mimics findings in animal models of RTT, providing a translational bridge between pre-clinical and human research.

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review.

OBJECTIVE: Systematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations). METHODS: Pubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards. RESULTS: ERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients. CONCLUSIONS: While there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms. SIGNIFICANCE: The review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.

Auditory sensory memory span for duration is severely curtailed in females with Rett syndrome.

Rett syndrome (RTT), a rare neurodevelopmental disorder caused by mutations in the MECP2 gene, is typified by profound cognitive impairment and severe language impairment, rendering it very difficult to accurately measure auditory processing capabilities behaviorally in this population. Here we leverage the mismatch negativity (MMN) component of the event-related potential to measure the ability of RTT patients to decode and store occasional duration deviations in a stream of auditory stimuli. Sensory memory for duration, crucial for speech comprehension, has not been studied in RTT.High-density electroencephalography was successfully recorded in 18 females with RTT and 27 age-matched typically developing (TD) controls (aged 6-22 years). Data from seven RTT and three TD participants were excluded for excessive noise. Stimuli were 1 kHz tones with a standard duration of 100 ms and deviant duration of 180 ms. To assess the sustainability of sensory memory, stimulus presentation rate was varied with stimulus onset asynchronies (SOAs) of 450, 900, and 1800 ms. MMNs with maximum negativity over fronto-central scalp and a latency of 220-230 ms were clearly evident for each presentation rate in the TD group, but only for the shortest SOA in the RTT group. Repeated-measures ANOVA revealed a significant group by SOA interaction. MMN amplitude correlated with age in the TD group only. MMN amplitude was not correlated with the Rett Syndrome Severity Scale. This study indicates that while RTT patients can decode deviations in auditory duration, the span of this sensory memory system is severely foreshortened, with likely implications for speech decoding abilities.

Neural gain control measured through cortical gamma oscillations is associated with sensory sensitivity.

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations. Recent studies in humans and nonhuman primates have shown that strong excitatory drive to the visual cortex leads to suppression of induced gamma oscillations, which may reflect inhibitory-based gain control of network excitation. The efficiency of the gain control measured through gamma oscillations may in turn affect sensory sensitivity in everyday life. To test this prediction, we assessed the link between self-reported sensitivity and changes in magneto-encephalographic gamma oscillations as a function of motion velocity of high-contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally elevated sensory sensitivity. We conclude that intensity-related suppression of gamma response is a promising biomarker of homeostatic control of the excitation-inhibition balance in the visual cortex.

Event-related potential (ERP) correlates of face processing in verbal children with autism spectrum disorders (ASD) and their first-degree relatives: a family study.

Background: Inherited abnormalities of perception, recognition, and attention to faces have been implicated in the etiology of autism spectrum disorders (ASD) including abnormal components of event-related brain potentials (ERP) elicited by faces. Methods: We examined familial aggregation of face processing ERP abnormalities previously implicated in ASD in 49 verbal individuals with ASD, 36 unaffected siblings (US), 18 unaffected fathers (UF), and 53 unrelated controls (UC). The ASD, US, and UC groups ranged in age from 12 to 21 years, the UF group ranged in age from 30 to 56 years. ERP responses to images of upright and inverted faces and houses were analyzed under disparate EEG reference schemes. Results: Face-sensitive features of N170 and P1 were readily observed in all groups. Differences between ASD and control groups depended upon the EEG reference scheme. Notably, the superiority of face over object for N170 latency was attenuated in ASD subjects, but not their relatives; this occurred exclusively with the average reference. The difference in N170 amplitude between inverted and upright faces was reduced in both ASD and US groups relative to UC, but this effect was significant only with the vertex reference. Furthermore, similar group differences were observed for both inverted faces and inverted houses, suggesting a lack of face specificity for the attenuation of the N170 inversion effect in ASD. Conclusion: The present findings refine understanding of face processing ERPs in ASD. These data provide only modest evidence for highly-selective ASD-sensitive ERP features, and underscore the sensitivity of these biomarkers to ERP reference scheme. These schemes have varied across published studies and must be accounted for in future studies of the relationship between these commonly acquired ERP characteristics, genotype, and ASD.