Different hemispheric lateralization for periodicity and formant structure of vowels in the auditory cortex and its changes between childhood and adulthood.

The spectral formant structure and periodicity pitch are the major features that determine the identity of vowels and the characteristics of the speaker. However, very little is known about how the processing of these features in the auditory cortex changes during development. To address this question, we independently manipulated the periodicity and formant structure of vowels while measuring auditory cortex responses using magnetoencephalography (MEG) in children aged 7-12 years and adults. We analyzed the sustained negative shift of source current associated with these vowel properties, which was present in the auditory cortex in both age groups despite differences in the transient components of the auditory response. In adults, the sustained activation associated with formant structure was lateralized to the left hemisphere early in the auditory processing stream requiring neither attention nor semantic mapping. This lateralization was not yet established in children, in whom the right hemisphere contribution to formant processing was strong and decreased during or after puberty. In contrast to the formant structure, periodicity was associated with a greater response in the right hemisphere in both children and adults. These findings suggest that left-lateralization for the automatic processing of vowel formant structure emerges relatively late in ontogenesis and pose a serious challenge to current theories of hemispheric specialization for speech processing.

Losses resulting from deliberate exploration trigger beta oscillations in frontal cortex.

We examined the neural signature of directed exploration by contrasting MEG beta (16-30 Hz) power changes between disadvantageous and advantageous choices in the two-choice probabilistic reward task. We analyzed the choices made after the participants have learned the probabilistic contingency between choices and their outcomes, i.e., acquired the inner model of choice values. Therefore, rare disadvantageous choices might serve explorative, environment-probing purposes. The study brought two main findings. Firstly, decision making leading to disadvantageous choices took more time and evidenced greater large-scale suppression of beta oscillations than its advantageous alternative. Additional neural resources recruited during disadvantageous decisions strongly suggest their deliberately explorative nature. Secondly, an outcome of disadvantageous and advantageous choices had qualitatively different impact on feedback-related beta oscillations. After the disadvantageous choices, only losses-but not gains-were followed by late beta synchronization in frontal cortex. Our results are consistent with the role of frontal beta oscillations in the stabilization of neural representations for selected behavioral rule when explorative strategy conflicts with value-based behavior. Punishment for explorative choice being congruent with its low value in the reward history is more likely to strengthen, through punishment-related beta oscillations, the representation of exploitative choices consistent with the inner utility model.

Learning of new associations invokes a major change in modulations of cortical beta oscillations in human adults.

Large-scale cortical beta (ß) oscillations were implicated in the learning processes, but their exact role is debated. We used MEG to explore the dynamics of movement-related ß-oscillations while 22 adults learned, through trial and error, novel associations between four auditory pseudowords and movements of four limbs. As learning proceeded, spatial-temporal characteristics of ß-oscillations accompanying cue-triggered movements underwent a major transition. Early in learning, widespread suppression of ß-power occurred long before movement initiation and sustained throughout the whole behavioral trial. When learning advanced and performance reached asymptote, ß-suppression after the initiation of correct motor response was replaced by a rise in ß-power mainly in the prefrontal and medial temporal regions of the left hemisphere. This post-decision ß-power predicted trial-by-trial response times (RT) at both stages of learning (before and after the rules become familiar), but with different signs of interaction. When a subject just started to acquire associative rules and gradually improved task performance, a decrease in RT correlated with the increase in the post-decision ß-band power. When the participants implemented the already acquired rules, faster (more confident) responses were associated with the weaker post-decision ß-band synchronization. Our findings suggest that maximal beta activity is pertinent to a distinct stage of learning and may serve to strengthen the newly learned association in a distributed memory network.

Gamma oscillations point to the role of primary visual cortex in atypical motion processing in autism.

Neurophysiological studies suggest that abnormal neural inhibition may explain a range of sensory processing differences in autism spectrum disorders (ASD). In particular, the impaired ability of people with ASD to visually discriminate the motion direction of small-size objects and their reduced perceptual suppression of background-like visual motion may stem from deficient surround inhibition within the primary visual cortex (V1) and/or its atypical top-down modulation by higher-tier cortical areas. In this study, we estimate the contribution of abnormal surround inhibition to the motion-processing deficit in ASD. For this purpose, we used a putative correlate of surround inhibition-suppression of the magnetoencephalographic (MEG) gamma response (GR) caused by an increase in the drift rate of a large annular high-contrast grating. The motion direction discrimination thresholds for the gratings of different angular sizes (1° and 12°) were assessed in a separate psychophysical paradigm. The MEG data were collected in 42 boys with ASD and 37 typically developing (TD) boys aged 7-15 years. Psychophysical data were available in 33 and 34 of these participants, respectively. The results showed that the GR suppression in V1 was reduced in boys with ASD, while their ability to detect the direction of motion was compromised only in the case of small stimuli. In TD boys, the GR suppression directly correlated with perceptual suppression caused by increasing stimulus size, thus suggesting the role of the top-down modulations of V1 in surround inhibition. In ASD, weaker GR suppression was associated with the poor directional sensitivity to small stimuli, but not with perceptual suppression. These results strongly suggest that a local inhibitory deficit in V1 plays an important role in the reduction of directional sensitivity in ASD and that this perceptual deficit cannot be explained exclusively by atypical top-down modulation of V1 by higher-tier cortical areas.

Altered visual cortex excitability in premenstrual dysphoric disorder: Evidence from magnetoencephalographic gamma oscillations and perceptual suppression.

Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by extreme mood shifts during the luteal phase of the menstrual cycle (MC) due to abnormal sensitivity to neurosteroids and unbalanced neural excitation/inhibition (E/I) ratio. We hypothesized that in women with PMDD in the luteal phase, these factors would alter the frequency of magnetoencephalographic visual gamma oscillations, affect modulation of their power by excitatory drive, and decrease perceptual spatial suppression. Women with PMDD and control women were examined twice-during the follicular and luteal phases of their MC. We recorded visual gamma response (GR) while modulating the excitatory drive by increasing the drift rate of the high-contrast grating (static, 'slow', 'medium', and 'fast'). Contrary to our expectations, GR frequency was not affected in women with PMDD in either phase of the MC. GR power suppression, which is normally associated with a switch from the 'optimal' for GR slow drift rate to the medium drift rate, was reduced in women with PMDD and was the only GR parameter that distinguished them from control participants specifically in the luteal phase and predicted severity of their premenstrual symptoms. Over and above the atypical luteal GR suppression, in both phases of the MC women with PMDD had abnormally strong GR facilitation caused by a switch from the 'suboptimal' static to the 'optimal' slow drift rate. Perceptual spatial suppression did not differ between the groups but decreased from the follicular to the luteal phase only in PMDD women. The atypical modulation of GR power suggests that neuronal excitability in the visual cortex is constitutively elevated in PMDD and that this E/I imbalance is further exacerbated during the luteal phase. However, the unaltered GR frequency does not support the hypothesis of inhibitory neuron dysfunction in PMDD.

Data-driven approach for the delineation of the irritative zone in epilepsy in MEG.

The reliable identification of the irritative zone (IZ) is a prerequisite for the correct clinical evaluation of medically refractory patients affected by epilepsy. Given the complexity of MEG data, visual analysis of epileptiform neurophysiological activity is highly time consuming and might leave clinically relevant information undetected. We recorded and analyzed the interictal activity from seven patients affected by epilepsy (Vectorview Neuromag), who successfully underwent epilepsy surgery (Engel > = II). We visually marked and localized characteristic epileptiform activity (VIS). We implemented a two-stage pipeline for the detection of interictal spikes and the delineation of the IZ. First, we detected candidate events from peaky ICA components, and then clustered events around spatio-temporal patterns identified by convolutional sparse coding. We used the average of clustered events to create IZ maps computed at the amplitude peak (PEAK), and at the 50% of the peak ascending slope (SLOPE). We validated our approach by computing the distance of the estimated IZ (VIS, SLOPE and PEAK) from the border of the surgically resected area (RA). We identified 25 spatiotemporal patterns mimicking the underlying interictal activity (3.6 clusters/patient). Each cluster was populated on average by 22.1 [15.0-31.0] spikes. The predicted IZ maps had an average distance from the resection margin of 8.4 ± 9.3 mm for visual analysis, 12.0 ± 16.5 mm for SLOPE and 22.7 ±. 16.4 mm for PEAK. The consideration of the source spread at the ascending slope provided an IZ closer to RA and resembled the analysis of an expert observer. We validated here the performance of a data-driven approach for the automated detection of interictal spikes and delineation of the IZ. This computational framework provides the basis for reproducible and bias-free analysis of MEG recordings in epilepsy.

What is the optimal duration of home-video-EEG monitoring for patients with <1 seizure per day? A simulation study.

Ambulatory "at home" video-EEG monitoring (HVEM) may offer a more cost-effective and accessible option as compared to traditional inpatient admissions to epilepsy monitoring units. However, home monitoring may not allow for safe tapering of anti-seizure medications (ASM). As a result, longer periods of monitoring may be necessary to capture a sufficient number of the patients' stereotypic seizures. We aimed to quantitatively estimate the necessary length of HVEM corresponding to various diagnostic scenarios in clinical practice. Using available seizure frequency statistics, we estimated the HVEM duration required to capture one, three, or five seizures on different days, by simulating 100,000 annual time-courses of seizure occurrence in adults and children with more than one and <30 seizures per month (89% of adults and 85% of children). We found that the durations of HVEM needed to record 1, 3, or 5 seizures in 80% of children were 2, 5, and 8 weeks (median 2, 12, and 21 days), respectively, and significantly longer in adults -2, 6, and 10 weeks (median 3, 14, and 26 days; p < 10-10 for all comparisons). Thus, longer HVEM than currently used is needed for expanding its clinical value from diagnosis of nonepileptic or very frequent epileptic events to a presurgical tool for patients with drug-resistant epilepsy. Technical developments and further studies are warranted.

Globally elevated excitation-inhibition ratio in children with autism spectrum disorder and below-average intelligence.

BACKGROUND: Altered neuronal excitation-inhibition (E-I) balance is strongly implicated in ASD. However, it is not known whether the direction and degree of changes in the E-I ratio in individuals with ASD correlates with intellectual disability often associated with this developmental disorder. The spectral slope of the aperiodic 1/f activity reflects the E-I balance at the scale of large neuronal populations and may uncover its putative alternations in individuals with ASD with and without intellectual disability. METHODS: Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with average and below-average (< 85) IQ. MEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6-15 years with IQ ranging from 54 to 128, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the beamformer approach and individual brain models. We then extracted the 1/f slope by fitting a linear function to the log-log-scale power spectra in the high-frequency range. RESULTS: The global 1/f slope averaged over all cortical sources demonstrated high rank-order stability between the two conditions. Consistent with previous research, it was steeper in the eyes-closed than in the eyes-open condition and flattened with age. Regardless of condition, children with ASD and below-average IQ had flatter slopes than either TD or ASD children with average or above-average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity. LIMITATIONS: Further research is needed to find out whether the observed changes in E-I ratios are characteristic of children with below-average IQ of other diagnostic groups. CONCLUSIONS: The atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E-I balance toward hyper-excitation. The spectral slope can provide an accessible noninvasive biomarker of the E-I ratio for making objective judgments about treatment effectiveness in people with ASD and comorbid intellectual disability.

Pupil dilation and response slowing distinguish deliberate explorative choices in the probabilistic learning task.

This study examined whether pupil size and response time would distinguish directed exploration from random exploration and exploitation. Eighty-nine participants performed the two-choice probabilistic learning task while their pupil size and response time were continuously recorded. Using LMM analysis, we estimated differences in the pupil size and response time between the advantageous and disadvantageous choices as a function of learning success, i.e., whether or not a participant has learned the probabilistic contingency between choices and their outcomes. We proposed that before a true value of each choice became known to a decision-maker, both advantageous and disadvantageous choices represented a random exploration of the two options with an equally uncertain outcome, whereas the same choices after learning manifested exploitation and direct exploration strategies, respectively. We found that disadvantageous choices were associated with increases both in response time and pupil size, but only after the participants had learned the choice-reward contingencies. For the pupil size, this effect was strongly amplified for those disadvantageous choices that immediately followed gains as compared to losses in the preceding choice. Pupil size modulations were evident during the behavioral choice rather than during the pretrial baseline. These findings suggest that occasional disadvantageous choices, which violate the acquired internal utility model, represent directed exploration. This exploratory strategy shifts choice priorities in favor of information seeking and its autonomic and behavioral concomitants are mainly driven by the conflict between the behavioral plan of the intended exploratory choice and its strong alternative, which has already proven to be more rewarding.

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.

Visual gamma oscillations predict sensory sensitivity in females as they do in males.

Gamma oscillations are driven by local cortical excitatory (E)-inhibitory (I) loops and may help to characterize neural processing involving excitatory-inhibitory interactions. In the visual cortex reliable gamma oscillations can be recorded with magnetoencephalography (MEG) in the majority of individuals, which makes visual gamma an attractive candidate for biomarkers of brain disorders associated with E/I imbalance. Little is known, however, about if/how these oscillations reflect individual differences in neural excitability and associated sensory/perceptual phenomena. The power of visual gamma response (GR) changes nonlinearly with increasing stimulation intensity: it increases with transition from static to slowly drifting high-contrast grating and then attenuates with further increase in the drift rate. In a recent MEG study we found that the GR attenuation predicted sensitivity to sensory stimuli in everyday life in neurotypical adult men and in men with autism spectrum disorders. Here, we replicated these results in neurotypical female participants. The GR enhancement with transition from static to slowly drifting grating did not correlate significantly with the sensory sensitivity measures. These findings suggest that weak velocity-related attenuation of the GR is a reliable neural concomitant of visual hypersensitivity and that the degree of GR attenuation may provide useful information about E/I balance in the visual cortex.

Rapid Cortical Plasticity Induced by Active Associative Learning of Novel Words in Human Adults.

Human speech requires that new words are routinely memorized, yet neurocognitive mechanisms of such acquisition of memory remain highly debatable. Major controversy concerns the question whether cortical plasticity related to word learning occurs in neocortical speech-related areas immediately after learning, or neocortical plasticity emerges only on the second day after a prolonged time required for consolidation after learning. The functional spatiotemporal pattern of cortical activity related to such learning also remains largely unknown. In order to address these questions, we examined magnetoencephalographic responses elicited in the cerebral cortex by passive presentations of eight novel pseudowords before and immediately after an operant conditioning task. This associative procedure forced participants to perform an active search for unique meaning of four pseudowords that referred to movements of left and right hands and feet. The other four pseudowords did not require any movement and thus were not associated with any meaning. Familiarization with novel pseudowords led to a bilateral repetition suppression of cortical responses to them; the effect started before or around the uniqueness point and lasted for more than 500 ms. After learning, response amplitude to pseudowords that acquired meaning was greater compared with response amplitude to pseudowords that were not assigned meaning; the effect was significant within 144-362 ms after the uniqueness point, and it was found only in the left hemisphere. Within this time interval, a learning-related selective response initially emerged in cortical areas surrounding the Sylvian fissure: anterior superior temporal sulcus, ventral premotor cortex, the anterior part of intraparietal sulcus and insula. Later within this interval, activation additionally spread to more anterior higher-tier brain regions, and reached the left temporal pole and the triangular part of the left inferior frontal gyrus extending to its orbital part. Altogether, current findings evidence rapid plastic changes in cortical representations of meaningful auditory word-forms occurring almost immediately after learning. Additionally, our results suggest that familiarization resulting from stimulus repetition and semantic acquisition resulting from an active learning procedure have separable effects on cortical activity.

Object recognition is enabled by an experience-dependent appraisal of visual features in the brain's value system.

This paper addresses perceptual synthesis by comparing responses evoked by visual stimuli before and after they are recognized, depending on prior exposure. Using magnetoencephalography, we analyzed distributed patterns of neuronal activity - evoked by Mooney figures - before and after they were recognized as meaningful objects. Recognition induced changes were first seen at 100-120 â€‹ms, for both faces and tools. These early effects - in right inferior and middle occipital regions - were characterized by an increase in power in the absence of any changes in spatial patterns of activity. Within a later 210-230 â€‹ms window, a quite different type of recognition effect appeared. Regions of the brain's value system (insula, entorhinal cortex and cingulate of the right hemisphere for faces and right orbitofrontal cortex for tools) evinced a reorganization of their neuronal activity without an overall power increase in the region. Finally, we found that during the perception of disambiguated face stimuli, a face-specific response in the right fusiform gyrus emerged at 240-290 â€‹ms, with a much greater latency than the well-known N170m component, and, crucially, followed the recognition effect in the value system regions. These results can clarify one of the most intriguing issues of perceptual synthesis, namely, how a limited set of high-level predictions, which is required to reduce the uncertainty when resolving the ill-posed inverse problem of perception, can be available before category-specific processing in visual cortex. We suggest that a subset of local spatial features serves as partial cues for a fast re-activation of object-specific appraisal by the value system. The ensuing top-down feedback from value system to visual cortex, in particular, the fusiform gyrus enables high levels of processing to form category-specific predictions. This descending influence of the value system was more prominent for faces than for tools, the fact that reflects different dependence of these categories on value-related information.

Spatial suppression in visual motion perception is driven by inhibition: Evidence from MEG gamma oscillations.

Spatial suppression (SS) is a visual perceptual phenomenon that is manifest in a reduction of directional sensitivity for drifting high-contrast gratings whose size exceeds the center of the visual field. Gratings moving at faster velocities induce stronger SS. The neural processes that give rise to such size- and velocity-dependent reductions in directional sensitivity are currently unknown, and the role of surround inhibition is unclear. In magnetoencephalogram (MEG), large high-contrast drifting gratings induce a strong gamma response (GR), which also attenuates with an increase in the gratings' velocity. It has been suggested that the slope of this GR attenuation is mediated by inhibitory interactions in the primary visual cortex. Herein, we investigate whether SS is related to this inhibitory-based MEG measure. We evaluated SS and GR in two independent samples of participants: school-age boys and adult women. The slope of GR attenuation predicted inter-individual differences in SS in both samples. Test-retest reliability of the neuro-behavioral correlation was assessed in the adults, and was high between two sessions separated by several days or weeks. Neither frequencies nor absolute amplitudes of the GRs correlated with SS, which highlights the functional relevance of velocity-related changes in GR magnitude caused by augmentation of incoming input. Our findings provide evidence that links the psychophysical phenomenon of SS to inhibitory-based neural responses in the human primary visual cortex. This supports the role of inhibitory interactions as an important underlying mechanism for spatial suppression.

Additive effect of contrast and velocity suggests the role of strong excitatory drive in suppression of visual gamma response.

It is commonly acknowledged that gamma-band oscillations arise from interplay between neural excitation and inhibition; however, the neural mechanisms controlling the power of stimulus-induced gamma responses (GR) in the human brain remain poorly understood. A moderate increase in velocity of drifting gratings results in GR power enhancement, while increasing the velocity beyond some 'transition point' leads to GR power attenuation. We tested two alternative explanations for this nonlinear input-output dependency in the GR power. First, the GR power can be maximal at the preferable velocity/temporal frequency of motion-sensitive V1 neurons. This 'velocity tuning' hypothesis predicts that lowering contrast either will not affect the transition point or shift it to a lower velocity. Second, the GR power attenuation at high velocities of visual motion can be caused by changes in excitation/inhibition balance with increasing excitatory drive. Since contrast and velocity both add to excitatory drive, this 'excitatory drive' hypothesis predicts that the 'transition point' for low-contrast gratings would be reached at a higher velocity, as compared to high-contrast gratings. To test these alternatives, we recorded magnetoencephalography during presentation of low (50%) and high (100%) contrast gratings drifting at four velocities. We found that lowering contrast led to a highly reliable shift of the GR suppression transition point to higher velocities, thus supporting the excitatory drive hypothesis. No effects of contrast or velocity were found in the alpha-beta range. The results have implications for understanding the mechanisms of gamma oscillations and developing gamma-based biomarkers of disturbed excitation/inhibition balance in brain disorders.

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.

Effortful verb retrieval from semantic memory drives beta suppression in mesial frontal regions involved in action initiation.

The contribution of the motor cortex to the semantic retrieval of verbs remains a subject of debate in neuroscience. Here, we examined whether additional engagement of the cortical motor system was required when access to verbs semantics was hindered during a verb generation task. We asked participants to produce verbs related to presented noun cues that were either strongly associated with a single verb to prompt fast and effortless verb retrieval, or were weakly associated with multiple verbs and more difficult to respond to. Using power suppression of magnetoencephalography beta oscillations (15-30 Hz) as an index of cortical activation, we performed a whole-brain analysis in order to identify the cortical regions sensitive to the difficulty of verb semantic retrieval. Highly reliable suppression of beta oscillations occurred 250 ms after the noun cue presentation and was sustained until the onset of verbal response. This was localized to multiple cortical regions, mainly in the temporal and frontal lobes of the left hemisphere. Crucially, the only cortical regions where beta suppression was sensitive to the task difficulty, were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. Stronger activation of the premotor cortex and supplementary motor area accompanied the effortful verb retrieval and preceded the preparation of verbal responses for more than 500 ms, thus, overlapping with the time window of verb retrieval from semantic memory. Our results suggest that reactivation of verb-related motor plans in higher order motor circuitry promotes the semantic retrieval of target verbs.

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.

Input-dependent modulation of MEG gamma oscillations reflects gain control in the visual cortex.

Gamma-band oscillations arise from the interplay between neural excitation (E) and inhibition (I) and may provide a non-invasive window into the state of cortical circuitry. A bell-shaped modulation of gamma response power by increasing the intensity of sensory input was observed in animals and is thought to reflect neural gain control. Here we sought to find a similar input-output relationship in humans with MEG via modulating the intensity of a visual stimulation by changing the velocity/temporal-frequency of visual motion. In the first experiment, adult participants observed static and moving gratings. The frequency of the MEG gamma response monotonically increased with motion velocity whereas power followed a bell-shape. In the second experiment, on a large group of children and adults, we found that despite drastic developmental changes in frequency and power of gamma oscillations, the relative suppression at high motion velocities was scaled to the same range of values across the life-span. In light of animal and modeling studies, the modulation of gamma power and frequency at high stimulation intensities characterizes the capacity of inhibitory neurons to counterbalance increasing excitation in visual networks. Gamma suppression may thus provide a non-invasive measure of inhibitory-based gain control in the healthy and diseased brain.

Simultaneous Processing of Noun Cue and to-be-Produced Verb in Verb Generation Task: Electromagnetic Evidence.

A long-standing but implicit assumption is that words strongly associated with a presented cue are automatically activated in the memory through rapid spread of activation within brain semantic networks. The current study was aimed to provide direct evidence of such rapid access to words' semantic representations and to investigate its neural sources using magnetoencephalography (MEG) and distributed source localization technique. Thirty-three neurotypical subjects underwent the MEG recording during verb generation task, which was to produce verbs related to the presented noun cues. Brain responses evoked by the noun cues were examined while manipulating the strength of association between the noun and the potential verb responses. The strong vs. weak noun-verb association led to a greater noun-related neural response at 250-400 ms after cue onset, and faster verb production. The cortical sources of the differential response were localized in left temporal pole, previously implicated in semantic access, and left ventrolateral prefrontal cortex (VLPFC), thought to subserve controlled semantic retrieval. The strength of the left VLPFC's response to the nouns with strong verb associates was positively correlated to the speed of verbs production. Our findings empirically validate the theoretical expectation that in case of a strongly connected noun-verb pair, successful access to target verb representation may occur already at the stage of lexico-semantic analysis of the presented noun. Moreover, the MEG results suggest that contrary to the previous conclusion derived from fMRI studies left VLPFC supports selection of the target verb representations, even if they were retrieved from semantic memory rapidly and effortlessly. The discordance between MEG and fMRI findings in verb generation task may stem from different modes of neural activation captured by phase-locked activity in MEG and slow changes of blood-oxygen-level-dependent (BOLD) signal in fMRI.