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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.

Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by extreme mood shifts, anxiety, and irritability during the premenstrual period. Abnormal sensitivity to allopregnanolone, a neurosteroid that normally potentiates inhibition, and an increased ratio of neural excitation-to-inhibition (E/I) have been linked to the pathophysiology of PMDD. We hypothesized that in subjects with PMDD these factors will lead to an altered frequency of magnetoencephalographic (MEG) visual gamma oscillations, altered modulation of their power by the strength of excitatory drive and to an altered perceptual spatial suppression.We examined women with PMDD and age-matched control women twice: during the asymptomatic follicular and symptomatic luteal phases of the menstrual cycle (MC). MEG gamma oscillations were recorded while modulating excitatory drive to the visual cortex by increasing drift rate of high-contrast visual grating. Visual perceptual suppression was assessed as the degree of deterioration of motion direction discrimination with increasing stimulus size.In women with PMDD, the peak frequency of the gamma response (GR) and its modulation by the drift rate were normal, whereas modulation of the GR power was significantly altered. A moderate increase in drift rate had an unusually strong facilitating effect on the GR power in PMDD, regardless of the MC phase. In contrast, the normally suppressive effect of a strong increase in drift rate was attenuated in PMDD during the luteal phase and predicted symptom severity assessed on the same day. Perceptual spatial suppression did not differ between the groups, but decreased from the follicular to the luteal phase only in PMDD subjects.The atypical GR power modulation suggests that neuronal excitability in the visual cortex is constitutively elevated in women with PMDD, and that this E/I imbalance is further exacerbated during the luteal phase, possibly due to an abnormal sensitivity to neurosteroids. However, the unchanged frequency of GR and normal spatial suppression in women with PMDD speak against the dysfunction of their inhibitory neurons, at least those involved in generation of visual gamma oscillations.Three key pointsAtypical modulation of visual gamma power by excitatory drive in women with PMDD suggests the presence of neuronal hyperexcitability, which is exacerbated during the symptomatic luteal phase, possibly due to altered sensitivity to neurosteroids.The peak frequency of gamma oscillations does not differ between women with PMDD and control women and demonstrates the luteal phase-specific effect of the 1st scan in both groups, which suggest normal functioning of inhibitory neurons in the visual cortex in PMDD.The presence of normal perceptual spatial suppression also speaks against inhibitory deficit in the visual cortex in PMDD.

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.

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.

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 ( 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.

BACKGROUNDAn altered balance of neuronal excitation and inhibition (E-I balance) might be implicated in the co-occurrence of autism and intellectual disability, but this hypothesis has never been tested. E-I balance changes can be estimated from the spectral slope of the aperiodic 1/f neural activity. Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with and without intellectual disability.METHODSMEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6-15 years with a broad range of IQs, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the LCMV beamformer approach. We then extracted the 1/f slope by fitting a linear function in to the log-log-scale power spectra in the high-frequency range.RESULTSThe grand averaged 1/f slope was steeper in the eyes closed than in the eyes open condition, but had high rank-order stability between them. In line with the previous research, the slope flattened with age. Children with ASD and below-average (CONCLUSIONSThe 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 non-invasive biomarker of the E-I ratio for translational research and making objective judgments about treatment effectiveness.

Human behavior in probabilistic environment is characterized by a preference for a more frequently reinforced option, yet people tend to make a few number of disadvantageous choices as well. We test the hypothesis that risky choices may reflect a bias to search for regularities in a random sequence of events. We measured pupil dilations as a marker of norepinephrine release in locus coeruleus, which may index subjects’ engagement in the exploratory behavior. Fifty-two healthy participants performed two-alternative serial choice task with the reward probability of 0.7 for one stimulus and 0.3 for the other. Feedback was presented with a delay of 1 s after the response. We performed ANOVA analysis of mean pupil area in a 1400 ms time window following feedback onset. We considered three factors that could trigger pupil dilations: riskiness of the current choice, its positive or negative outcome, and the riskiness of the following choice. We found that pupil dilation predicted the future risky choice, while it did not depend on the other two factors. The amplitude of pupil dilation before a persistent risky decision negatively correlated with the total number of risky choices. Taken together, these findings indicate that the latent process of preparation for risky decisions is associated with increased norepinephrine release. We suppose that the transitory increment of norepinephrine release may result from detection of a conflict between the pragmatic model of the advantageous strategy and the planned risky action by the cingulate cortex, which sends excitatory projections to the locus coeruleus.

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.

Background: Deficits in perception and production of vocal pitch are often observed in people with autism spectrum disorders (ASD), but the neural basis of these abnormalities 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 neuro-typical individuals is associated with low-level analysis of pitch in the ‘pitch processing center’ of the Heschl’s gyrus. Therefore, this auditory response may reflect vocal pitch processing abnormalities in ASD. The SF, however, has never been studied in people with these disorders. Methods: We used MEG and individual brain models to investigate the ASSR and SF evoked by monaural 40 Hz click trains in 7-13-year-old boys with ASD (N=35) and neuro-typical (NT) boys (N=35). 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 contralaterally to the stimulated ear. The ASSR increased with age in both NT and ASD children and did not differ between the groups. The SF did not change between 7 and 13 years. It was moderately decreased 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 have not tested language abilities of our participants. Therefore, the link between SF and processing of vocal pitch in children with ASD remains speculative. Conclusion: The selective left-hemispheric SF abnormalities found in children with ASD are consistent with a deficit at a low level of pitch processing, which in turn may contribute to their difficulties in perception and production of linguistic prosody.

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.

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.HighlightsThe role of surround inhibition in perceptual spatial suppression (SS) is debatedGR attenuation with increasing grating’s velocity may reflect surround inhibitionPeople with greater GR attenuation exhibit stronger SSThe neuro-behavioral correlation is replicated in school-age boys and adult womenThe surround inhibition in the V1 is an important mechanism underlying SS

В соответствии с теорией телесно-воплощенного познания, речь в значительной степени базируется на моторном и сенсорном опыте. Вопрос, критически важный для понимания природы речи, состоит в том, как наш мозг трансформирует сенсорно-моторный опыт в смысл, присваиваемый словам. Мы разработали слуховую-моторную экспериментальную задачу, позволяющую исследовать мозговые механизмы научения смыслу слов путем ассоциативного научения по типу "проб-и-ошибок", имитирующего важные аспекты естественного научения речи. Участникам предъявляли восемь псевдослов; четыре псевдослова в ходе научения приобретали смысл и обозначали движения конкретными частями тела; процедура включала в себя выполнение испытуемыми движений правыми или левыми конечностями и получение ими обратной связи. В ответ на остальные псевдослова никаких действий выполнять не требовалось, и они служили в качестве контрольных стимулов. Магнитоэнцефалограмму регистрировали во время пассивного прослушивания слов до и после научения. Кортикальные источники магнитных вызванных ответов реконструировали с помощью модели распределенных источников. Научение смыслу новых слов путем ассоциаций между словами и действиями селективным образом усилило специфическое сродство к этим словам в области слухового парапояса, ответственной за спектрально-временной анализ, а также в артикуляционных областях, причем обе области были локализованы в левом полушарии. Выраженность изменений в мозговой активности коррелировала со скоростью речевого научения, что подчеркивает физиологический вклад левой перисильвиллярной коры в успешность речевого научения.

Background. Previous studies have shown that brain response to a written word depends on the task: whether the word is a target in a version of lexical decision task or should be read silently. Although this effect has been interpreted as an evidence for an interaction between word recognition processes and task demands, it also may be caused by greater attention allocation to the target word. Objective. We aimed to examine the task effect on brain response evoked by non- target written words. Design. Using MEG and magnetic source imaging, we compared spatial-temporal pattern of brain response elicited by a noun cue when it was read silently either without additional task (SR) or with a requirement to produce an associated verb (VG). Results.The task demands penetrated into early (200-300 ms) and late (500-800 ms) stages of a word processing by enhancing brain response under VG versus SR condition. The cortical sources of the early response were localized to bilateral inferior occipitotemporal and anterior temporal cortex suggesting that more demanding VG task required elaborated lexical-semantic analysis. The late effect was observed in the associative auditory areas in middle and superior temporal gyri and in motor representation of articulators. Our results suggest that a remote goal plays a pivotal role in enhanced recruitment of cortical structures underlying orthographic, semantic and sensorimotor dimensions of written word perception from the early processing stages. Surprisingly, we found that to fulfil a more challenging goal the brain progressively engaged resources of the right hemisphere throughout all stages of silent reading. Conclusion. Our study demonstrates that a deeper processing of linguistic input amplifies activation of brain areas involved in integration of speech perception and production. This is consistent with theories that emphasize the role of sensorimotor integration in speech understanding.

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.

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.

Visual gamma oscillations are generated through interactions of excitatory and inhibitory neurons and are strongly modulated by sensory input. A moderate increase in excitatory drive to the visual cortex via increasing contrast or motion velocity of drifting gratings results in strengthening of the gamma response (GR). However, increasing the velocity beyond some ‘transition point’ leads to the suppression of the GR. There are two theoretical models that can explain such suppression. The ‘excitatory drive’ model infers that, at high drifting rates, GR suppression is caused by excessive excitation of inhibitory neurons. Since contrast and velocity have an additive effect on excitatory drive, this model predicts that the GR ‘transition point’ for low-contrast gratings would be reached at a higher velocity, as compared to high-contrast gratings. The alternative ‘velocity tuning’ model implies that the GR is maximal when the drifting rate of the grating corresponds to the preferable velocity of the motion-sensitive V1 neurons. This model predicts that lowering contrast either will not affect the transition point or will shift it to a lower drifting rate. We tested these models with magnetoencephalography-based recordings of the GR 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 model. No effects of contrast or velocity were found for the alpha-beta response power. The results have important implications for the understanding of the neural mechanisms underlying gamma oscillations and the development of gamma-based biomarkers of brain disorders.

Whether the motor cortex activation accompanying concrete verbs comprehension is necessary for verbs conceptual processing is still a hotly debated topic in the literature. Answering this question, we examined to what extent the more difficult access to verb semantics requires an additional engagement of cortical motor system in verb generation task. Using power suppression of MEG beta oscillations (15-30 Hz) as an index of sensorimotor activation, we presented to our participants the noun cues which either were strongly associated with a single verb and prompted the fast and effortless verb retrieval, or were weakly associated with multiple verbs and were more difficult to respond to. A whole-brain analysis of beta suppression revealed that the only cortical regions sensitive to the difficulty of semantic access were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. This differential activation of cortical motor system accompanied effortful verb retrieval and preceded the preparation of vocal response for more than 500 milliseconds. Since the mid-frontal frontal brain areas are involved in maintaining abstract representations of actions during their initiating and planning, we argue that our finding supports the view that motor associations contribute to retrieval of verb semantics.

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.

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.

We tested whether mirror visual feedback (MVF) from a moving hand induced high gamma oscillation (HGO) response in the hemisphere contralateral to the mirror and ipsilateral to the self-paced movement. MEG was recorded in 14 subjects under three conditions: bilateral synchronous movements of both index fingers (BILATERAL), movements of the right hand index finger while observing the immobile left index finger (NOMIRROR), and movements of the right hand index finger while observing its mirror reflection (MIRROR). The right hemispheric spatiospectral regions of interests (ROIs) in the sensor space, sensitive to bilateral movements, were found by statistical comparison of the BILATERAL spectral responses to baseline. For these ROIs, the post-movement HGO responses were compared between the MIRROR and NOMIRROR conditions. We found that MVF from the moving hand, similarly to the real movements of the opposite hand, induced HGOs (55-85Hz) in the sensorimotor cortex. This MVF effect was frequency-specific and did not spread to oscillations in other frequency bands. This is the first study demonstrating movement-related HGO induced by MVF from the moving hand in the absence of proprioceptive feedback signaling. Our findings support the hypothesis that MVF can trigger the feedback-based control processes specifically associated with perception of one's own movements.

Illusory contour (IC) perception, a fruitful model for studying the automatic contextual integration of local image features, can be used to investigate the putative impairment of such integration in children with autism spectrum disorders (ASD). We used the illusory Kanizsa square to test how the phase-locked (PL) gamma and beta electroencephalogram (EEG) responses of typically developing (TD) children aged 3-7 years and those with ASD were modulated by the presence of IC in the image. The PL beta and gamma activity strongly differentiated between IC and control figures in both groups of children (IC effect). However, the timing, topography, and direction of the IC effect differed in TD and ASD children. Between 40 msec and 120 msec after stimulus onset, both groups demonstrated lower power of gamma oscillations at occipital areas in response to IC than in response to the control figure. In TD children, this relative gamma suppression was followed by relatively higher parieto-occipital gamma and beta responses to IC within 120-270 msec after stimulus onset. This second stage of IC processing was absent in children with ASD. Instead, their response to IC was characterized by protracted (40-270 msec) relative reduction of gamma and beta oscillations at occipital areas. We hypothesize that children with ASD rely more heavily on lower-order processing in the primary visual areas and have atypical later stage related to higher-order processes of contour integration.

Unusual reactions to auditory stimuli are often observed in autism and may relate to ineffective inhibitory modulation of sensory input (sensory gating). A previous study of P50 sensory gating did not reveal abnormalities in high-functioning school age children [C. Kemner, B. Oranje, M.N. Verbaten, H. van Engeland, Normal P50 gating in children with autism, J. Clin. Psychiatry 63 (2002) 214-217]. Sensory gating deficit may, however, characterize younger children with autism or be a feature of retarded children with autism, reflecting imbalance of neuronal excitation/inhibition in these cohorts. We applied a paired clicks paradigm to study P50 sensory gating, and its relation to IQ and EEG gamma spectral power (as a putative marker of cortical excitability), in young (3-8 years) children with autism (N=21) and age-matched typically developing children (N=21). P50 suppression in response to the second click was normal in high-functioning children with autism, but significantly (p

Gamma oscillations are generated in networks of inhibitory fast-spiking (FS) parvalbumin-positive (PV) interneurons and pyramidal cells. In animals, gamma frequency is modulated by the velocity of visual motion; the effect of velocity has not been evaluated in humans. In this work, we have studied velocity-related modulations of gamma frequency in children using MEG/EEG. We also investigated whether such modulations predict the prominence of the “spatial suppression” effect (Tadin D, Lappin JS, Gilroy LA, Blake R. Nature 424: 312-315, 2003) that is thought to depend on cortical center-surround inhibitory mechanisms. MEG/EEG was recorded in 27 normal boys aged 8–15 yr while they watched high-contrast black-and-white annular gratings drifting with velocities of 1.2, 3.6, and 6.0°/s and performed a simple detection task. The spatial suppression effect was assessed in a separate psychophysical experiment. MEG gamma oscillation frequency increased while power decreased with increasing velocity of visual motion. In EEG, the effects were less reliable. The frequencies of the velocity-specific gamma peaks were 64.9, 74.8, and 87.1 Hz for the slow, medium, and fast motions, respectively. The frequency of the gamma response elicited during slow and medium velocity of visual motion decreased with subject age, whereas the range of gamma frequency modulation by velocity increased with age. The frequency modulation range predicted spatial suppression even after controlling for the effect of age. We suggest that the modulation of the MEG gamma frequency by velocity of visual motion reflects excitability of cortical inhibitory circuits and can be used to investigate their normal and pathological development in the human brain.

We examined the hypothesis of lower-level processing abnormalities related to perceptual grouping in boys with autism aged 3-6 years. We investigated event-related potentials response to visual elements that either formed perceptually coherent illusory contour or were arranged in a noncoherent way. The results showed that in healthy boys the illusory contour as compared with control stimulus elicited enhanced negativity of N1 peak (C effect), which has been previously found in adults. Autistic boys demonstrated the reliable inverted illusory contour effect, that is, more positive N1 amplitude to illusory contour. We hypothesized that boys with autism were sensitive to difference between illusory contour and control figures basing on collinearity processing mechanisms implemented in neural circuitry of primary visual cortex.

Background Recent studies link autism spectrum disorders (ASD) with an altered balance between excitation and inhibition (E/I balance) in cortical networks. The brain oscillations in high gamma-band (50–120 Hz) are sensitive to the E/I balance and may appear useful biomarkers of certain ASD subtypes. The frequency of gamma oscillations is mediated by level of excitation of the fast-spiking inhibitory basket cells recruited by increasing strength of excitatory input. Therefore, the experimental manipulations affecting gamma frequency may throw light on inhibitory networks dysfunction in ASD. Methods Here, we used magnetoencephalography (MEG) to investigate modulation of visual gamma oscillation frequency by speed of drifting annular gratings (1.2, 3.6, 6.0 °/s) in 21 boys with ASD and 26 typically developing boys aged 7–15 years. Multitaper method was used for analysis of spectra of gamma power change upon stimulus presentation and permutation test was applied for statistical comparisons. We also assessed in our participants visual orientation discrimination thresholds, which are thought to depend on excitability of inhibitory networks in the visual cortex. Results Although frequency of the oscillatory gamma response increased with increasing velocity of visual motion in both groups of participants, the velocity effect was reduced in a substantial proportion of children with ASD. The range of velocity-related gamma frequency modulation correlated inversely with the ability to discriminate oblique line orientation in the ASD group, while no such correlation has been observed in the group of typically developing participants. Conclusions Our findings suggest that abnormal velocity-related gamma frequency modulation in ASD may constitute a potential biomarker for reduced excitability of fast-spiking inhibitory neurons in a subset of children with ASD. Electronic supplementary material The online version of this article (doi:10.1186/s11689-015-9121-x) contains supplementary material, which is available to authorized users.