Andrey O. Prokofyev

Sensory gating in young children with autism: Relation to age, IQ, and EEG gamma oscillations

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<0.03) reduced in those with mental retardation. P50 gating improved with age in both typically developing children and those with autism. Higher ongoing EEG gamma power corresponded to lower P50 suppression in autism (p<0.02), but not in control group. The data suggest that ineffective inhibitory control of sensory processing is characteristic for retarded children with autism and may reflect excitation/inhibition imbalance in this clinical group.

High-frequency oscillatory response to illusory contour in typically developing boys and boys with autism spectrum disorders

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.

Inverted event-related potentials response to illusory contour in boys with autism

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.

The mirror illusion induces high gamma oscillations in the absence of movement

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 ones own movements.

Timing of cortical events preceding voluntary movement

We studied magnetic signals from the human brain recorded during a second before a self-paced finger movement. Sharp triangular peaks were observed in the averaged signals about 0.7 second before the finger movement. The amplitude of the peaks varied considerably from trial to trial, which indicated that the peaks were concurrent with much longer oscillatory processes. One can cluster trials into distinct groups with characteristic sequences of events. Prominent short trains of pulses in the beta frequency band were identified in the premovement period. This observation suggests that during preparation of the intended movement, cortical activity is well organized in time but differs from trial to trial. Magnetoencephalography can capture these processes with high temporal resolution and allows their study in fine detail.

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.

Modulation of visual gamma oscillation by excitatory drive and the excitation/inhibition balance in the visual cortex

Cortical gamma oscillations are generated in circuits that include excitatory (E) and inhibitory (I) neurons. Prominent MEG/EEG gamma oscillations in visual cortex can be induced by static or moving high-contrast edges stimuli. In a previous study in children, we observed that increasing velocity of visual motion substantially accelerated gamma oscillations, and led to the suppression of gamma response magnitude. These velocity-related modulations might reflect the balance between neural excitation induced by increasing excitatory drive, and efficacy of inhibition. Here, we searched for functional correlates of visual gamma modulations and assessed their development in 75 typically developing individuals aged 7-40 years. Gamma oscillations were measured with MEG in response to high-contrast annular gratings drifting at 1.2, 3.6, or 6.0 deg/s. In adults, we also recorded pupillary constriction as an indirect measure of excitatory drive. Pupil constriction increased with increasing velocity, thus suggesting increased excitatory drive to the cortex. Despite drastic developmental changes in gamma frequency and response strength, the magnitude of the velocity-related gamma modulations - a shift to higher frequency and amplitude suppression - remained remarkably stable. Based on the previous simulation studies, we hypothesized that gamma suppression might result from excessively strong excitatory drive caused by increasing motion velocity and reflects a trade-off between overexcited excitatory and inhibitory circuitry. In children, the stronger gamma suppression correlated with higher IQ, suggesting importance of an optimal E/I balance for cognitive functioning. The velocity-related changes in gamma response may appear useful to assess E/I balance 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.