Auditory Cortex Responses to Clicks and Sensory Modulation Difficulties in Children with Autism Spectrum Disorders (ASD)

Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD

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

Thermal Perceptual Thresholds are typical in Autism Spectrum Disorder but Strongly Related to Intra-individual Response Variability

Individuals with autism spectrum disorder (ASD) are often reported to exhibit an apparent indifference to pain or temperature. Leading models suggest that this behavior is the result of elevated perceptual thresholds for thermal stimuli, but data to support these assertions are inconclusive. An alternative proposal suggests that the sensory features of ASD arise from increased intra-individual perceptual variability. In this study, we measured method-of-limits warm and cool detection thresholds in 142 individuals (83 with ASD, 59 with typical development [TD], aged 7–54 years), testing relationships with diagnostic group, demographics, and clinical measures. We also investigated the relationship between detection thresholds and a novel measure of intra-individual (trial-to-trial) threshold variability, a putative index of “perceptual noise.” This investigation found no differences in thermal detection thresholds between individuals with ASD and typical controls, despite large differences between groups in sensory reactivity questionnaires and modest group differences in intra-individual variability. Lower performance IQ, male sex, and higher intra-individual variability in threshold estimates were the most significant predictors of elevated detection thresholds. Although no psychophysical measure was significantly correlated with questionnaire measures of sensory hyporeactivity, large intra-individual variability may partially explain the elevated psychophysical thresholds seen in a subset of the ASD population

Categorization for Faces and Tools—Two Classes of Objects Shaped by Different Experience—Differs in Processing Timing, Brain Areas Involved, and Repetition Effects

The brain mechanisms that integrate the separate features of sensory input into a meaningful percept depend upon the prior experience of interaction with the object and differ between categories of objects. Recent studies using representational similarity analysis (RSA) have characterized either the spatial patterns of brain activity for different categories of objects or described how category structure in neuronal representations emerges in time, but never simultaneously. Here we applied a novel, region-based, multivariate pattern classification approach in combination with RSA to magnetoencephalography data to extract activity associated with qualitatively distinct processing stages of visual perception. We asked participants to name what they see whilst viewing bitonal visual stimuli of two categories predominantly shaped by either value-dependent or sensorimotor experience, namely faces and tools, and meaningless images. We aimed to disambiguate the spatiotemporal patterns of brain activity between the meaningful categories and determine which differences in their processing were attributable to either perceptual categorization per se, or later-stage mentalizing-related processes. We have extracted three stages of cortical activity corresponding to low-level processing, category-specific feature binding, and supra-categorical processing. All face-specific spatiotemporal patterns were associated with bilateral activation of ventral occipito-temporal areas during the feature binding stage at 140–170 ms. The tool-specific activity was found both within the categorization stage and in a later period not thought to be associated with binding processes. The tool-specific binding-related activity was detected within a 210–220 ms window and was located to the intraparietal sulcus of the left hemisphere. Brain activity common for both meaningful categories started at 250 ms and included widely distributed assemblies within parietal, temporal, and prefrontal regions. Furthermore, we hypothesized and tested whether activity within face and tool-specific binding-related patterns would demonstrate oppositely acting effects following procedural perceptual learning. We found that activity in the ventral, face-specific network increased following the stimuli repetition. In contrast, tool processing in the dorsal network adapted by reducing its activity over the repetition period. Altogether, we have demonstrated that activity associated with visual processing of faces and tools during the categorization stage differ in processing timing, brain areas involved, and in their dynamics underlying stimuli learning

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

Reduced oblique effect in children with Autism Spectrum Disorders (ASD)

People are very precise in the discrimination of a line orientation relative to the cardinal (verti-cal and horizontal) axes, while their orientation discrimination sensitivity along the oblique ax-es is less refined. This difference in discrimination sensitivity along cardinal and oblique axes is called the oblique effect. Given that the oblique effect is a basic feature of visual pro-cessing with an early developmental origin, its investigation in children with Autism Spectrum Disorder (ASD) may shed light on the nature of visual sensory abnormalities frequently report-ed in this population. We examined line orientation sensitivity along oblique and vertical axes in a sample of 26 boys with ASD (IQ > 68) and 38 typically developing (TD) boys aged 7-15 years, as well as in a subsample of carefully IQ-matched ASD and TD participants. Children were asked to detect the direction of tilt of a high-contrast black-and-white grating relative to vertical (90°) or oblique (45°) templates. The oblique effect was reduced in children with ASD as compared to TD participants, irrespective of their IQ. This reduction was due to poor orien-tation sensitivity along vertical axis in ASD children, while their ability to discriminate line orientation along oblique axis was unaffected. We speculate that this deficit in sensitivity to vertical orientation may reflect disrupted mechanisms of early experience-dependent learning that takes place during the critical period for orientation selectivity

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

Abstract 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