Brain oscillations and connectivity in autism spectrum disorders (ASD):new approaches to methodology, measurement and modelling

Although atypical social behaviour remains a key characterisation of ASD, the presence ofsensory and perceptual abnormalities has been given a more central role in recentclassification changes. An understanding of the origins of such aberrations could thus prove afruitful focus for ASD research. Early neurocognitive models of ASD suggested that thestudy of high frequency activity in the brain as a measure of cortical connectivity mightprovide the key to understanding the neural correlates of sensory and perceptual deviations inASD. As our review shows, the findings from subsequent research have been inconsistent,with a lack of agreement about the nature of any high frequency disturbances in ASD brains.Based on the application of new techniques using more sophisticated measures of brainsynchronisation, direction of information flow, and invoking the coupling between high andlow frequency bands, we propose a framework which could reconcile apparently conflictingfindings in this area and would be consistent both with emerging neurocognitive models ofautism and with the heterogeneity of the condition

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Abstract Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently

Individual differences in sensory sensitivity: a synthesising framework and evidence from normal variation and developmental conditions

For some people, simple sensory stimuli (e.g., noises, patterns) may reliably evoke intense and aversive reactions. This is common in certain clinical groups (e.g., autism) and varies greatly in the neurotypical population. This paper critically evaluates the concept of individual differences in sensory sensitivity, explores its possible underlying neurobiological basis, and presents a roadmap for future research in this area. A distinction is made between subjective sensory sensitivity (self-reported symptoms); neural sensory sensitivity (the degree of neural activity induced by sensory stimuli); and behavioral sensory sensitivity (detection and discrimination of sensory stimuli). Whereas increased subjective and neural sensory sensitivity are assumed to increase together, the status of behavioral sensory sensitivity depends on the extent to which the increased neural activity is linked to signal or noise. A signal detection framework is presented that offers a unifying framework for exploring sensory sensitivity across different conditions. The framework is discussed, in more concrete terms, by linking it to four existing theoretical accounts of atypical sensory sensitivity (not necessarily mutually exclusive): increased excitation-to-inhibition ratio; predictive coding; increased neural noise; and atypical brain connectivity

A Neural “Tuning Curve” for Multisensory Experience and Cognitive-Perceptual Schizotypy

Our coherent perception of external events is enabled by the integration of inputs from different senses occurring within a range of temporal offsets known as the temporal binding window (TBW), which varies from person to person. A relatively wide TBW may increase the likelihood that stimuli originating from different environmental events are erroneously integrated and abnormally large TBW has been found in psychiatric disorders characterized by unusual perceptual experiences. Despite strong evidence of interindividual differences in TBW, both within clinical and nonclinical populations, the neurobiological underpinnings of this variability remain unclear. We adopted an integrated strategy linking TBW to temporal dynamics in functional magnetic resonance imaging (fMRI)-resting-state activity and cortical excitation/inhibition (E/I) balance, indexed by glutamate/Gamma-AminoButyric Acid (GABA) concentrations and common variation in glutamate and GABA genes in a healthy sample. Stronger resting-state longrange temporal correlations, indicated by larger power law exponent (PLE), in the auditory cortex, robustly predicted narrower audio-tactile TBW, which was in turn associated with lower cognitive-perceptual schizotypy. Furthermore, PLE was highest and TBW narrowest for individuals with intermediate levels of E/I balance, with shifts towards either extreme resulting in reduced multisensory temporal precision and increased schizotypy, effectively forming a neural ?tuning curve? for multisensory experience and schizophrenia risk. Our findings shed light on the neurobiological underpinnings of multisensory integration and its potentially clinically relevant inter-individual variability

Visual perception in infancy and its links to later autism

Alterations in primary sensory areas of the brain have been suggested to be at the roots of the well-documented visual perceptual differences in autism. However, despite the possible key role these sensory processing alterations may play in the early development of autism, few studies have tried to clarify the links. Moreover, not much is known about which specific sensory alterations are most strongly linked to the core autistic symptoms. The purpose of this thesis is to increase our knowledge about whether and how visual sensory processing differences manifest during early infancy and how they relate to later development of cognitive and social communicative abilities as well as to the emerging core social domain symptoms of autism. EEG neuroimaging was used as the means of investigation into infants’ brain activities. Comparisons between infants at elevated familial likelihood of developing autism and typically developing infants were done to see how the brain activity patterns differ. Study I inquired whether differences in low-level global and local visual (motion and form) processing at age 5 months are linked to the acquired motor and language abilities at age 14 months. Only global motion processing was found to be linked to later language ability, and this association was specific to language comprehension. Study II inquired whether differences in low-level global and local visual (motion and form) processing at age 5 months are in any way linked to the emerging core autistic symptoms at age 36 months, and how visual cortical organization that underlies such global and local perceptions differ between infants who later develop high levels of autistic symptoms and infants who do not develop the symptoms. Furthermore, relative influences of genes and environment on these low-level visual perceptual processes were assessed. Only global motion processing was found to be linked to the emerging autistic symptoms at 36 months, and this was specific to the social domain symptoms. Accordingly, and the global motion visual cortical organization in infants with later autism was found to be distinctive from the normative infants, showing an altered balance of activity between midline and lateral area. Global motion processing was found to be lowto-moderately heritable. Study III sought to clarify if the results of Study II could be linked to functional brain connectivity. Specifically, this study inquired whether i) visual cortical functional connectivity during processing of social and non-social stimuli at 5 months are linked to the contemporaneous global visual motion processing investigated in Study II; and ii) whether functional connectivity differences are in any way also linked to the emerging core autistic symptoms at age 36 months. Indeed, visual cortical gamma connectivity during social stimulus processing was found to be linked to global motion processing and it is also linked to the emerging autistic symptoms at 36 months. Furthermore, visual cortical theta connectivity during non-social stimulus processing was found to be strongly associated with the emerging autistic symptoms at 36 months, but not to motion processing. In summary, the results of these three studies demonstrate that atypical global visual motion processing, possibly linked to altered functional connectivity in the visual cortex, may occupy an important position in the pathways leading to the social domain symptoms of autism

Unreliable Evoked Responses in Autism

SummaryAutism has been described as a disorder of general neural processing, but the particular processing characteristics that might be abnormal in autism have mostly remained obscure. Here, we present evidence of one such characteristic: poor evoked response reliability. We compared cortical response amplitude and reliability (consistency across trials) in visual, auditory, and somatosensory cortices of high-functioning individuals with autism and controls. Mean response amplitudes were statistically indistinguishable across groups, yet trial-by-trial response reliability was significantly weaker in autism, yielding smaller signal-to-noise ratios in all sensory systems. Response reliability differences were evident only in evoked cortical responses and not in ongoing resting-state activity. These findings reveal that abnormally unreliable cortical responses, even to elementary nonsocial sensory stimuli, may represent a fundamental physiological alteration of neural processing in autism. The results motivate a critical expansion of autism research to determine whether (and how) basic neural processing properties such as reliability, plasticity, and adaptation/habituation are altered in autism

Impairment of perceptual closure in autism for vertex- but not edge-defined object images

One of the characteristics of autism spectrum disorder (ASD) is atypical sensory processing and perceptual integration. Here, we used an object naming task to test the significance of deletion of vertices versus extended contours (edges) in naming fragmented line drawings of natural objects in typically developing and ASD children. The basic components of a fragmented image in perceptual closure need to be integrated to make a coherent visual perception. When vertices were missing and only edges were visible, typically developing and ASD subjects performed similarly. But typically developing children performed significantly better than ASD children when only vertex information was visible. These results indicate impairment of binding vertices but not edges to form a holistic representation of an object in children with ASD