Autism Spectrum Disorder: Seeing Is Not Understanding

Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting impairments in behaviour, social and communication skills. These deficits may arise from aberrant functional connections that impact synchronization and effective neural communication. Neurofeedback training (NFT), based on operant conditioning of the electroencephalogram (EEG), has shown promise in addressing abnormalities in functional and structural connectivity. We tested the efficacy of NFT in reducing symptoms in children with ASD by targeting training to the mirror neuron system (MNS) via modulation of EEG mu rhythms. The human MNS has provided a neurobiological substrate for understanding concepts in social cognition relevant to behavioural and cognitive deficits observed in ASD. Furthermore, mu rhythms resemble MNS phenomenology supporting the argument that they are linked to perception and action. Thirty hours of NFT on ASD and typically developing (TD) children were assessed. Both groups completed an eyes-open/-closed EEG session as well as a mu suppression index assessment before and after training. Parents filled out pre- and post-behavioural questionnaires. The results showed improvements in ASD subjects but not in TDs. This suggests that induction of neuroplastic changes via NFT can normalize dysfunctional mirroring networks in children with autism, but the benefits are different for TD brains.

To probe the presence of mirror neurons in the human brain, cross-modal fMRI adaptation has been suggested as a suitable technique. The rationale behind this suggestion is that this technique allows making more accurate inferences about neural response properties underlying fMRI voxel activations, beyond merely showing shared voxels that are active during both action observation and execution. However, the validity of using cross-modal fMRI adaptation to demonstrate the presence of mirror neurons in parietal and premotor brain regions has been questioned given the inconsistent and weak results obtained in human studies. A better understanding of cross-modal fMRI adaptation effects in the macaque brain is required as the rationale for using this approach is based on several assumptions related to macaque mirror neuron response properties that still need validation. Here, we conducted a cross-modal fMRI adaptation study in macaque monkeys, using the same action execution and action observation tasks that successfully yielded mirror neuron region cross-modal action decoding in a previous monkey MVPA study. We scanned two male rhesus monkeys while they first executed a sequence of either reach-and-grasp or reach-and-touch hand actions and then observed a video of a human actor performing these motor acts. Both whole-brain and region-of-interest analyses failed to demonstrate cross-modal fMRI adaptation effects in parietal and premotor mirror neuron regions. Our results, in line with previous findings in non-human primates, show that cross-modal motor-to-visual fMRI adaptation is not easily detected in monkey brain regions known to house mirror neurons. Thus, our results advocate caution in using cross-modal fMRI adaptation as a method to infer whether mirror neurons can be found in the primate brain.

This study investigates the relationship between the perceived stress of parents with a child with (characteristics of) an autism spectrum disorder (ASD) and the degree of ASD characteristics within parents. Data from 222 children (mean age 7.8 years) and their primary caregivers, previously collected as part of the Social Spectrum Study, were analyzed. Linear regression analyses were used to investigate the association between experienced parenting stress and the influence of parents’ own ASD characteristics, taking into account relevant covariates. This study shows that the experienced parenting stress does not show a significant relationship with the ASD characteristics of parents when relevant covariates (such as own psychiatric problems, ASD characteristics of the child and the partner relationship) are added. This study finds indications that parenting stress in parents of children with ASD appears to be more strongly related to their general perceived psychopathology than to their specific ASD characteristics. Further replication is warranted, and we advise research into interventions for parents that possibly prevent (further) stress associated with raising a child with ASD (characteristics).

Neural mechanisms of imitation and ‘mirror neuron’ functioning in autistic spectrum disorder

A lack of imitative behavior is frequently described as a core feature of Autism Spectrum Disorder (ASD), and is consistent with claims of mirror neuron system dysfunction in these individuals. Previous research has questioned this characterization of ASD however, arguing that when tests of automatic imitation are used--which do not require higher-level cognitive processing--imitative behavior is intact or even enhanced in individuals with ASD. In Experiment 1, 60 adult individuals with ASD and a matched Control group completed an automatic imitation task in which they were required to perform an index or a middle finger lift while observing a hand making either the same, or the alternate, finger movement. Both groups demonstrated a significant imitation effect whereby actions were executed faster when preceded by observation of the same action, than when preceded by the alternate action. The magnitude of this "imitation effect" was statistically indistinguishable in the ASD and Control groups. Experiment 2 utilized an improved automatic imitation paradigm to demonstrate that, when automatic imitation effects are isolated from those due to spatial compatibility, increasing autism symptom severity is associated with an increased tendency to imitate. Notably, there was no association between autism symptom severity and spatial compatibility, demonstrating the specificity of the link between ASD symptoms and increased imitation. These results provide evidence against claims of a lack of imitative behavior in ASD, and challenge the "Broken Mirror Theory of Autism."

Impaired social functioning is a hallmark feature of autism spectrum disorder (ASD), often requiring treatment throughout the life span. PEERS(®) (Program for the Education and Enrichment of Relational Skills) is a parent-assisted social skills training for teens with ASD. Although PEERS(®) has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America, the efficacy of this treatment has yet to be established in cross-cultural validation trials. The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS(®) for enhancing social skills through a randomized controlled trial (RCT).The English version of the PEERS(®) Treatment Manual (Laugeson & Frankel, 2010) was translated into Korean and reviewed by 21 child mental health professionals. Items identified as culturally sensitive were surveyed by 447 middle school students, and material was modified accordingly. Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient (IQ) ≥ 65. Eligible teens were randomly assigned to a treatment group (TG) or delayed treatment control group (CG). Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD. Secondary outcome measures included scales for depressive symptoms, anxiety, and other behavioral problems. Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS(®) treatment. Independent samples t-tests revealed no significant differences at baseline across the TG and CG conditions with regard to age (14.04 ± 1.64 and 13.54 ± 1.50 years), IQ (99.39 ± 18.09 & 100.67 ± 16.97), parental education, socioeconomic status, or ASD symptoms (p < 0.05), respectively. Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule, interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale (p's < 0.01), social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge-Revised (p < 0.01), and decreased depressive symptoms on the Child Depression Inventory following treatment (p < 0.05). Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables (p < 0.05). Despite cultural and linguistic differences, the PEERS(®) social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment. In an RCT, participants receiving the PEERS(®) treatment showed significant improvement in social skills knowledge, interpersonal skills, and play/leisure skills, as well as a decrease in depressive symptoms and ASD symptoms. This study represents one of only a few cross-cultural validation trials of an established evidence-based treatment for adolescents with ASD.

Traditionally the mirror neuron system (MNS) only includes premotor and posterior parietal cortices. However, somatosensory cortices, BA1/2 in particular, are also activated during action execution and observation. Here, we examine whether BA1/2 and the parietofrontal MNS integrate information by using functional magnetic resonance imaging (fMRI)-guided continuous theta-burst stimulation (cTBS) to perturb BA1/2. Measuring brain activity using fMRI while participants are under the influence of cTBS shows local cTBS effects in BA1/2 varied, with some participants showing decreases and others increases in the BOLD response to viewing actions vs control stimuli. We show how measuring cTBS effects using fMRI can harness this variance using a whole-brain regression. This analysis identifies brain regions exchanging action-specific information with BA1/2 by mapping voxels away from the coil with cTBS-induced, action-observation-specific BOLD contrast changes that mirror those under the coil. This reveals BA1/2 exchanges action-specific information with premotor, posterior parietal and temporal nodes of the MNS during action observation. Although anatomical connections between BA1/2 and these regions are well known, this is the first demonstration that these connections carry action-specific signals during observation and hence, that BA1/2 plays a causal role in the human MNS.

The mirror neuron system compensates for amygdala dysfunction - associated social deficits in individuals with higher autistic traits

Since their discovery, mirror neurons--units in the macaque brain that discharge both during action observation and execution--have attracted considerable interest. Whether mirror neurons are an innate endowment or acquire their sensorimotor matching properties ontogenetically has been the subject of intense debate. It is widely believed that these units are an innate trait; that we are born with a set of mature mirror neurons because their matching properties conveyed upon our ancestors an evolutionary advantage. However, an alternative view is that mirror neurons acquire their matching properties during ontogeny, through correlated experience of observing and performing actions. The present article re-examines frequently overlooked neurophysiological reports of 'tool-use' and 'audiovisual' mirror neurons within the context of this debate. It is argued that these findings represent compelling evidence that mirror neurons are a product of sensorimotor experience, and not an innate endowment.

Language impairments, a hallmark feature of autism spectrum disorders (ASD), have been related to neuroanatomical and functional abnormalities. Abnormal lateralization of the functional language network, increased reliance on visual processing areas, and increased posterior brain activation have all been reported in ASD and proposed as explanatory models of language difficulties. Nevertheless, inconsistent findings across studies have prevented a comprehensive characterization of the functional language network in ASD. The aim of this study was to quantify common and consistent patterns of brain activation during language processing in ASD and typically developing control (TD) participants using a meta-analytic approach. Activation likelihood estimation (ALE) meta-analysis was used to examine 22 previously published functional Magnetic Resonance Imaging (fMRI)/positron emission tomography studies of language processing (ASD: N = 328; TD: N = 324). Tasks included in this study addressed semantic processing, sentence comprehension, processing figurative language, and speech production. Within-group analysis showed largely overlapping patterns of language-related activation in ASD and TD groups. However, the ASD participants, relative to TD participants, showed: (1) more right hemisphere activity in core language areas (i.e., superior temporal gyrus and inferior frontal gyrus), particularly in tasks where they had poorer performance accuracy; (2) bilateral MTG hypo-activation across many different paradigms; and (3) increased activation of the left lingual gyrus in tasks where they had intact performance. These findings show that the hypotheses reviewed here address the neural and cognitive aspects of language difficulties in ASD across all tasks only in a limited way. Instead, our findings suggest the nuances of language and brain in ASD in terms of its context-dependency. Autism Res 2016, 9: 1046-1057. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

The mirror neuron system consists of fronto-parietal regions and responds to both goal-directed action execution and observation. The broader action observation network is specifically involved in observation of actions and is thought to play a role in understanding the goals of the motor act, the intention of others, empathy, and language. Many, but not all, studies have found mirror neuron system or action observation network dysfunction in autism spectrum disorder. The objective of this study was to use observation of a goal-directed action fMRI paradigm to examine the action observation network in autism spectrum disorder and to determine whether fronto-parietal activation is associated with language ability. Adolescents with autism spectrum disorder (n = 23) were compared to typically developing adolescents (n = 20), 11-17years. Overall, there were no group differences in activation, however, the autism spectrum group with impaired expressive language (n = 13) had significantly reduced inferior frontal and inferior parietal activation during action viewing. In controls, right supramarginal gyrus activation was associated with higher expressive language; bilateral supramarginal and left pars opercularis activation was associated with better verbal-gesture integration. Results suggest that action-observation network dysfunction may characterize a subgroup of individuals with autism spectrum disorder with expressive language deficits. Therefore, interventions that target this dysfunctional network may improve expressive language in this autism spectrum subgroup. Future treatment studies should individualize therapeutic approaches based on brain-behavior relationships.

Among Leibniz’s contributions to the philosophy of mind, two topics bear relevance to contemporary discussions in cognitive sciences: the mind-body problem, and the universal language. Leibniz’s deterministic view rejects inter-substance causality between mental and bodily states, as well as between mental or bodily states of different individuals. In addition, Leibniz believed in the need to enhance communication through a universal language based on symbolic representations. Here I reconsider Leibniz’s ideas in the light of experimental evidence coming from mirror neurons. These recently discovered brain cells, responsive to both action execution and observation, are thought to enable the interpretation of the action performer’s intentions through their representation in the observer’s own brain, thus storing embodied shared representations. I propose that mirror neurons’ cross-modal responsiveness, whereby seeing an action being performed by somebody else triggers similar neural response to that of performing that action oneself, can be interpreted as an instantiation of intersubstance causality. I suggest that mirror neurons’ properties speak not only to the non-dualistic equation, supported by brain science in general, whereby in a given individual, mental states arise from bodily states but also introduce the possibility that bodily states may arise from someone else’s bodily states. In addition, I propose that this automatic embodied flow of information between individuals (from performer to observer) bears relevance to Leibniz’s intuitions on symbols. Specifically, I suggest that the shared representations stored in mirror neurons, thought to enable the interpretation of the action performer’s intentions, may be seen as a biological instantiation of Leibniz’s planned, but never realized, universal characteristic.

IntroductionDespite extensive investigation, the neurophysiological underpinnings of ASD remain poorly understood; a predominant hypothesis relates to the activity of the brain’s mu-rhythm (defined as the frequency band ranging between 8–14 Hz topographically centered over the sensorimotor cortex) and the so-called “Mirror Neuron System” (MNS), considered as an execution-imagination-observation matching system. In particular, mirror neurons (MN) are bimodal neurons located in the ventral premotor cortex, discharging both when a goal-directed action is performed and when it is observed. Previous studies investigating mu-wave suppression in individuals with ASD were limited by having consistently employed video clips filmed with a fixed camera position, hence not including the potential movement of the observer towards the other person (a condition perceived as more ecological and close to reality).ObjectivesAim of this study was to investigate differences in mu-wave modulation in individuals with Autism Spectrum Disorder (ASD) without intellectual disabilities with respect to a group of neurotypical controls (NT).MethodsThirty individuals with ASD and thirty NT underwent an EEG recording while watching short videos depicting goal-oriented action filmed from a fixed position, zooming in on the scene, and approaching the scene by means of a steadycam. Afterwards, participants underwent a rating task to evaluate their subjective viewing experience.ResultsSteadycam videos elicited enhanced event-related desynchronization (ERD), suggestive of an enhanced neural activity, in the NT group, and a reduced ERD in the ASD group, with respect to the other filming conditions. ASD participants also showed difficulties in returning to baseline mu-power levels after watching videos filmed from a fixed position. NT reported to feel more comfortable watching videos with movement, whereas participants with ASD did not exhibit differences between conditions.ConclusionsThe ecological nature of video recording (i.e., visual stimuli filmed with a steadycam) seems to have an opposite effect on the ASD an NT population, as it enhances mu-wave suppression in NT, and reduces it in individuals with ASD, bringing them to a level of desynchronization closer to the one of NT. Understanding these differences might help developing tailored interventions to support perceptual, cognitive, and social processes of people with ASD.Disclosure of InterestNone Declared

The aim of this study was to examine the relationship between emotion dysregulation and the core features of Autism Spectrum Disorder (ASD), which include social/communication deficits, restricted/repetitive behaviors, and sensory abnormalities. An 18-item Emotion Dysregulation Index was developed on the basis of expert ratings of the Child Behavior Checklist. Compared to typically developing controls, children and adolescents with ASD showed more emotion dysregulation and had significantly greater symptom severity on all scales. Within ASD participants, emotion dysregulation was related to all core features of the disorder, but the strongest association was with repetitive behaviors. These findings may facilitate the development of more effective therapeutic strategies targeting emotion dysregulation in order to optimize long-term outcomes for individuals with ASD.

Many human behaviours and pathologies have been attributed to the putative mirror neuron system, a neural system that is active during both the observation and execution of actions. While there are now a very large number of papers on the mirror neuron system, variations in the methods and analyses employed by researchers mean that the basic characteristics of the mirror response are not clear. This review focuses on three important aspects of the mirror response, as measured by modulations in corticospinal excitability: (1) muscle specificity; (2) direction; and (3) timing of modulation. We focus mainly on electromyographic (EMG) data gathered following single-pulse transcranial magnetic stimulation (TMS), because this method provides precise information regarding these three aspects of the response. Data from paired-pulse TMS paradigms and peripheral nerve stimulation (PNS) are also considered when we discuss the possible mechanisms underlying the mirror response. In this systematic review of the literature, we examine the findings of 85 TMS and PNS studies of the human mirror response, and consider the limitations and advantages of the different methodological approaches these have adopted in relation to discrepancies between their findings. We conclude by proposing a testable model of how action observation modulates corticospinal excitability in humans. Specifically, we propose that action observation elicits an early, non-specific facilitation of corticospinal excitability (at around 90ms from action onset), followed by a later modulation of activity specific to the muscles involved in the observed action (from around 200ms). Testing this model will greatly advance our understanding of the mirror mechanism and provide a more stable grounding on which to base inferences about its role in human behaviour.