Mirror neuron dysfunction in autism spectrum disorders

doi:10.1016/j.jocn.2010.01.026

Journal of Clinical Neuroscience

Volume 17, Issue 10, October 2010, Pages 1239-1243

https://doi.org/10.1016/j.jocn.2010.01.026 Get rights and content

Abstract

Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system has been suggested as a disturbance linked to the disorder. Mirror neurons (MNs) are visuomotor neurons which discharge both when performing and observing a goal directed action. Research suggests MNs may have a role in imitation, empathy, theory of mind and language. Although the research base is small, evidence from functional MRI, transcranial magnetic stimulation, and an electroencephalographic component called the mu rhythm suggests MNs are dysfunctional in subjects with ASD. These deficits are more pronounced when ASD subjects complete tasks with social relevance, or that are emotional in nature. Promising research has identified that interventions targeting MN related functions such as imitation can improve social functioning in ASDs. Boosting the function of MNs may improve the prognosis of ASDs, and contribute to diagnostic clarity.

Introduction

Autism spectrum disorders (ASDs) are pervasive, developmental, neurological conditions which adversely impact behaviour in three key domains: social interaction, verbal and nonverbal communication, and obsessive and/or stereotyped patterns of behaviour.¹ Abnormal or impaired social interaction is characterized by deficits in joint attention, reciprocity, imitation, empathy, relationships, as well as hyperactive/impulsive behaviour and social anxiety. Communicative deficits in language include odd prosody, failure to understand metaphors or statements with implied meaning, idiosyncratic use of words and delayed speech development. Obsessive interests and stereotyped patterns of behaviour including an intense interest in a particular subject matter, preoccupation with small details as opposed to global functioning, inflexible adherence to non-functional routines and rituals, and abnormal motor and sensory functioning.² Although presentation varies considerably across individuals, these core characteristics are defined as deviant relative to the individual’s developmental level.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM IV-TR),³ describes two major ASDs; Autistic disorder (AD) and Asperger’s syndrome (AS).⁴ Although subject to ongoing debate, AS is diagnostically differentiated from AD on the basis of normal language development, defined as expression of single words by age 2 years and communicative phrases by age 3 years.³ Where intellectual functioning is not impaired (IQ > 70–85) in AD, the condition is termed high functioning autism (HFA). A meta-analysis of 43 studies estimates the prevalence of autism (AD and HFA) to be approximately 0.13% of the population, and AS 0.03%.⁵

To date, an important issue confronting clinicians and researchers is the absence of definable and reliable, neurophysiological markers to the disorder. Diagnosis is made on the basis of behavioural symptoms, which reduces diagnostic clarity and limits the capacity to identify these conditions early and accurately. In 1999, two research groups independently suggested that a network of visuomotor cells known as mirror neurons (MNs) may contribute to some of the key symptoms that characterize autism.6, 7

Section snippets

Mirror neurons

MNs are activated by the performance or observation of object or goal directed actions. What distinguishes MNs from other motor neurons is they not only discharge when an individual performs a particular action (such as reaching for a piece of food), but also when an individual watches somebody else perform a similar action (such as a friend reaching for a piece of food).⁸

Studies in primates have identified a MN system consisting of the ventral premotor cortex (area F5) and inferior parietal

Initial theory

Prior to the discovery of MNs, a theory was penned that suggested a deficit in self-other matching may contribute to autism.¹⁷ This ability involves forming and coordinating mental representations of the self and others. Understanding others behaviours and social rules is achieved by extracting patterns of similarity between the self and other. It has now been acknowledged that this theory of autism is similar to the key role of MNs. Disruption of MN functioning may contribute to this

The case against mirror neurons

Despite this promising research base, numerous criticisms have been made toward the study of MNs in humans. Firstly, MNs have yet to be directly observed in humans.⁴² Secondly, MNs make up a small minority of observed cells in Macaques (approximately 6%; yet the distribution in humans remains unknown),⁹ which means interpretation of homologous areas in humans is not exclusively measuring suspected MN activity. Thirdly, it has been suggested that an exclusive MN explanation of imitation is too

Electroencephalograph (EEG)

One method to investigate MN activity in humans is via EEG. The mu wave measures large amplitude oscillations of the synchronized activity of sensorimotor neurons.⁴⁵ Whenever a voluntary movement is made, these sensorimotor neurons are desynchronized by input from pre-motor neurons (an area believed to house MNs), which blocks the mu wave. Of interest, it has been found that the mu wave is also blocked or suppressed when a person observes another individual performing a voluntary motor action.⁴⁶

Conclusions and future directions

In summary, there is evidence that brain regions believed to house MNs can be structurally and functionally disturbed in individuals with autism. Although it is premature to interpret findings with such a small research base, the current evidence suggests that MN disturbance is pronounced when information is of a social and emotional nature, or requires discrimination of different items (such as motor acts, or facial emotions). Abnormalities in MN areas have been strongly correlated to social

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There has also been a large body of work on the neural signature of action prediction in autism. The prediction of others' actions is implemented through motor system activation (Kilner et al., 2004, 2007; Monroy et al., 2019; Schubotz, 2007), and the Mirror Neuron Dysfunction theory posits a reduction in this activation in autism (Williams et al., 2001; Perkins et al., 2010). Motor system activation can be measured with EEG over the sensorimotor cortex, and is typically seen as a decrease in power in mu and beta frequency bands.
Most theoretical accounts of autism posit difficulties in predicting others' actions, and this difficulty has been proposed to be at the root of autistic individuals' social communication differences. Empirical results are mixed, however, with autistic individuals showing reduced action prediction in some studies but not in others. It has recently been proposed that this effect might be observed primarily when observed actions are less predictable, but this idea has yet to be tested. To assess the influence of predictability on neural and behavioural action prediction, the current study employed an action observation paradigm with multi-step actions that become gradually more predictable. Autistic and non-autistic adolescents showed similar patterns of motor system activation during observation, as seen in attenuated mu and beta power compared to baseline, with beta power further modulated by predictability in both groups. Bayesian statistics confirmed that action predictability influenced beta power similarly in both groups. The groups also made similar behavioural predictions, as seen in three eye-movement measures. We found no evidence that autistic adolescents responded differently than non-autistic adolescents to the predictability of an observed action. These findings show that autistic adolescents do spontaneously predict others’ actions, both neurally and behaviourally, which calls into question the role of action prediction as a key mechanism underlying autism.
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Hypoactivation in the mPFC, the ACC, and anterior paracingulate cortex have been reported in studies with theory of mind (ToM) paradigms (Castelli et al., 2000; Wang et al., 2007), but other studies found conflicting resutls (Baron-Cohen et al., 1999). Besides, ASD-related dysfunction in the MNS have been reported in motor mimicry, emotion processing (Dapretto et al., 2006), ToM (Perkins et al., 2010) and empathy (Greimel et al., 2010). In sum, dysfunction of social brain regions were found in individuals with ASD.
The social brain hypothesis is regarded as a powerful theory to understand social cognition. Individuals with autism spectrum disorder (ASD) have specific deficits in social and communicative behavior, but the exact relationship between these deficits and abnormalities in the social brain remains unclear. The high heritability of this disorder makes it important to focus on the first-degree relatives of those affected. Research focusing on genetically at-risk (yet healthy) relatives of patients with ASD is critical to the study of neuroimaging endophenotypes. We conducted a voxel-wise activation likelihood estimation (ALE) meta-analysis of 9 functional neuroimaging studies published during the period from 2006 to 2018. These studies included 200 individuals with ASD, 216 unaffected family members (UF), and 235 typical development controls (TD). The voxel-wise significance threshold was p < 0.01 (uncorrected p = 0.001).The ALE meta-analyses showed hyperactivation in the inferior frontal gyrus (IFG) and superior temporal gyrus (STG) among individuals with ASD and UF, compared with TD individuals. Group comparisons showed greater likelihood of hyperactivation in the amygdala for ASD, compared with UF and TD.
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The presence of corresponding deficits in ASD has given rise to the “Broken mirror theory” [10] which proposes that mirror neuron dysfunction contributes to core deficits of the disorder [11–13]. While the mechanism by which mirror neurons are impaired in ASD are not yet known, the enhancement or restoration of mirror neuron function has been promoted as one means of improving social cognition [14]. Mirror neurons are principally concentrated in the inferior frontal gyrus (IFG) and the inferior parietal lobe (IPL) in humans [12].
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The insular cortex, hidden within the lateral sulcus of the human brain, participates in a range of cognitive, affective, and sensory functions. Autism spectrum disorder (ASD), a neurodevelopmental condition affecting all of these functional domains, has increasingly been linked with atypical activation and connectivity of the insular cortices. Here we review the latest research linking atypical insular function to a range of behaviors characteristic of ASD, with an emphasis on neuroimaging findings in the domains of social cognition and executive function. We summarize some of the recent work linking the insula to interventions in autism, including oxytocin-based pharmacological treatments and music therapy. We suggest that future directions likely to yield significant insights into insular pathology in ASD include the analysis of the dynamics of this brain region. We also conclude that more basic research is necessary on the use of oxytocin pharmacotherapy, and larger studies addressing participant heterogeneity are needed on the use of music therapy in ASD. Long-term studies are needed to ascertain sustained effects of these interventions.
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No matter how well an animal, cellular or computation simulation model were developed; no model system can capture the full spectrum of clinical features and progression of human diseases. Therefore, the development of the best animal model possible with maximum potential to advance our knowledge on diseases such as Huntington's disease (HD) may better fit the mission. Transgenic HD monkeys that developed clinical features as the animals age are similar to those observed in human patients. Although HD monkeys hold great potential as a preclinical large animal model, HD monkey stem cells provide a unique platform for investigating the cellular pathogenesis and therapy discovery that is limited in HD monkeys. Here we present a fact check on the HD monkey model and HD monkey neural stem/progenitor cell model and their roles in advancing our knowledge in HD onset and development and their potential roles in future preclinical therapy development.
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This broken mirror neuron hypothesis of autism proposes that impaired social skills in autism are related to dysfunctions in the putative human mirror neuron system making it difficult for individuals with autism to simulate and thus understand others’ behavior (MNS; Altschuler et al., 2000; Ramachandran and Oberman, 2006). Some studies have offered supportive evidence for the involvement of the MNS (e.g. Perkins et al., 2010). However, both the validity of a broken MNS and a direct, causal relationship between the MNS and social skills in autism, have been challenged by other reports (e.g. Southgate and Hamilton, 2008).
Autism is a developmental condition, characterized by difficulties of social interaction and communication, as well as restricted interests and repetitive behaviors. Although several important conceptions have shed light on specific facets, there is still no consensus about a universal yet specific theory in terms of its underlying mechanisms. While some theories have exclusively focused on sensory aspects, others have emphasized social difficulties. However, sensory and social processes in autism might be interconnected to a higher degree than what has been traditionally thought. We propose that a mismatch in sensory abilities across individuals can lead to difficulties on a social, i.e. interpersonal level and vice versa. In this article, we, therefore, selectively review evidence indicating an interrelationship between perceptual and social difficulties in autism. Additionally, we link this body of research with studies, which investigate the mechanisms of action control in social contexts. By doing so, we highlight that autistic traits are also crucially related to differences in integration, anticipation and automatic responding to social cues, rather than a mere inability to register and learn from social cues. Importantly, such differences may only manifest themselves in sufficiently complex situations, such as real-life social interactions, where such processes are inextricably linked.

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Personal ViewMirror neuron dysfunction in autism spectrum disorders

Abstract

Introduction

Section snippets

Mirror neurons

Initial theory

The case against mirror neurons

Electroencephalograph (EEG)

Conclusions and future directions

Brain Res Cogn Brain Res

Neurosci Biobehav Rev

J Physiol-Paris

Neuroimage

Brain Res Cogn Brain Res

Neuropsychologia

Brain Res Rev

Neuron

Cognition

Cognition

Trends Cogn Sci

Trends Cogn Sci

Int J Psychophysiol

Brain Cogn

Neuropsychologia

Brain Res

Neuropsychologia

Neuroimage

Neuropsychologia

Curr Biol

The adult asperger assessment (AAA): a diagnostic method

J Autism Dev Disord

Autism: a window into the development of the social and the analytic brain

Annu Rev Neurosci

Diagnostic and statistical manual of mental disorders

The complete guide to Asperger’s syndrome

The changing epidemiology of autism

J Appl Res Intellect Disabil

The mirror-neuron system

Annu Rev Neurosci

Action recognition in the premotor cortex

Brain

Mirror neurons and mirror systems in monkeys and humans

Physiology

Action observation activates premotor and parietal areas in a somatopic manner: an fMRI study

Eur J Neurosci

Neural circuits involved in the recognition of actions performed by nonconspecifics: an fMRI study

J Cogn Neurosci

Personal View
Mirror neuron dysfunction in autism spectrum disorders