Clinical Study
Increased premotor cortex activation in high functioning autism during action observation

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Abstract

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger’s syndrome were compared to typically developing individuals (n = 12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system.

Introduction

Autism spectrum disorders (ASD) are pervasive, neurodevelopmental conditions, with a prevalence of approximately 1–2% of the population [1], [2]. According to the Diagnostic and Statistical Manual V (DSM V) [3], ASD is characterized by anomalies in two key domains: social communication, and repetitive and/or stereotyped patterns of behaviour. At present, the phenotype is broad and ill-defined where diagnosis is made on the basis of behavioural presentation.

In 1999, two research groups independently suggested that a network of visuomotor cells, mirror neurons (MN), might be a potential biomarker to ASD [4], [5]. MN can be distinguished from other motor neurons by discharging both when an individual performs an action (such as reaching for food), and when an individual watches another performing a similar action (such as a friend reaching for some food) [6]. Research using techniques such as functional MRI (fMRI) [7], [8], transcranial magnetic stimulation [9] and electroencephalography (EEG) [10] provide indirect evidence that MN constitute a fronto-parieto network in humans. These regions are the premotor cortex (PMC), the pars opercularis of the inferior frontal gyrus, the inferior parietal lobule and the superior temporal sulcus [11], [12], [13]. More recent depth electrode research on humans suggests neurons with mirror properties are located in supplementary motor areas and medial temporal areas, in addition to non-significant quantities in the anterior cingulate cortex (ACC) [14].

It has been theorized that MN may be a neural substrate to simulation-based theories of how we understand the actions of other people [15]. This theoretical link has prompted research into the potential role of MN in ASD. To date, EEG research has revealed evidence of both typical [16], [17] and atypical [4], [18], [19], [20] MN response in ASD. Regarding fMRI research, findings have been mixed. During observation of emotional stimuli, there is evidence of reduced [21], [22], [23] blood oxygen level dependent (BOLD) response in regions believed to possess MN in ASD compared to typically developing (TD) individuals. In contrast, paradigms requiring observation of non-emotional hand based actions have revealed both increased [24], [25] and equivalent [26], [27] BOLD responses in mirror regions of ASD compared to TD participants. These studies on hand actions have varied considerably in what stimuli are used as a baseline condition, including a non-moving hand [25], a blank screen [26] and geometric patterns [27], which is likely to contribute to the mixed findings.

Using fMRI, the present study will compare BOLD response of participants with high functioning autism and Asperger’s syndrome (HFA/AS) to TD individuals. Videos of goal directed hand actions will be contrasted with still images of a non-moving hand, making the paradigm comparable to previous research which reported a heightened BOLD response in MN regions in ASD [24], [25]. Based upon this limited literature, two hypotheses were generated. Firstly, that both groups would demonstrate significantly increased BOLD response in MN regions during observation of hand actions as compared to baseline. Secondly, when contrasting the groups, the HFA/AS group will demonstrate increased BOLD in frontal, parietal and temporal MN areas as compared to TD participants.

Section snippets

Participants

The present study compared 12 TD participants (mean age = 19.75 years) with 12 individuals who had a previous diagnosis of either autistic disorder or AS (mean age = 18.50 years). Participants with HFA/AS were recruited from various autism support organizations (such as Autism Victoria) and specialist schools (such as Western Autism). In this study, all participants were male, and the age range was from 16–30 years. An experienced clinical psychologist who has worked extensively in the autism field

Within group analysis

For both groups a significant signal increase was observed in all hypothesized MN regions, comprised of pre-frontal (pars opercularis, PMC), parietal (supramarginal gyrus) and temporal (superior temporal sulcus) regions. During the hand observation task, several other voxel clusters demonstrated a similar pattern of activation in both groups, corresponding to visual (middle occipital gyrus) and frontal (inferior and middle frontal gyrus) regions. Participants with HFA/AS demonstrated additional

Discussion

Using fMRI, the present study contrasted BOLD response of participants with HFA/AS to TD participants whilst observing hand actions. The first hypothesis that both groups would demonstrate a significant BOLD increase in MN regions during action observation compared to baseline was supported. Within group analyses demonstrated signal increases in frontal (BA6, BA44), parietal (BA40) and temporal (BA22) MN regions bilaterally in both groups. Activation in these brain regions whilst observing

Conflicts of Interest/Disclosures

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

Acknowledgments

The authors would like to thank all participants in this study and the MRI radiographers at the Brain Research Institute. The authors would also like to acknowledge the assistance of Danny Flanagan throughout this research, and Shawna Farquarson whose patience and technical expertise was greatly appreciated.

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