Movement interference in autism-spectrum disorder

Movement interference occurs when concurrently observing and executing incompatible actions and is believed to be due to co-activation of conflicting populations of mirror neurons. It has also been suggested that mirror neurons contribute towards the imitation of observed actions. However, the exact neural substrate of imitation may depend on task demands: a processing route for goal-directed meaningful actions may be distinct from one for non-goal-directed actions. A more controversial role proposed for these neurons is in theory of mind processing, along with the subsequent suggestion that impairment in the mirror neuron circuit can contribute to autism-spectrum disorder (ASD) where individuals have theory of mind deficits. We have therefore examined movement interference in nine ASD participants and nine matched controls while performing actions congruent and incongruent with observed meaningless arm movements. We hypothesised that if the mirror neuron system was impaired, reduced interference should be observed in the ASD group. However, control and ASD participants demonstrated an equivalent interference effect in an interpersonal condition, with greater movement variability in the incongruent compared to the congruent condition. A component of movement interference which is independent of congruency did differ between groups: ASD participants made generally more variable movements for the interpersonal task than for biological dot-motion task, while the reverse was true for the control participants. We interpret these results as evidence that the ASD participant group either rely to a greater extent on the goal-directed imitation pathway, supporting claims that they have a specific deficit of the non-goal-directed imitation pathway, or exhibit reduced visuomotor integration.     

More than an imitation game: Top-down modulation of the human mirror system

All interpersonal interactions are underpinned by action: perceiving and understanding the actions of others, and responding by planning and performing self-made actions. Perception of action, both self-made and observed, informs ongoing motor responses by iterative feedback within a perception-action loop. This fundamental phenomenon occurs within single-cells of the macaque brain which demonstrate sensory and motor response properties. These ‘mirror’ neurons have led to a swathe of research leading to the broadly accepted idea of a human mirror system. The current review examines the putative human mirror system literature to highlight several inconsistencies in comparison to the seminal macaque data, and ongoing controversies within human focused research (including mirror neuron origin and function). In particular, we will address the often-neglected other side to the ‘mirror’: complementary and opposing actions. We propose that engagement of the mirror system in meeting changing task-demands is dynamically modulated via frontal control networks.     

Cortical and subcortical mechanisms at the core of imitation

Imitation is thought to require a perception-action matching process that utilizes the "mirror neuron" system, but other cognitive functions such as error detection may also be required for even simple imitation. We sought to explore the core neural substrate of imitation by examining the imitation of simple finger actions using fMRI. Participants observed one of two actions and were instructed to imitate the action they observed, or to perform the alternative non-matching action. The contrast between imitation and non-matching actions was associated with activation in areas previously associated with imitation and "mirror neuron" functioning, including insula, intraparietal sulcus, dorsal premotor cortex, and superior temporal gyrus. Imitation was also specifically associated with activity in areas of prefrontal cortex, lateral orbitofrontal cortex (OFC), amygdala, red nucleus, thalamus, hippocampus, and substantia nigra. We suggest that lateral OFC responds to action-perception mismatch and other clusters reflect working memory, motor planning, associative learning, and visuo-motor integration of goal-directed action. Although computational models have predicted integration of these functions to enable imitation, their specific brain bases have not previously been identified. Together they offer a potentially powerful means through which matching one's actions to those of others can lead to behavioral modification and development.     

Cortical and subcortical mechanisms at the core of imitation

Abstract

Imitation is thought to require a perception–action matching process that utilizes the “mirror neuron” system, but other cognitive functions such as error detection may also be required for even simple imitation. We sought to explore the core neural substrate of imitation by examining the imitation of simple finger actions using fMRI. Participants observed one of two actions and were instructed to imitate the action they observed, or to perform the alternative non-matching action. The contrast between imitation and non-matching actions was associated with activation in areas previously associated with imitation and “mirror neuron” functioning, including insula, intraparietal sulcus, dorsal premotor cortex, and superior temporal gyrus. Imitation was also specifically associated with activity in areas of prefrontal cortex, lateral orbitofrontal cortex (OFC), amygdala, red nucleus, thalamus, hippocampus, and substantia nigra. We suggest that lateral OFC responds to action–perception mismatch and other clusters reflect working memory, motor planning, associative learning, and visuo-motor integration of goal-directed action. Although computational models have predicted integration of these functions to enable imitation, their specific brain bases have not previously been identified. Together they offer a potentially powerful means through which matching one's actions to those of others can lead to behavioral modification and development.     

Functions of the mirror neuron system: implications for neurorehabilitation.

Mirror neurons discharge during the execution of hand object-directed actions and during the observation of the same actions performed by other individuals. These neurons were first identified in the ventral premotor cortex (area F5) and later on in the inferior parietal lobule of monkey brain, thus constituting the mirror neuron system. More recently, mirror neurons for mouth object-directed actions have also been found in the monkey. Several pieces of experimental data demonstrate that a mirror neuron system devoted to hand, mouth, and foot actions is also present in humans. In the present paper we review the experimental evidence on the role of the mirror neuron system in action understanding, imitation learning of novel complex actions, and internal rehearsal (motor imagery) of actions. On the basis of features of the mirror neuron system and its role in action understanding and imitation, we discuss the possible use of action observation and imitation as an approach for systematic training in the rehabilitation of patients with motor impairment of the upper limb after stroke.     

Making mirrors: premotor cortex stimulation enhances mirror and counter-mirror motor facilitation

Mirror neurons fire during both the performance of an action and the observation of the same action being performed by another. These neurons have been recorded in ventral premotor and inferior parietal cortex in the macaque, but human brain imaging studies suggest that areas responding to the observation and performance of actions are more widespread. We used paired-pulse TMS to test whether dorsal as well as ventral premotor cortex is involved in producing mirror motor facilitation effects. Stimulation of premotor cortex enhanced mirror motor facilitation and also enhanced the effects of counter-mirror training. No differences were found between the two premotor areas. These results support an associative account of mirror neuron properties, whereby multiple regions that process both sensory and motor information have the potential to contribute to mirror effects.     

Is the mirror neuron system involved in imitation? A short review and meta-analysis

It has been suggested that the mirror neuron system provides an important neural substrate for humans’ ability to imitate. Mirror neurons have been found during single-cell recordings in monkeys in area F5 and PF. It is believed that the human equivalent of this mirror system in humans is the pars opercularis of the inferior frontal gyrus (area 44) and the rostral part of the inferior parietal lobule. This article critically reviews published fMRI studies that examined the role of frontal and parietal brain regions in imitation. A meta-analysis using activation likelihood estimation (ALE) revealed that the superior parietal lobule, inferior parietal lobule, and the dorsal premotor cortex but not the inferior frontal gyrus, are all commonly involved in imitation. An additional meta-analysis using a label-based review confirmed that in the frontal lobe, the premotor cortex rather than the inferior frontal gyrus is consistently active in studies investigating imitation. In the parietal region the superior and inferior parietal lobules are equally activated during imitation. Our results suggest that parietal and frontal regions which extend beyond the classical mirror neuron network are crucial for imitation.     

Aphasia,apraxia and the evolution of the language-ready brain

Background: The Mirror System Hypothesis offers the mirror system for grasping (i.e., neural mechanisms active for both execution and observation of grasping) as a neural “missing link” between the brains of our non-human ancestors of 20 million years ago and the modern human language-ready brain, stressing the importance of manual gesture in the evolution of mechanisms supporting language. Aims: To assess the view that neural mechanisms for both praxis and language share an evolutionary relationship to the ancestral mirror system for grasping. Main Contribution: The praxis system receives a new analysis based on the attempt to link human praxis to computational models of execution and observation of grasping in the macaque as well as the analysis of parallels between language and praxis. Conclusions: The conceptual analysis presented here may prove insightful for clinicians seeking to relate and differentiate aphasia and apraxia.     

Mirror neuron activation is associated with facial emotion processing

Theoretical accounts suggest that mirror neurons play a crucial role in social cognition. The current study used transcranial magnetic stimulation (TMS) to investigate the association between mirror neuron activation and facial emotion processing, a fundamental aspect of social cognition, among healthy adults (n=20). Facial emotion processing of static (but not dynamic) images correlated significantly with an enhanced motor response, proposed to reflect mirror neuron activation. These correlations did not appear to reflect general facial processing or pattern recognition, and provide support to current theoretical accounts linking the mirror neuron system to aspects of social cognition. We discuss the mechanism by which mirror neurons might facilitate facial emotion recognition.     

Imitation and action understanding in autistic spectrum disorders: how valid is the hypothesis of a deficit in the mirror neuron system?

The motor mirror neuron system supports imitation and goal understanding in typical adults. Recently, it has been proposed that a deficit in this mirror neuron system might contribute to poor imitation performance in children with autistic spectrum disorders (ASD) and might be a cause of poor social abilities in these children. We aimed to test this hypothesis by examining the performance of 25 children with ASD and 31 typical children of the same verbal mental age on four action representation tasks and a theory of mind battery. Both typical and autistic children had the same tendency to imitate an adult's goals, to imitate in a mirror fashion and to imitate grasps in a motor planning task. Children with ASD showed superior performance on a gesture recognition task. These imitation and gesture recognition tasks all rely on the mirror neuron system in typical adults, but performance was not impaired in children with ASD. In contrast, the ASD group were impaired on the theory of mind tasks. These results provide clear evidence against a general imitation impairment and a global mirror neuron system deficit in children with autism. We suggest this data can best be understood in terms of multiple brain systems for different types of imitation and action understanding, and that the ability to understand and imitate the goals of hand actions is intact in children with ASD.     

From self-observation to imitation: visuomotor association on a robotic hand

Being at the crux of human cognition and behaviour, imitation has become the target of investigations ranging from experimental psychology and neurophysiology to computational sciences and robotics. It is often assumed that the imitation is innate, but it has more recently been argued, both theoretically and experimentally, that basic forms of imitation could emerge as a result of self-observation. Here, we tested this proposal on a realistic experimental platform, comprising an associative network linking a 16 degrees of freedom robotic hand and a simple visual system. We report that this minimal visuomotor association is sufficient to bootstrap basic imitation. Our results indicate that crucial features of human imitation, such as generalization to new actions, may emerge from a connectionist associative network. Therefore, we suggest that a behaviour as complex as imitation could be, at the neuronal level, founded on basic mechanisms of associative learning, a notion supported by a recent proposal on the developmental origin of mirror neurons. Our approach can be applied to the development of realistic cognitive architectures for humanoid robots as well as to shed new light on the cognitive processes at play in early human cognitive development.     

Brain regions with mirror properties: a meta-analysis of 125 human fMRI studies

Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components.     

Mirror neuron dysfunction in autism spectrum disorders

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.     

The complex synaptic pathways onto a looming-detector neuron revealed using serial block-face scanning electron microscopy

The ability of locusts to detect looming stimuli and avoid collisions or predators depends on a neuronal circuit in the locust's optic lobe. Although comprehensively studied for over three decades, there are still major questions about the computational steps of this circuit. We used fourth instar larvae of Locusta migratoria to describe the connection between the lobula giant movement detector 1 (LGMD1) neuron in the lobula complex and the upstream neuropil, the medulla. Serial block-face scanning electron microscopy (SBEM) was used to characterize the morphology of the connecting neurons termed trans-medullary afferent (TmA) neurons and their synaptic connectivity. This enabled us to trace neurons over several hundred micrometers between the medulla and the lobula complex while identifying their synapses. We traced two different TmA neurons, each from a different individual, from their synapses with the LGMD in the lobula complex up into the medulla and describe their synaptic relationships. There is not a simple downstream transmission of the signal from a lamina neuron onto these TmA neurons; there is also a feedback loop in place with TmA neurons making outputs as well as receiving inputs. More than one type of neuron shapes the signal of the TmA neurons in the medulla. We found both columnar and trans-columnar neurons connected with the traced TmA neurons in the medulla. These findings indicate that there are computational steps in the medulla that have not been included in models of the neuronal pathway for looming detection.     

Recognition of point-light biological motion: mu rhythms and mirror neuron activity

Changes in power in the mu frequency band (8-13Hz) of the electroencephalogram (EEG) is thought to indirectly reflect the activity of mirror neurons in premotor cortex. Activation of these neurons by self-performed, observed or imagined motor actions is assumed to produce asynchronous firing and a reduction in mu rhythm oscillation (referred to as mu suppression) in sensorimotor cortex. A recent fMRI study by Saygin et al. [Saygin AP, Wilson SM, Hagler Jr DJ, Bates E, Sereno MI. Point-light biological motion perception activates human premotor cortex. J Neurosci 2004;24:6181-8] revealed that the premotor brain regions containing mirror-neurons are also activated in response to point-light human motion. The perceived movement of these light cues are integrated into one percept of a complete human action (e.g. jumping jacks), rather than seen as individual moving lights. The present study examined whether recruitment of the mirror neuron system, as reflected in mu rhythm suppression, mediates recognition of point-light biological motion. Changes in mu power were recorded while subjects viewed point-light biological motion videos, matched scrambled versions of these animations, and visual white-noise (baseline). The results revealed that point-light biological animations produced mu suppression relative to baseline, while scrambled versions of these animations did not. This supports the hypothesis that the mirror neuron system is involved in inferring human actions by recovering object information from sparse input.     

Progressive Supranuclear Palsy in a family with TDP-43 pathology

The discovery of mirror neurons in macaque has led to a resurrection of motor theories of speech perception. Although the majority of lesion and functional imaging studies have associated perception with the temporal lobes, it has also been proposed that the ‘human mirror system’, which prominently includes Broca's area, is the neurophysiological substrate of speech perception. Although numerous studies have demonstrated a tight link between sensory and motor speech processes, few have directly assessed the critical prediction of mirror neuron theories of speech perception, namely that damage to the human mirror system should cause severe deficits in speech perception. The present study measured speech perception abilities of patients with lesions involving motor regions in the left posterior frontal lobe and/or inferior parietal lobule (i.e., the proposed human ‘mirror system’). Performance was at or near ceiling in patients with fronto-parietal lesions. It is only when the lesion encroaches on auditory regions in the temporal lobe that perceptual deficits are evident. This suggests that ‘mirror system’ damage does not disrupt speech perception, but rather that auditory systems are the primary substrate for speech perception.     

Understanding mirror neurons: Evidence for enhanced corticospinal excitability during the observation of transitive but not intransitive hand gestures

Putative measures of mirror neuron activity suggest that mirror neurons respond preferentially to biological motion, but it remains unclear whether enhanced cortical activity occurs during the observation of any behaviour, or whether that behaviour needs to be associated with a particular object or goal. Forty-three healthy adults completed a transcranial magnetic stimulation (TMS) experiment that assessed corticospinal excitability while viewing intransitive and transitive hand gestures (compared with the presentation of a static hand). Visual presentations were designed to control for motoric and stimulus properties. A significant increase in corticospinal excitability (putatively reflecting mirror neuron activation) was seen only during the observation of transitive behaviour. These findings are consistent with the notion that human hand-related mirror neurons are sensitive to object- and goal-directed behaviour, rather than biological motion per se.     

Selective extracellular stimulation of individual neurons in ganglia

Selective control of individual neurons could clarify neural functions and aid disease treatments. To target specific neurons, it may be useful to focus on ganglionic neuron clusters, which are found in the peripheral nervous system in vertebrates. Because neuron cell bodies are found primarily near the surface of invertebrate ganglia, and often found near the surface of vertebrate ganglia, we developed a technique for controlling individual neurons extracellularly using the buccal ganglia of the marine mollusc Aplysia californica as a model system. We experimentally demonstrated that anodic currents can selectively activate an individual neuron and cathodic currents can selectively inhibit an individual neuron using this technique. To define spatial specificity, we studied the minimum currents required for stimulation, and to define temporal specificity, we controlled firing frequencies up to 45 Hz. To understand the mechanisms of spatial and temporal specificity, we created models using the NEURON software package. To broadly predict the spatial specificity of arbitrary neurons in any ganglion sharing similar geometry, we created a steady-state analytical model. A NEURON model based on cat spinal motor neurons showed responses to extracellular stimulation qualitatively similar to those of the Aplysia NEURON model, suggesting that this technique could be widely applicable to vertebrate and human peripheral ganglia having similar geometry.     

Mirror neurons and the social nature of language: the neural exploitation hypothesis

This paper discusses the relevance of the discovery of mirror neurons in monkeys and of the mirror neuron system in humans to a neuroscientific account of primates' social cognition and its evolution. It is proposed that mirror neurons and the functional mechanism they underpin, embodied simulation, can ground within a unitary neurophysiological explanatory framework important aspects of human social cognition. In particular, the main focus is on language, here conceived according to a neurophenomenological perspective, grounding meaning on the social experience of action. A neurophysiological hypothesis--the "neural exploitation hypothesis"--is introduced to explain how key aspects of human social cognition are underpinned by brain mechanisms originally evolved for sensorimotor integration. It is proposed that these mechanisms were later on adapted as new neurofunctional architecture for thought and language, while retaining their original functions as well. By neural exploitation, social cognition and language can be linked to the experiential domain of action.