Are there dedicated neural mechanisms for imitation? A study of grist and mills.

Are there brain regions that are specialized for the execution of imitative actions? We compared two hypotheses of imitation: the mirror neuron system (MNS) hypothesis predicts frontal and parietal engagement which is specific to imitation, while the Grist-Mills hypothesis predicts no difference in brain activation between imitative and matched non-imitative actions. Our delayed imitation fMRI paradigm included two tasks, one where correct performance was defined by a spatial rule and another where it was defined by an item-based rule. For each task, participants could learn a sequence from a video of a human hand performing the task, from a matched "Ghost" condition, or from text instructions. When participants executed actions after seeing the Hand demonstration (compared to Ghost and Text demonstrations), no activation differences occurred in frontal or parietal regions; rather, activation was localized primarily to occipital cortex. This adds to a growing body of evidence which indicates that imitation-specific responses during action execution do not occur in canonical mirror regions, contradicting the mirror neuron system hypothesis. However, activation differences did occur between action execution in the Hand and Ghost conditions outside MNS regions, which runs counter to the Grist-Mills hypothesis. We conclude that researchers should look beyond these hypotheses as well as classical MNS regions to describe the ways in which imitative actions are implemented by the brain.

Differential responses in the mirror neuron system during imitation of individual emotional facial expressions and association with autistic traits.

The mirror neuron system (MNS), including the inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and superior temporal sulcus (STS) plays an important role in action representation and imitation and may be dysfunctional in autism spectrum disorder (ASD). However, it's not clear how these three regions respond and interact during the imitation of different basic facial expressions and whether the pattern of responses is influenced by autistic traits. Thus, we conducted a natural facial expression (happiness, angry, sadness and fear) imitation task in 100 healthy male subjects where expression intensity was measured using facial emotion recognition software (FaceReader) and MNS responses were recorded using functional near-infrared spectroscopy (fNIRS). Autistic traits were measured using the Autism Spectrum Quotient questionnaire. Results showed that imitation of happy expressions produced the highest expression intensity but a small deactivation in MNS responses, suggesting a lower processing requirement compared to other expressions. A cosine similarity analysis indicated a distinct pattern of MNS responses during imitation of each facial expression with functional intra-hemispheric connectivity between the left IPL and left STS being significantly higher during happy compared to other expressions, while inter-hemispheric connectivity between the left and right IPL differed between imitation of fearful and sad expressions. Furthermore, functional connectivity changes during imitation of each different expression could reliably predict autistic trait scores. Overall, the results provide evidence for distinct patterns of functional connectivity changes between MNS regions during imitation of different emotions which are also associated with autistic traits.

Non-shared coding of observed and executed actions prevails in macaque ventral premotor mirror neurons.

According to the mirror mechanism the discharge of F5 mirror neurons of a monkey observing another individual performing an action is a motor representation of the observed action that may serve to understand or learn from the action. This hypothesis, if strictly interpreted, requires mirror neurons to exhibit an action tuning that is shared between action observation and execution. Due to insufficient data it remains contentious if this requirement is met. To fill in the gaps, we conducted an experiment in which identical objects had to be manipulated in three different ways in order to serve distinct action goals. Using three methods, including cross-task classification, we found that at most time points F5 mirror neurons did not encode observed actions with the same code underlying action execution. However, in about 20% of neurons there were time periods with a shared code. These time periods formed a distinct cluster and cannot be considered a product of chance. Population classification yielded non-shared coding for observed actions in the whole population, which was at times optimal and consistently better than shared coding in differentially selected subpopulations. These results support the hypothesis of a representation of observed actions based on a strictly defined mirror mechanism only for small subsets of neurons and only under the assumption of time-resolved readout. Considering alternative concepts and recent findings, we propose that during observation mirror neurons represent the process of a goal pursuit from the observer's viewpoint. Whether the observer's goal pursuit, in which the other's action goal becomes the observer's action goal, or the other's goal pursuit is represented remains to be clarified. In any case, it may allow the observer to use expectations associated with a goal pursuit to directly intervene in or learn from another's action.

Transdiagnostic investigation into the relationship between mirror neuron system activity, echo-phenomena, and theory of mind in major psychoses.

The association between social cognition and putative mirror neuron system (MNS)-activity in major psychoses might be contingent upon frontal dysregulation. We used a transdiagnostic ecological approach to enrich a specific behavioral phenotype (echophenomena or hyper-imitative states) across clinical diagnoses (mania and schizophrenia) to compare behavioral and physiological markers of social cognition and frontal disinhibition. We examined 114 participants with schizophrenia (N = 53) and mania (N = 61) for the presence and severity of echo-phenomena (echopraxia, incidental, and induced echolalia) using an ecological paradigm to simulate real-life social communication. Symptom severity, frontal release reflexes, and theory of mind performance were also assessed. In a proportion of these participants with (N = 20) and without (N = 20) echo-phenomena, we compared motor resonance (motor evoked potential facilitation during action observation compared to static image viewing) and cortical silent period (CSP) as putative markers of MNS-activity and frontal disinhibition, respectively, using Transcranial Magnetic Stimulation. While the prevalence of echo-phenomena was similar between mania and schizophrenia, incidental echolalia was more severe in mania. Participants with echo-phenomena (compared to those without) had significantly greater motor resonance with singlepulse (not with paired-pulse) stimuli, poorer theory of mind scores, higher frontal release reflexes but similar CSP, and greater symptom severity. None of these parameters significantly differed between participants with mania and schizophrenia. We observed relatively better phenotypic and neurophysiological characterization of major psychoses by categorizing participants based on the presence of echophenomena than clinical diagnoses. Higher putative MNS-activity was associated with poorer theory of mind in a hyper-imitative behavioral state.

Grasp-specific high-frequency broadband mirror neuron activity during reach-and-grasp movements in humans.

Broadly congruent mirror neurons, responding to any grasp movement, and strictly congruent mirror neurons, responding only to specific grasp movements, have been reported in single-cell studies with primates. Delineating grasp properties in humans is essential to understand the human mirror neuron system with implications for behavior and social cognition. We analyzed electrocorticography data from a natural reach-and-grasp movement observation and delayed imitation task with 3 different natural grasp types of everyday objects. We focused on the classification of grasp types from high-frequency broadband mirror activation patterns found in classic mirror system areas, including sensorimotor, supplementary motor, inferior frontal, and parietal cortices. Classification of grasp types was successful during movement observation and execution intervals but not during movement retention. Our grasp type classification from combined and single mirror electrodes provides evidence for grasp-congruent activity in the human mirror neuron system potentially arising from strictly congruent mirror neurons.

Imitative and contagious behaviors in animals and their potential roles in the study of neurodevelopmental disorders.

Social learning in the forms of imitative and contagious behaviors are essential for learning abilities and social interaction. However, children with neurodevelopmental disorders and intellectual disabilities show impairments in these behaviors, which profoundly affect their communication skills and cognitive functions. Although these deficits are well studied in humans, pre-clinical animal model assessments of imitative and contagious behavioral deficits are limited. Here, we first define various forms of social learning as well as their developmental and evolutionary significance in humans. We also explore the impact of imitative and contagious behavioral deficits in several neurodevelopmental disorders associated with autistic-like symptoms. Second, we highlight imitative and contagious behaviors observed in nonhuman primates and other social animals commonly used as models for neurodevelopmental disorders. Lastly, we conceptualize these behaviors in the contexts of mirror neuron activity, learning, and empathy, which are highly debated topics. Taken together, this review furthers the understanding of imitative and contagious behaviors. We hope to prompt and guide future behavioral studies in animal models of neurodevelopmental disorders.

Cognitive genomics of learning delay and low level of social performance monitoring in macaque.

Cognitive skills and the underlying neural architecture are under the influence of genetics. Cognitive genomics research explores the triadic relationship between genes, brain, and cognition, with its major strategy being genotype-driven. Here we show that an inverse strategy is feasible to identify novel candidate genes for particular neuro-cognitive phenotypes in macaques. Two monkeys, originally involved in separate psychological studies, exhibited learning delay and low levels of social performance monitoring. In one monkey, mirror neurons were fewer compared to controls and mu suppression was absent in the frontal cortex. The other monkey showed heightened visual responsiveness in both frontal cortex and dopamine-rich midbrain, with a lack of inter-areal synchronization. Exome analyses revealed that the two monkeys were most likely cousins and shared variants in MAP2, APOC1, and potentially HTR2C. This phenotype-driven strategy in cognitive genomics provides a useful means to clarify the genetic basis of phenotypic variation and develop macaque models of neuropsychiatric disorders.

Mirror neurons and empathy-related regions in psychopathy: Systematic review, meta-analysis, and a working model.

Mirror neurons have been associated with empathy. People with psychopathic traits present low levels of empathy. To analyze this, a systematic review of fMRI studies of people with psychopathic traits during an emotional facial expression processing task was performed. The regions of interest were structures associated with the mirror neuron system: ventromedial prefrontal cortex (vmPFC), inferior parietal lobe (IPL), inferior frontal gyrus and superior temporal sulcus. The analysis was also extended to structures related to affective empathy (insula, amygdala and anterior cingulate cortex) and to two more emotional processing areas (orbitofrontal cortex and fusiform gyrus). Hypoactivation was more frequently observed in regions of the mirror neuron system from people with high psychopathic traits, as well as in the emotional processing structures, and those associated with affective empathy, except for the insula, where it presented higher activity. Differences were observed for all types of emotions. The results suggest that the mirror neuron system is altered in psychopathy and their relationship with affective empathy deficits is discussed.

The degree of mu rhythm suppression in women is associated with presence of children as well as empathy and anxiety level.

In experiments on observing and performing social gestures, the level of mu rhythm suppression is associated with the activity of the mirror neuron system (MNS), which is responsible for the perception and understanding of nonverbal signals in social communication. In turn, while MNS activity may be associated primarily with empathy, it is also associated with other psychological and demographic factors affecting the effectiveness of cortical neural networks. In this study, we verified the influence of empathy, state and trait anxiety levels, presence and number of children, and age on the mu-suppression level in 40 women. We used 32-channel EEG recorded during observation, and synchronous execution of various hand movements. The ICA infomax method was used for decomposing and selecting the left hemisphere component of the mu-rhythm. Mu-suppression was higher in women with one child, with higher levels of empathy, and with lower anxiety levels. It is possible that MNS activity is stronger in women during parental care.

The Reaching Phase of Feeding and Self-Care Actions Optimizes Action Observation Effects in Chronic Stroke Subjects.

BACKGROUND: The Action Observation Therapy (AOT) is a well-established post-stroke rehabilitation treatment based on the theoretical framework of the Mirror Neuron System (MNS) activation. However, AOT protocols are still heterogeneous in terms of video contents of observed actions. OBJECTIVE: The aim of this study was to analyze electroencephalographic (EEG) recordings in stroke patients during the observation of different videos of task-specific upper limb movements, and to define which category of actions can elicit a stronger cortical activation in the observer's brain. METHODS: Signals were analyzed from 19 chronic stroke subjects observing customized videos that represented 3 different categories of upper limb actions: Finalized Actions, Non-Finalized Actions, and Control Videos. The Event-Related Desynchronization in the µ and ß bands was chosen to identify the involvement of the cerebral cortex: the area of the normalized power spectral density was calculated for each category and, deepening, for the reaching and completion sub-phases of Finalized Actions. For descriptive purposes, the time course of averaged signal power was described. The Kruskal-Wallis test (P < .05) was applied. RESULTS: The analysis showed a greater desynchronization when subjects observed Finalized Actions with respect to Non-Finalized in all recorded areas; Control videos provoked a synchronization in the same areas and frequency bands. The reaching phase of feeding and self-care actions evoked a greater suppression both in µ and ß bands. CONCLUSIONS: The observation of finalized arm movements seems to elicit the strongest activation of the MNS in chronic stroke patients. This finding may help the clinicians to design future AOT-based stroke rehabilitation protocols. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT04047134.

Mirror neuron brain regions contribute to identifying actions, but not intentions.

Previous studies have struggled to determine the relationship between mirror neuron brain regions and two distinct "action understanding" processes: identifying actions and identifying the intentions underlying those actions. This may be because the identification of intentions from others' actions requires an initial action identification process. Disruptive transcranial magnetic stimulation was administered to left inferior frontal gyrus (lIFG) during a novel cognitive task to determine which of these "action understanding" processes is subserved by mirror neuron brain regions. Participants identified either the actions performed by observed hand actions or the intentions underlying those actions. The extent to which intention identification was disrupted by lIFG (vs. control site) stimulation was dependent on the level of disruption to action identification. We subsequently performed functional magnetic resonance imaging during the same task. During action identification, responses were widespread within mirror neuron areas including lIFG and inferior parietal lobule. However, no independent responses were found in mirror neuron brain regions during intention identification. Instead, responses occurred in brain regions associated with two distinct mentalizing localizer tasks. This supports an account in which mirror neuron brain regions are involved in an initial action identification process, but the subsequent identification of intentions requires additional processing in mentalizing brain regions.

Mirror neurons 30 years later: implications and applications.

Mirror neurons (MNs) were first described in a seminal paper in 1992 as a class of monkey premotor cells discharging during both action execution and observation. Despite their debated origin and function, recent studies in several species, from birds to humans, revealed that beyond MNs properly so called, a variety of cell types distributed among multiple motor, sensory, and emotional brain areas form a 'mirror mechanism' more complex and flexible than originally thought, which has an evolutionarily conserved role in social interaction. Here, we trace the current limits and envisage the future trends of this discovery, showing that it inspired translational research and the development of new neurorehabilitation approaches, and constitutes a point of no return in social and affective neuroscience.

Functional integration of mirror neuron system and sensorimotor cortex under virtual self-actions visual perception.

Virtual reality (VR) technology, with the advantage of immersive visual experience, has been increasingly applied in the rehabilitation therapy of motor deficits. The functional integration of the mirror neuron system and the sensorimotor cortex under the visual perception of actions is one of the theoretical bases for the application of action observation in the neurorehabilitation of motor deficits. Whether the visual experience changes brought by VR technology can further promote this functional integration to be further confirmed. Using the exact low-resolution brain electromagnetic tomography (eLORETA) source localization method, we calculated and statistically tested the whole brain cortical voxel current density estimation under the Electroencephalogram (EEG) signals collected during action observation under the first-person and third-person perspectives in the VR scene for twenty healthy adults. Furthermore, the functional connectivity between the mirror neuron system and the sensorimotor cortex was analyzed using the lagged phase synchronization method. Under the first-person perspective in the VR scene, the current density changes of the core cortices of the mirror neuron system lead to a larger average event-related potential, more significant suppression in the α1 and α2 frequency bands of EEG signals, and a significant enhancement of functional connectivity between the core cortices of the mirror neuron system and the sensorimotor cortex. These findings indicate that compared with the traditional action observation, the visual reappearance of self-actions in the VR scene further stimulates the activity of the core cortices of the mirror neuron system, and promotes the functional integration of the core cortices of the mirror neuron system and the sensorimotor cortex.

Embodied cognition in neurodegenerative disorders: What do we know so far? A narrative review focusing on the mirror neuron system and clinical applications.

Embodied cognition is a theoretical perspective that considers every form of human knowledge and cognition "embodied", as they pass through bodily experience. The aim of this narrative review is to investigate the importance of mirror neurons system in EC, as well as the EC role in neurodegenerative diseases. This narrative review shows deep connections between body and mind: body states influence mental functions such as perception and reasoning, while mental states cause changes in the body, especially in neurodegenerative disorders. Indeed, abnormalities in EC were found in dementia, Parkinson's Disease and Amyotrophic Lateral sclerosis, also in the absence of other cognitive deficits, negatively affecting patients' outcomes. Exploiting EC mechanisms for rehabilitation purposes, also using innovation technologies, could be a promising therapeutic way to increase motor and cognitive outcomes in patients affected by different neurological disorders.

Developmental differences in brain functional connectivity during social interaction in middle childhood.

The transition from childhood to adolescence is marked by significant changes in peer interactions. However, limited research has examined the brain systems (e.g., mentalizing and reward networks) involved in direct peer interaction, particularly during childhood and early adolescence. Here, we analyzed fMRI data from 50 children aged 8-12 years while they participated in a task in which they chatted with a peer (Peer) or answered questions about a story character (Character). Using a beta-series correlation analysis, we investigated how social interaction modulates functional connectivity within and between mentalizing and reward networks and whether this modulation changes with age. We observed effects of social interaction on functional connectivity were modulated by age within the mentalizing and reward networks. Further, greater connectivity within and between these networks during social interaction was related to faster reaction time to the Peer versus Character condition. Similar effects were found in the salience and mirror neuron networks. These findings provide insights into age-related differences in how the brain supports social interaction, and thus have the potential to advance our understanding of core social difficulties in social-communicative disorders, such as autism spectrum disorder.

Effective connectivity of the human mirror neuron system during social cognition.

The human mirror neuron system (MNS) can be considered the neural basis of social cognition. Identifying the global network structure of this system can provide significant progress in the field. In this study, we use dynamic causal modeling (DCM) to determine the effective connectivity between central regions of the MNS for the first time during different social cognition tasks. Sixty-seven healthy participants completed fMRI scanning while performing social cognition tasks, including imitation, empathy and theory of mind. Superior temporal sulcus (STS), inferior parietal lobule (IPL) and Brodmann area 44 (BA44) formed the regions of interest for DCM. Varying connectivity patterns, 540 models were built and fitted for each participant. By applying group-level analysis, Bayesian model selection and Bayesian model averaging, the optimal family and model for all experimental tasks were found. For all social-cognitive processes, effective connectivity from STS to IPL and from STS to BA44 was found. For imitation, additional mutual connections occurred between STS and BA44, as well as BA44 and IPL. The results suggest inverse models in which the motor regions BA44 and IPL receive sensory information from the STS. In contrast, for imitation, a sensory loop with an exchange of motor-to-sensory and sensory-to-motor information seems to exist.

What Happened to Mirror Neurons?

Ten years ago, Perspectives in Psychological Science published the Mirror Neuron Forum, in which authors debated the role of mirror neurons in action understanding, speech, imitation, and autism and asked whether mirror neurons are acquired through visual-motor learning. Subsequent research on these themes has made significant advances, which should encourage further, more systematic research. For action understanding, multivoxel pattern analysis, patient studies, and brain stimulation suggest that mirror-neuron brain areas contribute to low-level processing of observed actions (e.g., distinguishing types of grip) but not to high-level action interpretation (e.g., inferring actors' intentions). In the area of speech perception, although it remains unclear whether mirror neurons play a specific, causal role in speech perception, there is compelling evidence for the involvement of the motor system in the discrimination of speech in perceptually noisy conditions. For imitation, there is strong evidence from patient, brain-stimulation, and brain-imaging studies that mirror-neuron brain areas play a causal role in copying of body movement topography. In the area of autism, studies using behavioral and neurological measures have tried and failed to find evidence supporting the "broken-mirror theory" of autism. Furthermore, research on the origin of mirror neurons has confirmed the importance of domain-general visual-motor associative learning rather than canalized visual-motor learning, or motor learning alone.