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

https://doi.org/10.1016/j.neubiorev.2011.07.004Get rights and content

Abstract

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.

Highlights

► We performed a meta-analysis based on 125 fMRI studies on brain regions with mirror properties. ► We show that an extensive brain network has been attributed mirror-like properties. ► A core fronto-parietal network is active during observation and execution of actions. ► Additional mirror areas are recruited during tasks that engage non-motor functions.

Introduction

Mirror neurons were originally described as visuomotor neurons that fire both when an action is performed, and when a similar or identical action is passively observed (Rizzolatti and Craighero, 2004). These neurons were first discovered using single-cell recordings in macaque area F5 (di Pellegrino et al., 1992, Gallese et al., 1996, Rizzolatti et al., 1996a) and later in the PF/PFG complex within the inferior parietal cortex (Gallese et al., 2002). Since these original studies there has been an explosion of interest in mirror neurons, both in the scientific literature and the popular media, in part because of their purported role in a diverse range of cognitive functions, from imitation and action understanding to social cognition (Iacoboni, 2005, Iacoboni, 2009, Iacoboni et al., 2005, Fogassi et al., 2005, Keysers et al., 2010, Rizzolatti and Fabbri-Destro, 2008, Rizzolatti and Sinigaglia, 2010). Mirror neurons have also been implicated in a range of neurological and psychiatric disorders, including multiple sclerosis (Rocca et al., 2008), schizophrenia (Arbib and Mundhenk, 2005), autism spectrum disorder (ASD) (Cattaneo et al., 2007, Dapretto et al., 2006, Iacoboni and Dapretto, 2006, Williams, 2008) and alexithymia (Moriguchi et al., 2009). Other investigators have argued that evidence for the existence of human mirror neurons is lacking (Dinstein et al., 2008a, Dinstein et al., 2008b, Jonas et al., 2007, Lingnau et al., 2009, Turella et al., 2009), or have challenged claims for the role of mirror neurons in language function (Johnson-Frey, 2003), action understanding (Hickok, 2009) and imitation (Makuuchi, 2005, Molenberghs et al., 2009).

Immediately following the initial reports of mirror neurons in the macaque brain, investigators sought evidence for an analogous mechanism in humans. Based on early human brain-imaging studies that compared neural activity during perceived and executed actions (Rizzolatti et al., 1996b, Decety et al., 1997, Iacoboni et al., 1999), it was widely assumed that the ventral premotor cortex and the pars opercularis of the posterior inferior frontal gyrus (Brodmann area 44) are human homologues of macaque mirror area F5; and that the rostral inferior parietal lobule (IPL) is the human equivalent of mirror area PF/PFG (Rizzolatti et al., 2001, Rizzolatti, 2005, Rizzolatti and Craighero, 2004). Subsequent investigations have used behavioural approaches, transcranial magnetic stimulation (TMS), electroencephalography (EEG), functional magnetic resonance imaging (fMRI) and human single-cell recordings (Mukamel et al., 2010) to provide further evidence for fronto-parietal mirror neuron regions in humans (for recent reviews see Iacoboni and Dapretto, 2006, Fabbri-Destro and Rizzolatti, 2008, Keysers and Fadiga, 2008, Keysers et al., 2010, Cattaneo and Rizzolatti, 2009, Rizzolatti and Fabbri-Destro, 2010, Rizzolatti and Sinigaglia, 2010). These studies have used a variety of tasks to uncover “mirror activity”. Some have employed action observation and execution tasks, analogous to those used in the original monkey investigations (e.g., Chong et al., 2008, Gazzola and Keysers, 2009, Kilner et al., 2009, Molenberghs et al., 2010). Others have used tasks involving stimuli across a range of modalities, including audition (e.g., Gazzola et al., 2006, Lewis et al., 2005, Tettamanti et al., 2005), somatosensation (e.g., Keysers et al., 2004, Schaefer et al., 2009), vision only (e.g., Molnar-Szakacs et al., 2006, Newman-Norlund et al., 2010); as well as tasks employing stimuli with emotional (affective) content (e.g., Carr et al., 2003, Leslie et al., 2004). This wide variety of approaches in humans has led to an ever-expanding number of brain regions being implicated in mirror mechanism functioning.

The aim of the current investigation was to draw together imaging results from all relevant fMRI studies of the human mirror regions, with the goal of determining the range and extent of brain regions implicated. Based upon the original single-cell findings in monkeys (di Pellegrino et al., 1992, Gallese et al., 1996, Rizzolatti et al., 1996a, Gallese et al., 2002), it might be predicted that the human homologues of macaque areas F5 and PF/PFG – the inferior frontal gyrus and inferior parietal lobule, respectively – should be reliably engaged by tasks designed to elicit mirror neuron activity. On the other hand, it has recently been proposed that mirror activity is widespread in the human brain (e.g., Keysers and Gazzola, 2009, Heyes, 2010). If this is true, it might be predicted that brain regions outside the classically defined mirror network would be engaged, depending on task demands. To address these predictions, we performed a meta-analysis of all human fMRI studies in which the authors attributed their findings to mirror neuron functioning. We used a quantitative meta-analysis technique, known as activation likelihood estimation (ALE; Eickhoff et al., 2009), to investigate which brain regions are most reliably associated with human mirror neuron functions. Contrary to previous ALE studies that focused exclusively on action observation (Caspers et al., 2010), imitation (Caspers et al., 2010, Molenberghs et al., 2009), and the role of the mirror system in action understanding (Van Overwalle and Baetens, 2009), our meta-analysis included all fMRI studies in which significant activations were attributed to the mirror system, regardless of task requirements. We also performed a label-based review to determine the Brodmann areas most consistently associated with mirror neuron regions. In follow-up analyses, we separated studies based on whether they targeted the “classical” (motor) mirror neurons, or instead examined activity during observation of auditory, somatosensory or emotional (affective) stimuli.

Section snippets

Literature selection and exclusion criteria

We searched the Web of Science database (http://apps.isiknowledge.com) using the keywords ‘fMRI’ and ‘mirror system’. As of January 2011, this search revealed 438 published, peer-reviewed papers. The inclusion criteria for our analyses were as follows:

  • 1.

    Studies that explicitly mentioned the mirror system were included, whereas those that did not were excluded (e.g., the search also uncovered studies about “mirrored” hand movements). Three hundred and thirty (330) of the 438 papers met this

Meta-analysis across all included studies

The ALE meta-analysis of all 125 included studies (supplementary Table 2) revealed 14 significant clusters in total (see Fig. 1, Fig. 6 and Table 1 for details), extending over 9 different Brodmann areas and the cerebellum.

Consistent with previous claims for a “classical” fronto-parietal mirror regions in humans (Rizzolatti et al., 2001), we found evidence for consistent activation in the left and right inferior frontal gyrus, the ventral premotor cortex, and the inferior parietal lobule. The

Discussion

The last 20 years has seen a rapid growth in studies on mirror neurons first described in the macaque by Rizzolatti and his colleagues (di Pellegrino et al., 1992, Gallese et al., 1996). The aim of the current investigation was to draw together all relevant findings from published fMRI studies on human mirror neuron regions, with the goal of determining which areas are most reliably active in tasks designed to tap mirror mechanism functioning.

The most striking outcome of our ALE analyses of 125

Acknowledgements

This work was supported by a Project Grant from the National Health and Medical Research Council of Australia (511148), awarded to RC and JBM and a UQ Postdoctoral Fellowship awarded to PM.

References (75)

  • C. Keysers et al.

    Expanding the mirror: vicarious activity for actions, emotions, and sensations

    Curr. Opin. Neurobiol.

    (2009)
  • K.R. Leslie et al.

    Functional imaging of face and hand imitation: towards a motor theory of empathy

    Neuroimage

    (2004)
  • P. Molenberghs et al.

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

    Neurosci. Biobehav. Rev.

    (2009)
  • I. Molnar-Szakacs et al.

    Observing complex action sequences: the role of the fronto-parietal mirror neuron system

    Neuroimage

    (2006)
  • R. Mukamel et al.

    Single-neuron responses in humans during execution and observation of actions

    Curr. Biol.

    (2010)
  • R. Newman-Norlund et al.

    The role of inferior frontal and parietal areas in differentiating meaningful and meaningless object-directed actions

    Brain Res.

    (2010)
  • K.L. Phan et al.

    Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI

    Neuroimage

    (2002)
  • G. Rizzolatti et al.

    Premotor cortex and the recognition of motor actions

    Cogn. Brain Res.

    (1996)
  • G. Rizzolatti et al.

    The mirror system and its role in social cognition

    Curr. Opin. Neurobiol.

    (2008)
  • K. Sergerie et al.

    The role of the amygdala in emotional processing: a quantitative meta-analysis of functional neuroimaging studies

    Neurosci, Biobehav. Rev.

    (2008)
  • H. Sakata et al.

    Somatosensory properties of neurons in the superior parietal cortex (area 5) of the rhesus monkey

    Brain Res.

    (1973)
  • L. Turella et al.

    Mirror neurons in humans: consisting or confounding evidence?

    Brain Lang.

    (2009)
  • P.E. Turkeltaub et al.

    Meta-analysis of the functional neuroanatomy of single-word reading: method and validation

    Neuroimage

    (2002)
  • F. Van Overwalle et al.

    Understanding others’ actions and goals by mirror and mentalizing systems: a meta-analysis

    Neuroimage

    (2009)
  • B. Wicker et al.

    Both of us disgusted in my insula: the common neural basis of seeing and feeling disgust

    Neuron

    (2003)
  • G. Buccino et al.

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

    Eur. J. Neurosc.

    (2001)
  • L. Carr et al.

    Neural mechanisms of empathy in humans: a relay from neural systems for imitation to limbic areas

    Proc. Natl. Acad. Sci. U.S.A.

    (2003)
  • L. Cattaneo et al.

    Impairment of actions chains in autism and its possible role in intention understanding

    Proc. Natl. Acad. Sci. U.S.A.

    (2007)
  • L. Cattaneo et al.

    The mirror neuron system

    Arch. Neurol.

    (2009)
  • E.S. Cross et al.

    Sensitivity of the action observation network to physical and observational learning

    Cereb. Cortex

    (2009)
  • M. Dapretto et al.

    Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders

    Nat. Neurosci.

    (2006)
  • J. Decety et al.

    Brain activity during observation of actions. Influence of action content and subject's strategy

    Brain

    (1997)
  • G. di Pellegrino et al.

    Understanding motor events: a neurophysiological study

    Exp. Brain Res.

    (1992)
  • I. Dinstein et al.

    Executed and observed movements have different distributed representations in human aIPS

    J. Neurosci.

    (2008)
  • S.J.H. Ebisch et al.

    The sense of touch: embodied simulation in a visuotactile mirroring mechanism for observed animate or inanimate touch

    J. Cogn. Neurosci.

    (2008)
  • S.B. Eickhoff et al.

    Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty

    Hum. Brain Mapp.

    (2009)
  • M. Fabbri-Destro et al.

    Mirror neurons and mirror systems in monkeys and humans

    Physiology

    (2008)
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