Single-Neuron Responses in Humans during Execution and Observation of Actions

“In monkeys, however, neurons with mirroring properties have been reported in a variety of areas on the lateral wall of the primate brain [3, 7, 21, 24, 25].”

“This interpretation is in line with the hypothesis ofmultiplemirroring mechanisms in the primate brain, a hypothesis that can easily account for the presence of mirroring cells in many cortical areas [1, 3–5, 7, 8, 24, 25].”

“In humans, indirect measures of neural activity support the existence of sensory-motor mirroring mechanisms in homolog frontal and parietal areas [10, 11], other motor regions [12–15], and also the existence of multisensory mirroring mechanisms in nonmotor regions [16–19].”

“In humans, indirect measures of neural activity support the existence of sensory-motor mirroring mechanisms in homolog frontal and parietal areas [10, 11], other motor regions [12–15], and also the existence of multisensory mirroring mechanisms in nonmotor regions [16–19].”

“For example, the mirror mechanism in the insula might underlie the capacity to understand a specific emotion (disgust) in others [16, 19], whereas the mirror mechanism in the parietofrontal circuit may help understanding the goal of observed motor acts and the intentions behind them [21].”

“, a picture of a smiling face and the execution cue word ‘‘smile’’ [33].”

“This interpretation is in line with the hypothesis ofmultiplemirroring mechanisms in the primate brain, a hypothesis that can easily account for the presence of mirroring cells in many cortical areas [1, 3–5, 7, 8, 24, 25].”

“…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,…”

“A more extended study with depth electrode recordings in human mirror neurons investigated 21 patients undergoing surgery for otherwise intractable epilepsy (Mukamel et al., 2010).”

“A similar finding for humans was also reported by Mukamel et al. (2010): some cells showed reverse mirror properties, that is, suppression of activity during action observation.”

“…mostly been confined to ventral PMC and IPL, measurements in humans using single-unit recording and fMRI conjunction suggest that MNs are more widespread (e.g. Arnstein, Cui, Keysers, Maurits, & Gazzola, 2011; Gazzola & Keysers, 2009; Landmann et al., 2011; Mukamel et al., 2010; Vogt et al., 2007).”

“The exact relationship between mirror neurons and brain areas that support action perception in the human brain remains a topic of debate (e.g. Dinstein et al., 2007; Chong et al., 2008; Kilner et al., 2009; Mukamel et al., 2010).”

“There has, however, also been a report of single neuron activity recorded from human neurosurgical patients that has demonstrated mirror neuron activity [32].”

“We hypothesize that such an interface could be provided by neurons such as those found in the mirror neuron system, which have the property of being active both during the execution of goal-oriented actions with a biological effector and during the observation of the same actions performed by biological effectors of o…”

“The first, apparently accidental, discovery of these neurons was from direct electrophysiological recordings from the motor cortex of macaque monkeys that observed reaching and grasping behaviours in other monkeys and humans, and while the most direct evidence comes from animal studies, there is an increasingly persua…”

“The human mirror mechanism Most studies stemming from the MN discovery have been carried out in humans, but only one recorded single-neuron activity while patients executed or observed hand-grasping actions and facial emotional expressions, providing direct evidence of the mirror mechanism in several very different hu…”

“Subsequently, neurons with mirror properties were also described in cortical areas outside the parietofrontal circuit, such as the mesial frontal cortex [14] in non-human primates and the hippocampus [15] in humans.”

“However, the relevance and generalization of mirror neurons are debated [113], with validation occurring primarily with small hand movements and limited validity to multi-joint movements and environmental stimuli [114].”

“…relevance of mirror neurons (Rizzolatti et al., 1996) and related sensorimotor cells (Bruce and Goldberg, 1985) in monkeys and humans (Mukamel et al., 2010) for cognitive processes, it seems essential to briefly address their significance for brain theory in general and for language…”

“By 2011, doubts about the presence of mirror neurons in the human brain had been assuaged by studies using single-cell recording in presurgical patients (Mukamel et al., 2010) and the repetition suppression fMRI procedure in healthy volunteers (Kilner et al.”

“…principles of resonance (Umilta et al., 2001; Kilner et al., 2003; Oztop et al., 2005; Press et al., 2005), the particular role of mirror neurons in this process still needs to be determined (Dinstein et al., 2007; Chong et al., 2008; Kilner et al., 2009; Mukamel et al., 2010; Saygin et al., 2012).”

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“(Mukamel et al., 2010).”

“In a recent study, Mukamel et al. (2010) reported that neurons in the human medial temporal lobe, including the hippocampus and the amygdala, fired both during the execution and the observation of similar actions.”

“The locations of the sVx are consistent with past findings (Grèzes et al., 2003; Dinstein et al., 2007; Filimon et al., 2007; Gazzola et al., 2006, 2007; Gazzola and Keysers, 2009; Turella et al., 2009; Caspers et al., 2010) and include BA2, BA44, dPM, the SMA, IPL and SPL (Fig.”

“Electrophysiological recordings in humans have further confirmed the presence of single neurons within these regions with these same mirroring properties (Mukamel et al., 2010).”

“Other brain regions contain mirror neurons as well [25–27] but to illustrate how the Hebbian learning account of the emergence of mirror neurons could in principle explain the emergence of mirror neurons a simple system encompassing only two brain regions, STS and PM, together with reciprocal connections from STS to P…”

“…systems are stimulated by more signals, fast and accurate selection of body gaits is dependent on the mode selection in an isolated neuron and cooper‐ ation between more functional neurons (FourcaudTrocmé et al., 2003; Guan and Rao, 2003; Mukamel et al., 2010; Turrigiano, 2012; Yu et al., 2021).”

“Both have been reported in humans as well (Quiroga et al., 2005; Mukamel et al., 2010).”

“This view is consistent with other accounts suggesting that neural processes responsible for action planning are engaged during action observation in order to model others' behaviors (Mattar and Gribble, 2005; Wilson et al., 2004; Mukamel et al., 2010).”

“There is now extensive neurophysiological evidence that monkeys—and possibly humans—are equipped with a particular class of neurons active during action execution and action perception (Cattaneo and Rizzolatti, 2009; Mukamel et al., 2010).”

“Such invasive techniques are not readily applicable in humans (but see [1,23]); therefore an animal model of emotional empathy would be essential to further our understanding of empathy.”

“The only known single neuron recordings of the proposed mirror system in the human brain comes from Mukamel et al. (2010), who intriguingly found activity in the hippocampus, an area never before included in the classical mirror system.”

“These brain regions are known to harbour neurons with mirror properties (Mukamel et al., 2010) and have a crucial role in understanding intentions and actions (Iacoboni et al.”

“Importantly, direct recording of cell activity in the human brain (Mukamel et al., 2010) showed that double-duty neurons involved in action perception and action execution are found in a variety of cortical areas (e.g. medio-temporal cortex, supplementary motor area, hippocampus).”

“…of actions also has been shown in some MTL regions (parahippocampal gyrus, hippocampus, and entorhinal cortex), suggesting that not only motor cortex is sensitive to perceived actions performed by others, but sensory cortex is also sensitive to self-performed actions (Mukamel et al. 2010a).”

“Recently, existence of a human MNS was directly indicated by invasive single-cell recordings during neurosurgery (Mukamel et al. 2010) and located to the inferior frontal gyrus, posterior superior temporal sulcus, ventral premotor, and somatosensory parietal cortices by neuroimaging meta-analysis…”

“This scenario found recent support from data obtained both in monkeys (Kraskov, Dancause, Quallo, Shepherd, & Lemon, 2010) and humans (Mukamel et al. 2010).”

“[9], however, could not choose where to look for mirror neurons.”

“…studies employing single-cell activity recordings showed that mirror neurons constitute less than 17% of all recorded cells (Gallese et al., 1996, Mukamel et al., 2010), techniques measuring activation of whole brain structures cannot verify whether the mirror neurons are actually involved in a…”

“executing movements [2–3].”

“, 2013), and responses to mirror actions (Mukamel et al., 2010).”

“…activation in Brodmann area 44 when participants deliberately imitate other people’s facial expressions (Carr et al., 2003). van der Gaag et al. (2007) could further show common activations in the IFG and IPL (both termed “classical” MNS sites) as well as the STS, MTG, insula, amygdala, SMA,…”

“…(facilitatory) and “incompatibility” (inhibitory) effects between an observed movement or posture and an executed movement (see Hommel, 2010 and Heyes, 2011 for reviews), suggesting a bidirectional influence of action observation on motor performance and of action execution on action perception.”

“Neurons with similar properties have been observed in the human brain as well (17).”

“…are believed homologous to areas of the brain in which single cells with perception-action matching ( " mirror " ) properties have been extensively studied in the macaque (di Pellegrino et al., 1992; Fogassi et al., 2005; Tkach et al., 2007) and more recently in humans (Mukamel et al., 2010).”

“While the existence of mirror neurons in humans has been documented by a few single- cell studies (Mukamel et al., 2010), hundreds of studies using non- invasive techniques described general brain regions with “mirror” properties active for both viewing and performing a motor action (Ferrari &…”

“In line with this prediction, our results show activation of such networks during pain empathy, with consistent activation observed in the IPL, ventral premotor cortex, and caudal part of the IFG, SPL and SMA.”

“, 1995), intracranial single-unit recordings (Mukamel et al., 2010), magnetoencephalography (MEG; e.”

“Recent data suggest that even the hippocampus and posterior medial frontal cortex exhibit overlapping engagement during action observation and imitation (Mukamel, Ekstrom, Kaplan, Iacoboni, & Fried, 2010 ).”

“Note, however, that a recent study shows that single cell recordings in the human brain have been able to identify mirror neurons, although at locations which typically have not been part of the so-called “mirror neuron network” (Mukamel et al., 2010).”

“…study Areas Results Davis et al. 2005 Single unit Caudal ACC Attention-demanding stroop task involving emotional content can alter the firing rate Mukamel et al. 2010 Single unit SMA, MTL Responsive firing for emotional face perception and execution Chassagnon et al. 2008 Stimulation Cingulate…”

“Correlations were also found with signal changes in left hippocampus and parahippocampal gyrus (PHG), recently found to contain mirror neurons in humans during single cell recordings while subjects observed and executed facial emotional expressions [Mukamel et al., 2010] (Fig.”

“The mirror neurons found were located in the supplementary motor area and medial temporal cortex.[13]”

“However, it was demonstrated recently that neurons with mirror properties can also be found outside of these areas, such as in the medial temporal lobe, in the somatosensory cortices, and in the anterior cingulate cortex (Keysers and Gazzola, 2010; Keysers et al., 2010; Mukamel et al., 2010).”

“network (Cisek and Kalaska, 2004; Dushanova and Donoghue, 2010; Mukamel et al., 2010; Suminski et al., 2009; Tkach et al., 2007).”

“In spite of this fact, Mukamel et al. (2010) recorded extracellular activity from neurons of 21 patients with pharmacologically intractable epilepsy while they was observing or performing a grasping action or facial gestures.”

“Accordingly, evidence for the supplementary motor cortex playing such a role was provided by Mukamel, Ekstrom, Kaplan, Iacoboni, and Fried ( 2010 ).”

“Some studies suggest that the SMA has mirror properties (Gazzola and Keysers, 2009; Mukamel et al., 2010) and a role in action prediction (Ramnani andMiall, 2004).”

“…result there is an argument that sensorimotor cortex may now be considered an intrinsic part of the MNS [it seems likely that if there are indeed mirror neurons in multiple areas (see also Mukamel et al., 2010), neurons in the different areas are mirroring distinct aspects of the observed actions].”

“2007), the supplementary motor area (SMA; Mukamel et al. 2010), primary motor cortex (M1; Raos et al.”

“This action execution-observation dissociation suggests the presence of amygdala neurons dedicated to self-agency via activation/inhibition during execution/observation (Mukamel et al., 2010), which further underscores a role of amygdala in behavioral relevance.”

“Although very tentative, a possible explanation could be that, during the observation of fi­ nalized actions performed with a tool, the inhibitory process known to prevent the imitation of the observed actions (e.g. Stamos et al., 2010; Mukamel et al., 2010), can have some role in preventing the updating of the body s…”

“The methodological approach used here is based on the assumption of overlapping neural circuits underpinning the perception and experience of social functions, including emotions (Bastiaansen et al., 2009), pain (Singer et al., 2004) and social action (Mukamel et al., 2010).”

“In addition, thanks to its multimodal nature (Mukamel et al., 2010) and similarly to TPJ (Rodriguez Moreno et al.”

“Recently, similar findings have been demonstrated in humans (Cochin et al., 1999, 1998; Hari et al., 1998; Mukamel et al., 2010).”

“The SMA is one of the brain areas where neurons with mirror properties were first recorded in humans (Mukamel, Ekstrom, Kaplan, Iacoboni & Fried, 2010).”