Elsevier

Neuroscience

Volume 358, 1 September 2017, Pages 300-315
Neuroscience

Neuroscience Forefront Review
Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways

https://doi.org/10.1016/j.neuroscience.2017.06.052Get rights and content

Highlights

  • The mouth and hand MN sectors have distinct and specific connections.

  • Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions.

  • Facial/communicative visual input could reach mouth MNs through VLPF.

  • Mouth MN sector has strong connections with limbic structures.

Abstract

The vast majority of functional studies investigating mirror neurons (MNs) explored their properties in relation to hand actions, and very few investigated how MNs respond to mouth actions or communicative gestures. Since hand and mouth MNs were recorded in two partially overlapping sectors of the ventral precentral cortex of the macaque monkey, there is a general assumption that they share a same neuroanatomical network, with the parietal cortex as a main source of visual information. In the current review, we challenge this perspective and describe the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is connected with premotor, parietal areas mostly related to the somatosensory and motor representation of the face/mouth, and with area PrCO, involved in processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions. Such information related to face/communicative behaviors could come from the ventrolateral prefrontal cortex. Further strong connections derive from limbic structures involved in encoding emotional facial expressions and motivational/reward processing. These brain structures include the anterior cingulate cortex, the anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral amygdala. The mirror mechanism is therefore composed and supported by at least two different anatomical pathways: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and is connected with limbic structures, involved in communication/emotions and reward processing.

Introduction

The anterior part of the ventral premotor cortex of the monkey has been investigated from anatomical and functional points of view by several researchers. The anatomical work by Matelli and colleagues (1985) showed that the most ventral portion of the agranular frontal cortex, extending from the central sulcus to the inferior limb of the arcuate sulcus, is formed by three different architectonic areas: the primary motor area F1, located in the depth of the anterior bank of the central sulcus and in the convexity immediately rostral to it, and the ventral premotor areas F4 (caudal) and F5 (rostral). In recent years, the combination of the cytoarchitectonic techniques with the neurochemical ones has proven to be useful for providing a more detailed definition of areal borders (see Belmalih et al., 2007). This multi-architectonic approach led to the parcellation of F5 into three sectors: F5c (convexity), F5p (posterior) and F5a (anterior). F5c extends on the convexity of the postarcuate cortex adjacent to the inferior arcuate sulcus, F5p and F5a lie within the postarcuate bank, at different antero-posterior levels (Fig. 1A).

Several neurophysiological investigations (Kurata and Tanji, 1986, Gentilucci et al., 1988, Rizzolatti et al., 1988, di Pellegrino et al., 1992, Hepp-Reymond et al., 1994, Gallese et al., 1996, Ferrari et al., 2003, Maranesi et al., 2012) showed that area F5 hosts a motor representation of the hand (medially) and of the mouth (laterally) and plays a role in the generation and control of goal-directed motor acts such as grasping or biting (Fig. 1B). In addition, other neurons have been described which have visuomotor properties in F5. These neurons fall into two classes: “canonical” neurons and “mirror” neurons. Canonical neurons discharge to the observation of graspable objects and during the execution of a grasping movements (Murata et al., 1997, Raos et al., 2006); mirror neurons (MNs) fire both when the monkey is performing a motor act and also when the same, or a similar act is performed by another individual (di Pellegrino et al., 1992, Gallese et al., 1996, Ferrari et al., 2003, Caggiano et al., 2009, Kraskov et al., 2009, Maranesi et al., 2012, Maranesi et al., 2015, Bonini et al., 2014, Coudé et al., 2016). Other studies found MNs also in regions anatomically connected with the premotor cortex (PMv) such as the parietal cortex (Fogassi et al., 2005, Pani et al., 2014, Maeda et al., 2015), the dorsal premotor cortex (Tkach et al., 2007), and the primary motor cortex (Vigneswaran et al., 2013). The properties of MNs in these areas were investigated in relation to hand/arm movement directed toward a target. Despite some differences in neuronal specificity among MNs recorded in different anatomical areas, it is acknowledged that they are probably part of a more extended network subserving the processing of the one’s own or other’s actions (Bonini, 2015, Rizzolatti and Sinigaglia, 2016, Tramacere and Ferrari, 2016).

The vast majority of functional studies investigating MNs has explored their properties in relation to hand actions, and was thus focused on the medial part of F5, where the hand is the most represented effector (see Rizzolatti and Luppino, 2001, Rizzolatti et al., 2001, Rizzolatti et al., 2014, Borra et al., 2010, Maier et al., 2013, Bonini, 2015). More specifically, neuroanatomical and functional studies have shown that the hand sector of F5 has direct anatomical connections with different hand sectors of the parietal cortex, including areas AIP and PFG (Rozzi et al., 2006, Borra et al., 2008, Bonini et al., 2010, Gerbella et al., 2011). Similarly to F5, these parietal areas host motor neurons coding goal-directed motor acts and visuomotor neurons, including MNs in relation to hand actions (Gallese et al., 2002, Fogassi et al., 2005, Rozzi et al., 2008, Maeda et al., 2015). Within the mirror circuit (so called because of the well-established AIP/PFG-F5 connections), it has been proposed that these parietal areas convey visual information regarding hand grasping movements, and are the first hub of the visual input deriving from the temporal cortex, within the superior temporal sulcus (STS) region. A neuroimaging study in the macaque has further confirmed the idea that information regarding observed hand action is forwarded from the region of the STS to area F5 through two different routes passing from the parietal areas AIP and PFG (Nelissen et al., 2011; see Fig. 2). Further neurophysiological studies have shown that these parietal-premotor circuits are also essential to support important cognitive functions in relation to action observation such as the understanding of others’ actions and intentions (Fogassi et al., 2005, Bonini et al., 2011).

Other anatomical studies showed that the parietal and premotor mirror areas share numerous other anatomical connections that may extend the functional properties of this neural mechanism beyond the classically described functions (Rizzolatti et al., 2014, Bonini, 2015, Borra et al., 2017). Among these connections, in particular, area F5 is anatomically connected with other cortical motor regions such as F1, F2vr (ventrorostral) and F6, which also are endowed with mirror properties or with properties related to self-other behaviors (Cisek and Kalaska, 2004, Kraskov et al., 2009, Yoshida et al., 2011). In addition, cortico-cortical connections of F5 extend to areas of the prefrontal cortex (Borra et al., 2011, Gerbella et al., 2011, Gerbella et al., 2013) where movement-related neurons have been described (Hoshi et al., 1998, Bruni et al., 2015, Simone et al., 2015). This evidence suggests that a specific sector of the ventrolateral prefrontal cortex (VLPC) is involved in context-based control of actions (either performing with the hand or the mouth) and in action observation (Simone et al., 2017).

Despite the fact that monkey mirror neurons have been investigated in several neurophysiological studies, most of these studies were focused exclusively on the visuomotor properties of these neurons in relation to hand actions. The original study by Gallese and colleagues (1996) reported the presence of mirror neurons responding to mouth actions, but the neurophysiological descriptions of the neuronal properties have been limited to hand actions. The work by Ferrari and colleagues (2003) was the first to describe the properties of a new category of MNs responding to mouth actions. The basic properties of visuo-motor congruence described for the hand MNs were also confirmed in that study, but surprisingly, a small percentage of mouth MNs were responding to communicative gestures, such as lipsmacking, a typical macaque affiliative gesture (Fig. 3). Mouth MNs were found in the most lateral part of F5 probably extending also over the fronto-opercular region (Ferrari et al., 2003, Maranesi et al., 2012). Further experiments, demonstrated that, within the lateral sector of the ventral PMv, neurons discharging for mouth, hand actions or gestures are often intermingled, thus showing a significant overlap of hand and mouth motor representations (Maranesi et al., 2012). Within this lateral part of the premotor-opercular region, neurons were found that fired when the monkey produced conditioned vocalizations after a prolonged period of training (Coudé et al., 2011).

Unfortunately, the neurophysiological properties and anatomical properties of this region have received very little attention and therefore there is an assumption that the same neuroanatomical network supporting the hand MNs is also characterizing mouth MNs. There are several considerations and experimental evidence that suggest that this is not the case: 1. From a theoretical point of view it has been suggested that mouth and hand MNs are formed through different developmental trajectories with the former, being involved in communication, relying on face-to-face interactions occurring in the first phases of postnatal life (Casile et al., 2011, Cook et al., 2014, Tramacere and Ferrari, 2016). Hand mirror neurons, instead, are probably formed through the tuning and coupling of motor signals that are visually coupled during infant’s first reaching movement and therefore they could be originally formed to sustain the visual tracking of the own hand. This hypothesis seems to be supported by the neurophysiological finding that some hand MNs respond not only during the observation of others’ actions but modulate neuronal activity during the observation of the own hand grasping (Sakaguchi et al., 2010, Maeda et al., 2015, Maranesi et al., 2015). Such own hand visual feedback modulation seems to be important for self-action monitoring, which is key for infant development of reaching-grasping actions. 2. The lateral part of the ventral premotor cortex, at the border with the opercular region has a different pattern of connectivity from the medial part of F5 where hand MNs have been mostly studied (Matelli et al., 1986, Morecraft et al., 2001, Jürgens, 2002, Simonyan and Jürgens, 2002, Gerbella et al., 2011, Gharbawie et al., 2011). This region of the cortex, for example, projects to the facial nucleus for the innervation of the lower part of the face, likely involved in motor control of the mimic facial muscles (Morecraft et al., 2001). Other anatomical studies showed that the opercular region of the face, has motor representations of the larynx muscles and is anatomically connected with different brainstem nuclei, the putamen, and the reticular formation (Jürgens, 2002, Simonyan and Jürgens, 2002). In addition to the above-mentioned considerations, it should be noted that mouth mirror neurons are mostly located in the ventral sector of PMv, but their presence has also been described in the adjacent opercular region (Ferrari et al., 2003 see Fig. 3): the dorsal opercular, area DO, and the granular frontal opercular area, GrFO (Fig. 1, Belmalih et al., 2009, Gerbella et al., 2016).

In the current review we are aiming at further investigating the connectivity pattern of the mouth mirror region. We hypothesize that the pattern of connectivity in this region differs from the adjacent and most medial F5 hand cortical sector. In order to test this hypothesis, we first review the pattern of connectivity of the areas belonging to the mouth regions of the premotor and opercular areas (i.e. F5, DO and GrFO) previously published (Gerbella et al., 2016) and compare them with those of the premotor hand region where hand MNs have been found. Second, we present a new case in which we have previously recorded mouth mirror neurons (Ferrari et al., 2003) and tract the anatomical connections of its core region, which was located in between F5, DO and GrFO.

Section snippets

Anatomical connections of the mouth mirror areas

Area F5, DO and GrFO share connections with numerous cortical regions and subcortical structures but each of them also has characterizing connections. In this paragraph we will describe the main connectional features of these architectonic areas. In a more recent study (Gerbella et al., 2016) neural tracers were injected in different parts of the monkey frontal opercular regions, including areas DO and GrFO (Fig. 4) where mouth MNs were previously found (Ferrari et al., 2003).

Analysis of a new case in which mouth MNs were recorded

Fig. 5 shows the reconstruction of the injection site and the location of penetrations (see details of methods in legend of Fig. 5) in which mouth mirror neurons have been recorded (see also Ferrari et al., 2003). These penetrations extend over the location of the ventral part of area F5c, area DO and GrFO. The large majority of mouth mirror neurons were found in the cortical convexity (more than 85% at a depth ranging from 200 to 1500 μm). Accordingly, the injection site is located in the

Two different anatomo-functional pathways supporting hand and mouth mirror neurons

The objective of this manuscript was to assess the hypothesis that the region containing mouth MNs and corresponding, not only to the lateral part of F5c, but also encompassing the cytoarchitectonic areas GrFO and DO, have a pattern of connectivity different from the one described for the hand motor regions of the PMv, which contains hand MNs. To this end, we first reviewed the anatomical literature describing the pattern of connectivity of the lateral part of F5 and of the frontal opercular

Conclusions

The findings described here overall indicate that MNs are present in different cytoarchitectonic areas and that their specific properties are linked not only to the type of effector involved (hand or mouth) but also to different anatomical pathways. In fact, we provided evidence that mouth MNs are present in the later part of F5c and the frontal opercular region, which have different anatomical connections from the medial sector of F5c where hand MNs have been described. One of the most

Acknowledgments

We thank Giuseppe Luppino for his comments on an early draft of the manuscript. This work was supported by the Division of Intramural Research, NICHD, and NIH P01HD064653.

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