Marzio Gerbella

Action observation circuits in the macaque monkey cortex

In both monkeys and humans, the observation of actions performed by others activates cortical motor areas. An unresolved question concerns the pathways through which motor areas receive visual information describing motor acts. Using functional magnetic resonance imaging (fMRI), we mapped the macaque brain regions activated during the observation of grasping actions, focusing on the superior temporal sulcus region (STS) and the posterior parietal lobe. Monkeys viewed either videos with only the grasping hand visible or videos with the whole actor visible. Observation of both types of grasping videos activated elongated regions in the depths of both lower and upper banks of STS, as well as parietal areas PFG and anterior intraparietal (AIP). The correlation of fMRI data with connectional data showed that visual action information, encoded in the STS, is forwarded to ventral premotor cortex (F5) along two distinct functional routes. One route connects the upper bank of the STS with area PFG, which projects, in turn, to the premotor area F5c. The other connects the anterior part of the lower bank of the STS with premotor areas F5a/p via AIP. Whereas the first functional route emphasizes the agent and may relay visual information to the parieto-frontal mirror circuit involved in understanding the agents intentions, the second route emphasizes the object of the action and may aid in understanding motor acts with respect to their immediate goal.

Cortical connections of the anterior (F5a) subdivision of the macaque ventral premotor area F5

We traced the cortical connections of the anterior sector (F5a) of the macaque ventral premotor (PMv) area F5 and compared them with those of the adjacent F5 sectors, F5c and F5p. F5a displays a very dense “intrinsic” connectivity with F5c and F5p, premotor connections limited to F4 and F6/pre-SMA, relatively robust prefrontal connections with areas 46v and 12, and dense connections with rostral opercular frontal areas. Outside the frontal cortex, connections of F5a are dense with the SII region, relatively robust with inferior parietal areas PFG and AIP, weak with the inferior parietal area PF, and moderate with area 24. The comparison with data from injections in F5c and F5p showed that F5a, though sharing some common parietal connections with the other F5 sectors, displays several characterizing features providing robust evidence for its connectional distinctiveness. The present study provides evidence for a general organization of the PMv similar to that of the medial and dorsal premotor cortex, with F5a representing a pre-PMv area. Specifically, the present data suggest that F5a is a privileged site of integration, in the PMv, of parietal sensory-motor signals with higher-order information originating from prefrontal, rostral frontal opercular areas, and F6/pre-SMA. The results of this integration can be then broadcasted to the adjacent F5 sectors for the generation and control of hand actions and cognitive motor functions.

Cortical connections of the macaque caudal ventrolateral prefrontal areas 45A and 45B.

We have found that the 2 architectonic subdivisions of the prefrontal area 45, 45A and 45B, display connectivity patterns that clearly distinguish them from one another and from their neighboring architectonic areas. Area 45A is primarily connected to the frontal areas 45B, 12l, caudal 12r, 12o, 10, rostrodorsal 46, 9/8B, 44, 8/FEF (frontal eye field), and the SEF (supplementary eye field), temporal area IPa, and unique among all the studied areas, to the superior temporal polysensory (STP) area and auditory parabelt areas. Area 45B displayed much stronger frontal connections with the oculomotor areas 8/FEF, 8r, and the SEF than those of area 45A, primary connections with areas 12l, caudal 12r, 12o, and 8B, and unlike area 45A, with areas ventrorostral 46, rostral 12r, 12m, and 13m. Temporal connections were all virtually confined to areas IPa, intermediate TEa/m, and TE. Additional labeling was found in lateral intraparietal area. Our data suggest that 45A and 45B are 2 distinct areas, possibly playing a differential role in nonspatial information processing: area 45A corresponds to the prefrontal sector for which a role in communication behavior and homology with the human area 45 was proposed, whereas area 45B is a distinct prearcuate area, possibly affiliated to the oculomotor frontal system.

Multimodal architectonic subdivision of the rostral part (area F5) of the macaque ventral premotor cortex

We used a cyto‐, myelo‐, and chemoarchitectonic (distribution of SMI‐32 and calbindin immunoreactivity) approach to assess whether the rostral histochemical area F5 of the ventral premotor cortex (PMv) comprises architectonically distinct areas, possibly corresponding to functionally different fields. Three areas were identified, occupying different parts of F5. One area, designated as “convexity” F5 (F5c), extends on the postarcuate convexity cortex adjacent to the inferior arcuate sulcus and is characterized, cytoarchitectonically, by a poorly laminated appearance, resulting from an overall cell population rather homogeneous in size and density. The other two areas, designated as “posterior” and “anterior” F5 (F5p and F5a, respectively), lie within the postarcuate bank at different anteroposterior levels. Major cytoarchitectonic features of F5p are a layer III relatively homogeneous in cell size and density, a cell‐dense layer Va, and the presence of relatively large pyramids in layer Vb. Major cytoarchitectonic features of F5a are the presence of relatively large pyramids in lowest layer III and a prominent, homogenous layer V. Furthermore, our results showed that F5c and F5p border caudally with a caudal PMv area corresponding to histochemical area F4, providing additional evidence for a general subdivision of the macaque PMv into a caudal and a rostral part, corresponding to F4 and to the F5 complex, respectively. The present data, together with other functional and connectional data, suggest that the three rostral PMv areas F5p, F5a, and F5c correspond to distinct cortical entities, possibly involved in different aspects of motor control and cognitive motor functions. J. Comp. Neurol. 512:183–217, 2009.

Projections of the hand field of the macaque ventral premotor area F5 to the brainstem and spinal cord

In the present study we first assessed that the hand motor field of the macaque ventral premotor area F5, involved in visuomotor control of hand actions, is connected to both the hand field of the primary motor cortex (M1) and the spinal cord. We then injected retroanterograde tracers in this field to completely illustrate its possible descending motor projections. In the brainstem the F5 hand motor field projects to the intermediate and deep layers of the superior colliculus (SC) and to sectors of the mesencephalic, pontine, and bulbar reticular formation, which are the sources of spinal projections. In the spinal cord, labeled terminals were virtually all confined to the C2–T1 segments, mostly contralaterally. At C6–T1 levels the labeling was weaker and mostly clustered laterally in the intermediate zone. At C2–C5 levels, labeled terminals were much denser and diffusely distributed over the mid‐dorsal part of the intermediate zone where a propriospinal system that directly controls hand muscle motoneurons and mediates commands for the control of dexterous finger movements is located (Isa et al. [2007] Physiology 22:145–152). Thus, the F5 hand motor field has a weaker direct access and a stronger indirect access to spinal segments where hand muscle motoneurons are located, suggesting a role of this field in the generation and control of hand movements not only at the M1 level, but also at the spinal cord level. These projections may represent the neural substrate for the F5 hand motor fields role in the recovery of manual dexterity after M1 lesions. J. Comp. Neurol. 518:2570–2591, 2010.

Anatomical Evidence for the Involvement of the Macaque Ventrolateral Prefrontal Area 12r in Controlling Goal-Directed Actions

The macaque ventrolateral prefrontal (VLPF) area 12r is thought to be involved in higher-order nonspatial information processing. We found that this area is connectionally heterogeneous, and the intermediate part is fully integrated in a cortical network involved in selecting and controlling object-oriented hand and mouth actions. Specifically, intermediate area 12r displayed dense connections with the caudal half of area 46v and orbitofrontal areas and relatively strong extraprefrontal connections involving the following: (1) the hand- and mouth-related ventral premotor area F5 and the anterior intraparietal (AIP) area, jointly involved in visuomotor transformations for grasping; (2) the SII sector that is connected to AIP and F5; (3) a sector of the inferotemporal area TEa/m, primarily corresponding to the sector densely connected to AIP; and (4) the insular and opercular frontal sectors, which are connected to AIP and F5. This connectivity pattern differed markedly from those of the caudal and rostral parts of area 12r. Caudal area 12r displayed dense connections with the caudal part of the VLPF, including oculomotor areas 8/FEF and 45B, relatively weak orbitofrontal connections and extraprefrontal connections limited to the inferotemporal cortex. Rostral area 12r displayed connections mostly with rostral prefrontal and orbitofrontal areas and relatively weaker connections with the fundus and the upper bank of the superior temporal sulcus. The present data suggest that the intermediate part of area 12r is involved in nonspatial information processing related to object properties and identity, for selecting and controlling goal-directed hand and mouth actions.

Connectional Heterogeneity of the Ventral Part of the Macaque Area 46

We found that the ventral part of the prefrontal area 46 (46v) is connectionally heterogeneous. Specifically, the rostral part (46vr) displayed an almost exclusive and extensive intraprefrontal connectivity and extraprefrontal connections limited to area 24 and inferotemporal areas. In contrast, the caudal part (46vc) mostly displayed intraprefrontal connectivity with ventrolateral areas and robust connectivity with frontal and parietal sensorimotor areas. Based on a topographic organization of these connections, 3 fields were identified in area 46vc. A caudal field (caudal 46vc) was preferentially connected to oculomotor prearcuate (8/FEF, 45B, and 8r) and inferior parietal areas. The other 2, located more rostrally, in the bank of the principal sulcus (rostral 46vc/bank) and on the ventrolateral convexity cortex (rostral 46vc/convexity), respectively, were connected with hand/mouth-related (F5a, 44) ventral premotor areas, area SII, and the insula. However, rostral 46vc/convexity was also connected to the hand-related area AIP, whereas rostral 46vc/bank to hand/arm-related areas PFG and PG, to PGop, and to areas 11 and 24. The present data suggest a differential role in executive functions of areas 46vr and 46vc and a differential involvement of different parts of area 46vc in higher level integration for oculomotor behavior and goal-directed arm, hand, and mouth actions.

Multimodal architectonic subdivision of the caudal ventrolateral prefrontal cortex of the macaque monkey.

The caudal part of the macaque ventrolateral prefrontal cortex (VLPF) is part of several functionally distinct domains. In the present study we combined a cyto- and a myeloarchitectonic approach with a chemoarchitectonic approach based on the distribution of SMI-32 and Calbindin immunoreactivity, to determine the number and extent of architectonically distinct areas occupying this region. Several architectonically distinct areas, completely or partially located in the caudal VLPF, were identified. Two areas are almost completely limited to the anterior bank of the inferior arcuate sulcus, a dorsal one—8/FEF—which extends also more dorsally and should represent the architectonic counterpart of the frontal eye field, and a ventral one—45B—which occupies the ventral half of the bank. Two other areas occupy the ventral prearcuate convexity cortex, a caudal one—area 8r—located just rostral to area 8/FEF and a rostral one—area 45A—which extends as far as the inferior frontal sulcus. Area 45A borders dorsally, in the proximity of the principal sulcus, with area 46 and, ventrally, with area 12. The present data show the existence of two distinct prearcuate convexity areas (8r and 45A), extending other architectonic subdivisions of the caudal VLPF and providing a new, multiarchitectonic frame of reference for this region. The present architectonic data, together with other functional and connectional data, suggest that areas 8/FEF, 45B and 8r are part of the oculomotor frontal cortex, while area 45A is a distinct entity of the VLPF domain involved in high-order processing of nonspatial information.

A multiarchitectonic approach for the definition of functionally distinct areas and domains in the monkey frontal lobe

Over the last century, anatomical studies have shown that the cerebral cortex can be subdivided into structurally distinct regions, giving rise to a new branch of neuroanatomy: ‘architectonics’. Since then, architectonics has been often accused of being overly subjective, and its validity for the definition of functionally different cortical fields has been seriously questioned. Since the late 1980s, however, the problem of localization has become particularly important in functional studies of the primate motor cortex, because of evidence that (1) the primate motor cortex is made up of a mosaic of functionally specialized areas and (2) the human motor cortex shares several general organizational principles with the monkey motor cortex. Studies of the macaque agranular frontal cortex that used a multimodal cyto‐, myelo‐ and immuno‐architectonic approach have shown that architectonic borders can be reliably and consistently defined across different individuals, even at a qualitative level of analysis. The validity of this approach has been confirmed by its ability to localize functionally distinct areas precisely and to predict the existence of new functional areas. After more than a century, architectonics as a discipline goes far beyond its original aim of generating cortical maps.

A shared neural network for emotional expression and perception: An anatomical study in the macaque monkey

Over the past two decades, the insula has been described as the sensory “interoceptive cortex”. As a consequence, human brain imaging studies have focused on its role in the sensory perception of emotions. However, evidence from neurophysiological studies in non-human primates have shown that the insula is also involved in generating emotional and communicative facial expressions. In particular, a recent study demonstrated that electrical stimulation of the mid-ventral sector of the insula evoked affiliative facial expressions. The present study aimed to describe the cortical connections of this “affiliative field”. To this aim, we identified the region with electrical stimulation and injected neural tracers to label incoming and outgoing projections. Our results show that the insular field underlying emotional expression is part of a network involving specific frontal, cingulate, temporal, and parietal areas, as well as the amygdala, the basal ganglia, and thalamus, indicating that this sector of the insula is a site of integration of motor, emotional, sensory and social information. Together with our previous functional studies, this result challenges the classic view of the insula as a multisensory area merely reflecting bodily and internal visceral states. In contrast, it supports an alternative perspective; that the emotional responses classically attributed to the insular cortex are endowed with an enactive component intrinsic to each social and emotional behavior.