Stefano Rozzi

Functional organization of inferior parietal lobule convexity in the macaque monkey: electrophysiological characterization of motor, sensory and mirror responses and their correlation with cytoarchitectonic areas

The general view on the functional role of the monkey inferior parietal lobule (IPL) convexity mainly derives from studies carried out more than two decades ago and does not account for the functional complexity suggested by more recent neuroanatomical findings. We investigated this issue by recording multi‐ and single units in the IPL convexity of two monkeys and characterizing their somatosensory, visual and motor responses, using a naturalistic (ethologically relevant) approach. These properties were then matched with IPL cytoarchitectonic parcellation. A further aim of this study was to describe the general properties and the localization of IPL mirror neurons, until now not investigated in detail. Results showed that each studied cytoarchitectonic subdivision of the IPL (PF, PFG, PG) is characterized by specific sensory and motor properties. A key feature of the recorded motor neurons is that of coding goal‐directed motor acts. Motor responses are somatotopically organized in a rostro‐caudal fashion, with mouth, hand and arm represented in PF, PFG and PG, respectively, with a certain degree of overlap between adjacent representations. In each subdivision the motor activity is associated with specific somatosensory and visual responses, suggesting that each area organizes motor acts in different space sectors. Mirror neurons have been found mainly in area PFG and their general features appear to be very similar to those of ventral premotor mirror neurons. The present data suggest that the IPL plays an important role in both action organization and action understanding and should be considered part of the motor system.

Mirror Neurons Responding to Observation of Actions Made with Tools in Monkey Ventral Premotor Cortex

In the present study, we describe a new type of visuomotor neurons, named tool-responding mirror neurons, which are found in the lateral sector of monkey ventral premotor area F5. Tool-responding mirror neurons discharge when the monkey observes actions performed by an experimenter with a tool (a stick or a pair of pliers). This response is stronger than that obtained when the monkey observes a similar action made with a biological effector (the hand or the mouth). These neurons respond also when the monkey executes actions with both the hand and the mouth. The visual and the motor responses of each neuron are congruent in that they share the same general goal, that is, taking possession of an object and modifying its state. It is hypothesized that after a relatively long visual exposure to tool actions, a visual association between the hand and the tool is created, so that the tool becomes as a kind of prolongation of the hand. We propose that tool-responding mirror neurons enable the observing monkey to extend action-understanding capacity to actions that do not strictly correspond to its motor representations. Our findings support the notion that the motor cortex plays a crucial role in understanding action goals.

Prefrontal and agranular cingulate projections to the dorsal premotor areas F2 and F7 in the macaque monkey

The superior sector of Brodmann area 6 (dorsal premotor cortex, PMd) of the macaque monkey consists of a rostral and a caudal architectonic area referred to as F7 and F2, respectively. The aim of this study was to define the origin of prefrontal and agranular cingulate afferents to F7 and F2, in the light of functional and hodological evidence showing that these areas do not appear to be functionally homogeneous. Different sectors of F7 and F2 were injected with neural tracers in seven monkeys and the retrograde labelling was qualitatively and quantitatively analysed. The dorsorostral part of F7 (supplementary eye field, F7‐SEF) was found to be a target of strong afferents from the frontal eye field (FEF), from the dorsolateral prefrontal regions located dorsally (DLPFd) and ventrally (DLPFv) to the principal sulcus and from cingulate areas 24a, 24b and 24c. In contrast, the remaining part of F7 (F7‐non SEF) is only a target of the strong afferents from DLPFd. Finally, the ventrorostral part of F2 (F2vr), but not the F2 sector located around the superior precentral dimple (F2d), receives a minor, but significant, input from DLPFd and a relatively strong input from the cingulate gyrus (areas 24a and 24b) and area 24d. Present data provide strong hodological support in favour of the idea that areas F7 and F2 are formed by two functionally distinct sectors.

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.

Neurons Controlling Voluntary Vocalization in the Macaque Ventral Premotor Cortex

The voluntary control of phonation is a crucial achievement in the evolution of speech. In humans, ventral premotor cortex (PMv) and Brocas area are known to be involved in voluntary phonation. In contrast, no neurophysiological data are available about the role of the oro-facial sector of nonhuman primates PMv in this function. In order to address this issue, we recorded PMv neurons from two monkeys trained to emit coo-calls. Results showed that a population of motor neurons specifically fire during vocalization. About two thirds of them discharged before sound onset, while the remaining were time-locked with it. The response of vocalization-selective neurons was present only during conditioned (voluntary) but not spontaneous (emotional) sound emission. These data suggest that the control of vocal production exerted by PMv neurons constitutes a newly emerging property in the monkey lineage, shedding light on the evolution of phonation-based communication from a nonhuman primate species.

Grasping Neurons of Monkey Parietal and Premotor Cortices Encode Action Goals at Distinct Levels of Abstraction during Complex Action Sequences

Natural actions are formed by distinct motor acts, each of which is endowed with its own motor purpose (i.e., grasping), chained together to attain the final action goal. Previous studies have shown that grasping neurons of parietal area PFG and premotor area F5 can code the goal of simple actions in which grasping is embedded. While during simple actions the target is usually visible, directly cueing the final goal, during complex action sequences is often concealed and has to be kept in mind to shape action unfolding. The aim of this study was to assess the relative contribution of sensory-cued or memory-driven information about the final goal to PFG and F5 grasping neurons activity. To this purpose, we trained two monkeys to perform complex action sequences, each including two successive grasping acts, aimed at specific final goals (eating or placing). We recorded 122 PFG and 89 F5 neurons. Forty-seven PFG and 26 F5 neurons displayed action goal selectivity only during the late phase of the action, when sensory information cueing the action goal became available. Reward contingency did not affect neuronal selectivity. Notably, 17 PFG neurons reflected the final goal from the early phase of action unfolding, when only memory-driven information was available. Crucially, when monkeys were prevented from obtaining such information before action onset, neurons lost their early selectivity. Our findings suggest that external sensory cues and individuals motor intention integrate at different level of abstraction within a large anatomo-functional network, encompassing parietal and premotor cortices.

Projections from the superior temporal sulcus to the agranular frontal cortex in the macaque

The aim of this study was to investigate the organization of the projections from the superior temporal sulcus (STS) to the various areas forming the agranular frontal cortex. Injections of retrograde neuronal tracers were made in the various agranular areas, in nine macaque monkeys. The results showed that two rostral premotor areas, F6 (pre‐SMA) and F7, and the ventrorostral part of area F2 (F2vr) are targets of projections from the upper bank of the STS (uSTS). F6 and the dorsorostral part of F7 (supplementary eye field, SEF) are targets of projections from the rostral part of the uSTS, corresponding to the so‐called ‘superior temporal polysensory area’ (STP). In contrast, the ventral part of area F7 (not including the SEF) and F2vr are targets of afferents from the caudal part of the uSTS. Ventral F7 is the target of weak afferents from the caudalmost and dorsalmost part of the uSTS (area 7a), whilst F2vr is the target of projections from a relatively more rostral and ventral sector of the uSTS, close to the fundus of the sulcus. This sector should correspond to area MST. In conclusion, F6 and SEF receive high order information from STP, whereas ventral F7 and F2vr receive information from areas of the dorsal visual stream.