In recent years, many new cortical areas have been identified in the macaque monkey. The number of identified connections between areas has increased even more dramatically. We report here on (1) a summary of the layout of cortical areas associated with vision and with other modalities, (2) a computerized database for storing and representing large amounts of information on connectivity patterns, and (3) the application of these data to the analysis of hierarchical organization of the cerebral cortex. Our analysis concentrates on the visual system, which includes 25 neocortical areas that are predominantly or exclusively visual in function, plus an additional 7 areas that we regard as visual-association areas on the basis of their extensive visual inputs. A total of 305 connections among these 32 visual and visual-association areas have been reported. This represents 31% of the possible number of pathways if each area were connected with all others. The actual degree of connectivity is likely to be closer to 40%. The great majority of pathways involve reciprocal connections between areas. There are also extensive connections with cortical areas outside the visual system proper, including the somatosensory cortex, as well as neocortical, transitional, and archicortical regions in the temporal and frontal lobes. In the somatosensory/motor system, there are 62 identified pathways linking 13 cortical areas, suggesting an overall connectivity of about 40%. Based on the laminar patterns of connections between areas, we propose a hierarchy of visual areas and of somatosensory/motor areas that is more comprehensive than those suggested in other recent studies. The current version of the visual hierarchy includes 10 levels of cortical processing. Altogether, it contains 14 levels if one includes the retina and lateral geniculate nucleus at the bottom as well as the entorhinal cortex and hippocampus at the top. Within this hierarchy, there are multiple, intertwined processing streams, which, at a low level, are related to the compartmental organization of areas V1 and V2 and, at a high level, are related to the distinction between processing centers in the temporal and parietal lobes. However, there are some pathways and relationships (about 10% of the total) whose descriptions do not fit cleanly into this hierarchical scheme for one reason or another. In most instances, though, it is unclear whether these represent genuine exceptions to a strict hierarchy rather than inaccuracies or uncertainities in the reported assignment.

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Distributed Hierarchical Processing in the Primate Cerebral Cortex

Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

We recorded electrical activity from 532 neurons in the rostral part of inferior area 6 (area F5) of two macaque monkeys. Previous data had shown that neurons of this area discharge during goal-directed hand and mouth movements. We describe here the properties of a newly discovered set of F5 neurons ("mirror neurons', n = 92) all of which became active both when the monkey performed a given action and when it observed a similar action performed by the experimenter. Mirror neurons, in order to be visually triggered, required an interaction between the agent of the action and the object of it. The sight of the agent alone or of the object alone (three-dimensional objects, food) were ineffective. Hand and the mouth were by far the most effective agents. The actions most represented among those activating mirror neurons were grasping, manipulating and placing. In most mirror neurons (92%) there was a clear relation between the visual action they responded to and the motor response they coded. In approximately 30% of mirror neurons the congruence was very strict and the effective observed and executed actions corresponded both in terms of general action (e.g. grasping) and in terms of the way in which that action was executed (e.g. precision grip). We conclude by proposing that mirror neurons form a system for matching observation and execution of motor actions. We discuss the possible role of this system in action recognition and, given the proposed homology between F5 and human Brocca's region, we posit that a matching system, similar to that of mirror neurons exists in humans and could be involved in recognition of actions as well as phonetic gestures.

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Action recognition in the premotor cortex

Prologue 1. Introduction: vision from a biological point of view 2. Visual processing in the primate visual cortex 3. 'Cortical blindness' 4. Disorders of spatial perception and the visual control of action 5. Disorders of visual recognition 6. Dissociations between perception and action in normal subjects 7. Attention, consciousness, and the coordination of behaviour 8. Epilogue: twelve years on

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The visual brain in action

http://www.fulminiesaette.it/_uploads/foto/legame/Rizzolatti1996.pdf

Premotor cortex and the recognition of motor actions.

The functional properties of neurons located in the rostral part of inferior area 6 were studied in awake, partially restrained macaque monkeys. The most interesting property of these neurons was that their firing correlated with specific goal-related motor acts rather than with single movements made by the animal. Using the motor acts as the classification criterion we subdivided the neurons into six classes, four related to distal motor acts and two related to proximal motor acts. The distal classes are: "Grasping-with-the-hand-and-the-mouth neurons", "Grasping-with-the-hand neurons", "Holding neurons" and "Tearing neurons". The proximal classes are: "Reaching neurons" and "Bringing-to-the-mouth-or-to-the-body neurons". The vast majority of the cells belonged to the distal classes. A particularly interesting aspect of distal class neurons was that the discharge of many of them depended on the way in which the hand was shaped during the motor act. Three main groups of neurons were distinguished: "Precision grip neurons", "Finger prehension neurons", "Whole hand prehension neurons". Almost the totality of neurons fired during motor acts performed with either hand. About 50% of the recorded neurons responded to somatosensory stimuli and about 20% to visual stimuli. Visual neurons were more difficult to trigger than the corresponding neurons located in the caudal part of inferior area 6 (area F4). They required motivationally meaningful stimuli and for some of them the size of the stimulus was also critical. In the case of distal neurons there was a relationship between the type of prehension coded by the cells and the size of the stimulus effective in triggering the neurons. It is proposed that the different classes of neurons form a vocabulary of motor acts and that this vocabulary can be assessed by somatosensory and visual stimuli.

Functional organization of inferior area 6 in the macaque monkey. II. Area F5 and the control of distal movements.

The monkey mesial area 6 comprises two distinct cytoarchitectonic areas: F3 [supplementary motor area properly defined (SMA-proper)], located caudally, and F6 (pre-SMA), located rostrally. The aim of the present study was to describe the corticocortical connections of these two areas. To this purpose restricted injections of neuronal tracers (wheat germ-agglutinin conjugated to horseradish peroxidase, fluorescent tracers) were made in different somatotopic fields of F3, F6, and F1 (area 4) and their transport plotted. The results showed that F3 and F6 differ markedly in their cortical connections. F3 is richly linked with F1 and the posterior premotor and cingulate areas (F2, F4, 24d). Connections with the anterior premotor and cingulate areas (F6, F7, F5, 24c) although present, are relatively modest. There is no input from the prefrontal lobe. F3 is also connected with several postrolandic cortical areas. These connections are with areas PC, PE, and PEa in the superior parietal lobule, cingulate areas 23 and PEci, the opercular parietal areas (PFop, PGop, SII) and the granular insula. F6 receives a rich input from the anterior premotor areas (especially F5) and cingulate area 24c, whereas its input from the posterior premotor and cingulate areas is very weak. A strong input originates from area 46. There are no connections with F1. The connections with the postrolandic areas are extremely meagre. They are with areas PG and PFG in the inferior parietal lobule, the disgranular insula, and the superior temporal sulcus. A further result was the demonstration of a differential connectivity pattern of the cingulate areas 24d and 24c. Area 24d is strongly linked with F1 and F3, whereas area 24c is connected mostly with F6. The present data support the notion that the classical SMA comprises two functionally distinct areas. They suggest that F6 (the rostral area) is responsible for the "SMA" so-called high level motor functions, whereas F3 (the caudal area) is more closely related to movement execution.

Corticocortical connections of area F3 (SMA‐proper) and area F6 (pre‐SMA) in the macaque monkey

Two series of experiments are reported in this paper. The first concerns the movement representation in the macaque inferior area 6, the second the functional properties of neurons located in the caudal part of this area (histochemical area F4). By combining single neuron recording and intracortical microstimulation, we found that inferior area 6 is somatotopically organized. The axio-proximal movements are represented caudally, the distal movements are represented near the arcuate sulcus. The mouth field is located laterally, the hand field medially. There is no leg field. A comparison between neuron properties and histochemical characteristics of inferior area 6 showed that the proximal movements representation includes most of area F4, whereas the distal movements representation corresponds to area F5 and to the rostral part of F4. Neurons located in that part of F4 where proximal movements are represented respond very well to tactile stimuli. They have large receptive fields mostly located on the face and on the upper part of the body. A large number of these neurons respond to visual stimuli. Objects approaching the animal are particularly effective. The tactile and the visual receptive fields are in register. The most represented movements are reaching movements, movements bringing the hand to the mouth or to the body and facial movements. There is a congruence between location of visual fields and preferred arm movements. It is argued that the receptive field arrangement and the response properties are more complex in area F4 than in the primary motor cortex and that area F4 neurons are involved in the control of arm movements towards different space sectors.

Functional organization of inferior area 6 in the macaque monkey. I. Somatotopy and the control of proximal movements.

The mesial agranular frontal cortex that lies rostral to area 4 (F1) is formed by two distinct cytoarchitectonic areas: F3, located caudally, and F6, located rostrally. In the present experiments we investigated the organization of F3 and F6 by observing the motor responses evoked by their intracortical electrical microstimulation. Our main purpose was to find out whether the cytoarchitectonic subdivision of the mesial agranular frontal cortex into two areas has a physiological counterpart. The result showed that F3 (the caudal area) contains a complete motor representation with hindlimb movements located caudally, forelimb movements located centrally, and orofacial movements located rostrally. The great majority of limb movements involved proximal joints. With respect to F1, F3 showed the following functional characteristics: (1) lack of segregation between proximal and distal movements, (2) larger percentage of complex movements, and (3) higher excitability threshold. Movements were more difficult to elicit from F6 (the rostral area) than from F3. However, by using a longer stimulus train duration (100 ms) 39.3% of tested sites produced body movements. This percentage increased (50.5%) when the electrical stimulation was applied during monkey natural movements instead of when the monkey was still in its chair. Most of the evoked movements concerned the forelimb. More rarely, neck and upper face movements were observed. Unlike F1 and F3 where most movements were fast, slow movements were frequently observed with stimulation of F6. Many of them mimicked natural movements of the animal. Eye movements were evoked from F7 (superior area 6) but not from F6. An additional motor representation was found in the dorsocaudal part of area 24 (24d). This area is topographically organized with a forelimb representation located caudally and ventrally and a hindlimb representation located rostrally and dorsally. The excitability threshold of area 24d is higher than that of F1 and F3. Evoked movements were occasionally observed also after stimulation of area 24c. In conclusion, on the mesial cortical wall rostral to F1, there are at least three independent motor representations. On the basis of somatotopic organization and excitability properties, we propose that the term supplementary motor area (SMA-proper) should be reserved to F3.

Multiple representations of body movements in mesial area 6 and the adjacent cingulate cortex : an intracortical microstimulation study in the macaque monkey

The rostral part of the agranular frontal cortex (area 6) can be subdivided on the basis of its cytoarchitecture, enzymatic properties, and connections into two large sectors: a superior region, lying medial to the spur of the arcuate sulcus, and an inferior region, lying lateral to it. In this study we traced the afferent and efferent connections of the inferior region of area 6 by injecting small amounts of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and fluorescent tracers (fast blue and diamidino yellow) into restricted parts of inferior area 6 and in physiologically determined fields of area 4. There is an ordered topographic pattern of connections between inferior area 6 and area 4. The region near the spur of the arcuate sulcus (hand field) projects to the area 4 hand field while the lateral part of inferior area 6 (mouth field) is connected with the corresponding field in area 4. The organization of the connections between the two fields is, however, different. The hand fields in area 6 and 4 have direct reciprocal projections, whereas the mouth field in the postarcuate cortex relays information to area 4 via a zone intermediate between the arcuate and the central sulcus. This zone corresponds to the cytochrome oxidase area F4 (Matelli, Luppino, and Rizzolatti: Behav. Brain Res. 18: 125-137, '85). The inferior area 6 also has topographically organized connections with the supplementary motor area. The inferior area 6 receives and sends fibers to a series of discrete cortical areas located in the lower cortical moiety (Sanides: The Structure and Function of the Nervous Tissue, Vol. 5. New York: Academic Press, pp 329-453, '72). These areas that form a broad ring around the central sulcus are the ventral bank of the principal sulcus and the adjacent area 46, the precentral operculum (PrOC), area SII (Jones and Burton: J. Comp. Neurol. 168:197-248, '76), the parietal operculum, and the rostral part of the inferior parietal lobule including the lower bank of the intraparietal sulcus. Finally, the inferior area 6 has sparse but consistent connections with insular and cingulate cortices. The functional significance of this complex pattern of connections is discussed.

R. Camarda

Papers

Functional organization of inferior area 6 in the macaque monkey. II. Area F5 and the control of distal movements.

Corticocortical connections of area F3 (SMA‐proper) and area F6 (pre‐SMA) in the macaque monkey

Functional organization of inferior area 6 in the macaque monkey. I. Somatotopy and the control of proximal movements.

Multiple representations of body movements in mesial area 6 and the adjacent cingulate cortex : an intracortical microstimulation study in the macaque monkey

Afferent and efferent projections of the inferior area 6 in the macaque monkey.