Ventral Premotor Area F5 Research Articles

Differential neural dynamics underlying pragmatic and semantic affordance processing in macaque ventral premotor cortex

Premotor neurons play a fundamental role in transforming physical properties of observed objects, such as size and shape, into motor plans for grasping them, hence contributing to “pragmatic” affordance processing. Premotor neurons can also contribute to “semantic” affordance processing, as they can discharge differently even to pragmatically identical objects depending on their behavioural relevance for the observer (i.e. edible or inedible objects). Here, we compared the response of monkey ventral premotor area F5 neurons tested during pragmatic (PT) or semantic (ST) visuomotor tasks. Object presentation responses in ST showed shorter latency and lower object selectivity than in PT. Furthermore, we found a difference between a transient representation of semantic affordances and a sustained representation of pragmatic affordances at both the single neuron and population level. Indeed, responses in ST returned to baseline within 0.5 s whereas in PT they showed the typical sustained visual-to-motor activity during Go trials. In contrast, during No-go trials, the time course of pragmatic and semantic information processing was similar. These findings suggest that premotor cortex generates different dynamics depending on pragmatic and semantic information provided by the context in which the to-be-grasped object is presented.

Spatial and viewpoint selectivity for others\u2019 observed actions in monkey ventral premotor mirror neurons

The spatial location and viewpoint of observed actions are closely linked in natural social settings. For example, actions observed from a subjective viewpoint necessarily occur within the observer’s peripersonal space. Neurophysiological studies have shown that mirror neurons (MNs) of the monkey ventral premotor area F5 can code the spatial location of live observed actions. Furthermore, F5 MN discharge can also be modulated by the viewpoint from which filmed actions are seen. Nonetheless, whether and to what extent MNs can integrate viewpoint and spatial location of live observed actions remains unknown. We addressed this issue by comparing the activity of 148 F5 MNs while macaque monkeys observed an experimenter grasping in three different combinations of viewpoint and spatial location, namely, lateral view in the (1) extrapersonal and (2) peripersonal space and (3) subjective view in the peripersonal space. We found that the majority of MNs were space-selective (60.8%): those selective for the peripersonal space exhibited a preference for the subjective viewpoint both at the single-neuron and population level, whereas space-unselective neurons were view invariant. These findings reveal the existence of a previously neglected link between spatial and viewpoint selectivity in MN activity during live-action observation.

The extended object-grasping network.

Grasping is the most important skilled motor act of primates. It is based on a series of sensorimotor transformations through which the affordances of the objects to be grasped are transformed into appropriate hand movements. It is generally accepted that a circuit formed by inferior parietal areas AIP and PFG and ventral premotor area F5 represents the core circuit for sensorimotor transformations for grasping. However, selection and control of appropriate grip should also depend on higher-order information, such as the meaning of the object to be grasped, and the overarching goal of the action in which grasping is embedded. In this review, we describe recent findings showing that specific sectors of the ventrolateral prefrontal cortex are instrumental in controlling higher-order aspects of grasping. We show that these prefrontal sectors control the premotor cortex through two main gateways: the anterior subdivision of ventral area F5-sub-area F5a-, and the pre-supplementary area (area F6). We then review functional studies showing that both F5a and F6, besides being relay stations of prefrontal information, also play specific roles in grasping. Namely, sub-area F5a is involved in stereoscopic analysis of 3D objects, and in planning cue-dependent grasping activity. As for area F6, this area appears to play a crucial role in determining when to execute the motor program encoded in the parieto-premotor circuit. The recent discovery that area F6 contains a set of neurons encoding specific grip types suggests that this area, besides controlling "when to go", also may control the grip type, i.e., "how to go". We conclude by discussing clinical syndromes affecting grasping actions and their possible mechanisms.

Extending the Cortical Grasping Network: Pre-supplementary Motor Neuron Activity During Vision and Grasping of Objects.

Grasping relies on a network of parieto-frontal areas lying on the dorsolateral and dorsomedial parts of the hemispheres. However, the initiation and sequencing of voluntary actions also requires the contribution of mesial premotor regions, particularly the pre-supplementary motor area F6. We recorded 233 F6 neurons from 2 monkeys with chronic linear multishank neural probes during reaching–grasping visuomotor tasks. We showed that F6 neurons play a role in the control of forelimb movements and some of them (26%) exhibit visual and/or motor specificity for the target object. Interestingly, area F6 neurons form 2 functionally distinct populations, showing either visually-triggered or movement-related bursts of activity, in contrast to the sustained visual-to-motor activity displayed by ventral premotor area F5 neurons recorded in the same animals and with the same task during previous studies. These findings suggest that F6 plays a role in object grasping and extend existing models of the cortical grasping network.

Multimodal Encoding of Goal-Directed Actions in Monkey Ventral Premotor Grasping Neurons.

Visuo-motor neurons of the ventral premotor area F5 encode "pragmatic" representations of object in terms of the potential motor acts (e.g., precision grip) afforded by it. Likewise, objects with identical pragmatic features (e.g., small spheres) but different behavioral value (e.g., edible or inedible) convey different "semantic" information and thus afford different goal-directed behaviors (e.g., grasp-to-eat or grasp-to-place). However, whether F5 neurons can extract distinct behavioral affordances from objects with similar pragmatic features is unknown. We recorded 134 F5 visuo-motor neurons in 2 macaques during a contextually cued go/no-go task in which the monkey grasped, or refrained from grasping, a previously presented edible or inedible target to eat it or placing it, respectively. Sixty-nine visuo-motor neurons showed motor selectivity for the target (35 food and 34 object), and about half of them (N = 35) exhibited congruent visual preference. Interestingly, when the monkey grasped in complete darkness and could identify the target only based on haptic feedback, visuo-motor neurons lost their precontact selectivity, but most of them (80%) showed it again 60 ms after hand-target contact. These findings suggest that F5 neurons possess a multimodal access to semantic information on objects, which are transformed into motor representations of the potential goal-directed actions afforded by them.

Mirror neuron activation prior to action observation in a predictable context.

A fundamental capacity of social animals consists in the predictive representation of upcoming events in the outside world, such as the actions of others. Here, we tested the activity of ventral premotor area F5 mirror neurons (MNs) while monkeys observed an experimenter performing (Action condition) or withholding (Inaction condition) a grasping action, which could be predicted on the basis of previously presented auditory instructions. Many of the recorded MNs discharged only during action observation (Action MNs), but one-third also encoded the experimenter's withheld action (Inaction MNs). Interestingly, while most of Action MNs exhibited reactive discharge during action observation, becoming active after the go signal, the majority of Inaction MNs showed predictive discharge. MN population activity as a whole displayed an overall predictive activation pattern, becoming active, on average, 340 ms before the go signal. Furthermore, MNs became active earlier when the observed action was performed in the monkeys' extrapersonal rather than peripersonal space, suggesting that context-based neural prediction of others' actions plays different roles depending on the monkeys' ability to interact with the observed agent.

Space-Dependent Representation of Objects and Other's Action in Monkey Ventral Premotor Grasping Neurons

The macaque ventral premotor area F5 hosts two types of visuomotor grasping neurons: "canonical" neurons, which respond to visually presented objects and underlie visuomotor transformation for grasping, and "mirror" neurons, which respond during the observation of others' action, likely playing a role in action understanding. Some previous evidence suggested that canonical and mirror neurons could be anatomically segregated in different sectors of area F5. Here we investigated the functional properties of single neurons in the hand field of area F5 using various tasks similar to those originally designed to investigate visual responses to objects and actions. By using linear multielectrode probes, we were able to simultaneously record different types of neurons and to precisely localize their cortical depth. We recorded 464 neurons, of which 243 showed visuomotor properties. Canonical and mirror neurons were often present in the same cortical sites; and, most interestingly, a set of neurons showed both canonical and mirror properties, discharging to object presentation as well as during the observation of experimenter's goal-directed acts (canonical-mirror neurons). Typically, visual responses to objects were constrained to the monkey peripersonal space, whereas action observation responses were less space-selective. Control experiments showed that space-constrained coding of objects mostly relies on an operational (action possibility) rather than metric (absolute distance) reference frame. Interestingly, canonical-mirror neurons appear to code object as target for both one's own and other's action, suggesting that they could play a role in predictive representation of others' impending actions.

Activity in ventral premotor cortex is modulated by vision of own hand in action

Parietal and premotor cortices of the macaque monkey contain distinct populations of neurons which, in addition to their motor discharge, are also activated by visual stimulation. Among these visuomotor neurons, a population of grasping neurons located in the anterior intraparietal area (AIP) shows discharge modulation when the own hand is visible during object grasping. Given the dense connections between AIP and inferior frontal regions, we aimed at investigating whether two hand-related frontal areas, ventral premotor area F5 and primary motor cortex (area F1), contain neurons with similar properties. Two macaques were involved in a grasping task executed in various light/dark conditions in which the to-be-grasped object was kept visible by a dim retro-illumination. Approximately 62% of F5 and 55% of F1 motor neurons showed light/dark modulations. To better isolate the effect of hand-related visual input, we introduced two further conditions characterized by kinematic features similar to the dark condition. The scene was briefly illuminated (i) during hand preshaping (pre-touch flash, PT-flash) and (ii) at hand-object contact (touch flash, T-flash). Approximately 48% of F5 and 44% of F1 motor neurons showed a flash-related modulation. Considering flash-modulated neurons in the two flash conditions, ∼40% from F5 and ∼52% from F1 showed stronger activity in PT- than T-flash (PT-flash-dominant), whereas ∼60% from F5 and ∼48% from F1 showed stronger activity in T- than PT-flash (T-flash-dominant). Furthermore, F5, but not F1, flash-dominant neurons were characterized by a higher peak and mean discharge in the preferred flash condition as compared to light and dark conditions. Still considering F5, the distribution of the time of peak discharge was similar in light and preferred flash conditions. This study shows that the frontal cortex contains neurons, previously classified as motor neurons, which are sensitive to the observation of meaningful phases of the own grasping action. We conclude by discussing the possible functional role of these populations.

Selectivity for grip type and action goal in macaque inferior parietal and ventral premotor grasping neurons

Grasping objects requires the selection of specific grip postures in relation to the objects' physical properties. Furthermore, grasping acts can be embedded in actions aimed at different goals, depending on the context in which the action is performed. Here we assessed whether information on grip and action type integrate at the single-neuron level within the parieto-frontal motor system. For this purpose, we trained three monkeys to perform simple grasp-to-eat and grasp-to-place actions, depending on contextual cues, in which different grip types were required in relation to target features. We recorded 173 grasping neurons: 86 from the inferior parietal area PFG and 87 from the ventral premotor area F5. Results showed that most neurons in both areas are selective for grip type, but the discharge of many of them, particularly in PFG, appears to differ in relation to action context. Kinematics data and control experiments indicated that neuronal selectivity appears more likely to depend on the action goal triggered by the context than on specific contextual elements. The temporal dynamics of grip and goal selectivity showed that grasping neurons reflect first "how" the object has to be grasped (grip), to guide and monitor the hand shaping phase, and then "why" the action is performed (goal), very likely to facilitate subsequent motor acts following grasping. These findings suggest that, in the parieto-frontal system, grip types and action goals are processed by both parallel and converging pathways, and area PFG appears to be particularly relevant for integrating this information for action organization.

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.

Grasping-Related Functional Magnetic Resonance Imaging Brain Responses in the Macaque Monkey

Research in recent decades has suggested the existence of a dedicated brain network devoted to the organization and execution of grasping, one of the most important and skilled movements of primates. Grasping an object requires the transformation of intrinsic object properties such as size, orientation, and shape into an appropriate motor scheme shaping the hand. Although electrophysiological recordings in the monkey model have proven invaluable for gaining insights into the neuronal substrate underlying this complex behavior, knowledge concerning the existence and organization of a similar system in the human brain is derived mainly from imaging studies. Here, we present for the first time functional magnetic resonance imaging (fMRI) of brain activity while macaque monkeys performed reaching and grasping movements in a 3 tesla MR scanner. Grasping in the dark (compared with reaching) yielded significant activations in anterior intraparietal area and ventral premotor area F5, in addition to area PFG in the rostral inferior parietal lobule, somatosensory areas (SI, SII, area 5), and the hand field of F1. Whole-brain macaque fMRI motor studies will be instrumental in establishing possible homologies concerning grasping organization in the human and monkey brains, bridging the gap between human imaging and monkey electrophysiology.

Decoding the activity of grasping neurons recorded from the ventral premotor area F5 of the macaque monkey

Many neurons in the monkey ventral premotor area F5 discharge selectively when the monkey grasps an object with a specific grip. Of these, the motor neurons are active only during grasping execution, whereas the visuomotor neurons also respond to object presentation. Here we assessed whether the activity of 90 task-related F5 neurons recorded from two macaque monkeys during the performance of a visually-guided grasping task can be used as input to pattern recognition algorithms aiming to decode different grips. The features exploited for the decoding were the mean firing rate and the mean interspike interval calculated over different time spans of the movement period (all neurons) or of the object presentation period (visuomotor neurons). A support vector machine (SVM) algorithm was applied to the neural activity recorded while the monkey grasped two sets of objects. The original set contained three objects that were grasped with different hand shapes, plus three others that were grasped with the same grip, whereas the six objects of the special set were grasped with six distinctive hand configurations. The algorithm predicted with accuracy greater than 95% all the distinct grips used to grasp the objects. The classification rate obtained using the first 25% of the movement period was 90%, whereas it was nearly perfect using the entire period. At least 16 neurons were needed for accurate performance, with a progressive increase in accuracy as more neurons were included. Classification errors revealed by confusion matrices were found to reflect similarities of hand grips used to grasp the objects. The use of visuomotor neurons' responses to object presentation yielded grip classification accuracy similar to that obtained from actual grasping execution. We suggest that F5 grasping-related activity might be used by neural prostheses to tailor hand shape to the specific object to be grasped even before movement onset.

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.

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 field's role in the recovery of manual dexterity after M1 lesions.

Ventral Premotor and Inferior Parietal Cortices Make Distinct Contribution to Action Organization and Intention Understanding

It is well known that ventral premotor area F5 codes the goal of executed and observed motor acts. This area is anatomically connected with part of the inferior parietal cortex (area PFG), which has been recently shown to play a role in action organization and intention understanding. The aims of the present study were 1) to assess whether the discharge of F5 motor neurons and mirror neurons (MNs) codes action goals and 2) to clarify the relative contribution of F5 and PFG in action organization and intention understanding. To this purpose, we first recorded from F5 motor neurons and MNs of 2 monkeys while performing a motor task constituted by 2 actions ("grasp-to-eat" and "grasp-to-place") or observing the same task done by an experimenter. Results showed that some F5 neurons code grasping according to the goal of the action in which it is embedded. Subsequently, we recorded from PFG motor neurons and MNs of the same monkeys, using the same tasks. The comparison between the neuronal properties of F5 and PFG motor neurons suggests that PFG plays a major role in organizing natural actions. Furthermore, the similarities between MNs properties of the 2 areas indicate that they constitute a functional circuit underlying others' intention understanding.

The role of ventral premotor cortex in action execution and action understanding

The human ventral premotor cortex overlaps, at least in part, with Broca’s region in the dominant cerebral hemisphere, that is known to mediate the production of language and contributes to language comprehension. This region is constituted of Brodmann’s areas 44 and 45 in the inferior frontal gyrus. We summarize the evidence that the motor related part of Broca’s region is localized in the opercular portion of the inferior frontal cortex, mainly in area 44 of Brodmann. According to our own data, there seems to be a homology between Brodmann area 44 in humans and the monkey area F5. The non-language related motor functions of Broca’s region comprise complex hand movements, associative sensorimotor learning and sensorimotor integration. Brodmann’s area 44 is also a part of a specialized parieto-premotor network and interacts significantly with the neighbouring premotor areas. In the ventral premotor area F5 of monkeys, the so called mirror neurons have been found which discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding not only to the observation of mouth actions, but also to sounds characteristic to actions have been found. In humans, through an fMRI study, it has been shown that the observation of actions performed with the hand, the mouth and the foot leads to the activation of different sectors of Broca’s area and premotor cortex, according to the effector involved in the observed action, following a somatotopic pattern which resembles the classical motor cortex homunculus. On the other hand the evidence is growing that human ventral premotor cortex, especially Brodmann’s area 44, is involved in polymodal action processing. These results strongly support the existence of an execution–observation matching system (mirror neuron system). It has been proposed that this system is involved in polymodal action recognition and might represent a precursor of language processing. Experimental evidence in favour of this hypothesis both in the monkey and humans is shortly reviewed.

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.

Functional Properties of Grasping-Related Neurons in the Ventral Premotor Area F5 of the Macaque Monkey

We investigated the motor and visual properties of F5 grasping neurons, using a controlled paradigm that allows the study of the neuronal discharge during both observation and grasping of many different three-dimensional objects with and without visual guidance. All neurons displayed a preference for grasping of an object or a set of objects. The same preference was maintained when grasping was performed in the dark without visual feedback. In addition to the motor-related discharge, about half of the neurons also responded to the presentation of an object or a set of objects, even when a grasping movement was not required. Often the object evoking the strongest activity during grasping also evoked optimal activity during its visual presentation. Hierarchical cluster analysis indicated that the selectivity of both the motor and the visual discharge of the F5 neurons is determined not by the object shape but by the grip posture used to grasp the object. Because the same paradigm has been used to study the properties of hand-grasping neurons in the dorsal premotor area F2, and in the anterior intraparietal area (AIP), a comparison of the functional properties of grasping-related neurons in the three cortical areas (F5, F2, AIP) is addressed for the first time.

When vision guides movement: a functional imaging study of the monkey brain

Goal-directed reaching requires a precise neural representation of the arm position and the target location. Parietal and frontal cortical areas rely on visual, somatosensory, and motor signals to guide the reaching arm to the desired position in space. To dissociate the regions processing these signals, we applied the quantitative [ 14C]-deoxyglucose method on monkeys reaching either in the light or in the dark. Nonvisual (somatosensory and memory-related) guidance of the arm, during reaching in the dark, induced activation of discrete regions in the parietal, premotor, and motor cortices. These included the dorsal part of the medial bank of the intraparietal sulcus, the ventral premotor area F4, the dorsal premotor area F2 below the superior precentral dimple, and the primary somatosensory and motor cortices. Additional parietal and premotor regions comprising the ventral intraparietal cortex, ventral premotor area F5, and the ventral part of dorsal premotor area F2 were activated by visual guidance of the arm during reaching in the light. This study provides evidence that different regions of the parieto–premotor circuit process the visual, somatosensory, and motor-memory-related signals which guide the moving arm.