Anatomo-functional basis of emotional and motor resonance elicited by facial expressions.

Simulation theories predict that the observation of other's expressions modulates neural activity in the same centers controlling their production. This hypothesis has been developed by two models, postulating that the visual input is directly projected either to the motor system for action recognition (motor resonance) or to emotional/interoceptive regions for emotional contagion and social synchronization (emotional resonance). Here we investigated the role of frontal/insular regions in the processing of observed emotional expressions by combining intracranial recording, electrical stimulation and effective connectivity. First, we intracranially recorded from prefrontal, premotor or anterior insular regions of 44 patients during the passive observation of emotional expressions, finding widespread modulations in prefrontal/insular regions (anterior cingulate cortex, anterior insula, orbitofrontal cortex and inferior frontal gyrus) and motor territories (rolandic operculum and inferior frontal junction). Subsequently, we electrically stimulated the activated sites, finding that (a) in the anterior cingulate cortex and anterior insula, the stimulation elicited emotional/interoceptive responses, as predicted by the 'emotional resonance model', (b) in the rolandic operculum it evoked face/mouth sensorimotor responses, in line with the 'motor resonance' model, and (c) all other regions were unresponsive or revealed functions unrelated to the processing of facial expressions. Finally, we traced the effective connectivity to sketch a network-level description of these regions, finding that the anterior cingulate cortex and the anterior insula are reciprocally interconnected while the rolandic operculum is part of the parieto-frontal circuits and poorly connected with the formers. These results support the hypothesis that the pathways hypothesized by the 'emotional resonance' and the 'motor resonance' models work in parallel, differing in terms of spatio-temporal fingerprints, reactivity to electrical stimulation and connectivity patterns.

Investigating form and content of emotional and non-emotional laughing.

As cold actions (i.e. actions devoid of an emotional content), also emotions are expressed with different vitality forms. For example, when an individual experiences a positive emotion, such as laughing as expression of happiness, this emotion can be conveyed to others by different intensities of face expressions and body postures. In the present study, we investigated whether the observation of emotions, expressed with different vitality forms, activates the same neural structures as those involved in cold action vitality forms processing. To this purpose, we carried out a functional magnetic resonance imaging study in which participants were tested in 2 conditions: emotional and non-emotional laughing both conveying different vitality forms. There are 3 main results. First, the observation of emotional and non-emotional laughing conveying different vitality forms activates the insula. Second, the observation of emotional laughing activates a series of subcortical structures known to be related to emotions. Furthermore, a region of interest analysis carried out in these structures reveals a significant modulation of the blood-oxygen-leveldependent (BOLD) signal during the processing of different vitality forms exclusively in the right amygdala, right anterior thalamus/hypothalamus, and periaqueductal gray. Third, in a subsequent electromyography study, we found a correlation between the zygomatic muscles activity and BOLD signal in the right amygdala only.

Activation of Cerebellum, Basal Ganglia and Thalamus During Observation and Execution of Mouth, hand, and foot Actions.

Humans and monkey studies showed that specific sectors of cerebellum and basal ganglia activate not only during execution but also during observation of hand actions. However, it is unknown whether, and how, these structures are engaged during the observation of actions performed by effectors different from the hand. To address this issue, in the present fMRI study, healthy human participants were required to execute or to observe grasping acts performed with different effectors, namely mouth, hand, and foot. As control, participants executed and observed simple movements performed with the same effectors. The results show that: (1) execution of goal-directed actions elicited somatotopically organized activations not only in the cerebral cortex but also in the cerebellum, basal ganglia, and thalamus; (2) action observation evoked cortical, cerebellar and subcortical activations, lacking a clear somatotopic organization; (3) in the territories displaying shared activations between execution and observation, a rough somatotopy could be revealed in both cortical, cerebellar and subcortical structures. The present study confirms previous findings that action observation, beyond the cerebral cortex, also activates specific sectors of cerebellum and subcortical structures and it shows, for the first time, that these latter are engaged not only during hand actions observation but also during the observation of mouth and foot actions. We suggest that each of the activated structures processes specific aspects of the observed action, such as performing internal simulation (cerebellum) or recruiting/inhibiting the overt execution of the observed action (basal ganglia and sensory-motor thalamus).

Laminar Origin of Corticostriatal Projections to the Motor Putamen in the Macaque Brain.

In the macaque brain, projections from distant, interconnected cortical areas converge in specific zones of the striatum. For example, specific zones of the motor putamen are targets of projections from frontal motor, inferior parietal, and ventrolateral prefrontal hand-related areas and thus are integral part of the so-called "lateral grasping network." In the present study, we analyzed the laminar distribution of corticostriatal neurons projecting to different parts of the motor putamen. Retrograde neural tracers were injected in different parts of the putamen in 3 Macaca mulatta (one male) and the laminar distribution of the labeled corticostriatal neurons was analyzed quantitatively. In frontal motor areas and frontal operculum, where most labeled cells were located, almost everywhere the proportion of corticostriatal labeled neurons in layers III and/or VI was comparable or even stronger than in layer V. Furthermore, within these regions, the laminar distribution pattern of corticostriatal labeled neurons largely varied independently from their density and from the projecting area/sector, but likely according to the target striatal zone. Accordingly, the present data show that cortical areas may project in different ways to different striatal zones, which can be targets of specific combinations of signals originating from the various cortical layers of the areas of a given network. These observations extend current models of corticostriatal interactions, suggesting more complex modes of information processing in the basal ganglia for different motor and nonmotor functions and opening new questions on the architecture of the corticostriatal circuitry.SIGNIFICANCE STATEMENT Projections from the ipsilateral cerebral cortex are the major source of input to the striatum. Previous studies have provided evidence for distinct zones of the putamen specified by converging projections from specific sets of interconnected cortical areas. The present study shows that the distribution of corticostriatal neurons in the various layers of the primary motor and premotor areas varies depending on the target striatal zone. Accordingly, different striatal zones collect specific combinations of signals from the various cortical layers of their input areas, possibly differing in terms of coding, timing, and direction of information flow (e.g., feed-forward, or feed-back).

Rostro-caudal Connectional Heterogeneity of the Dorsal Part of the Macaque Prefrontal Area 46.

Based on neural tracer injections we found evidence for 3 connectionally distinct sectors of the dorsal part of the macaque prefrontal area 46 (46d), located at different rostro-caudal levels. Specifically, a rostral sector displayed an almost exclusive and extensive intraprefrontal connectivity and extraprefrontal connections limited to superior temporal areas and the caudal cingulate area 31. Conversely, both a middle and a caudal sector were characterized by robust, topographically organized connections with parietal and frontal sensorimotor areas. Both these sectors shared connections with caudal and medial superior parietal areas (V6A and PGm) where visuospatial information is combined with gaze- and arm-related signals for visuomotor control of arm reaching and/or eye movements. However, the caudal sector was preferentially connected to parietal and frontal oculomotor areas, whereas the middle one was preferentially connected to skeletomotor, mostly arm-related, parietal and premotor areas. The present study provides evidence for a rostro-caudal organization of area 46d similar to that described for the ventrolateral prefrontal cortex, in which more caudal areas are relatively more directly involved in controlling different aspects of motor behavior and more rostral areas are most likely involved in higher order, possibly more abstract, cognitive functions.

Anterior Intraparietal Area: A Hub in the Observed Manipulative Action Network.

Current knowledge regarding the processing of observed manipulative actions (OMAs) (e.g., grasping, dragging, or dropping) is limited to grasping and underlying neural circuitry remains controversial. Here, we addressed these issues by combining chronic neuronal recordings along the anteroposterior extent of monkeys' anterior intraparietal (AIP) area with tracer injections into the recorded sites. We found robust neural selectivity for 7 distinct OMAs, particularly in the posterior part of AIP (pAIP), where it was associated with motor coding of grip type and own-hand visual feedback. This cluster of functional properties appears to be specifically grounded in stronger direct connections of pAIP with the temporal regions of the ventral visual stream and the prefrontal cortex, as connections with skeletomotor related areas and regions of the dorsal visual stream exhibited opposite or no rostrocaudal gradients. Temporal and prefrontal areas may provide visual and contextual information relevant for manipulative action processing. These results revise existing models of the action observation network, suggesting that pAIP constitutes a parietal hub for routing information about OMA identity to the other nodes of the network.

Motor and emotional behaviours elicited by electrical stimulation of the human cingulate cortex.

The cingulate cortex is a mosaic of different anatomical fields, whose functional characterization is still a matter of debate. In humans, one method that may provide useful insights on the role of the different cingulate regions, and to tackle the issue of the functional differences between its anterior, middle and posterior subsectors, is intracortical electrical stimulation. While previous reports showed that a variety of integrated behaviours could be elicited by stimulating the midcingulate cortex, little is known about the effects of the electrical stimulation of anterior and posterior cingulate regions. Moreover, the internal arrangement of different behaviours within the midcingulate cortex is still unknown. In the present study, we extended previous stimulation studies by retrospectively analysing all the clinical manifestations induced by intracerebral high frequency electrical stimulation (50 Hz, pulse width: 1 ms, 5 s, current intensity: average intensity of 2.7 ± 0.7 mA, biphasic) of the entire cingulate cortex in a cohort of 329 drug-resistant epileptic patients (1789 stimulation sites) undergoing stereo-electroencephalography for a presurgical evaluation. The large number of patients, on one hand, and the accurate multimodal image-based localization of stereo-electroencephalography electrodes, on the other hand, allowed us to assign specific functional properties to modern anatomical subdivisions of the cingulate cortex. Behavioural or subjective responses were elicited from the 32.3% of all cingulate sites, mainly located in the pregenual and midcingulate regions. We found clear functional differences between the pregenual part of the cingulate cortex, hosting the majority of emotional, interoceptive and autonomic responses, and the anterior midcingulate sector, controlling the majority of all complex motor behaviours. Particularly interesting was the 'actotopic' organization of the anterior midcingulate sector, arranged along the ventro-dorsal axis: (i) whole-body behaviours directed to the extra-personal space, such as getting-up impulses, were elicited ventrally, close to the corpus callosum; (ii) hand actions in the peripersonal space were evoked by the stimulation of the intermediate position; and (iii) body-directed actions were induced by the stimulation of the dorsal branch of the cingulate sulcus. The caudal part of the midcingulate cortex and the posterior cingulate cortex were, in contrast, poorly excitable, and mainly devoted to sensory modalities. In particular, the caudal part of the midcingulate cortex hosted the majority of vestibular responses, while posterior cingulate cortex was the principal recipient of visual effects. We will discuss our data in the light of current controversies on the role of the cingulate cortex in cognition and emotion.

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.

Corticostriate Projections from Areas of the "Lateral Grasping Network": Evidence for Multiple Hand-Related Input Channels.

Corticostriatal projections from the primate cortical motor areas partially overlap in different zones of a large postcommissural putaminal sector designated as "motor" putamen. These zones are at the origin of parallel basal ganglia-thalamocortical subloops involved in modulating the cortical motor output. However, it is still largely unknown how parietal and prefrontal areas, connected to premotor areas, and involved in controlling higher order aspects of motor control, project to the basal ganglia. Based on tracer injections at the cortical level, we analyzed the corticostriatal projections of the macaque hand-related ventrolateral prefrontal, ventral premotor, and inferior parietal areas forming a network for controlling purposeful hand actions (lateral grasping network). The results provided evidence for partial overlap or interweaving of these projections in correspondence of 2 putaminal zones, distinct from the motor putamen, one located just rostral to the anterior commissure, the other in the caudal and ventral part. Thus, the present data provide evidence for partial overlap or interweaving in specific striatal zones (input channels) of projections from multiple, even remote, areas taking part in a large-scale functionally specialized cortical network. Furthermore, they suggest the presence of multiple hand-related input channels, possibly differentially involved in controlling goal-directed hand actions.

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.

Projections from caudal ventrolateral prefrontal areas to brainstem preoculomotor structures and to Basal Ganglia and cerebellar oculomotor loops in the macaque.

The caudal part of the macaque ventrolateral prefrontal (VLPF) cortex hosts several distinct areas or fields--45B, 45A, 8r, caudal 46vc, and caudal 12r--connected to the frontal eye field (area 8/FEF). To assess whether these areas/fields also display subcortical projections possibly mediating a role in controlling oculomotor behavior, we examined their descending projections, based on anterograde tracer injections in each area/field, and compared them with those of area 8/FEF. All the studied areas/fields displayed projections to brainstem preoculomotor structures, precerebellar centers, and striatal sectors that are also targets of projections originating from area 8/FEF. Specifically, these projections involved: (1) the intermediate and superficial layers of the superior colliculus; (2) the mesencephalic and pontine reticular formation; (3) the dorsomedial and lateral pontine nuclei and the reticularis tegmenti pontis; and (4) the body of the caudate nucleus. Furthermore, area 45B projected also to the regions around the trochlear nucleus and to the raphe interpositus. The present data provide evidence for a role of the caudal VLPF areas/fields in controlling oculomotor behavior not only through their connections to area 8/FEF, but also in parallel through a direct access to preoculomotor brainstem structures and to the cerebellar and basal ganglia oculomotor loops.

Projections to the superior colliculus from inferior parietal, ventral premotor, and ventrolateral prefrontal areas involved in controlling goal-directed hand actions in the macaque.

We found that the macaque inferior parietal (PFG and anterior intraparietal [AIP]), ventral premotor (F5p and F5a), and ventrolateral prefrontal (rostral 46vc and intermediate 12r) areas forming a network involved in controlling purposeful hand actions ("lateral grasping network") are a source of corticotectal projections. Based on injections of anterograde tracers at the cortical level, the results showed that all these areas displayed relatively dense projections to the intermediate and deep gray layers of the ipsilateral superior colliculus (SC) and to the ventrally adjacent mesencephalic reticular formation. In the SC, the labeling tended to be richer in the lateral part along almost the entire rostro-caudal extent, that is, in regions controlling microsaccades and downward gaze shifts and hosting arm-related neurons and neurons modulated by the contact of the hand with the target. These projections could represent a descending motor pathway for controlling proximo-distal arm synergies. Furthermore, they could broadcast to the SC information related to hand action goals and object affordances extraction and selection. This information could be used in the SC for controlling orienting behavior (gaze and reaching movements) to the targets of object-oriented actions and for the eye-hand coordination necessary for appropriate hand-object interactions.

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.

Ventrolateral prefrontal neurons of the monkey encode instructions in the 'pragmatic' format of the associated behavioral outcomes.

The prefrontal cortex plays an important role in coding rules and producing context-appropriate behaviors. These processes necessarily require the generation of goals based on current context. Indeed, instructing stimuli are prospectively encoded in prefrontal cortex in relation to behavioral demands, but the coding format of this neural representation is, to date, largely unknown. In order to study how instructions and behaviors are encoded in prefrontal cortex, we recorded the activity of monkeys (Macaca mulatta) ventrolateral prefrontal neurons in a task requiring to perform (Action condition) or withhold (Inaction condition) grasping actions on real objects. Our data show that there are neurons responding in different task phases, and that the neuronal population discharge is stronger in the Inaction condition when the instructing cue is presented, and in the Action condition in the subsequent phases, from object presentation to action execution. Decoding analyses performed on neuronal populations showed that the neural activity recorded during the initial phases of the task shares the same type of format with that recorded during the final phases. We propose that this format has a pragmatic nature, that is instructions and goals are encoded by prefrontal neurons as predictions of the behavioral outcome.

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.

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 agent's intentions, the second route emphasizes the object of the action and may aid in understanding motor acts with respect to their immediate goal.

Specific tractography differences in autism compared to developmental coordination disorder.

About 85% of children with autism spectrum disorder (ASD) experience comorbid motor impairments, making it unclear whether white matter abnormalities previously found in ASD are related to social communication deficits, the hallmark of ASD, or instead related to comorbid motor impairment. Here we aim to understand specific white matter signatures of ASD beyond those related to comorbid motor impairment by comparing youth (aged 8-18) with ASD (n = 22), developmental coordination disorder (DCD; n = 16), and typically developing youth (TD; n = 22). Diffusion weighted imaging was collected and quantitative anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity were compared between the three groups and correlated with social and motor measures. Compared to DCD and TD groups, diffusivity differences were found in the ASD group in the mid-cingulum longitudinal and u-fibers, the corpus callosum forceps minor/anterior commissure, and the left middle cerebellar peduncle. Compared to the TD group, the ASD group had diffusivity differences in the right inferior frontal occipital/extreme capsule and genu of the corpus callosum. These diffusion differences correlated with emotional deficits and/or autism severity. By contrast, children with DCD showed unique abnormality in the left cortico-spinal and cortico-pontine tracts.Trial Registration All data are available on the National Institute of Mental Health Data Archive: https://nda.nih.gov/edit_collection.html?id=2254 .

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.

Thalamic projections to the macaque caudal ventrolateral prefrontal areas 45A and 45B.

We studied the sources of thalamic projections to the caudal ventrolateral prefrontal areas 45A and 45B, which display markedly distinct cortical connections [M. Gerbella et al. (2010) Cereb. Cortex, 20, 141-168], and compared them with those to area 8/FEF (frontal eye field). Both areas 45A and 45B were the targets of highly predominant projections from the mediodorsal nucleus (MD) and of additional projections, mostly from the magnocellular ventral anterior and the medial pulvinar nucleus. The projection profiles from different MD subdivisions clearly distinguished these two areas from one another and from area 8/FEF. Area 45A was the target of predominant projections from parvicellular MD and of minor, albeit robust, projections from magnocellular MD. The opposite was true for area 45B: magnocellular MD was the major source of projections and parvicellular MD contributed minor, albeit robust, projections. Furthermore, area 45B, but not area 45A, was targeted by robust projections from multiform MD, the principal thalamic nucleus for area 8/FEF. These results provide further evidence for the distinctiveness of areas 45A and 45B, and support the idea that area 45B is affiliated with the frontal oculomotor system, challenging the proposed homology of this area with part of the human language-related area 45 (rostral part of Broca's region). Furthermore, the present data provide evidence for potentially robust trans-thalamic (via magnocellular MD) afferent, as well as direct and reciprocal, amygdaloid connections of areas 45A and 45B, suggesting the contribution of emotional information to the differential role of these two areas in non-spatial information processing.