Claustral Input to the Macaque Medial Posterior Parietal Cortex (Superior Parietal Lobule and Adjacent Areas).

The projections from the claustrum to cortical areas within and adjacent to the superior parietal lobule were studied in 10 macaque monkeys, using retrograde tracers, computerized reconstructions, and quantitative methods. In contrast with the classical view that posterior parietal areas receive afferents primarily from the dorsal and posterior regions of the claustrum, we found that these areas receive more extensive projections, including substantial afferents from the anterior and ventral regions of the claustrum. Moreover, our findings uncover a previously unsuspected variability in the precise regions of the claustrum that originate the projections, according to the target areas. For example, areas dominated by somatosensory inputs for control of body movements tend to receive most afferents from the dorsal-posterior claustrum, whereas those which also receive significant visual inputs tend to receive more afferents from the ventral claustrum. In addition, different areas within these broadly defined groups differ in terms of quantitative emphasis in the origin of projections. Overall, these results argue against a simple model whereby adjacency in the cortex determines adjacency in the sectors of claustral origin of projections and indicate that subnetworks defined by commonality of function may be an important factor in defining claustrocortical topography.

The superior parietal lobule of primates: a sensory-motor hub for interaction with the environment.

The superior parietal lobule of the macaque monkey occupies the postero-medial part of the parietal lobe and plays a crucial role in the integration of different sources of information (from visual, motor and somatosensory brain regions) for the purpose of high-level cognitive functions, as perception for action. This region encompasses the intraparietal sulcus and the parieto-occipital sulcus and includes also the precuneate cortex in the mesial surface of the hemisphere. It hosts several areas extensively studied in the macaque: PE, PEip, PEci anteriorly and PEc, MIP, PGm and V6A posteriorly. Recently studies based on functional MRI have suggested putative human homologue of some of the areas of the macaque superior parietal lobule. Here we review the anatomical subdivision, the cortico-cortical and thalamo-cortical connections of the macaque superior parietal lobule compared with their functional properties and the homology with human organization in physiological and lesioned situations. The knowledge of this part of the macaque brain could help in understanding pathological conditions that in humans affect the normal behaviour of arm-reaching actions and can inspire brain computer interfaces performing in more accurate ways the sensorimotor transformations needed to interact with the surrounding environment.

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.

Uniformity and Diversity of Cortical Projections to Precuneate Areas in the Macaque Monkey: What Defines Area PGm?

We report on the corticocortical connections of areas on the mesial surface of the macaque posterior parietal cortex, based on 10 retrograde tracer injections targeting different parts of the precuneate gyrus. Analysis of afferent connections supported the existence of two areas: PGm (also known as 7 m) and area 31. Both areas received major afferents from the V6A complex and from the external subdivision of area 23, but they differed in most other aspects. Area 31 showed greater emphasis on connections with premotor and parietal sensorimotor areas, whereas PGm received a greater proportion of its afferents from visuomotor structures involved in spatial cognition (including the lateral intraparietal cortex, inferior parietal lobule, and the putative visual areas in the ventral part of the precuneus). Medially, the anterior cingulate cortex (area 24) preferentially targeted area 31, whereas retrosplenial areas preferentially targeted PGm. These results indicate that earlier views on the connections of PGm were based on tracer injections that included parts of adjacent areas (including area 31), and prompt a reassessment of the limits of PGm. Our findings are compatible with a primary role of PGm in visuospatial cognition (including navigation), while supporting a role for area 31 in sensorimotor planning and coordination.

Cortical connectivity suggests a role in limb coordination for macaque area PE of the superior parietal cortex.

In macaques, superior parietal lobule area 5 has been described as occupying an extensive region, which includes the caudal half of the postcentral convexity as well as the medial bank of the intraparietal sulcus. Modern neuroanatomical methods have allowed the identification of various areas within this region. In the present study, we investigated the corticocortical afferent projections of one of these subdivisions, area PE. Our results demonstrate that PE, defined as a single architectonic area that contains a topographic map of the body, forms specific connections with somatic and motor fields. Thus, PE receives major afferents from parietal areas, mainly area 2, PEc, several areas in the medial bank of the intraparietal sulcus, opercular areas PGop/PFop, and the retroinsular area, frontal afferents from the primary motor cortex, the supplementary motor area, and the caudal subdivision of dorsal premotor cortex, as well as afferents from cingulate areas PEci, 23, and 24. The presence and relative strength of these connections depend on the location of injection sites, so that lateral PE receives preferential input from anterior sectors of the medial bank of intraparietal sulcus and from the ventral premotor cortex, whereas medial PE forms denser connections with area PEc and motor fields. In contrast with other posterior parietal areas, there are no projections to PE from occipital or prefrontal cortices. Overall, the sensory and motor afferents to PE are consistent with functions in goal-directed movement but also hint at a wider variety of motor coordination roles.

Cortical connections of area V6Av in the macaque: a visual-input node to the eye/hand coordination system.

The goal of the present study was to elucidate the corticocortical afferent connections of area V6Av, the ventral subregion of area V6A, using retrograde neuronal tracers combined with physiological and cytoarchitectonic analyses in the macaque monkey. The results revealed that V6Av receives many of its afferents from extrastriate area V6, and from regions of areas V2, V3, and V4 subserving peripheral vision. Additional extrastriate visual projections originate in dorsal stream areas MT and MST. Area V6Av does not receive projections directly from V1; such connections were only observed when the injection sites crossed into area V6. The strongest parietal lobe afferents originate in fields V6Ad, PGm, MIP (medial intraparaietal), and PG, with frontal lobe afferents originating from the frontal eye field, caudal area 46, and the rostral subdivision of the dorsal premotor area (F7). A comparison of their respective connections supports the view that V6Av is functionally distinct from adjacent areas (V6 and V6Ad). The strong afferents from V6 and other extrastriate areas are consistent with physiological data that suggest that V6Av is primarily a visual area, supporting the notion that V6Av is part of a dorsomedial cortical network performing fast form and motion analyses needed for the visual guidance of action.

Cortical connections of parietal field PEc in the macaque: linking vision and somatic sensation for the control of limb action.

The cortical projections to the caudal part of the superior parietal lobule (area PEc) were studied in 6 cynomolgus monkeys using fluorescence tracers. Significant numbers of labeled cells were found in a restricted network of parietal, mesial, and frontal areas. Quantitative analysis demonstrated that approximately 30% of the total projection neurons originated in the adjacent areas of the dorsocaudal part of the superior parietal lobule (areas PE and V6A). The medial bank of the intraparietal sulcus, inferior parietal lobule, and frontal lobe (mainly the dorsocaudal part of premotor area F2) each contributed approximately 15% of the projection neurons. About 15% of the labeled neurons were located in the posterior cingulate area (PEci) and another 10% in other areas of the mesial surface of the hemisphere. Based on these data, we suggest that PEc processes information about the position of the limbs. The specific anatomical links between PEc and motor and premotor areas that host a representation of the lower limbs, together with the link with vestibular cortex and with areas involved in the analysis of optic flow and spatial navigation, imply a role for PEc in locomotion and coordinated limb movement in the environment.

Vision for action: thalamic and cortical inputs to the macaque superior parietal lobule.

The dorsal visual stream, the cortical circuit that in the primate brain is mainly dedicated to the visual control of actions, is split into two routes, a lateral and a medial one, both involved in coding different aspects of sensorimotor control of actions. The lateral route, named "lateral grasping network", is mainly involved in the control of the distal part of prehension, namely grasping and manipulation. The medial route, named "reach-to-grasp network", is involved in the control of the full deployment of prehension act, from the direction of arm movement to the shaping of the hand according to the object to be grasped. In macaque monkeys, the reach-to-grasp network (the target of this review) includes areas of the superior parietal lobule (SPL) that hosts visual and somatosensory neurons well suited to control goal-directed limb movements toward stationary as well as moving objects. After a brief summary of the neuronal functional properties of these areas, we will analyze their cortical and thalamic inputs thanks to retrograde neuronal tracers separately injected into the SPL areas V6, V6A, PEc, and PE. These areas receive visual and somatosensory information distributed in a caudorostral, visuosomatic trend, and some of them are directly connected with the dorsal premotor cortex. This review is particularly focused on the origin and type of visual information reaching the SPL, and on the functional role this information can play in guiding limb interaction with objects in structured and dynamic environments.

Structural connectivity and functional properties of the macaque superior parietal lobule.

Despite the consolidated belief that the macaque superior parietal lobule (SPL) is entirely occupied by Brodmann's area 5, recent data show that macaque SPL also hosts a large cortical region with structural and functional features similar to that of Brodmann's area 7. According to these data, the anterior part of SPL is occupied by a somatosensory-dominated cortical region that hosts three architectural and functional distinct regions (PE, PEci, PEip) and the caudal half of SPL by a bimodal somato-visual region that hosts four areas: PEc, MIP, PGm, V6A. To date, the most studied areas of SPL are PE, PEc, and V6A. PE is essentially a high-order somatomotor area, while PEc and V6A are bimodal somatomotor-visuomotor areas, the former with predominant somatosensory input and the latter with predominant visual input. The functional properties of these areas and their anatomical connectivity strongly suggest their involvement in the control of limb movements. PE is suggested to be involved in the preparation/execution of limb movements, in particular, the movements of the upper limb; PEc in the control of movements of both upper and lower limbs, as well as in their interaction with the visual environment; V6A in the control of reach-to-grasp movements performed with the upper limb. In humans, SPL is traditionally considered to have a different organization with respect to macaques. Here, we review several lines of evidence suggesting that this is not the case, showing a similar structure for human and non-human primate SPLs.

Thalamic afferents emphasize the different functions of macaque precuneate areas.

We studied the thalamic afferents to cortical areas in the precuneus using injections of retrograde fluorescent neuronal tracers in four male macaques (Macaca fascicularis). Six injections were within the limits of cytoarchitectural area PGm, one in area 31 and one in area PEci. Precuneate areas shared strong input from the posterior thalamus (lateral posterior nucleus and pulvinar complex) and moderate input from the medial, lateral, and intralaminar thalamic regions. Area PGm received strong connections from the subdivisions of the pulvinar linked to association and visual function (the medial and lateral nuclei), whereas areas 31 and PEci received afferents from the oral division of the pulvinar. All three cytoarchitectural areas also received input from subdivisions of the lateral thalamus linked to motor function (ventral lateral and ventral anterior nuclei), with area PEci receiving additional input from a subdivision linked to somatosensory function (ventral posterior lateral nucleus). Finally, only PGm received substantial limbic association afferents, mainly via the lateral dorsal nucleus. These results indicate that area PGm integrates information from visual association, motor and limbic regions of the thalamus, in line with a hypothesized role in spatial cognition, including navigation. By comparison, dorsal precuneate areas (31 and PEci) are more involved in sensorimotor functions, being akin to adjacent areas of the dorsal parietal cortex.

Open access resource for cellular-resolution analyses of corticocortical connectivity in the marmoset monkey.

Understanding the principles of neuronal connectivity requires tools for efficient quantification and visualization of large datasets. The primate cortex is particularly challenging due to its complex mosaic of areas, which in many cases lack clear boundaries. Here, we introduce a resource that allows exploration of results of 143 retrograde tracer injections in the marmoset neocortex. Data obtained in different animals are registered to a common stereotaxic space using an algorithm guided by expert delineation of histological borders, allowing accurate assignment of connections to areas despite interindividual variability. The resource incorporates tools for analyses relative to cytoarchitectural areas, including statistical properties such as the fraction of labeled neurons and the percentage of supragranular neurons. It also provides purely spatial (parcellation-free) data, based on the stereotaxic coordinates of 2 million labeled neurons. This resource helps bridge the gap between high-density cellular connectivity studies in rodents and imaging-based analyses of human brains.

Thalamo-cortical projections to the macaque superior parietal lobule areas PEc and PE.

The exposed surface of the superior parietal lobule in macaque brain contains two architectonically defined areas named PEc and PE. The aim of the present study is the characterization of thalamic afferents of these two areas. For this purpose, retrograde neuronal tracers were injected, or placed in crystal form, in areas PEc and PE. We found that the two areas show a similar pattern of thalamic inputs, mainly originating from Lateral Posterior (LP), Pulvinar (Pul), Ventral Posterior Lateral (VPL), and Ventral Lateral (VL) nuclei, all structures known to be involved in visual, somatosensory, and/or sensorimotor processing. Minor afferents were observed from the Centromedian/Parafascicular complex (CM/PF), Central Lateral (CL), Ventral Anterior (VA), and Medial Dorsal (MD) nuclei. LP and VL were more strongly connected to PEc than to PE, while the other main thalamic inputs to the two areas showed slight differences in strength. The part of the Pul mostly connected with areas PEc and PE was the Medial Pul. No labeled cells were found in the retinotopically organized Lateral and Inferior Pul. In the somatotopically organized VPL and VL nuclei, labeled neurons were mainly found in regions likely to correspond to the trunk and limb representations (in particular the legs). These findings are in line with the sensory-motor nature of areas PEc and PE, and with their putative functional roles, being them suggested to be involved in the preparation and control of limb interaction with the environment, and in locomotion.

Sensory properties of the caudal aspect of the macaque's superior parietal lobule.

In the superior parietal lobule (SPL), the anterior part (area PE) is known to process somatosensory information, while the caudalmost part (areas V6Av and V6) processes visual information. Here we studied the visual and somatosensory properties of the areas PEc and V6Ad located in between the somatosensory and visual domains of SPL. About 1500 neurons were extracellularly recorded in 19 hemispheres of 12 monkeys (Macaca fascicularis). Visual and somatosensory properties of single neurons were generally studied separately, while in a subpopulation of neurons, both the sensory properties were tested. Visual neurons were more represented in V6Ad and somatosensory neurons in PEc. The visual neurons of these two areas showed similar properties and represented a large part of the contralateral visual field, mostly the lower part. In contrast, somatosensory neurons showed remarkable differences. The arms were overrepresented in both the areas, but V6Ad represented only the upper limbs, whereas PEc both the upper and lower limbs. Interestingly, we found that in both the areas, bimodal visual-somatosensory cells represented the proximal part of the arms. We suggest that PEc is involved in locomotion and in the control of hand/foot interaction with the objects of the environment, while V6Ad is in the control of the object prehension specifically performed with the upper limbs. Neuroimaging and lesion studies from literature support a strict homology with humans.

Somatosensory cells in area PEc of macaque posterior parietal cortex.

PEc is an area defined on cytoarchitectural grounds, located in the posterior part of the superior parietal lobule of macaque brain (Pandya and Seltzer, 1982). The aim of this work was to assess whether passive somatosensory stimulation elicited responses in PEc neurons. Extracellular recordings were performed in three awake Macaca fascicularis. Passive somatosensory stimulation was performed in darkness, and eye movements were monitored continuously. Recording sites were assigned to different areas according to the cytoarchitectonic criteria described by Pandya and Seltzer (1982) and Luppino et al. (2005). Only recording sites within the limits of the cytoarchitecturally defined area PEc were taken into account in this work. Of 147 PEc cells, 83 (56%) were modulated by passive somatosensory stimulation. The majority of them (73%) responded to joint rotations, and 24% responded to tactile skin stimulation. The majority of PEc somatosensory responses (90%) were evoked by contralateral stimulation. Joint-modulated cells were mostly activated by the upper limbs (82%). The majority of tactile receptive fields (61%) were located on the arms, and a minority was located on the legs and trunk. One-half of PEc somatosensory cells were polysensory, because they were sensitive to visual stimulation. The majority of PEc somatosensory cells were activated by active reaching movements. Somatosensory cells, somatosensory submodalities, and body part representations were not clustered in PEc subregions; in other words, PEc does not show a somatotopic organization. Although the caudal sector of the superior parietal lobule has been traditionally considered as a somatosensory area, this is the first demonstration of the presence of somatosensory cells in this cortical region.

Claustral afferents of superior parietal areas PEc and PE in the macaque.

The exposed surface of the primate superior parietal cortex includes two cytoarchitectonically defined areas, the PEc and PE. In the present study we describe the distribution of neurons projecting from the claustrum to these areas. Retrograde neuronal tracers were injected by direct visualization of regions of interest, and the location of injection sites was reconstructed relative to cytoarchitectural borders. For comparison, the patterns of claustral label that resulted from injections involving neighboring cytoarchitectonic areas were analyzed. We found that the claustral territories sending projections to areas PE and PEc partially overlapped zones previously shown to form projections to the posterior parietal, somatosensory, visual, and motor cortex. The projection zones to the PE and PEc overlapped extensively, and consisted of multiple patches separated by label-free zones. Most of the labeled neurons were located in the posterior-ventral part of the claustrum. Area PE received additional inputs from a posterior-dorsal part of the claustrum, which has been previously reported to project to the somatosensory cortex, while the PEc receives additional input from an anterior-ventral region of the claustrum, which has been reported to project to the visual association cortex. These observations reflect the known functional properties of the PE and PEc, with the former containing neurons that are predominantly involved in somatosensory processing, and the latter including both somatosensory and visual neurons. The present results suggest that the claustrum projections may help coordinate the activity of an extensive neural circuit involved in sensory and motor processing for movement execution. J. Comp. Neurol. 525:1475-1488, 2017. © 2016 Wiley Periodicals, Inc.

Cortical Afferents and Myeloarchitecture Distinguish the Medial Intraparietal Area (MIP) from Neighboring Subdivisions of the Macaque Cortex.

The parietal reach region (PRR) in the medial bank of the macaque intraparietal sulcus has been a subject of considerable interest in research aimed at the development of brain-controlled prosthetic arms, but its anatomical organization remains poorly characterized. We examined the anatomical organization of the putative PRR territory based on myeloarchitecture and retrograde tracer injections. We found that the medial bank includes three areas: an extension of the dorsal subdivision of V6A (V6Ad), the medial intraparietal area (MIP), and a subdivision of area PE (PEip). Analysis of corticocortical connections revealed that both V6Ad and MIP receive inputs from visual area V6; the ventral subdivision of V6A (V6Av); medial (PGm, 31), superior (PEc), and inferior (PFG/PF) parietal association areas; and intraparietal areas AIP and VIP. They also receive long-range projections from the superior temporal sulcus (MST, TPO), cingulate area 23, and the dorsocaudal (area F2) and ventral (areas F4/F5) premotor areas. In comparison with V6Ad, MIP receives denser input from somatosensory areas, the primary motor cortex, and the medial motor fields, as well as from visual cortex in the ventral precuneate cortex and frontal regions associated with oculomotor guidance. Unlike MIP, V6Ad receives stronger visual input, from the caudal inferior parietal cortex (PG/Opt) and V6Av, whereas PEip shows marked emphasis on anterior parietal, primary motor, and ventral premotor connections. These anatomical results suggest that MIP and V6A have complementary roles in sensorimotor behavior, with MIP more directly involved in movement planning and execution in comparison with V6A.

Neural activity in the medial parietal area V6A while grasping with or without visual feedback.

Recent works have reported that grasping movements are controlled not only by the dorsolateral visual stream, as generally thought, but also by the dorsomedial visual stream, and in particular by the medial posterior parietal area V6A. To date, the grasping activity of V6A neurons has been studied only in darkness. Here we studied the effect of visual feedback on grasp-related discharges of V6A neurons while the monkey was preparing and executing the grasping of a handle. We found that V6A grasping activity could be excited or inhibited by visual information. The neural population was divided into Visual, Motor, and Visuomotor cells. The majority of Visual and Visuomotor neurons did not respond to passive observation of the handle, suggesting that vision of action, rather than object vision, is the most effective factor. The present findings highlight the role of the dorsomedial visual stream in integrating visual and motor signals to monitor and correct grasping.

Thalamic projections to visual and visuomotor areas (V6 and V6A) in the Rostral Bank of the parieto-occipital sulcus of the Macaque.

The medial posterior parietal cortex of the primate brain includes different functional areas, which have been defined based on the functional properties, cyto- and myeloarchitectural criteria, and cortico-cortical connections. Here, we describe the thalamic projections to two of these areas (V6 and V6A), based on 14 retrograde neuronal tracer injections in 11 hemispheres of 9 Macaca fascicularis. The injections were placed either by direct visualisation or using electrophysiological guidance, and the location of injection sites was determined post mortem based on cyto- and myeloarchitectural criteria. We found that the majority of the thalamic afferents to the visual area V6 originate in subdivisions of the lateral and inferior pulvinar nuclei, with weaker inputs originating from the central densocellular, paracentral, lateral posterior, lateral geniculate, ventral anterior and mediodorsal nuclei. In contrast, injections in both the dorsal and ventral parts of the visuomotor area V6A revealed strong inputs from the lateral posterior and medial pulvinar nuclei, as well as smaller inputs from the ventrolateral complex and from the central densocellular, paracentral, and mediodorsal nuclei. These projection patterns are in line with the functional properties of injected areas: "dorsal stream" extrastriate area V6 receives information from visuotopically organised subdivisions of the thalamus; whereas visuomotor area V6A, which is involved in the sensory guidance of arm movement, receives its primary afferents from thalamic nuclei that provide high-order somatic and visual input.

Cortical connections of the visuomotor parietooccipital area V6Ad of the macaque monkey.

Area V6A, a functionally defined region in the anterior bank of the parietooccipital sulcus, has been subdivided into dorsal and ventral cytoarchitectonic fields (V6Ad and V6Av). The aim of this study was to define the cortical connections of the cytoarchitectonic field V6Ad. Retrograde and bidirectional neuronal tracers were injected into the dorsal part of the anterior bank of parietooccipital sulcus of seven macaque monkeys (Macaca fascicularis). The limits of injection sites were compared with those of cytoarchitectonic fields. The major connections of V6Ad were with areas of the superior parietal lobule. The densest labeling was observed in the medial intraparietal area (MIP). Areas PEc, PGm, and V6Av were also strongly connected. Labeled cells were found in medial parietal area 31; in cingulate area 23; in the anterior (AIP), ventral (VIP), and lateral (LIP) intraparietal areas; in the inferior parietal lobule (fields Opt and PG); and in the medial superior temporal area (MST). In the frontal lobe, the main projection originated from F2, although labeled cells were also found in F7 and area 46. Preliminary results obtained from injections in nearby areas PEc and V6Av revealed connections different from those of V6Ad. In agreement with functional data, the strong connections with areas where arm-reaching activity is represented suggest that V6Ad is part of a parietofrontal circuit involved in the control of prehension, and connections with AIP specifically support an involvement in the control of grasping. Connections with areas LIP and Opt are likely related to the oculomotor activities observed in V6Ad.