Kathleen J. Burman

Cytoarchitectonic subdivisions of the dorsolateral frontal cortex of the marmoset monkey (Callithrix jacchus), and their projections to dorsal visual areas

We describe the organization of the dorsolateral frontal areas in marmoset monkeys using a combination of architectural methods (Nissl, cytochrome oxidase, and myelin stains) and injections of fluorescent tracers in extrastriate areas (the second visual area [V2], the dorsomedial and dorsoanterior areas [DM, DA], the middle temporal area and middle temporal crescent [MT, MTc], and the posterior parietal cortex [area 7]). Cytoarchitectural field 8 comprises three subdivisions: 8Av, 8Ad, and 8B. The ventrolateral subdivision, 8Av, forms the principal source of frontal projections to the “dorsal stream,” having connections with each of the injected visual areas. The cytoarchitectural characteristics of 8Av suggest that this subdivision corresponds to the marmosets frontal eye field. The intermediate subdivision of area 8 (8Ad) has efferent projections to area 7, while the dorsomedial subdivision (8B) has few or no connections with extrastriate cortex. Area 46, located rostrolateral to area 8Av, has substantial connections with the medial extrastriate areas (DM, DA, and area 7) and with MT, while the cortex lateral to 8Av (area 12/45) projects primarily to MT and to the MTc. The rostromedial prefrontal (area 9) and frontopolar (area 10) regions have very few extrastriate projections. Finally, cells in dorsal area 6 (6d) have sparse projections to DM, MT, and the MTc, as well as strong projections to DA and to area 7. These results illuminate aspects of the evolutionary development of the primate frontal cortex, and serve as a basis for further research into cognitive functions using a marmoset model. J. Comp. Neurol. 495:149–172, 2006.

Connections of the Dorsomedial Visual Area: Pathways for Early Integration of Dorsal and Ventral Streams in Extrastriate Cortex

The dorsomedial area (DM), a subdivision of extrastriate cortex characterized by heavy myelination and relative emphasis on peripheral vision, remains the least understood of the main targets of striate cortex (V1) projections in primates. Here we placed retrograde tracer injections encompassing the full extent of this area in marmoset monkeys, and performed quantitative analyses of the numerical strengths and laminar patterns of its afferent connections. We found that feedforward projections from V1 and from the second visual area (V2) account for over half of the inputs to DM, and that the vast majority of the remaining connections come from other topographically organized visual cortices. Extrastriate projections to DM originate in approximately equal proportions from adjacent medial occipitoparietal areas, from the superior temporal motion-sensitive complex centered on the middle temporal area (MT), and from ventral stream-associated areas. Feedback from the posterior parietal cortex and other association areas accounts for <10% of the connections. These results do not support the hypothesis that DM is specifically associated with a medial subcircuit of the dorsal stream, important for visuomotor integration. Instead, they suggest an early-stage visual-processing node capable of contributing across cortical streams, much as V1 and V2 do. Thus, although DM may be important for providing visual inputs for guided body movements (which often depend on information contained in peripheral vision), this area is also likely to participate in other functions that require integration across wide expanses of visual space, such as perception of self-motion and contour completion.

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 Input to the Frontal Pole of the Marmoset Monkey

We used fluorescent tracers to map the pattern of cortical afferents to frontal area 10 in marmosets. Dense projections originated in several subdivisions of orbitofrontal cortex, in the medial frontal cortex (particularly areas 14 and 32), and in the dorsolateral frontal cortex (particularly areas 8Ad and 9). Major projections also stemmed, in variable proportions depending on location of the injection site, from both the inferior and superior temporal sensory association areas, suggesting a degree of audiovisual convergence. Other temporal projections included the superior temporal polysensory cortex, temporal pole, and parabelt auditory cortex. Medial area 10 received additional projections from retrosplenial, rostral calcarine, and parahippocampal areas, while lateral area 10 received small projections from the ventral somatosensory and premotor areas. There were no afferents from posterior parietal or occipital areas. Most frontal connections were balanced in terms of laminar origin, giving few indications of an anatomical hierarchy. The pattern of frontopolar afferents suggests an interface between high-order representations of the sensory world and internally generated states, including working memory, which may subserve ongoing evaluation of the consequences of decisions as well as other cognitive functions. The results also suggest the existence of functional differences between subregions of area 10.

Architectural subdivisions of medial and orbital frontal cortices in the marmoset monkey (Callithrix jacchus).

Although the common marmoset has become a model for the study of several neurological conditions that affect the frontal lobe, knowledge of the boundaries of the areas located in the orbital and medial frontal regions has remained incomplete. Here we examined histological sections stained for myelin, Nissl substance, and cytochrome oxidase, allowing identification of likely homologues of most of the architectural fields defined in Old World monkeys. Ventrally, we identified three granular fields at or near the frontal pole (area 10, and the medial and lateral subregions of area 11), and two granular fields along the lateral margin of the orbitofrontal cortex (medial and orbital subdivisions of area 12). More caudal and medially, dysgranular and agranular cortices included four subdivisions of area 13 as well as rostral and caudal subdivisions of area 14 (at the ventromedial convexity). The ventral frontotemporal transition encompassed at least two subdivisions of agranular insular cortex, as well as the likely homologues of the gustatory cortices. Most of the medial surface was encompassed by area 10 (which projected a caudomedial finger‐like extension toward the subgenual cortex), together with a relatively large dysgranular area 32 and an agranular area 25 (in subgenual cortex). Finally, the caudal limit of the medial frontal cortex included two fields of agranular cingulate cortex (areas 24a and 24b). These findings enhance our understanding of the architectural organization of the marmoset frontal cortex and highlight a highly conserved basic organization across simian primates, allowing the informed interpretation of experimental neurological studies. J. Comp. Neurol. 514:11–29, 2009.

Anatomical and physiological definition of the motor cortex of the marmoset monkey

We used a combination of anatomical and physiological techniques to define the primary motor cortex (M1) of the marmoset monkey and its relationship to adjacent cortical fields. Area M1, defined as a region containing a representation of the entire body and showing the highest excitability to intracortical microstimulation, is architecturally heterogeneous: it encompasses both the caudal part of the densely myelinated “gigantopyramidal” cortex (field 4) and a lateral region, corresponding to the face representation, which is less myelinated and has smaller layer 5 pyramidal cells (field 4c). Rostral to M1 is a field that is strongly reminiscent of field 4 in terms of cyto‐ and myeloarchitecture but that in the marmoset is poorly responsive to microstimulation. Anatomical tracing experiments revealed that this rostral field is interconnected with visual areas of the posterior parietal cortex, whereas M1 itself has no such connections. For these reasons, we considered this field to be best described as part of the dorsal premotor cortex and adopted the designation 6Dc. Histological criteria were used to define other fields adjacent to M1, including medial and ventral subdivisions of the premotor cortex (fields 6M and 6V) and the rostral somatosensory field (area 3a), as well as a rostral subdivision of the dorsal premotor area (field 6Dr). These results suggest a basic plan underlying the histological organization of the caudal frontal cortex in different simian species, which has been elaborated during the evolution of larger species of primate by creation of further morphological and functional subdivisions. J. Comp. Neurol. 506:860–876, 2008.

Parallel pathways mediating manual dexterity in the macaque

Abstract Transmission of information along appropriately structured parallel pathways ensures that a great deal of information can be transferred from the source to the target very quickly, and with great security-essential features of any motor control system. Studies over the last two decades have established that the corticospinal and corticocerebellar pathways mediating manual dexterity in the primate are structurally organized to sustain the parallel transmission of sensorimotor information in multiple pathways. Serial, hierarchical control systems now seem insufficient to regulate voluntary hand movements. To achieve the required coordination, and precision and speed of execution, they must be combined with parallel control systems, which themselves incorporate elaborate feedforward and feedback controls. To illustrate these issues, two aspects of the structural organization of parallel sensorimotor pathways mediating manual dexterity in the macaque are reviewed. First, we examine the structure of the multiple corticospinal neuron subpopulations projecting from different areas of the frontoparietal cortex and how they are modified following hemisection of the cervical spinal cord. The remarkable recovery of hand function following spinal hemisection, despite the absence of any structural ’bridging’ of the interrupted spinal pathways, and the fact that this is accountable in a parallel but not in a purely serial transmission system, are then reviewed. The second aspect of parallel distributed transmission examined is its occurrence within a single population of relay neurons. Our recent structural analysis of the somatic/dendritic organization of rubrospinal neurons in macaque red nucleus is used. The very large dendritic fields of individual neurons, extending over one-third or more of the nucleus, provide a framework for extracting precise somatotopic information from an input population whose axon terminal arbors overlap extensively, and, which, without effective filtering, would provide poor spatial resolution.

Contrasting Patterns of Cortical Input to Architectural Subdivisions of the Area 8 Complex: A Retrograde Tracing Study in Marmoset Monkeys

Contemporary studies recognize 3 distinct cytoarchitectural and functional areas within the Brodmann area 8 complex, in the caudal prefrontal cortex: 8b, 8aD, and 8aV. Here, we report on the quantitative characteristics of the cortical projections to these areas, using injections of fluorescent tracers in marmoset monkeys. Area 8b was distinct from both 8aD and 8aV due to its connections with medial prefrontal, anterior cingulate, superior temporal polysensory, and ventral midline/retrosplenial areas. In contrast, areas 8aD and 8aV received the bulk of the projections from posterior parietal cortex and dorsal midline areas. In the frontal lobe, area 8aV received projections primarily from ventrolateral areas, while both 8aD and 8b received dense inputs from areas on the dorsolateral surface. Whereas area 8aD received the most significant auditory projections, these were relatively sparse, in comparison with those previously reported in macaques. Finally, area 8aV was distinct from both 8aD and 8b by virtue of its widespread input from the extrastriate visual areas. These results are compatible with a homologous organization of the prefrontal cortex in New and Old World monkeys, and suggest significant parallels between the present pathways, revealed by tract-tracing, and networks revealed by functional connectivity analysis in Old World monkeys and humans.

Connections of the marmoset rostrotemporal auditory area: express pathways for analysis of affective content in hearing

The current hierarchical model of primate auditory cortical processing proposes a core of ‘primary‐like’ areas, which is surrounded by secondary (belt) and tertiary (parabelt) regions. The rostrotemporal auditory cortical area (RT) remains the least well characterized of the three proposed core areas, and its functional organization has only recently come under scrutiny. Here we used injections of anterograde and retrograde tracers in the common marmoset (Callithrix jacchus) to examine the connectivity of RT and its adjacent areas. As expected from the current model, RT exhibited dense core‐like reciprocal connectivity with the ventral division of the medial geniculate body, the rostral core area and the auditory belt, but had weaker connections with the parabelt. However, RT also projected to the ipsilateral rostromedial prefrontal cortex (area 10), the dorsal temporal pole and the ventral caudate nucleus, as well as bilaterally to the lateral nucleus of the amygdala. Thus, RT has connectivity with limbic structures previously believed to connect only with higher‐order auditory association cortices, and is probably functionally distinct from the other core areas. While this view is consistent with a proposed role of RT in temporal integration, our results also indicate that RT could provide an anatomical ‘shortcut’ for processing affective content in auditory information.

Development of non‐phosphorylated neurofilament protein expression in neurones of the New World monkey dorsolateral frontal cortex

We studied developmental changes in the expression of non‐phosphorylated neurofilament protein (NNF) (a marker of the structural maturation of pyramidal neurones) in the dorsolateral frontal cortex of marmoset monkeys, between embryonic day 130 and adulthood. Our focus was on cortical fields that send strong projections to extrastriate cortex, including the dorsal and ventral subdivisions of area 8A, area 46 and area 6d. For comparison, we also investigated the maturation of prefrontal area 9, which has few or no connections with visual areas. The timing of expression of NNF immunostaining in early life can be described as the result of the interaction of two developmental gradients. First, there is an anteroposterior gradient of maturation in the frontal lobe, whereby neurones in caudal areas express NNF earlier than those in rostral areas. Second, there is a laminar gradient, whereby the first NNF‐immunoreactive neurones emerge in layer V, followed by those in progressively more superficial parts of layer III. Following a peak in density of NNF‐immunopositive cell numbers in layer V at 2–3 months of age, there is a gradual decline towards adulthood. In contrast, the density of immunopositive cells in layer III continues to increase throughout the first postnatal year in area 6d and until late adolescence (> 1.5 years of age) in prefrontal areas. The present results support the view that the maturation of visual cognitive functions involves relatively late processes linked to structural changes in frontal cortical areas.