Principal Sulcus Research Articles

An area specialized for spatial working memory in human frontal cortex.

Working memory is the process of maintaining an active representation of information so that it is available for use. In monkeys, a prefrontal cortical region important for spatial working memory lies in and around the principal sulcus, but in humans the location, and even the existence, of a region for spatial working memory is in dispute. By using functional magnetic resonance imaging in humans, an area in the superior frontal sulcus was identified that is specialized for spatial working memory. This area is located more superiorly and posteriorly in the human than in the monkey brain, which may explain why it was not recognized previously.

Increase of extracellular dopamine in primate prefrontal cortex during a working memory task.

Increase of extracellular dopamine in primate prefrontal cortex during a working memory task. J. Neurophysiol. 78: 2795-2798, 1997. The dopamine innervation of the prefrontal cortex is involved importantly in cognitive processes, such as tested in working memory tasks. However, there have been no studies directly investigating prefrontal dopamine levels in relation to cognitive processes. We measured frontal extracellular dopamine concentration using in vivo microdialysis in monkeys performing in a delayed alternation task as a typical working memory paradigm and in a sensory-guided control task. We observed a significant increase in dopamine level in the delayed alternation task as compared both with the sensory-guided control task and the basal resting level. The increase was seen in the dorsolateral prefrontal but not in the arcuate or orbitofrontal areas. The increase appeared to reflect the working memory component of the task and was observed mainly in the lip areas of principal sulcus. Although there was no significant difference in dopamine level between delayed alternation and sensory-guided control tasks in the premotor area, significant increases in dopamine concentration were observed during both tasks as compared with the basal resting level, indicating the importance of premotor dopamine for the motor response itself.

Noradrenergic Effects on Activity of Prefrontal Cortical Neurons in Behaving Monkeys

This chapter summarizes that iontophoretic application of the α 2 -receptor antagonist yohimbine to prefrontal neurons in the monkey attenuated delay-period activity, indicating that activation of α 2 receptors plays a critical role in maintaining the directional or mnemonic coding of prefrontal neurons. Of 57 neurons recorded during oculomotor delayed-response (ODR) performance, the researchers concentrate on 31 neurons that showed delay-period activity of which magnitude differed significantly with the direction of cue-response, because such directional delay-period activity has been suggested to play a central role in the working memory process for visuospatial information. These neurons are located in the principal sulcus or immediately adjacent cortex. It has been demonstrated that iontophoretic application of the selective α 2 -adrenergic receptor antagonist, yohimbine, attenuate the directional delay-period activity of prefrontal neurons during ODR performance. At the same time, yohimbine attenuated the sharpness of directional tuning, examined by fitting to a cosine function, of directional delay-period activity. These findings suggest that the activation of α 2 receptors plays a modulatory role in maintaining the directional tuning of delay-period activity of prefrontal cortical neurons during ODR performance. As the directional delay-period activity with tuning is considered to represent mnemonic coding for visuospatial working memory, it can be concluded that the activation of α 2 receptor plays a modulatory role in maintaining mnemonic coding of neuronal activity for the working-memory process in primate prefrontal cortex.

Corticocortical input to the smooth and saccadic eye movement subregions of the frontal eye field in Cebus monkeys.

1. The locations and connections of the smooth and saccadic eye movement subregions of the frontal eye field (FEFsem and FEFsac, respectively) were investigated in seven hemispheres of five Cebus monkeys. The supplementary eye field was also mapped in seven hemispheres and the hand/arm regions of the dorsal and ventral premotor areas were localized in five hemispheres. Monkeys were immobilized during experiments with Telazol, a dissociative anesthetic agent that has no significant effect on microstimulation-induced eye movement parameters (threshold, velocity, and duration). The functional subregions were defined with the use of low threshold intracortical microstimulation (current < or = 50 microA). Then different retrogradely transported fluorescent tracers were placed into these functionally defined regions. 2. The FEFsac in Cebus monkey is in the same location as the one in macaque monkeys, which is in Walker's areas 8a and 45. The FEFsem is located in the posterior shoulder of the superior arcuate sulcus near its medial tip and is therefore more accessible for tracer injections than the one in macaque monkeys. This subregion is within cytoarchitectural area 6a beta, which is distinct from the adjacent area 6a alpha (dorsal premotor area). This smooth eye movement subregion may be comparable with the one in macaque monkeys. 3. Cortical connection patterns of the FEFsac and FEFsem are similar and parallel to each other. The predominant neural input to these two subregions originates in other cortical eye fields, including the supplementary eye field, the parietal eye field, the middle superior temporal area, and the principal sulcus region. These cortical eye fields each contain two separate, almost non-overlapping, distributions of labeled neurons that project to the corresponding frontal eye field (FEF) subregions. These results suggest that there may be similar, but relatively independent, parallel corticocortical networks to control pursuit and saccadic eye movements. The weak connections between the middle temporal area (MT) and FEF suggest that the MT may not provide the major source of visuomotion inputs to the FEF, but that it rather plays a role in mediating visual information that is relayed from the striate and extrastriate cortices via MT to the parietal cortex and then to the FEF. In addition to the well-known neural connections between the lateral intraparietal area and the FEF, additional parietal projections have been demonstrated from the dorsomedial visual area area specifically to the FEFsac and from area 7m specifically to the FEFsem.

1808 The cortico- and thalamo-cortical connections of the anterior bank of the posterior ectosylvian sulcus in the cat

Monkeys were trained to perform a visual short-term memory task (delayed matching to sample). In some of the animals, cooling probes were implanted over dorsolateral prefrontal cortex, covering sulcus principalis and adjacent areas; microelectrode pedestals were implanted over inferotemporal cortex. Other animals were fitted with converse implants: cooling probes over a portion of the inferotemporal cortical convexity and microelectrode pedestals over prefrontal cortex. In the awake and behaving monkeys, bilateral cooling of either the prefrontal or the inferotemporal region (to 20 °C) induced, in the other region, reversible changes of spontaneous and task-related cell discharge. In the two cortices remote cooling induced augmentations and diminutions of cell reaction to the color samples which the animal had to retain for correct performance of the task. The same was true for cell discharge during the delay, the retention period which followed each sample. However, a net effect of remote cooling was, in both cortices, a diminution of color-dependent differences in the reactions and delay-discharge of some cells. Concomitantly, errors of task-performance increased. Cells that as a result of remote cortical cooling showed changes of reaction to the color samples were found more commonly in supragranular than infragranular layers. The results are interpreted as evidence of mutual influences between inferotemporal and prefrontal areas probably mediated by corticocortical connections. The single-cell data, together with the behavioral data, suggest that those influences are functionally important for visual discrimination and short-term memory.

Augmentation of prefrontal cortical monoaminergic activity inhibits dopamine release in the caudate nucleus: an in vivo neurochemical assessment in the rhesus monkey.

Prefrontal cortical modulation of caudate nucleus dopamine release was investigated in the rhesus monkey using the in vivo microdialysis technique. Reliable and stable basal caudate nucleus dopamine levels were quickly attained within hours following insertion of the dialysis probes. High-potassium (60 mM) or tetrodotoxin (10 microM) infusions significantly altered caudate nucleus dopamine levels in the dialysate indicating that measured dopamine levels reflected impulse-dependent release from the presynaptic pool. Pharmacological augmentation of monoaminergic transmission in the sulcus principalis region of the prefrontal cortex resulted in significant alterations in caudate nucleus dopamine levels. Increase of monoaminergic activity by infusion of either D-amphetamine (100 microM) or cocaine hydrochloride (100 microM) resulted in a gradual and prolonged decrease in caudate nucleus dopamine levels. Similar decreases were noticed in caudate nucleus dopamine metabolite levels. The present results indicate that in non-human primates modulation of dorsolateral prefrontal cortical monoaminergic transmission results in alterations in dopamine levels in subcortical structures. This observation may have clinical implications for therapeutic management of certain neuropsychiatric disorders, particularly schizophrenia.

Visual-spatial localization by patients with frontal-lobe lesions invading or sparing area 46.

Monkeys with unilateral principal sulcus (PS) lesions show a contralateral deficit in localizing remembered targets, especially as the recall interval is lengthened. We tested 20 patients with unilateral frontal-lobe excisions that invaded (FI) or spared (FS) area 46 (putative homologue of PS) and 32 normal controls (NC) on a task where subjects had to indicate the location of a light dot either immediately, or after 30 s, with or without interference. The FI group was worse than the NC group following both delay conditions. NC and FS groups differed only after interference. We concluded that area 46 is involved in recalling the location of visual targets, but unlike the monkey, the deficit is not restricted to a particular part of the visual field.

Impairments on nonspatial self-ordered and externally ordered working memory tasks after lesions of the mid-dorsal part of the lateral frontal cortex in the monkey

Monkeys with lesions of the mid-dorsal part of the lateral frontal cortex, which extends above the sulcus principalis as far as the midline (MDL lesions), were shown to exhibit severe and long-lasting impairments on certain nonspatial working memory tasks: the self-ordered and externally ordered tasks (experiments 1, 2, 3, 5, 6, and 8). These tasks, which were modeled on similar ones previously used with patients, measure the capacity to monitor, within working memory, self-generated choices and the occurrence of externally ordered stimuli. Monkeys with lesions of the adjacent posterior dorsolateral frontal cortex, which surrounds the arcuate sulcus (PA lesions), performed as well as the normal control animals on these tasks. Experiments 4 and 5 showed that the critical variable accounting for the impairment on the self-ordered and externally ordered working memory tasks by monkeys with MDL lesions is the size of the set of stimuli that must be monitored. Furthermore, the MDL lesions did not affect basic recognition memory (experiment 6), or primacy and recency mnemonic effects [i.e., the capacity to discriminate between the initial (or final) items and other items in a list of stimuli (experiments 4 and 7), or the capacity to select from a set of stimuli on the basis of a learned fixed sequence (experiment 9)]. Thus, lesions of the mid-dorsal part of the lateral frontal cortex give rise to an impairment in working memory that depends on the size of the set of the stimuli that have to be monitored.

Coactivation of prefrontal cortex and inferior parietal cortex in working memory tasks revealed by 2DG functional mapping in the rhesus monkey

Functional studies of the dorsolateral prefrontal cortex and the inferior parietal lobe of the rhesus monkey have implicated the former in spatial mnemonic function and the latter in visuospatial processing. We used the 14C-2-deoxyglucose (2DG) method to assess the contribution of these cortical regions to the cognitive performance of monkeys on working memory tasks. In these experiments, one group of monkeys (WORK) was trained to perform tasks (delayed spatial alternation, spatial delayed response, or delayed object alternation) that specifically engaged working memory processing. Local cerebral glucose utilization (LCGU) rates in the WORK group was compared with LCGU rates for a second group of monkeys (CONT) tested on one of two tasks (visual pattern discrimination or sensory-motor) that relied upon associative memory. The results showed that in comparison to the CONT group, working memory performance significantly enhanced LCGU by 19% in the principal sulcus region of prefrontal cortex and by 11-20% in regions of the inferior parietal cortex corresponding to areas 7A, 7B, 7IP, and 7M. By contrast, LCGU in the auditory cortex was similar for both groups. In all areas examined, metabolic activation peaked in lower layer III where the majority of associational and callosal neurons lie. Correlation analyses of LCGU and behavioral task parameters indicated that LCGU in the parietal subdivisions was significantly related either to the accuracy of performance or to the number of trials completed on the 2DG test. In contrast, LCGU in the principal sulcus was positively correlated with task difficulty. These findings suggest that the enhancement of LCGU in the principal sulcus was primarily influenced by the mnemonic components of the tasks whereas LCGU in the inferior parietal cortex was influenced by their sensory-motor demands. These are the first results showing concurrent metabolic activation of the prefrontal and parietal cortex in monkeys performing working memory tasks and they support the suggestion that these cortical regions represent two important nodes in a neural network mediating spatial working memory in the monkey (Goldman-Rakic, 1988). Further, the present report reinforces the power of the 2DG method for functional mapping as these areal and laminar results could not be readily appreciated at this resolution in any other methodological context.

Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe.

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.

The effects of aging on area 46 of the frontal cortex of the rhesus monkey.

An examination of cortex of area 46 in the floor of the principal sulcus in the frontal lobe of the rhesus monkey has been carried out using three young (4-6 years of age), one middle-aged (12 years of age), and five old (25-32 years of age) rhesus monkeys. Light microscopic examination revealed no age-related change in the thickness of the cortex, and no changes in the frequency of profiles of neurons displaying nuclei and contained in 250-micron-wide strips of 1-micron-thick sections. Since the diameters of the nuclei of the neurons were found to be the same in the young and old monkeys, it was concluded that there was no change in the numbers of neurons beneath similar areas of cortical surface of area 46 with age. This conclusion was reinforced by an electron microscopic examination, since there was no suggestion of degeneration of the cell bodies of the neurons, which accumulated but little lipofuscin in the old monkeys. However, there were signs of degeneration in some of the dendrites in the upper layers of the cortex in the old monkeys, especially in layer 1, in which many of the dendrites had lost organelles from their cytoplasm. The other notable change was a degeneration of myelinated axons in the deep layers and white matter in some of the old monkeys. In contrast to the neurons, the effects of aging on the neuroglial cells and pericytes were very obvious, since in the old monkeys each type of neuroglial cell accumulated large inclusions within its cytoplasm. Prior to fixation, these monkeys had been behaviorally tested using a series of spatial and visual recognition tasks, which revealed that relative to the young monkeys, the old monkeys as a group displayed memory impairment. On one task, the extent of the impairment for each old monkey correlated well with the extent of degeneration of myelinated fibers in the cortex and white matter. Consequently, it is suggested that age-related cognitive changes are unlikely to be a result of a loss of neurons, but might be due to an alteration in connections between the cortex and other brain structures.

Topography of pyramidal neuron intrinsic connections in macaque monkey prefrontal cortex (areas 9 and 46).

An understanding of the normal organization of prefrontal cortex is essential to the recognition of pathology underlying human behavioral disorders believed to depend on this region. We have therefore studied the pattern of intrinsic intra- and interlaminar pyramidal neuron connectivity in prefrontal areas 9 and 46 (of Walker) in macaque monkey cerebral cortex (anterior to the arcuate sulcus between the principal sulcus and midline). We made focal (200-400 microns) injections of biocytin and mapped the pattern of orthogradely transported label. Injections made into the superficial layers label wide-ranging lateral projections within the same areas of prefrontal cortex. Projections local to such small injections form a narrow band of terminals in layers 1-3 (200-400 microns wide, 2-4 mm long) centered on the injection site. Collateral fibers spread orthogonal to this terminal band, making frequent bifurcations, to establish a series of parallel bands of terminals with uninnervated bands between, spaced regularly across the cortex (center to center 500-600 microns). The entire pattern of terminal label is stripe-like, with occasional narrower interbands and crosslinks between the bands, and can extend over 7-8 mm across the cortex. These projections arise from pyramidal neurons in layers 2, 3, and 5 and terminate in layers 1-3. The stripe-like pattern contrasts with patch-like patterns in other cortical regions (V1, V2, V4, motor, somatosensory) and is smaller in scale than stripe-like zones of corticocortical afferent terminals to this region, reported to be 300-750 microns wide and spaced 1.0-1.5 mm center to center.

Changes in cortical field potentials during learning processes of go/no-go reaction time hand movement with tone discrimination in the monkey

Field potentials were recorded with electrodes implanted in various cortical areas while a monkey acquired a task of go/no-go reaction time hand movement with discrimination between tone stimuli of different frequencies. After a few weeks of training, a surface-negative, depth-positive (s-N, d-P) potential (no-go potential) emerged in the dorsal bank of the principal sulcus. As the potential increased in size in 1–3 months, the monkey gradually discriminated between go and no-go stimuli. The no-go potential is considered to be related to judgement not to move and suppression of motor execution. In the superior temporal gyrus, a s-N, d-P potential at a shorter latency than the no-go potential augmented in size on both go and no-go trials, as the monkey learned the discrimination task. The s-N, d-P potential in this gyrus may reflect an information processing prior to the discrimination in the prefrontal cortex.

Topography of projections to the frontal lobe from the macaque frontal eye fields.

Efferents from the frontal eye fields (FEF) to the ipsilateral frontal lobe were studied by autoradiography of tritiated tracers (leucine, proline, and fucose) in seven macaque monkeys that were used previously to describe subcortical connections. In four of the cases, tracer injection sites were confirmed by low thresholds for the electrical elicitation of saccadic eye movements. Cases were grouped as lFEF of sFEF cases according to large or small saccades that were characteristic of the injection site. Projections from the FEF terminated in five frontal regions: 1) area FD on the dorsomedial convexity; 2) area FC (containing SEF) medial to the upper limb of the arcuate sulcus; 3) areas FD and FD delta along the walls of the principal sulcus; 4) area FCBm on the deep, posterior wall of the arcuate sulcus inferior to the sulcal spur; and 5) the inferolateral cortex (area FDi) on the convexity and lateral two thirds of the anterior wall of the arcuate sulcus. Projections in sFEF cases tended to be confined to medial parts of dorsomedial FD and FC and the lateral wall of the principal sulcus and inferolateral convexity. Neither lFEF nor sFEF appeared to project to the SMA or pericingulate cortex. Label in these areas was found only in the cases in which tracer spread into non-FEF areas. FEF projections terminated in column-like patches of about 500-600 microns in diameter. Labeled axons and terminals were seen in all cortical layers regardless of location in the frontal lobe.

Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic "scotomas"

The spatial memory functions of the monkey's prefrontal cortex were examined with oculomotor delayed-response (ODR) paradigms that required the animal to remember the spatial location of peripheral visual cues, while maintaining fixation on a central visual target during the presentation of each cue and during a subsequent 1.5-8 sec delay period. Four rhesus monkeys received unilateral or serial prefrontal lesions in and around the principal sulcus after they reached criterion performance on the ODR tasks. Unilateral lesions disrupted the performance of memory-guided eye movements to spatial cues in the visual field contralateral to the hemisphere in which the lesion was placed. Memory-guided eye movements to ipsilateral cues were mildly affected by unilateral lesions, and these lesions had little or no effect on performance in visually guided control tasks. With addition of a second lesion in the opposite hemisphere, the deficit was extended to include the opposite hemifield. The impairment was characterized by eye movements of inappropriate direction, and, excepting the one lesion that extended into the frontal eye field region of the arcuate sulcus, saccadic reaction times and velocities were the same before and after the lesions. The effect of the lesions was delay dependent: performance was rarely altered at the shortest (1.5 sec) delay but became progressively worse as the delay period was lengthened. The present results strengthen the evidence that the delayed-response deficits of monkeys with prefrontal lesions are caused by failure to maintain a transient memory "trace" in working memory, and indicate for the first time that working memory mechanisms are lateralized: memories for visuo-spatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. These findings provide evidence for the concept of mnemonic hemianopias and mnemonic scotomas, that is, memory deficits for particular hemifields or visual field locations, unaccompanied by simple sensory or motor deficits.

Smooth eye movements elicited by microstimulation in the primate frontal eye field.

1. We electrically stimulated the macaque monkey's frontal eye field (FEF) region to localize and to analyze the smooth pursuit eye movement representation. Rhesus monkeys were trained to fixate stationary spots of light, and trains of stimulation (usually 250-500 ms at 10-100 microA) were applied while the fixation targets remained lit and stationary. This paradigm was used in a total of 485 electrode penetrations through the arcuate sulcus region of six hemispheres in three adult monkeys. Smooth eye movements (SEMs), clearly distinct from saccades, were elicited at 86 sites in 53 of these penetrations. These SEMs had an average peak velocity of 11 degrees/s and an average latency of 39 ms. 2. The initial acceleration and peak velocity of elicited SEMs increased with stimulation intensity at any given site. On the other hand, SEM direction was characteristic of a given stimulation site and did not vary with stimulation intensity. These findings indicate that SEM amplitude is coded by the intensity of neural activity, and SEM direction is coded by the location of this activity within the cortex ("rate" vs. "place" codes). 3. SEMs elicited in the presence of a stationary fixation target (closed-loop conditions) typically reached a plateau velocity early in the stimulation and maintained that velocity throughout most of the stimulation train. However, when retinal slip was eliminated by artificially stabilizing the fixation target on the fovea (open-loop conditions), the electrical stimulation caused the eye to accelerate for longer periods and to attain higher velocities than in the closed-loop condition. Eye velocities obtained at the same site in open- and closed-loop conditions diverged from one another approximately 100 ms after SEM onset, consistent with the visual latency of the pursuit system. These findings suggest that the FEF primarily conveys an eye acceleration signal, rather than an eye velocity goal, to the pursuit system, and that this signal can be affected by visual retinal errors before effecting the smooth eye movements. 4. SEMs were elicited from a small portion of the arcuate fundus and neighboring posterior bank lying directly posterior to the principal sulcus. Functionally, this SEM region was surrounded by the saccadic FEF and by somatic premotor cortex. 5. Even though ipsilateral, contralateral, and vertical SEMs were elicited, the distribution of SEM directions was skewed toward ipsilateral movements. This tendency was more pronounced for sites in the arcuate fundus, whereas SEMs elicited from the posterior arcuate bank were often directed contralaterally and vertically.(ABSTRACT TRUNCATED AT 400 WORDS)

Local circuit neurons of developing and mature macaque prefrontal cortex: Golgi and immunocytochemical characteristics

A study has been made of the nonpyramidal, local circuit neurons in developing and mature macaque monkey prefrontal cortex with Golgi and immunocytochemical techniques. The area chosen for study is located between the cingulate gyrus and the ventral bank of the principal sulcus, and contains areas 9 and 46 as described by Walker (J. Comp. Neurol. 73:59-86, '40). In Golgi studies, the unique axonal features of impregnated neurons made possible the identification of thirteen separate classes of local circuit neurons. Five of these cell types, in their general characteristics, resembled classes identified in human prefrontal cortex, as well as in other cortical areas of macaque monkeys and other species. Measurements of the scale of axon arbors and dendritic fields of the Golgi-stained local circuit neurons also suggested particular spatial relationships of certain classes to the scale of intrinsic lattice connections made by the axons of pyramidal neurons in the same region. Similarities in morphology between cells described in human prefrontal cortex and neuron varieties described in this study indicate that this region of monkey prefrontal cortex may serve as a useful model for neuron populations in human prefrontal cortex. Sufficient morphological detail was present in immunocytochemical studies to suggest one or more identifying biochemical characteristics for seven of the thirteen classes of local circuit neurons. The calcium binding proteins, parvalbumin, calbindin D-28K, and calretinin, were found in chandelier and wide arbor neurons, neurogliaform cells, and double bouquet neurons, respectively. In addition, cholecystokinin immunoreactivity was present in medium arbor neurons and in narrow arbor cells connecting layers 2 and 4. Somatostatin 28(1-12) immunoreactivity was detected in beaded axon neurons in layers 5 and 6. This biochemical characterization of local circuit neurons, although incomplete, confirms the separate identity of at least some of the varieties distinguished by Golgi morphology, and allows a start to be made on studies examining changes in their functional state. The general inhibitory nature of these interneurons suggests that they are likely to play a crucial role in determining patterns of neural activation in the prefrontal cortex.

Regional distribution of functions in dorsolateral prefrontal cortex of the monkey

Single-cell responses were obtained from 352 neurons in dorsolateral prefrontal cortex (Walker's areas 9 and 46) of three monkeys. The neurons were classified functionally according to their responsiveness to visual, auditory and somatosensory stimulation, and to correlation of their activity with spontaneous eye or limb movements. A comparison between the distribution of different functions and known modality-specific anatomical connections to various sectors of this area showed a good correspondence. On average somatosensory and motor neurons were located more ventrally than the remaining ones, and were concentrated to the middle third of the inferior bank of principal sulcus and adjacent inferior convexity, where a number of somatosensory projections overlap. Oculomotor neurons were found caudally in both banks of principal sulcus and in a narrow band on the dorsal convexity, coinciding with the projection fields of areas 7a and 7ip of posterior parietal cortex, superior colliculus, and paramedian pontine tegmentum. Other functions were scatteredly distributed. Visual neurons which preferred moving to stationary stimuli were located more caudally and dorsally than other visual neurons. The present study shows that a parcellation of dorsolateral prefrontal cortex proposed on the basis of anatomical connectivity is also functionally evident.

Objective analysis of the topological organization of the primate cortical visual system.

The primate cortical visual system is composed of many structurally and functionally distinct areas, each receiving and sending about 10 projections from and to other cortical areas. The visual cortex is thus served by many cortico-cortical connections to form a network of considerable complexity. Thus the gross organization of this cortical processing system presents a formidable topological problem: although the spatial position of the areas in the brain is reasonably well established, the gross 'processing architecture' defined by the connections, is less well understood. Here I report an optimization approach that gives both qualitative and quantitative insight into the connectional topology of the primate cortical visual system. This approach supports suggestions that the system is divided into a dorsal 'stream' and a ventral 'stream' with limited cross-talk, that these two streams reconverge in the region of the principal sulcus (area 46) and in the superior temporal polysensory areas, that the system is hierarchically organized, and that the majority of the connections are from 'nearest-neighbour' and 'next-door-but-one' areas.

The synaptology of parvalbumin-immunoreactive neurons in the primate prefrontal cortex.

Electron microscopy and immunocytochemistry with a monoclonal antibody against parvalbumin (PV) were combined to analyze the distribution and morphology of PV-immunoreactive (PV-IR) neurons and the synaptology of PV-IR processes in the principal sulcus of the macaque prefrontal cortex. Parvalbumin-IR neurons are present in layers II-VI of the macaque principal sulcus (Walker's area 46) and are concentrated in a band centered around layer IV. PV-IR cells are exclusively non-pyramidal in shape and are morphologically heterogeneous with soma sizes ranging from less than 10 microns to greater than 20 microns. Well-labeled neurons that could be classified on the basis of soma size and dendritic configuration resembled large basket and chandelier cells. A novel finding is that supragranular PV-IR neurons exhibit dendritic patterns with predominantly vertical orientations, whereas infragranular cells exhibit mostly horizontal or oblique dendritic orientations. PV-IR cells within layer IV exhibit a mixture of dendritic arrangements. Vertical rows of PV-IR puncta, 15-30 microns in length, resembling the "cartridges" of chandelier cell axons were most dense in layers II, superficial III, and the granular layer IV but were not observed in the infragranular layers. Cartridges were often present beneath unlabeled, presumed pyramidal cells. PV-IR puncta also formed pericellular nests around pyramidal cell somata and proximal dendrites, suggestive of basket cell innervation. PV-IR axons were occasionally observed in the white matter underlying the principal sulcus. Electron microscopic analysis revealed that PV-IR somata and dendrites are densely innervated by nonimmunoreactive terminals forming asymmetric (Gray type I) synapses as well as by fewer terminals forming symmetric (Gray type II) synapses. The majority of terminals forming symmetric synapses with PV-IR post-synaptic structures were not immunolabeled; however, some of these boutons did contain PV-immunoreactivity. PV-IR boutons exclusively form symmetric synapses and heavily innervate layer II/III pyramidal cells. PV-IR axon cartridges formed numerous axo-axonic synapses with the axon initial segments of pyramidal cells 15-20 microns beneath the axon hillock and also terminated on large axonal spines of the initial segment. Furthermore, we failed to observe a mixture of PV-immunoreactive and non-immunoreactive boutons composing a single axon cartridge. Pyramidal cell somata and proximal dendrites were also heavily innervated by PV-IR boutons forming symmetric synapses, again, consistent with basket cell innervation. In addition, PV-IR axon terminals frequently formed symmetric synapses with dendritic shafts and spines of unidentified neurons.(ABSTRACT TRUNCATED AT 400 WORDS)