Showing papers in "Cerebral Cortex in 1995"

Neural Mechanisms of Visual Guidance of Hand Action in the Parietal Cortex of the Monkey

Abstract: We studied the functional properties of the hand manipulation task-related neurons (N = 136) in the posterior bank of the intraparietal sulcus (IPS) using four kinds of objects for manipulation. We performed cluster analysis by comparing the profiles of activity of these neurons across objects during manipulation in the light, and classified them into nine groups, four highly selective, four moderately selective, and one nonselective group. Activity profiles of these neurons across objects were analyzed in four task conditions: object manipulation and object fixation both in the light and in the dark. Cells were classified as "motor-dominant," "visual-dominant," and "visual and motor" neurons, and the latter two were further subdivided into object type and non-object type. Most of the highly selective neurons (35 of 136) preferred the same object for manipulation in the dark as in the light. The object type "visual and motor" neurons preferred the same object for manipulation and fixation, suggesting that these neurons play an important role in matching the pattern of hand movement to the visuo-spatial characteristics of the object to be manipulated. A large majority of highly selective hand manipulation neurons were localized in the rostral part of the posterior bank of IPS, which we designated as the anterior intraparietal (AIP) area. We propose a conceptual model of the system for visual guidance of hand action including parietal hand manipulation neurons.

The Ontogeny of Human Gyrification

Abstract: During development the human cortex changes from a smooth lissencephalic structure to one that is highly convoluted. Increases in the degree of cortical folding are associated with brain size only for the first part of brain growth; during the second half, differences in cortical folding match those of brain size, resulting in no change in the degree of folding. When the degree of cortical folding is studied as a function of age, a brief postnatal overshoot, an effect of brain size, is observed. The analysis suggests that the mechanical hypothesis of cortical buckling can best explain the degree of cortical folding, but that other hypotheses, like gyrogenesis, are required to explain the placement and orientation of sulci. The adult asymptote in degree of cortical folding is associated with the onset and disappearance of single subplate lamina, suggesting that subplate:cortical plate associations should be examined as causal for gyrification. Areas whose sulci differ in length between the two hemispheres have similar degrees of convolutedness, supporting interpretations that the sizes of gyri are asymmetric in the two hemispheres. The ontogenetic data support the thesis that human cortical proportions evolved when the brain enlarged in size and that the process was not one of neoteny.

Feature Article: Distributed Modular Architectures Linking Basal Ganglia, Cerebellum, and Cerebral Cortex: Their Role in Planning and Controlling Action

Abstract: The motor system includes structures distributed widely through the CNS, and in this feature article we present a scheme for how they might cooperate in the control of action. Distributed modules, which constitute the basic building blocks of our model, include recurrent loops connecting distant brain structures, as well as local circuitry that modulates loop activity. We consider interconnections among the basal ganglia, cerebellum, and cerebral cortex and the specialized properties of certain cell types within each of those structures, namely, striatal spiny neurons, cerebellar Purkinje cells, and neocortical pyramidal cells. In our model, striatal spiny neurons of the basal ganglia function in contextual pattern recognition under the training influence of reinforcement signals transmitted in dopamine fibers. Cerebellar Purkinje cells also function in pattern recognition, in their case to select and execute actions through training supervised by climbing fibers, which signal discoordination. Neocortical pyramidal cells perform collective computations learned through a local training mechanism and also function as information stores for other modular operations. We discuss how distributed modules might function in a parallel, cooperative manner to plan, modulate, and execute action.

Cytoarchitectonic Definition of Prefrontal Areas in the Normal Human Cortex: II. Variability in Locations of Areas 9 and 46 and Relationship to the Talairach Coordinate System

Abstract: The human prefrontal cortex can be divided into structurally and functionally distinct cytoarchitectonic areas, but the extent of individual variation in the position, size, and shape of these areas is unknown. Using criteria described in the preceding companion article (Rajkowska and Goldman-Rakic, 1995), as well as visual inspection, we have mapped areas 9 and 46 in the frontal lobe of seven postmortem human brains, and completely reconstructed these dorsolateral regions in five of the seven cases. The lateral reconstructions in these five cases were analyzed and superimposed on the lateral view of the Talairach and Tournoux (1988) coordinate system in such a way as to render both the variability and the regions of overlap for the two prefrontal areas in the five different brains. Based on this exercise, we developed a set of conservative Talairach coordinates to define area 9 and 46. Area 9 is located on the dorsal, lateral, and dorsomedial surfaces of the frontal lobe extending along the middle third of the superior frontal gyrus and adjacent portions of the middle frontal gyrus in all cases examined. Area 46 lies on the dorsolateral convexity and is either partially or completely surrounded by area 9. It is consistently found on one or more convolutions of the middle frontal gyrus. The superior border of area 46 with adjacent cortex is also variable within the middle and superior frontal sulci, as is the inferior border within the upper wall of the inferior frontal sulcus. The genuine variability in the morphology of the human frontal lobe indicated by our findings suggests that the differences among the classical maps of Brodmann, von Economo and Koskinas, and Sarkissov and others may have been due to normal variation among the brains they analyzed. Such variation may underlie individual differences in the visuospatial and cognitive capacities subserved by these areas.

Representing Spatial Information for Limb Movement: Role of Area 5 in the Monkey

Abstract: How is spatial information for limb movement encoded in the brain? Computational and psychophysical studies suggest that beginning hand position, via-points, and target are specified relative to the body to afford a comparison between the sensory (e.g., kinesthetic) reafferences and the commands that generate limb movement. Here we propose that the superior parietal lobule (Brodmann area 5) might represent a substrate for a body-centered positional code. Monkeys made arm movements in different parts of 3D space in a reaction-time task. We found that the activity of area 5 neurons can be related to either the starting point, or the final point, or combinations of the two. Neural activity is monotonically tuned in a body-centered frame of reference, whose coordinates define the azimuth, elevation, and distance of the hand. Each spatial coordinate tends to be encoded in a different subpopulation of neurons. This parcellation could be a neural correlate of the psychophysical observation that these spatial parameters are processed in parallel and largely independent of each other in man.

Cytoarchitectonic Definition of Prefrontal Areas in the Normal Human Cortex: I. Remapping of Areas 9 and 46 using Quantitative Criteria

Abstract: The classical cytoarchitectonic maps of human prefrontal areas produced by various cartographers in the early part of this century, though similar in gross topography, differ from one another in their descriptions of the size, shape, and precise location of specific regions within the frontal promontory. The current advances in human neurobiology stimulated us to reinvestigate the cytoarchitecture of the human prefrontal cortex, beginning with areas 9 and 46, to establish a set of objective cytometric criteria for identification of these areas. Nisslstained and Gallyas-stained celloidin-embedded sections were prepared from the left hemispheres of 17 human subjects 23-73 years old, without history of neurological disease. In eight cases, light microscopic observations were supplemented by morphometric data collected on a research microscope equipped with differential interference contrast optics and interfaced to a TV monitor with video mixing equipment and a microcomputer. We used the three-dimensional counting method of Williams and Rakic (1988) to measure (1) total cortical and relative laminar thickness, (2) neuronal packing density per 0.001 mm3 in individual cortical layers, and (3) sizes of neuronal somata in selected cortical layers. Light microscopic analysis confirmed that the cortical layers are more differentiated in area 46 than in area 9, particularly at the borders of layer IV. Layers III and V exhibit clearer sublamination in area 9, while layer IV is also somewhat wider in area 46 than in area 9 (9.3% vs 6.4% of cortical thickness); the overall thickness of the cortex is the same in both areas. Cytometric analysis revealed that layer IV neurons of area 46 are more densely packed than those in area 9 (55.38 +/- 7.26 vs 45.80 +/- 4.45 neurons/0.001 mm3), as are neurons in the supragranular layers II and III combined (53.51 +/ 6.33 vs 45.69 +/ 3.81 neurons/0.001 mm3). Finally, neurons in area 46 are more homogeneous in size than those in area 9. Differences in myeloarchitecture are also evident: each area contains numerous, well-stained radial striae and two pronounced bands of horizontal fibers, but in general, area 46 is less myelinated than area 9. Objective cytometric methods can clearly distinguish two adjacent areas within the human prefrontal lobe. These findings may prove useful in the areal parcellation of the human cerebral cortex as well as provide a baseline for analysis of pathological changes in neurological and psychiatric disorders such as a schizophrenia, Huntington's or Alzheimer's diseases.

Encoding of Intention and Spatial Location in the Posterior Parietal Cortex

Abstract: The posterior parietal cortex is functionally situated between sensory cortex and motor cortex. The responses of cells in this area are difficult to classify as strictly sensory or motor, since many have both sensory- and movement-related activities, as well as activities related to higher cognitive functions such as attention and intention. In this review we will provide evidence that the posterior parietal cortex is an interface between sensory and motor structures and performs various functions important for sensory-motor integration. The review will focus on two specific sensory-motor tasks-the formation of motor plans and the abstract representation of space. Cells in the lateral intraparietal area, a subdivision of the parietal cortex, have activity related to eye movements the animal intends to make. This finding represents the lowest stage in the sensory-motor cortical pathway in which activity related to intention has been found and may represent the cortical stage in which sensory signals go "over the hump" to become intentions and plans to make movements. The second part of the review will discuss the representation of space in the posterior parietal cortex. Encoding spatial locations is an essential step in sensory-motor transformations. Since movements are made to locations in space, these locations should be coded invariant of eye and head position or the sensory modality signaling the target for a movement Data will be reviewed demonstrating that there exists in the posterior parietal cortex an abstract representation of space that is constructed from the integration of visual, auditory, vestibular, eye position, and propriocaptive head position signals. This representation is in the form of a population code and the above signals are not combined in a haphazard fashion. Rather, they are brought together using a specific operation to form "planar gain fields" that are the common foundation of the population code for the neural construct of space.

Oculocentric Spatial Representation in Parietal Cortex

Abstract: Parietal cortex comprises several distinct areas. Neurons in each area are selective for particular stimulus dimensions and particular regions of space. The representation of space in a given area reflects a particular motor output by which a stimulus can be acquired. Neurons in the lateral intraparietal area (LIP) are active in relation to both visual and motor events. LIP neurons do not transmit an unambiguous saccadic command. Rather, they signal the location at which an event has occurred. These spatial locations are encoded in oculocentric coordinates, that is, with respect to the current or anticipated position of the center of gaze. When an eye movement brings the spatial location of a recently flashed stimulus into the receptive field of an LIP neuron, the neuron responds to the memory trace of that stimulus. This result indicates that, for nearly all LIP neurons, stored visual information is remapped in conjunction with saccades. Remapping of the memory trace maintains the alignment between the current image on the retina and the stored representation in cortex. Further, when an eye movement is about to occur, more than a third of LIP neurons transiently shift the location of their receptive fields. This anticipatory remapping allows the neuron to begin to respond to a visual stimulus even before the saccade is initiated that will bring the stimulus into the fixation-defined receptive field. Both kinds of remapping serve to create a constantly updated representation of stimulus location that is always in terms of distance and direction from the fovea. This oculocentric representation has the advantage that it already matches that known to exist in the frontal eye fields and the superior colliculus, the output targets of LIP, and it does not require further coordinate transformation in order to contribute to spatially accurate behavior. These results indicate that LIP can analyze visual space without ever forming a representation of absolute target position.

Deciding Not to GO: Neuronal Correlates of Response Selection in a GO/NOGO Task in Primate Premotor and Parietal Cortex

Abstract: Monkeys performed reaching movements in two opposite directions in a symmetrically rewarded GO/NOGO task with an instructed-delay period. Instructional cues were presented at the target locations. The decision not to move was clearly reflected in cell activity in dorsal premotor cortex, but not in parietal cortex area 5. In premotor cortex, the initial response (< 250 msec) of most cells to the appearance of the instructional cues in GO and NOGO trials was similar. However, by the end of the delay period, the responses of most cells were statistically different between the two trial types, and the population signals were much less directional in the NOGO trials than in the GO trials. In area 5, in contrast, single-cell and population signals were generally similar and strongly directional in both GO and NOGO trials. This result suggests a role for area 5 in visuomotor analysis for the guidance of limb movements. It further suggests that separate representations of potential motor responses to external inputs and of the intended response to that input can coexist in parietal and premotor cortex, respectively.

Psychophysical and Physiological Evidence for Viewer-centered Object Representations in the Primate

Abstract: A key question concerning the perception of 3D objects is the spatial reference frame used by the brain to represent them. The celerity of the recognition process could be explained by the visual system's ability to quickly transform stored models of familiar 3D objects, or by its ability to specify the relationship among viewpoint-invariant features or volumetric primitives that can be used to accomplish a structural description of an image. Alternatively, viewpoint-invariant recognition could be realized by a system endowed with the ability to perform an interpolation between a set of stored 2D templates, created for each experienced viewpoint. In the present study we set out to examine the nature of object representation in the primate in combined psychophysical-electrophysiological experiments. Monkeys were trained to recognize novel objects from a given viewpoint and subsequently were tested for their ability to generalize recognition for views generated by mathematically rotating the objects around any arbitrary axis. The perception of 3D novel objects was found to be a function of the object's retinal projection at the time of the recognition encounter. Recognition became increasingly difficult for the monkeys as the stimulus was rotated away from its familiar attitude. The generalization field for novel wire-like and spheroidal objects extended to about +/- 40 degrees around an experienced viewpoint. When the animals were trained with as few as three views of the object, 120 degrees apart, they could often interpolate recognition for all views resulting from rotations around the same axis. Recordings from inferotemporal cortex during the psychophysical testing showed a number of neurons with remarkable selectivity for individual views of those objects that the monkey had learned to recognize. Plotting the response of neurons as a function of rotation angle revealed systematic view-tuning curves for rotations in depth. A small percentage of the view-selective cells responded strongly for a particular view and its mirror-symmetrical view. For some of the tested objects, different neurons were found to be tuned to different views of the same object; the peaks of the view-tuning curves were 40-50 degrees apart. Neurons were also found that responded to the sight of unfamiliar objects or distractors. Such cells, however, gave nonspecific responses to a variety of other patterns presented while the monkey performed a simple fixation task.

Visual Memory, Visual Imagery, and Visual Recognition of Large Field Patterns by the Human Brain: Functional Anatomy by Positron Emission Tomography

Abstract: We measured the regional cerebral blood flow (rCBF) in 11 healthy volunteers with PET (positron emission tomography). The main purpose was to map the areas of the human brain that changed rCBF during (1) the storage, (2) retrieval from long-term memory, and (3) recognition of complex visual geometrical patterns. A control measurement was done with subjects at rest. Perception and learning of the patterns increased rCBF in V1 and 17 cortical fields located in the cuneus, the lingual, fusiform, inferior temporal, occipital, and angular gyri, the precuneus, and the posterior part of superior parietal lobules. In addition, rCBF increased in the anterior hippocampus, anterior cingulate gyrus, and in several fields in the prefrontal cortex. Recognition of the patterns increased rCBF in 18 identically located fields overlapping those activated in learning. In addition, recognition provoked differentially localized increases in the pulvinar, posterior hippocampus, and prefrontal cortex. Learning and recognition of the patterns thus activated identical visual regions, but different extravisual regions. A surprising finding was that the hippocampus was also active in recognition. Recall of the patterns from long-term memory was associated with rCBF increases in yet different fields in the prefrontal cortex, and the anterior cingulate cortex. In addition, the posterior inferior temporal lobe, the precuneus, the angular gyrus, and the posterior superior parietal lobule were activated, but not any spot within the occipital cortex. Activation of V1 or immediate visual association areas is not a prerequisite for visual imagery for the patterns. The only four fields activated in storage recall and recognition were those in the posterior inferior temporal lobe, the precuneus, the angular gyrus, and the posterior superior parietal lobule. These might be the storage sites for such visual patterns. If this is true, storage, retrieval, and recognition of complex visual patterns are mediated by higher-level visual areas. Thus, visual learning and recognition of the same patterns make use of identical visual areas, whereas retrieval of this material from the storage sites activates only a subset of the visual areas. The extravisual networks mediating storage, retrieval, and recognition differ, indicating that the ways by which the brain accesses the storage sites are different.

Sequence Seeking and Counter Streams: A Computational Model for Bidirectional Information Flow in the Visual Cortex

Abstract: A computational model is proposed for some general aspects of information flow in the visual cortex. The basic process, called "sequence seeking," is a search for a sequence of mappings, or transformations, linking source and target patterns. The process has two main characteristics: it is bidirectional, bottom-up as well as top-down, and it explores in parallel a large number of alternative sequences. This operation is performed in a "counter streams" structure, in which multiple sequences are explored along two complementary pathways, an ascending and a descending one, seeking to meet. A biological embodiment of this model in cortical circuitry is proposed. The model serves to account for known aspects of cortical interconnections and to derive new predictions.

Anatomical Evidence for MT and Additional Cortical Visual Areas in Humans

Abstract: We stained human visual cortex for myelin, cytochrome oxidase, and the monoclonal antibody CAT-301 in an attempt to demonstrate and map MT (V5) and other visual cortical areas in humans. Both flattened and unflattened cortical tissue was examined. A likely candidate for area MT (V5), which we refer to as MT, was demonstrated using all three stains. Myelin and CAT-301 labels for MT were demonstrated to be coincident by comparing results from the two stains in adjacent sections. In all three stains, MT was an oval area approximately 1.2 x 2.0 cm, located 5-6 cm anterior and dorsal to the foveal V1-V2 border. The position and size of MT as defined by the present anatomy are consistent with MT (V5) as defined by functional measures in humans. In addition, flattened cortical tissue stained for cytochrome oxidase revealed a distinctive staining topography in several cortical areas, including areas V1, V2, MT, PX, and VX. Similar studies in flattened cortex of macaque and green monkeys demonstrated distinctive dark cytochrome oxidase staining in MT, PX, MTc, and V3.

Glutamate-like Immunoreactivity and Fate of Cajal-Retzius Cells in the Murine Cortex as Identified with Calretinin Antibody

Abstract: Cortical layers VI to II develop between two layers of older neurons, the marginal and subplate zones, which are believed to have unique roles in cortical development While subplate cells have been found essential for the establishment of thalamocortical relationships, the function of the marginal zone and in particular of the neurons of Cajal-Retzius has not been elucidated Here we show that an antibody against the calcium-binding protein calretinin labels the population of Cajal-Retzius cells throughout their life in the murine cerebral cortex In prenatal and early postnatal stages, Cajal-Retzius cells were found evenly distributed throughout the murine cerebral cortex Cajal-Retzius-like neurons were also found in the developing hippocampus and dentate gyrus, which indicates that they may have a general function in cortical development From P8 onward Cajal-Retzius cells disappeared from the neocortex and hippocampus, at the same time as degenerating immunoreactive neurons were observed Calretinin-positive Cajal-Retzius cells were glutamate immunoreactive and their presumed axon terminals formed asymmetric synapses These observations indicate that Cajal-Retzius cells may provide a tonic excitatory input, essential for the maturation of cortical neurons Furthermore, since neuronal migration has been shown to be dependent on glutamate receptors, we propose that Cajal-Retzius cells releasing glutamate may direct migrating neuroblasts toward the marginal lamina, therefore creating the "inside-out" sequence of cortical development

GABAA Receptor Subunit Gene Expression in Human Prefrontal Cortex: Comparison of Schizophrenics and Controls

Abstract: The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of schizophrenics, the previously reported upregulation of muscimol binding sites and downregulation of benzodiazepine binding sites in the prefrontal and adjacent cingulate cortex of schizophrenics are possibly due to posttranscriptional modifications of mRNAs and their translated polypeptides.

Neurophysiological Evidence for a Role of Posterior Parietal Cortex in Redirecting Visual Attention

Abstract: Lesions of the posterior parietal cortex in humans and monkeys result in a spatial neglect syndrome characterized by defects in visual-spatial perception, oculomotor function, and directing visual attention. Although symptoms of spatial neglect can result from lesions to other cortical and subcortical areas, patients with posterior parietal lesions are particularly impaired in their ability to disengage and reorient visual attention. Neurophysiological experiments in area 7a of behaving monkeys reveal a large class of neurons that respond to visual stimuli and are powerfully modulated by states of attention. These cells respond better to passive visual stimuli presented during states of attentive fixation than to identical stimuli presented in nonattentive states. The responses of the majority of these cells are also influenced by covert shifts of attention away from the point of fixation; they respond to stimuli presented anywhere within their receptive fields except the covertly attended location. The combined effect of facilitation during attentive fixation and lack of response at the attended location results in a sensitivity for visual stimuli that appear at one location while attention is directed to another. The special sensitivity for unattended stimuli in this group of neurons in area 7a suggests that they may play a role in reorienting attention, possibly by providing signals of the spatial locations of novel stimuli.

Computational Methods for Reconstructing and Unfolding the Cerebral Cortex

Abstract: We describe computational methods for constructing three-dimensional models and unfolded, two-dimensional maps of the cerebral cortex. These methods consist of four procedures, including (1) sampling of a surface within the cortex, (2) reconstruction of a three-dimensional model of that surface, (3) unfolding of the surface to generate a two-dimensional cortical map, and (4) visualization of data on the model and the map. These methods produce structurally accurate representations of the cortex and have practical advantages over previous manual and automated approaches for flattening the cortex. We illustrate the application of these methods to neuroanatomical data obtained from histological sections of cerebral cortex in the macaque monkey. The approach should be equally useful for structural and functional studies in other species, including humans.

Functional Anatomy of Reaching and Visuomotor Learning: A Positron Emission Tomography Study

Abstract: The purpose of this study was to identify the functional cortical fields involved in reaching for targets in extrapersonal space, and to identify the specific fields representing visual target information in long-term memory. Ten healthy subjects were asked to learn the positions of seven circular targets that were repeatedly projected on a screen. The regional cerebral blood flow was measured with positron emission tomography during a rest state, at an early learning stage, at a later learning stage, and finally at 30 min after the course of learning had been completed. Mean rCBF change images for each task minus rest were calculated and fields of significant rCBF changes were identified. In all three task states, cortical fields were consistently activated in the left motor and premotor areas, the posterior part of the superior parietal lobule, and the right angular gyrus. When learning of the target positions had been achieved, additional fields appeared bilaterally in the posterior part of the superior parietal lobule, the right superior occipital gyrus, the left motor and premotor areas, the medial aspect of the superior frontal gyrus, the postcentral gyrus, the superior part of the cuneus, the inferior part of the angular gyrus, and the anterior part of the insula. The results indicate that there are at least two different types of functional fields in the posterior part of the superior parietal lobule; one is active during reaching for the targets when guided by internal representations of target positions; the other likely represents the storage sites of visual target information that is addressed in long-term memory.

Mechanisms of Stereopsis in Monkey Visual Cortex

Abstract: A substantial proportion of neurons in the striate and prestriate cortex of monkeys have stereoscopic properties; that is, they respond differentially to binocular stimuli that are known in humans to provide cues for stereoscopic depth perception. Stereoscopic neurons, as these cells may be called, are selective for horizontal positional disparity (i.e., display disparity selectivity) and for the textural correlation between images over their receptive fields (i.e., they show correlation selectivity). Many neurons have tuned disparity response profiles that collectively cover the entire range of physiological disparities. Neurons with peak responses at or about the zero disparity ("tuned zero neurons," excitatory or inhibitory) have narrow and symmetrical profiles. Neurons that are tuned to larger disparities, either crossed ("tuned near neurons") or uncrossed ("tuned far neurons"), have broader excitatory profiles that are asymmetrically wider toward the smaller disparities, and commonly include an inhibitory component about the zero disparity. Other stereoscopic neurons have reciprocal profiles ("near" or "far" neurons, respectively) in the sense that they respond with excitation to crossed or uncrossed disparities, and with suppression to disparities of opposite sign. Stereoscopic neurons can also signal the textural correlation between paired retinal images by giving different responses to random-dot patterns that have, and to those that do not have, the same dot distribution over the neuron's left and right receptive fields. Tuned-zero excitatory neurons characteristically respond to uncorrelation with suppression; tuned-zero inhibitory neurons, with excitation; and both types give the opposite responses to correlated stereopatterns. Neurons selective for nonzero disparities, both tuned and reciprocal, also give excitatory responses to uncorrelated stimuli, but these responses are smaller and more variable than those evoked by correlated patterns at the effective disparities. These findings suggest that stereoscopic neurons in the visual cortex of the macaque comprise three operational systems: (1) a zero-disparity system that is involved in fine depth discrimination with the obligatory singleness of vision, and the maintenance of vergence; and (2) a near-, and (3) a far-disparity system that together signal qualitative estimates of depth with double vision, and vergence responses to large disparities.

The Parietal System and Some Higher Brain Functions

Abstract: A quarter century has passed since electrophysiological studies of the homotypical cortex in waking monkeys began. These are made as monkey subjects emit behavioral acts sufficiently complex to qualify as those generated and controlled by the "higher" functions of the neocortex. The general experimental plan is an extension to the study of higher functions of an approach proven successful in earlier studies of the neocortical mechanisms in sensation and perception, and the control of movement. The early phase of exploratory experiments on the homotypical cortex has now given way to more precise experiments, quantitative analysis, and model testing, and it is clear that we can look forward to a rapid acquisition of knowledge of these complex neocortical operations. If progress during the early phase was less rapid than had been hoped for, the reasons are easy to find. At the experimental level the linkage between behavioral events and neural activity in homotypical cortical areas is always less precise than in primary areas; in many cases it is conditional in nature and influenced by central state functions of the brain, and interpretations are plagued by the ever difficult transition from causation to causality. Interpretations are always beset by varying concept: command or re-afference, attention or neglect, active intention or passive reception, and so on? Indeed, the neurophysiologist who ventured into the homotypical cortex in the 1970s entered a foreign country in which new and unlabeled neural events were encountered at every turn, or rather, in nearly every microelectrode penetration!

Brain (A)Symmetry in Monozygotic Twins

Abstract: Origin and ontogenesis of human brain laterality are unknown. Using in vivo magnetic resonance morphometry we measured cerebral hemispheric asymmetry of the planum temporale, a structural substrate of functional laterality, in pairs of monozygotic twins concordant or discordant for handedness. In both groups, intraclass (i.e., within twin pair) correlations were low. The right-handers showed leftward asymmetry whereas the left-handers lacked asymmetry. The discordance for lateralized brain anatomy can be accounted for by ontogenetic models assuming twinning of an asymmetrical germ or differential action of nongenetic factors within twin pairs in utero. The findings confirm a coupling of lateralized structure and function of the human brain. At least in monozygotic twins, early epigenetic factors must play a role in anatomofunctional laterality development.

Role of Prefrontal Cortex in Generation of the Contingent Negative Variation

Abstract: The contingent negative variation (CNV) is a brain potential generated during delay periods that has been proposed to measure prefrontal cortex (PFCx) activity. The CNV was recorded in neurological patients with PFCx damage centered in Brodmann areas 9, 44, 45, and 46 in a classical auditory S1-S2 paradigm employing a 3 sec interstimulus interval. Subjects pressed a button upon detection of an acoustically cued imperative tone (S2, 1000 Hz, GO). Responses were withheld if the warning tone (S1, 1500 Hz in GO trials) was lower in frequency (500 Hz, NOGO). The early phase of the CNV (500-700 msec after S1) was not reduced in patients with PFCx damage. PFCx lesions reduced the later phase of the CNV beginning about 1000 msec prior to S2. Reductions were maximal over PFCx sites but extended to posterior scalp electrodes over the lesioned hemisphere. The results are consistent with a late CNV generator in dorsolateral PFCx that also modulates generation of the potential in posterior regions of the ipsilateral hemisphere. The CNV findings coupled with behavioral evidence of impaired preparatory processes in these patients support the role of PFCx in sustaining distributed neural activity during delay periods.

Postnatal Maturation of the Direct Corticospinal Projections in the Macaque Monkey

Abstract: Postnatal changes in the topography of the multiple corticospinal projections in the macaque monkey were followed using retrogradely transported fluorescent tracers, and related to the monkey's acquisition of manual dexterity; both behavioral and anatomical maturation were completed by about 8 postnatal months. Cortical origins of the corticospinal projections were examined by constructing planar projection maps of the distributions of labeled corticospinal neuron somas; these somas were found only in lamina V. At birth elaborate somatotopically organized corticospinal projections from primary motor cortex (area 4), the mesial supplementary motor area and cingulate areas 23 and 24, area 12, dorsolateral area 6a beta, the dorsolateral and ventral area 6a alpha (area F4), parietal areas 2/5, 7b and the peri-insular cortex (including area SII), were clearly defined, with axons extending to all spinal cord segments. While this pattern of regional projections broadly resembled that of the mature macaque, there were, however, substantial maturational changes during the 8 months after birth. These included (1) a halving of the area of cerebral cortex from which the contralateral corticospinal projection originated and (2) a threefold reduction in the number of labeled corticospinal neurons projecting to all segments of the cord. Collateral elimination rather than neuronal cell death was the likely mechanism for this reduction in the population and areal extent of corticospinal neurons in the maturing macaque. The surviving corticospinal axon terminals also developed substantially during the postnatal period. At birth some terminals had invaded the intermediate zone in each spinal segment, but few had penetrated the dorsal and ventral horns. By 6 postnatal months, however, many corticospinal neurons were retrogradely labeled following the injection of fluorescent labels into each of these spinal zones in cervical and lumbar spinal segments. These data demonstrate a considerable postnatal reduction in corticospinal neurons projecting to the contralateral spinal cord, and imply that many of the axons that are eliminated never synapse on spinal neurons. It is suggested that during the middle fetal period the axons of many of the cortical neurons in lamina V that in the mature monkey will terminate on particular neuron populations in the thalamus, brainstem, or spinal cord, traverse a common pathway down through the internal capsule into the spinal cord, passing close to these successive targets, and possibly forming collaterals at these levels. In the postnatal period each such neuron establishes a stable, effective synaptic input to only one or a few of these subcortical target populations, and the remaining collateral branches regress. The postnatal maturation of corticospinal neurons, examined in this study, is compatible with such a model.

Properties of Excitatory Synaptic Events in Neurons of Primary Somatosensory Cortex of Neonatal Rats

Abstract: We have characterized the development of synaptic responses from neurons of rat parietal cortex. Whole-cell recording was used in slice preparations in vitro. Neurons were stained with biocytin to allow their identification, and the sample included pyramidal neurons and Cajal-Retzius cells. Dye-coupling of 3-12 cells was frequently observed from the day of birth (P0) to P3. On average, when recorded with Cs(+)-filled electrodes, the input resistances of neonatal cells were large (mean = 1.1 G omega) and resting membrane potentials were relatively depolarized (mean = -45 mV) when compared to mature neocortical neurons. The application of an NMDA receptor antagonist usually hyperpolarized cells by 5-10 mV and increased their input resistance (mean increase = 83%), suggesting that immature neurons are tonically activated by excitatory amino acids (EAA) in our preparation. Excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) could be obtained from animals as young as P0 by brief stimulation of the subplate. Synaptic responses at these early ages had long durations, often lasting over hundreds of milliseconds, they reversed polarity around 0 mV, and they were blocked by tetrodotoxin and EAA antagonists. Pharmacology and current-voltage relationships demonstrated the presence of both NMDA receptor- and non-NMDA receptor-dependent components in most EPSPs. Unlike synaptic responses of mature neurons, neonatal synaptic responses were composed largely of NMDA receptor-dependent components. We did not observe inhibitory synaptic inputs before P6. In some neurons, single shocks to the subplate region initiated spontaneous EPSPs that lasted > 1 min. This study clearly demonstrates functional synapses in the neocortex of rats on the day of birth. Large NMDA receptor-mediated EPSPs with long duration could have a major influence on the development of cortical circuits in the neonate.

Cortical Metabolic Activation in Humans during a Visual Memory Task

Abstract: A delayed match-to-sample (DMS) task of abstract, visual memory was performed during the uptake period of 18F-fluorodeoxyglucose. The increase in glucose uptake of cortical and subcortical regions ("activation") during the DMS task was compared with that during a control, immediate match-to-sample task using positron emission tomography. Both discriminant analysis and paired t tests supported the observation that the dorsolateral prefrontal area underwent the greatest activation, while a factor analysis revealed the functional correlation matrices of the tasks. Activations in the ventral premotor cortex and supramarginal and angular gyri were highly correlated with the change in the dorsolateral prefrontal cortex. The basal forebrain/ventral pole region showed a smaller but independently significant change. The findings support the role of the dorsal prefrontal region in the nonspatial working memory of humans.

Developmental remodeling of primate visual cortical pathways

Abstract: The pre- and postnatal developmental changes of the cortical afferents to area 17 were studied in the macaque monkey. Paired injections of the retrograde tracers fast blue and diamidino yellow were made in area 17. Quantitative techniques were used to examine the spatial patterns of labeling in three distinct locations of the extrastriate cortex that correspond to known visual areas. In the adult, each cortical region has a characteristic laminar distribution. In the fetus the proportion of supragranular layer neurons in all cortical regions was much higher than in the adult. The present study shows that despite the very high levels of labeled supragranular layer neurons, there is some early areal specialization so that the adult configuration does not emerge from a uniform distribution. The developmental decline in the proportion of labeled supragranular neurons is complete by 1 month after birth. Each injection of tracer gave rise in each cortical area to dense labeling in a restricted region (projection zone). Areal measurements of projection zones in the supra- and infragranular layers showed that the developmental decrease in the proportion of labeled supragranular layer neurons is accompanied by a relative change of the dimensions of supra- and infragranular projection zones: the supragranular projection zone in the fetus is larger than the infragranular projection zone and vice versa in the adult. In the fetus, the two projection zones corresponding to each of the two tracers overlap in the supragranular layers whereas they are largely separated in the infragranular layers. During development there is a progressive decrease in the overlap of the supragranular projection zones and an increase in the overlap in the infragranular layers. Again, the adult configuration is achieved 1 month after birth. This developmental inversion of the areal dimensions of the projection zones in supra- and infragranular layers is accompanied by a drastic decrease in the proportion of double-labeled neurons located in supragranular layers. These results clearly show that early in development, axonal projections to area V1 are modified in very different ways according to whether they originate from supra- or infragranular layers. This developmental process lasts for about 80 d. These findings show that in the primate there is a prolonged remodeling of axonal projections that is a highly characteristic feature of this species.

Mechanisms of LTP Induction in Rat Motor Cortex in vitro

Abstract: The motor cortex displays remarkable plasticity in response to changes in sensory and motor experience; however, the synaptic mechanisms underlying functional plasticity are not known. It is believed that synaptic processes that alter the strength of neuronal connections, such as long-term potentiation (LTP), are mechanisms by which synaptic circuits are modified by experience, resulting in functional adaptations. In the present study, we examined the mechanisms of LTP of synaptic responses in layers II/III to vertical (stimulation in layers V/VI) and horizontal (stimulation in layers II/III) inputs, in slices from rat motor cortex. Tetanic stimulation in layers V/VI or II/III induced LTP in 60% of the field potentials (n = 20) and in 73% of the intracellularly recorded postsynaptic potentials (n = 33). LTP was induced in cells with firing patterns characteristic of regular-spiking, fast-spiking, or bursting cells. LTP was expressed, for the most part, in kainate/AMPA receptor-mediated responses; however, potentiation of NMDA receptor-mediated components was also observed. Induction of LTP was prevented when either NMDA receptors or dihydropyridine-sensitive Ca2+ channels (DSCCs) were blocked, although blockade of DSCCs was less effective in preventing LTP induction. Based on the present data and previous LTP studies, we suggest that in many forms of LTP more than one mechanism participates in the induction process. The present findings may be relevant to the synaptic mechanisms underlying functional plasticity in motor cortex.

Prefrontal Alterations during Memory Processing in Aging

Abstract: Studies of human amnesia provide evidence for a short-term memory store with information transfer to long-term memory occurring within 60 sec of encoding. Frontal cortical activation is critical for maintenance of the short-term store, and limbic structure are necessary for access to the long-term store. The P3 and N4 components of the event-related potential (ERP) are generated during memory processes mediated by these brain regions. The current study examines the effects of age on ERPs generated to correctly identified stimuli presented at delays of 1-150 sec in a visual recognition memory task. Consistently different evoked potentials and performance were obtained to stimuli repeated at 1.2 sec delay as opposed to stimuli repeated at delays of over 4 sec in all subjects. At the 1.2 sec delay, the performance and posterior P3 amplitudes generated by old and young subjects were comparable. At longer delays, the older subjects had impaired performance and decreased P3 amplitude at posterior scalp sites. In addition, fronto-central N4 activity was reduced at long delays in the elderly. Older subjects generated a sustained frontal positivity (50-800 msec) to both short and long delay stimuli that was not observed in the younger group. The late phase of the frontal positivity was enhanced at long delays in the elderly. The data provide evidence of intact rapid and impaired delayed recognition memory in aging. Alternations in frontal cortical control of posterior and limbic regions may contribute to the memory changes observed in aging.

View-based models of 3D object recognition: invariance to imaging transformations.

Abstract: This report describes the main features of a view-based model of object recognition. The model does not attempt to account for specific cortical structures; it tries to capture general properties to be expected in a biological architecture for object recognition. The basic module is a regularization network (RBF-like; see Poggio and Girosi, 1989; Poggio, 1990) in which each of the hidden units is broadly tuned to a specific view of the object to be recognized. The network output, which may be largely view independent, is first described in terms of some simple simulations. The following refinements and details of the basic module are then discussed: (1) some of the units may represent only components of views of the object--the optimal stimulus for the unit, its "center," is effectively a complex feature; (2) the units' properties are consistent with the usual description of cortical neurons as tuned to multidimensional optimal stimuli and may be realized in terms of plausible biophysical mechanisms; (3) in learning to recognize new objects, preexisting centers may be used and modified, but also new centers may be created incrementally so as to provide maximal view invariance; (4) modules are part of a hierarchical structure--the output of a network may be used as one of the inputs to another, in this way synthesizing increasingly complex features and templates; (5) in several recognition tasks, in particular at the basic level, a single center using view-invariant features may be sufficient.

The Temporal/Spatial Evolution of Optical Signals in Human Cortex

Abstract: Intraoperative measures of functioning brain are an important aspect to understanding normal and diseased cortical response. Previous studies, in animal models, have used optical reflectance maps to illustrate the location and timing of functional activity. We used optical reflectance mapping in patients undergoing parietal tumor resection to reveal the temporal/spatial evolution of perfusion and other related metabolic responses of sensorimotor cortex to peripheral somesthetic stimulation. The somatosensory cortex of seven anesthetized patients was mapped in response to transcutaneous electrical median and ulnar nerve stimulation using optical reflectance imaging. The time course and spatial extent of this response were measured and correlated with evoked potential maps collected during the same conditions. Observable signals first appeared within 1-2 sec, peaked at 3 sec, and disappeared by 9 sec. These signals colocalized with the largest evoked potentials in both the sensory and motor regions and demonstrated topological specificity with median and ulnar nerve stimulation. Maps of this temporal/spatial resolution illustrate the integrative and dynamic nature of the neuronal, vascular, and metabolic responses of human cortex. These data also provide insight to the mechanisms responsible for signals obtained using other brain imaging techniques such as PET and fMRI.