Object-based attention in the primary visual cortex of the macaque monkey

Typical natural visual scenes contain many objects, which need to be segregated from each other and from the background. Present theories subdivide the processes responsible for this segregation into a pre-attentive and attentive system. The pre-attentive system segregates image regions that 'pop out' rapidly and in parallel across the visual field. In the primary visual cortex, responses to pre-attentively selected image regions are enhanced. When objects do not segregate automatically from the rest of the image, the time-consuming attentive system is recruited. Here we investigate whether attentive selection is also associated with a modulation of firing rates in area V1 of the brain in monkeys trained to perform a curve-tracing task. Neuronal responses to the various segments of a target curve were simultaneously enhanced relative to responses evoked by a distractor curve, even if the two curves crossed each other. This indicates that object-based attention is associated with a response enhancement at the earliest level of the visual cortical processing hierarchy.     

Effects of early environments on monkey cortex neuroanatomical changes following somatomotor experience: Effects on layer III pyramidal cells in monkey cortex.

Sixteen infant stumptail monkeys were reared to 6 months under four conditions. Behaviors and cortical neuroanatomy were compared. Earlier studies showed effects on stellate cell dendrites. Here are reported the results in six cortical areas on basilar dendrites of layer III pyramidal cells. Basilar dendrites show significantly larger numbers (p?     

Processing of contrast polarity of visual images in inferotemporal cortex of the macaque monkey

Cells in the anterior part of the inferotemporal cortex (anterior IT) respond to moderately complex stimulus features of object images. To study dependency of their responses on contrast polarity of stimulus images, we selected cells with optimal stimuli that were defined only by shape and not related to texture or color, and examined effects of reversing the contrast of the image or removing it except for edges between dark and bright parts of the image ("outlining"). The contrast reversal produced a reduction of the response to the optimal stimulus by > 50% in 60% of tested cells; the outlining, in 70%. When the two transformations were considered together, 94% of the cells showed a reduction by > 50%. Effects of the transformations on shape selectivity were also studied by comparing responses to several different shapes each of whose contours were expressed in different ways. Statistically significant changes in relative effectiveness of the different shapes as a function of contour expression were observed in more than half of the cells. These results suggest that responses of individual cells in anterior IT carry information about contrast polarity as well as about shape.     

Cortical hierarchy reflected in the organization of intrinsic connections in macaque monkey visual cortex

Neuronal response properties vary markedly at increasing levels of the cortical hierarchy. At present it is unclear how these variations are reflected in the organization of the intrinsic cortical circuitry. Here we analyze patterns of intrinsic horizontal connections at different hierarchical levels in the visual cortex of the macaque monkey. The connections were studied in tangential sections of flattened cortices, which were injected with the anterograde tracer biocytin. We directly compared the organization of connections in four cortical areas representing four different levels in the cortical hierarchy. The areas were visual areas 1, 2, 4 and Brodman's area 7a (V1, V2, V4 and 7a, respectively). In all areas studied, injections labeled numerous horizontally coursing axons that formed dense halos around the injection sites. Further away, the fibers tended to form separate clusters. Many fibers could be traced along the way from the injection sites to the target clusters. At progressively higher order areas, there was a striking increase in the spread of intrinsic connections: from a measured distance of 2.1 mm in area V1 to 9.0 mm in area 7a. Average interpatch distance also increased from 0.61 mm in area V1 to 1.56 mm in area 7a. In contrast, patch size changed far less at higher order areas, from an average width of 230 micron(s) in area V1 to 310 micron(s) in area 7a. Analysis of synaptic bouton distribution along axons revealed that average interbouton distance remained constant at 6.4 micron(s) (median) in and out of the clusters and in the different cortical areas. Larger injections resulted in a marked increase in the number of labeled patches but only a minor increase in the spread of connections or in patch size. Thus, in line with the more global computational roles proposed for the higher order visual areas, the spread of intrinsic connections is increased with the hierarchy level. On the other hand, the clustered organization of the connections is preserved at higher order areas. These clusters may reflect the existence of cortical modules having blob-like dimensions throughout macaque monkey visual cortex.     

Responsiveness of neurons in the posterior inferotemporal cortex to visual patterns in the macaque monkey

Using anesthetized and immobilized monkeys, responses of neurons in the posterior inferotemporal cortex to visual patterns were examined. Response properties were compared between the sulcus and the gyrus, extending between the anterior tip of the posterior middle temporal sulcus and the inferior occipital sulcus. Of 682 neurons tested, 37% in the sulcus (134/365) and 36% in the gyrus (113/317) responded to one or more patterns. The preference of neurons for patterns varied from neuron to neuron; some neurons responded selectively to one particular pattern, whereas others responded to two or more patterns. To evaluate response properties of neurons, two indices were calculated (the pattern preference index and the pattern selectivity index). The distributions of these indices in the sulcus did not differ significantly from those of the gyrus. Furthermore, the relationship between the pattern preference index and the pattern selectivity index for each neuron was almost the same in these two portions; most neurons responding to a small number of patterns showed inhibitory or weak responses to the worst pattern. In both portions, most neurons had receptive fields with small eccentricities and receptive field sizes were almost the same. These results suggest that the cortex in the sulcus in the posterior inferotemporal cortex is involved in the detection of features of visual patterns, similarly to the cortex in the gyrus.     

Development of the dendritic fields of layer 3 pyramidal cells in the kitten's visual cortex

The cat's visual cortex is immature at birth and undergoes extensive postnatal development. For example, cells of layers 2 and 3 do not complete migration until about 3 weeks after birth. Despite the importance of dendritic growth for synaptic and functional development, there have been few studies of dendritic development in the cat's visual cortex to correlate with numerous studies of functional and synaptic development. Accordingly, we used the Golgi method to study the development of the dendrites of layer 3 pyramidal cells in the visual cortex of a series of cats ranging in age from 2 days to 3 years. Blocks of visual cortex were impregnated by the Golgi-Kopsch method and sectioned in the tangential plane. Layer 3 pyramidal cells were drawn with a camera lucida and analyzed by Sholl diagrams and vector addition. In kittens < 1 week old, these cells were very immature, with only an apical dendrite and no basal dendrites. Basal dendrites appeared during the second week. By 2 weeks, all of the basal dendrites had emerged from the soma, but they had few branches and were tipped with growth cones. By 4 weeks, they had finished branching but continued to grow in length until, by 5 weeks, they reached their adult size. Examination of the basal dendritic fields in the tangential plane revealed that their dendritic fields were more elongated at 2 weeks than at later ages, perhaps because of their smaller size. The distribution of dendritic field orientations was uniform at all ages except 3 and 4 weeks, when there was a preponderance of fields oriented in the rostrocaudal direction. Because dendritic growth and branching occurred very rapidly over a period that precedes and overlaps with the peak periods of synaptogenesis and of sensitivity to the effects of early visual experience, they may depend on afferent visual activity. The early emergence of primary dendrites, however, suggests that this process is independent of afferent activity. The coincident timing of dendritic branching with the presence of dendritic growth cones suggests that branching may occur at growth cones.     

Postnatal maturation of the layer III pyramidal neurons in the human prefrontal cortex: a quantitative Golgi analysis

In this study we examined the morphological maturation of the basal dendritic field of layer III pyramidal neurons located in the human dorsolateral prefrontal cortex in subjects ranging from 7.5 months after birth up to 27 years. The sections were stained with the Golgi-Cox method and the three-dimensional branching pattern was measured with a semi-automatic dendrite measuring system. Results show a rapid growth phase of the dendritic field from 7.5 months after birth up to one year. A marked increase in total dendritic length is observed, for which elongation of the terminal segments, longer intermediate segments and an increase in number of segments is an explanation. The dendritic length appears to have stabilized after one year, leading us to conclude that the postnatal morphological maturation of the layer III pyramidals does not continue well into childhood, but is completed at a much younger age. Additionally we analyzed the effect of varying section thickness on dendritic parameters and found no tendency for higher dendritic values with increasing section thickness for the range of thickness values of the histological sections used.     

Contributions of individual layer 2-5 spiny neurons to local circuits in macaque primary visual cortex

We studied excitatory local circuits in the macaque primary visual cortex (VI) to investigate their relationships to the magnocellular (M) and parvocellular (P) streams. Sixty-two intracellularly labeled spiny neurons in layers 2-5 were analyzed. We made detailed observations of the laminar and columnar specificity of axonal arbors and noted correlations with dendritic arbors. We find evidence for considerable mixing of M and P streams by the local circuitry in VI. Such mixing is provided by neurons in the primary geniculate recipient layer 4C, as well as by neurons in both the supragranular and infragranular layers. We were also interested in possible differences in the axonal projections of neurons with different dendritic morphologies. We found that layer 4B spiny stellate and pyramidal neurons have similar axonal arbors. However, we identified two types of layer 5 pyramidal neuron. The majority have a conventional pyramidal dendritic morphology, a dense axonal arbor in layers 2.4B, and do not project to the white matter. Layer 5 projection neurons have an unusual "backbranching" dendritic morphology (apical dendritic branches arc downward rather than upward) and weak or no axonal arborization in layers 2-4B, but have long horizontal axonal projections in layer 5B. We find no strong projection from layer 5 pyramidal neurons to layer 6. In macaque V1 there appears to be no single source of strong local input to layer 6; only a minority of cells in layers 2-5 have axonal branches in layer 6 and these are sparse. Our results suggest that local circuits in V1 mediate interactions between M and P input that are complex and not easily incorporated into a simple framework.     

Representation of foveal visual fields in the ventral bank of the superior temporal sulcus in the posterior inferotemporal cortex of the macaque monkey

A fast and sensitive analytical method was developed to characterize artemether and its metabolites in small amounts in body fluids. The extracts were derivatized with N-methyl-N-trimethylsilyltrifluoroacetamide, separated on an optimized capillary gas chromatographic system and identified by chemical ionization mass spectrometry by using ammonia as reagent gas. The analytical assay is demonstrated on samples extracted from bovine hemoglobin, rat blood and dog blood. Full mass spectra of artemether and three metabolites were obtained at a level of 1 x 10(-6) g/ml.     

Temporal dynamics of chromatic tuning in macaque primary visual cortex

The ability to distinguish colour from intensity variations is a difficult computational problem for the visual system because each of the three cone photoreceptor types absorb all wavelengths of light, although their peak sensitivities are at relatively short (S cones), medium (M cones), or long (L cones) wavelengths. The first stage in colour processing is the comparison of the outputs of different cone types by spectrally opponent neurons in the retina and upstream in the lateral geniculate nucleus. Some neurons receive opponent inputs from L and M cones, whereas others receive input from S cones opposed by combined signals from L and M cones. Here we report how the outputs of the L/M- and S-opponent geniculate cell types are combined in time at the next stage of colour processing, in the macaque primary visual cortex (V1). Some V1 neurons respond to a single chromatic region, with either a short (68-95 ms) or a longer (96-135 ms) latency, whereas others respond to two chromatic regions with a difference in latency of 20-30 ms. Across all types, short latency responses are mostly evoked by L/M-opponent inputs whereas longer latency responses are evoked mostly by S-opponent inputs. Furthermore, neurons with late S-cone inputs exhibit dynamic changes in the sharpness of their chromatic tuning over time. We propose that the sparse, S-opponent signal in the lateral geniculate nucleus is amplified in area V1, possibly through recurrent excitatory networks. This results in a delayed, sluggish cortical S-cone signal which is then integrated with L/M-opponent signals to rotate the lateral geniculate nucleus chromatic axes.     

Linearity and normalization in simple cells of the macaque primary visual cortex

Simple cells in the primary visual cortex often appear to compute a weighted sum of the light intensity distribution of the visual stimuli that fall on their receptive fields. A linear model of these cells has the advantage of simplicity and captures a number of basic aspects of cell function. It, however, fails to account for important response nonlinearities, such as the decrease in response gain and latency observed at high contrasts and the effects of masking by stimuli that fail to elicit responses when presented alone. To account for these nonlinearities we have proposed a normalization model, which extends the linear model to include mutual shunting inhibition among a large number of cortical cells. Shunting inhibition is divisive, and its effect in the model is to normalize the linear responses by a measure of stimulus energy. To test this model we performed extracellular recordings of simple cells in the primary visual cortex of anesthetized macaques. We presented large stimulus sets consisting of (1) drifting gratings of various orientations and spatiotemporal frequencies; (2) plaids composed of two drifting gratings; and (3) gratings masked by full-screen spatiotemporal white noise. We derived expressions for the model predictions and fitted them to the physiological data. Our results support the normalization model, which accounts for both the linear and the nonlinear properties of the cells. An alternative model, in which the linear responses are subject to a compressive nonlinearity, did not perform nearly as well.     

The orientation and direction selectivity of cells in macaque visual cortex

Quantitative data are presented on the orientation and direction specificity of the responses of cells in macaque monkey striate cortex. There is a bimodal distribution of direction-specific and nondirection-specific cells, with similar orientation tuning in each class. Cells range in orientation bandwidth at half amplitude from 6 degrees to 360 degrees (i.e. no orientation tuning), with a median near 40 degrees. Foveal-parafoveal and simple-complex subsamples show similar ranges of orientation bandwidths as well as similar medians (the bandwidths being somewhat broader than those found in cat cortex). The foveal subsample and a high-spatial-frequency subsample have more horizontal and vertical optimal orientations than oblique ones. Most cells show inhibition to some orientations, as well as excitation to others. Minimum-response orientations are generally less than 90 degrees from the optimal orientation--indicating maximum inhibition adjacent to the excitatory orientations. Three simple receptive field models are shown to differ in their abilities to account for these results.     

Hemispheric differences in layer III pyramidal neurons of the anterior language area

OBJECTIVE: The major objective of this study was to determine if the lateralization of motor speech functions may be associated with hemispheric differences in the size of layer III pyramidal neurons in Brodmann's area 45. DESIGN: A case series design involving postmortem human specimens was used to compare the cross-sectional area of NissI-stained layer III pyramidal neurons of Brodmann's area 45 from the left and right hemispheres. SUBJECTS: A convenience sample consisting of seven cases with no known neurological or psychiatric disorders was obtained at autopsy. MAIN OUTCOME MEASURES: The cross-sectional area of layer III pyramidal neurons in both left and right hemispheres was measured in four fields per hemisphere per brain using a computerized image analysis system. Measurements of both the largest layer III pyramids and of all layer III pyramids were done. RESULTS: The largest layer III pyramidal neurons of area 45 were significantly larger in the left than in the right hemisphere in both an unblinded and a blinded series of measurements. However, this hemispheric difference appeared to be restricted to the largest neurons, since the mean size of all layer III pyramids in this area was not significantly different in the left and right hemispheres. CONCLUSIONS: The presence of a unique population of large pyramidal neurons in left Brodmann's area 45 may be related to the involvement of this region in the circuitry that mediates motor speech functions.     

A visuo-somatomotor pathway through superior parietal cortex in the macaque monkey: cortical connections of areas V6 and V6A

This report addresses the connectivity of the cortex occupying middle to dorsal levels of the anterior bank of the parieto-occipital sulcus in the macaque monkey. We have previously referred to this territory, whose perimeter is roughly circumscribed by the distribution of interhemispheric callosal fibres, as area V6, or the 'V6 complex'. Following injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA-HRP) into this region, we examined the laminar organization of labelled cells and axonal terminals to attain indications of relative hierarchical status among the network of connected areas. A notable transition in the laminar patterns of the local, intrinsic connections prompted a sub-designation of the V6 complex itself into two separate areas, V6 and V6A, with area V6A lying dorsal, or dorsomedial to V6 proper. V6 receives ascending input from V2 and V3, ranks equal to V3A and V5, and provides an ascending input to V6A at the level above. V6A is not connected to area V2 and in general is less heavily linked to the earliest visual areas; in other respects, the two parts of the V6 complex share similar spheres of connectivity. These include regions of peripheral representation in prestriate areas V3, V3A and V5, parietal visual areas V5A/MST and 7a, other regions of visuo-somatosensory association cortex within the intraparietal sulcus and on the medial surface of the hemisphere, and the premotor cortex. Subcortical connections include the medial and lateral pulvinar, caudate nucleus, claustrum, middle and deep layers of the superior colliculus and pontine nuclei. From this pattern of connections, it is clear that the V6 complex is heavily engaged in sensory-motor integration. The specific somatotopic locations within sensorimotor cortex that receive this input suggest a role in controlling the trunk and limbs, and outward reaching arm movements. There is a secondary contribution to the brain's complex oculomotor circuitry. That the medial region of the cortex is devoted to tightly interconnected representations of the sensory periphery, both visual and somatotopic-which are routinely stimulated in concert-would appear to be an aspect of the global organization of the cortex which must facilitate multimodal integration.     

Eye position effects on the neuronal activity of dorsal premotor cortex in the macaque monkey

Visual inputs to the brain are mapped in a retinocentric reference frame, but the motor system plans movements in a body-centered frame. This basic observation implies that the brain must transform target coordinates from one reference frame to another. Physiological studies revealed that the posterior parietal cortex may contribute a large part of such a transformation, but the question remains as to whether the premotor areas receive visual information, from the parietal cortex, readily coded in body-centered coordinates. To answer this question, we studied dorsal premotor cortex (PMd) neurons in two monkeys while they performed a conditional visuomotor task and maintained fixation at different gaze angles. Visual stimuli were presented on a video monitor, and the monkeys made limb movements on a panel of three touch pads located at the bottom of the monitor. A trial begins when the monkey puts its hand on the central pad. Then, later in the trial, a colored cue instructed a limb movement to the left touch pad if red or to the right one if green. The cues lasted for a variable delay, the instructed delay period, and their offset served as the go signal. The fixation spot was presented at the center of the screen or at one of four peripheral locations. Because the monkey's head was restrained, peripheral fixations caused a deviation of the eyes within the orbit, but for each fixation angle, the instructional cue was presented at nine locations with constant retinocentric coordinates. After the presentation of the instructional cue, 133 PMd cells displayed a phasic discharge (signal-related activity), 157 were tonically active during the instructed delay period (set-related or preparatory activity), and 104 were active after the go signal in relation to movement (movement-related activity). A large proportion of cells showed variations of the discharge rate in relation to limb movement direction, but only modest proportions were sensitive to the cue's location (signal, 43%; set, 34%; movement, 29%). More importantly, the activity of most neurons (signal, 74%; set, 79%; movement, 79%) varied significantly (analysis of variance, P < 0.05) with orbital eye position. A regression analysis showed that the neuronal activity varied linearly with eye position along the horizontal and vertical axes and can be approximated by a two-dimensional regression plane. These data provide evidence that eye position signals modulate the neuronal activity beyond sensory areas, including those involved in visually guided reaching limb movements. Further, they show that neuronal activity related to movement preparation and execution combines at least two directional parameters: arm movement direction and gaze direction in space. It is suggested that a substantial population of PMd cells codes limb movement direction in a head-centered reference frame.     

Mechanisms underlying direction selectivity of neurons in the primary visual cortex of the macaque

1. We studied the effects of blocking intracortical inhibition by microiontophoretic administration of bicuculline methiodide (BMI), a selective antagonist for gamma-aminobutyric acid-A receptors, on direction sensitivity of 103 neurons in the primary visual cortex (VI) of anesthetized and paralyzed monkeys. 2. The direction selectivity index (DSI) of each cell was calculated for the control response and response during the BMI administration at the optimal stimulus orientation to assess the directionality of an individual cell. 3. The averaged direction tuning of visual responses of cells was sharp in layers IVa and IVb, moderate in both interblob and blob regions of layer II/III and layers V and VI, and poor in layers IVc alpha and IVc beta. 4. Iontophoretic administration of BMI uncovered or facilitated responses to stimuli moving in the nonpreferred direction, and reduced DSIs of cells to a varying extent in all the layers except layer VI. Responses to stimuli moving in the preferred direction were also facilitated so that a slight bias of response toward the originally preferred direction remained during BMI administration in most cells. 5. Most of the cells in layers II/III (both blobs and interblobs) and IVb that receive inputs from layers IVc alpha and IVc beta showed a clear reduction of direction selectivity during BMI administration. This result suggests that intracortical inhibition plays an important role in the elaboration of direction selectivity at the second stage of information processing in VI. 6. The direction selectivity of cells in layer VI was most resistant to the effects of BMI, suggesting that it is dependent on excitatory inputs that are already direction selective, even though the sample size of this layer was small. 7. In direction-selective cells outside layer VI, responses to a stimulus moving in the preferred direction were enhanced in a way that was linearly related with those in the nonpreferred direction as the BMI dose was increased. This suggests that various amounts of inhibition interact linearly with directionally biased excitatory inputs to raise the firing threshold to various levels so as to produce various degrees of directionality. 8. These results suggest that, in most of the directionally sensitive cells except for those in layer VI, there are excitatory inputs which are bidirectional but slightly biased to one direction, and that the intracortical inhibition raises a threshold level of responses to excitatory inputs so that the response become direction selective.     

Dopamine decreases the excitability of layer V pyramidal cells in the rat prefrontal cortex

In both primates and rodents, the prefrontal cortex (PFC) is highly innervated by dopaminergic fibers originating from the ventral tegmental area, and activation of this mesocortical dopaminergic system decreases spontaneous and evoked activity in the PFC in vivo. We have examined the effects of dopamine (DA), over a range of concentrations, on the passive and active membrane properties of layer V pyramidal cells from the rat medial PFC (mPFC). Whole-cell and perforated-patch recordings were made from neurons in rat mPFC. As a measure of cell excitability, trains of action potentials were evoked with 1-sec-long depolarizing current steps. Bath application of DA (0.05-30 microM) produced a reversible decrease in the number of action potentials evoked by a given current step. In addition, DA reversibly decreased the input resistance (RN) of these cells. In a subset of experiments, a transient increase in excitability was observed after the washout of DA. Control experiments suggest that these results are not attributable to changes in spontaneous synaptic activity, age-dependent processes, or strain-specific differences in dopaminergic innervation and physiology. Pharmacological analyses, using D1 agonists (SKF 38393 and SKF 81297), a D1 antagonist (SCH 23390), a D2 receptor agonist (quinpirole), and a D2 antagonist (sulpiride) suggest that decreases in spiking and RN are mediated by D2 receptor activation. Together, these results demonstrate that DA, over a range of concentrations, has an inhibitory effect on layer V pyramidal neurons in the rat mPFC, possibly through D2 receptor activation.     

Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.     

Axonal sprouting in layer V pyramidal neurons of chronically injured cerebral cortex

We performed experiments to determine whether axonal sprouting occurs in neurons of chronic neocortical epileptogenic lesions. Partially isolated somatosensory cortical islands with intact pial blood supply were prepared in mature rats. Neocortical slices from these lesions, studied 6-39 d later, generated spontaneous and/or evoked epileptiform field potentials (Prince and Tseng, 1993) during which neurons displayed prolonged polyphasic excitatory and inhibitory synaptic potentials/currents. Single electrophysiologically characterized layer V pyramidal neurons in control and epileptogenic slices were filled with biocytin using sharp and patch-electrode techniques, their axonal arbors reconstructed and compared quantitatively. Neurons in injured cortex had a 56% increase in total axonal length, a 64% increase in the number of axonal collaterals and more than a doubling (115% increase) of the number of axonal swellings. The presumed boutons were smaller and more closely spaced than those of control cells. In some neurons the main descending axon had hypertrophic segments from which branches arose. These highly significant changes were most marked in the perisomatic region of layer V. The axonal sprouting was associated with a decrease in somatic area but no significant change in dendritic arbors. Results suggest that a significant degree of axonal reorganization takes place in the chronically injured cortex where it might be an adaptive mechanism for recovery of function after injury, or might be maladaptive and play an important role in the generation of epileptiform events by increasing the numbers and density of synaptic contacts between neurons.     

Postnatal development of corticospinal projections from motor cortex to the cervical enlargement in the macaque monkey

The postnatal development of corticospinal projections was investigated in 11 macaques by means of the anterograde transport of wheat germ agglutin-horseradish peroxidase injected into the primary motor cortex hand area. Although the fibers of the corticospinal tract reached all levels of the spinal cord white matter at birth, their penetration into the gray matter was far from complete. At birth, as in the adult, corticospinal projections were distributed to the same regions of the intermediate zone, although they showed marked increases in density during the first 5 months. The unique feature of the primate corticospinal tract, namely direct cortico-motoneuronal projections to the spinal motor nuclei innervating hand muscles, was not present to a significant extent at birth. The density of these cortico-motoneuronal projections increased rapidly during the first 5 months, followed by a protracted period extending into the second year of life. The densest corticospinal terminations occupied only 40% of the hand motor nuclei in the first thoracic segment at 1 month, 73% at 5 months, and 75.5% at 3 years. A caudo-rostral gradient of termination density within the hand motor nuclei was present throughout development and persisted into the adult. As a consequence, the more caudal the segment within the cervical enlargement, the earlier the adult pattern of projection density was reached. No transitory corticospinal projections were found. The continuous postnatal expansion of cortico-motoneuronal projections to hand motor nuclei in primates is in marked contrast to the retraction of exuberant projections that characterizes the development of other sensory and motor pathways in subprimates.