Impact of Monocular Retinal Lesions on Blob Size in Adult Human V1.

We studied the attributes of cytochrome c oxidase (CytOx)-rich blobs and ocular dominance columns (OD) in human V1 associated with monocular retinal lesions. Interblob distance, blob cross-sectional area, OD width, and OD arrangement pattern were analyzed in CytOx-reacted tangential sections of flat-mounted V1 preparations. Monocular deprivation induces differential expression of CytOx in the corresponding ODs in V1. We were thereby able to identify the V1 regions associated with the lesioned area in the retina, assign which OD was associated with each eye, and assign the corresponding blob in Layer III as deprived or nondeprived of visual input. We found that nondeprived blobs are more conspicuously stained than blobs outside the lesioned area. Notably, we found a selective expansion of blobs associated with the nonlesioned eye, whereas blobs associated with the deprived eye showed no significant change in size. Blob size in the latter condition was similar to the one observed in normal participants. These effects were present throughout the representation of the lesion in V1, suggesting that the underlying plasticity mechanisms do not depend on eccentricity. Retinal lesion caused no change in interblob distance, which was comparable to the normal brain (i.e., participants with no retinal lesion). This indicates that blob center is a stable hallmark of cortical organization. Finally, the width of ODs associated with the nonlesioned eye tended to be larger compared with ODs of the lesioned eye. However, this effect did not reach statistical significance. The stability of ODs thereby contrasts with blob plasticity, suggesting that the retinal lesion-triggered imbalance in the thalamocortical projection to Layer IVc has a limited impact on OD CytOx reactivity. On the other hand, we argue that ocular imbalance supports intracortical lateral competition that increases CytOx reactivity in the periblob region associated with the nonlesioned eye, accounting for the blob expansion we observe.

Cortical maps as a fundamental neural substrate for visual representation.

Visual perception is the product of serial hierarchical processing, parallel processing, and remapping on a dynamic network involving several topographically organized cortical visual areas. Here, we will focus on the topographical organization of cortical areas and the different kinds of visual maps found in the primate brain. We will interpret our findings in light of a broader representational framework for perception. Based on neurophysiological data, our results do not support the notion that vision can be explained by a strict representational model, where the objective visual world is faithfully represented in our brain. On the contrary, we find strong evidence that vision is an active and constructive process from the very initial stages taking place in the eye and from the very initial stages of our development. A constructive interplay between perceptual and motor systems (e.g., during saccadic eye movements) is actively learnt from early infancy and ultimately provides our fluid stable visual perception of the world.

Architecture of the inferior parietal cortex in capuchin monkey.

We studied the organization of the inferior parietal cortex (IPC) in five capuchin monkey (6 hemispheres) using cytoarchitectonic (Nissl), myeloarchitectonic (Gallyas), and immune-architectonic (SMI-32 monoclonal antibody) techniques. We partitioned the IPC into five distinct areas: PFG, PG, Opt, PFop, and PGop. Since we used parasagittal sections, we were not able to study area PF due to its far lateral position, which yielded slices that were tangential to the pial surface. Areas PFG, PG, and Opt were in the convexity close to the lateral sulcus, while PFop and PGop were positioned more posteriorly, in the opercular region of IPC. Of all the five regions, area Opt was the one most similar to its analogue in the macaque, especially as revealed with SMI-32 staining. Namely, in both primate species area Opt showed a low density of large pyramidal neurons. Additionally, the apical dendrites of these neurons were sparse and vertically orientated, resembling columns. We also found area PG to be similar: both species exhibited cell body layers with a radial arrangement. On the other hand, Nissl staining revealed area PFG to be architectonically different between New and Old-World monkeys: PFG in the capuchin showed a comparatively higher cell density than in macaques, especially in layers II and IV. These results suggest that evolution may have enabled the functional specialization of these brain regions based on behavioral demands of upper limb use. The small differences in the IPC of the two primates may be linked to interspecies variability.

Spontaneous variability in gamma dynamics described by a damped harmonic oscillator driven by noise.

Circuits of excitatory and inhibitory neurons generate gamma-rhythmic activity (30-80 Hz). Gamma-cycles show spontaneous variability in amplitude and duration. To investigate the mechanisms underlying this variability, we recorded local-field-potentials (LFPs) and spikes from awake macaque V1. We developed a noise-robust method to detect gamma-cycle amplitudes and durations, which showed a weak but positive correlation. This correlation, and the joint amplitude-duration distribution, is well reproduced by a noise-driven damped harmonic oscillator. This model accurately fits LFP power-spectra, is equivalent to a linear, noise-driven E-I circuit, and recapitulates two additional features of gamma: (1) Amplitude-duration correlations decrease with oscillation strength; (2) amplitudes and durations exhibit strong and weak autocorrelations, respectively, depending on oscillation strength. Finally, longer gamma-cycles are associated with stronger spike-synchrony, but lower spike-rates in both (putative) excitatory and inhibitory neurons. In sum, V1 gamma-dynamics are well described by the simplest possible model of gamma: A damped harmonic oscillator driven by noise.

Effects of MT lesions on visuomotor performance in macaques.

Monkeys with selective bilateral lesions of area MT were trained on tasks designed to examine visuomotor function. They were required to: 1- retrieve a small food pellet from a narrow slot; 2- locate and retrieve a loose peanut mounted on a background of fixed peanuts; and 3- retrieve an erratically moving food pellet from a spinning bowl. After the lesions, these monkeys were behaviorally impaired relative to their own preoperative performances and also relative to the postoperative performances of the control monkeys with lesions in optic radiation fibers (OR) under MT or lesions in the posterior parietal cortex (PP). Although their performance improved with practice and time, the MT-lesioned monkeys showed long-term impairments twenty weeks after surgery. Control monkeys performed no worse on the tasks after their lesions. Another task which required the monkeys to retrieve a food pellet without visual guidance revealed that all the animals performed equally poorly when visual cues were unavailable, but that only the control monkeys benefited when visual cues were available. None of the monkeys were impaired on a pattern discrimination learning task. Besides that, direct observations revealed that the MT-lesioned animals grasped peanuts in a manner different from the control animals.

Tangential distribution of cell type and direction selectivity in monkey area MT.

We studied the multiunit responses to moving and static stimuli from 585 cell clusters in area MT using multi-electrode arrays. Our aim was to explore if MT columns exhibit any larger-scale tangential organization or clustering based on their response properties. Neurons showing both motion and orientation selectivity were classified into four categories: 1- Type I (orientation selectivity orthogonal to the axis of motion); 2- Type II (orientation selectivity coaxial to the axis of motion); 3- Type DS (significant response to moving stimuli, but non-significant response to static stimuli); and 4- Type OS (significant orientation selectivity, but non-significant direction selectivity). Type I (34%), Type II (24%) and Type DS (32%) clusters were the most predominant and may be associated with different stages of motion processing in MT. On the other hand, the rarer Type OS (9%) may be integrating motion and form processing. Type I and unidirectional sites were the only classes to exhibit significant clustering. Type OS sites showed a trend for clustering, which did not reach statistical significance. We also found a trend for unidirectional sites to have bidirectional sites as neighbors. In conclusion, neuronal clustering associated with these four categories may be related to distinct MT functional circuits.

A Distinct Class of Bursting Neurons with Strong Gamma Synchronization and Stimulus Selectivity in Monkey V1.

Cortical computation depends on interactions between excitatory and inhibitory neurons. The contributions of distinct neuron types to sensory processing and network synchronization in primate visual cortex remain largely undetermined. We show that in awake monkey V1, there exists a distinct cell type (>>30% of neurons) that has narrow-waveform (NW) action potentials and high spontaneous discharge rates and fires in high-frequency bursts. These neurons are more stimulus selective and phase locked to 30- to 80-Hz gamma oscillations than other neuron types. Unlike other neuron types, their gamma-phase locking is highly predictive of orientation tuning. We find evidence for strong rhythmic inhibition in these neurons, suggesting that they interact with interneurons to act as excitatory pacemakers for the V1 gamma rhythm. We did not find a similar class of NW bursting neurons in L2-L4 of mouse V1. Given its properties, this class of NW bursting neurons should be pivotal for the encoding and transmission of stimulus information.

The Multiple Representations of Complex Digit Movements in Primary Motor Cortex Form the Building Blocks for Complex Grip Types in Capuchin Monkeys.

In the present study, we investigated motor cortex (M1) and a small portion of premotor and parietal cortex using intracortical microstimulation in anesthetized capuchin monkeys. Capuchins are the only New World monkeys that have evolved an opposable thumb and use tools in the wild. Like most Old World monkeys and humans, capuchin monkeys have highly dexterous hands. We surveyed a large extent of M1 and found that ~22% of all evoked movements in M1 involved the digits, and the majority of these consisted of finger flexions and extensions. Different subtypes of movements could be identified, including opposable movements of digits 1 and 2 (D1 and D2). Interestingly, the pattern of such movements varied between animals. In one case, movements involved the adduction of the medial surface of D1 toward the lateral surface of D2, whereas in the other case, the tips of D1 and D2 came in contact. Unlike other primates examined, we also found extensive representations of the prehensile foot and tail. We propose that the manual behavioral repertoire of capuchin monkeys, which includes the use of tools in the wild, is well represented within the motor cortex in the form of muscle synergies between different body parts that compose these larger, complex behaviors.SIGNIFICANCE STATEMENT The ability to use tools is a milestone in human evolution. Capuchin monkeys are one of the few non-human primates that use tools in the wild. The present study is the first detailed exploration of the motor cortex of these primates using long-train intracortical microstimulation. Within primary motor cortex, we evoked finger movements involving flexions and extensions of multiple digits, or of the first and second digits alone. Interestingly, flexion of tail and toes could also be evoked. Together, these results suggest that the functional organization of the motor cortex represents not just muscles of the body, but muscle synergies that form the building blocks of the complex behavioral repertoire of these animals.

Task-related hemodynamic responses are modulated by reward and task engagement.

Hemodynamic recordings from visual cortex contain powerful endogenous task-related responses that may reflect task-related arousal, or "task engagement" distinct from attention. We tested this hypothesis with hemodynamic measurements (intrinsic-signal optical imaging) from monkey primary visual cortex (V1) while the animals' engagement in a periodic fixation task over several hours was varied through reward size and as animals took breaks. With higher rewards, animals appeared more task-engaged; task-related responses were more temporally precise at the task period (approximately 10-20 seconds) and modestly stronger. The 2-5 minute blocks of high-reward trials led to ramp-like decreases in mean local blood volume; these reversed with ramp-like increases during low reward. The blood volume increased even more sharply when the animal shut his eyes and disengaged completely from the task (5-10 minutes). We propose a mechanism that controls vascular tone, likely along with local neural responses in a manner that reflects task engagement over the full range of timescales tested.

Distribution of cytochrome oxidase-rich patches in human primary visual cortex.

We studied the tangential distribution of cytochrome oxidase (CytOx)-rich patches (blobs) in the striate cortex (V1) of normally sighted Homo sapiens. We analyzed the spatial density and cross-sectional area of patches in CytOx-reacted tangential sections of flat-mounted preparations of V1 and surrounding areas. CytOx-rich patches were most clearly defined in the supragranular cortical layers of V1, particularly at middle levels of layer III. Variations in patch spatial density were subtle across different visual eccentricity representations. Within the binocular representation of V1, the average patch spatial density decreased slightly with increasing cortical eccentricity, from around 1.0 patch/mm2 in the foveal representation to 0.6 patch/mm2 at the representation of ∼60° eccentricity, but seemed to increase again at the representation of the monocular crescent. Across the entire sample, the cross-sectional area of patches (i.e., patch size) varied from approximately 0.2-0.8 mm2 , with a mean value of 0.32 mm2 . Notably, there was no significant variation in the mean patch size across eccentricity representations. Human patches are on average larger than those reported for nonhuman primate brains, and analysis of species with different brain sizes suggests an approximately linear relationship between V1 area and patch size. The relative constancy of patch metrics across eccentricities is in stark contrast with the exponential variation in V1 cortical magnification, suggesting a nearly invariant modular organization throughout human V1.

Partitioning of the primate intraparietal cortex based on connectivity pattern and immunohistochemistry for Cat-301 and SMI-32.

We propose a partitioning of the primate intraparietal sulcus (IPS) using immunoarchitectural and connectivity criteria. We studied the immunoarchitecture of the IPS areas in the capuchin monkey using Cat-301 and SMI-32 immunohistochemistry. In addition, we investigated the IPS projections to areas V4, TEO, PO, and MT using retrograde tracer injections in nine hemispheres of seven animals. The pattern and distribution of Cat-301 and SMI-32 immunostaining revealed multiple areas in the IPS, in the adjoining PO cleft and in the annectant gyrus, with differential staining patterns found for areas V3d, DM, V3A, DI, PO, POd, CIP-1, CIP-2, VIPa, VIPp, LIPva, LIPvp, LIPda, LIPdp, PIPv, PIPd, MIPv, MIPd, AIPda, AIPdp, and AIPv. Areas V4, TEO, PO, MT, which belong to different cortical streams of visual information processing, receive projections from at least twenty different areas within the IPS and adjoining regions. In six animals, we analyzed the distribution of retrogradely labeled cells in tangential sections of flat-mount IPS preparations. The lateral bank of the IPS projects to regions belonging both to the ventral (V4 and TEO) and dorsal (PO and MT) streams. The region on the floor of the IPS (i.e., VIP) projects predominantly to dorsal stream areas. Finally, the medial bank of the IPS (i.e., MIP) projects solely to the dorsalmedial stream (PO). Therefore, our data suggest that ventral and dorsal streams remain segregated within the IPS, and that its projections to the dorsal stream can be further segregated based on those targeting the dorsolateral versus the dorsomedial subdivisions.

Neuronal response properties across cytochrome oxidase stripes in primate V2.

Cytochrome oxidase histochemistry reveals large-scale cortical modules in area V2 of primates known as thick, thin, and interstripes. Anatomical, electrophysiological, and tracing studies suggest that V2 cytochrome oxidase stripes participate in functionally distinct streams of visual information processing. However, there is controversy whether the different V2 compartments indeed correlate with specialized neuronal response properties. We used multiple-electrode arrays (16 × 2, 8 × 4 and 4 × 4 matrices) to simultaneously record the spiking activity (N = 190 single units) across distinct V2 stripes in anesthetized and paralyzed capuchin monkeys (N = 3 animals, 6 hemispheres). Visual stimulation consisted of moving bars and full-field gratings with different contrasts, orientations, directions of motion, spatial frequencies, velocities, and color contrasts. Interstripe neurons exhibited the strongest orientation and direction selectivities compared to the thick and thin stripes, with relatively stronger coding for orientation. Additionally, they responded best to higher spatial frequencies and to lower stimulus velocities. Thin stripes showed the highest proportion (80%) of neurons selective to color contrast (compared to 47% and 21% for thick and interstripes, respectively). The great majority of the color selective cells (86%) were also orientation selective. Additionally, thin stripe neurons continued to increase their firing rate for stimulus contrasts above 50%, while thick and interstripe neurons already exhibited some degree of response saturation at this point. Thick stripes best coded for lower spatial frequencies and higher stimulus velocities. In conclusion, V2 CytOx stripes exhibit a mixed degree of segregation and integration of information processing, shedding light into the early mechanisms of vision.

Introduction.

The pulvinar can be subdivided into well-delimitated regions based on chemoarchitectural, cytoarchitectural, myeloarchitectural, connectivity, and electrophysiological criteria. Subdivisions of the pulvinar based on its chemoarchitectural features are the most consistently preserved across species of New and Old World monkeys. It is reasonable to speculate that the occurrence and distribution of calcium-binding proteins in the pulvinar, such as calbindin and parvalbumin, have been preserved along evolution. Therefore, they have proven to be valuable tools capable of probing the basic pulvinar scaffold across primate species. Along this review, we will provide an overview of the available data regarding the various subdivisions of the pulvinar that have been proposed based on architectural criteria such as the distribution of molecular markers, neuronal morphology, and fiber layout.

Cytoarchitecture and Myeloarchitecture of the Pulvinar.

In this chapter, we discuss the different ways in which the primate pulvinar has been subdivided, based on cytoarchitectural and myeloarchitectural criteria. One original criterion, based on cytoarchitecture, subdivided the pulvinar into nucleus pulvinaris medialis (PM), nucleus pulvinaris lateralis (PL), and nucleus pulvinaris inferior (PI). Later, the anterior limits of the pulvinar were extended and a subdivision was added to this nucleus, named pulvinar oralis (PO). PO occupies the anterior portion of the pulvinar and appears between the nucleus centrum medianum (CM) and the nucleus ventralis posterior lateralis (VPL).

Chemoarchitecture of the Pulvinar.

Cytochemical and immunocytochemical methods reveal details of the pulvinar architecture that are not apparent from Nissl and myelin staining. The results of these techniques have been interpreted in different ways by different investigators, each adopting different sets of nomenclature for the various pulvinar subdivisions. In this chapter, we discuss the notion that the differentiation of the pulvinar along primate evolution took place upon a relatively rigid chemoarchitectonic scaffold.

Visual Map Representations in the Primate Pulvinar.

The pulvinar receives direct visual information from the retina and indirect visual information from several cortical and subcortical areas. In this chapter, we discuss the visuotopic organization of the primate pulvinar. Electrophysiological techniques have been systematically employed to study pulvinar visuotopy in the owl, capuchin, and macaque monkeys. A single map of the visual field has been described in the pulvinar of the owl monkey, while two independent maps have been described in the capuchin and macaque pulvinar.

Connectivity of the Pulvinar.

Pulvinar connectivity has been studied using a variety of neuroanatomical tracing techniques in both New and Old World monkeys. Connectivity studies have revealed additional maps of the visual field other than those described using electrophysiological techniques, such as P3 in the capuchin monkey and P3/P4 in the macaque monkey. In this chapter, we argue that with increasing cortical size, the pulvinar developed new functional subdivisions in order to effectively interconnect and interact with the cortex.

Reestablishing the Chemoarchitectural Borders Based on Electrophysiological and Connectivity Data.

In this chapter, we discuss the poor agreement between visuotopic maps described using electrophysiological and connectivity data and the subdivisions of the pulvinar based on chemoarchitecture. We focus on the differences and similarities between New and Old World monkeys to evaluate how this agreement evolved during evolution. There is some agreement in the localization of P1, described using electrophysiological and connectivity data, and the lateral and central portions of the nucleus pulvinaris inferior (PI), defined based on chemoarchitectural criteria. Similarly, there is some colocalization between P3 and the medial portion of PI in both New and Old World monkeys. One difference between primates refers to P2, which is present in the Old World macaque monkey but absent in the New World monkeys. P4, which has not been studied in all primates, shows a partial spatial agreement with the dorsal portion of the chemoarchitecturally defined PL.

Visual Topography of the Pulvinar Projection Zones.

In this chapter, we describe the visuotopy of the pulvinar subdivisions P1, P2, and P4. In all primates, P1 colocalizes with the chemoarchitecturally defined PI and a small portion of PL. The peripheral visual field is represented anteriorly in the medial portion of PI, while central vision is represented more posteriorly in the medial portion of PL. The vertical meridian representation is located on the lateral edge of P1, while the horizontal meridian is represented obliquely from the lateral to the medial extent of P1. The upper visual field is represented ventrally, while the lower field is located dorsally. P2 has only been described in the macaque monkey. It contains a representation of the peripheral visual field, located in its anterior portion, and of the central field, which is located in posterior PL. P4 has a complex topographic arrangement. The representation of the vertical meridian is located on the dorsal edge of P4, while the representation of the horizontal meridian divides P4 into dorsal and ventral portions.

Comparative Pulvinar Organization Across Different Primate Species.

In this chapter, we compare the pattern of pulvinar immunohistochemical staining for the calcium-binding proteins calbindin and parvalbumin and for the neurofilament protein SMI-32 in macaque, capuchin, and squirrel monkeys. This group of New and Old World primates shares five similar pulvinar subdivisions: PIP, PIM, PIC, PIL, and PILS. In the Old World macaque monkey, the inferior-lateral pulvinar can be subdivided into the P1 and P2 fields based on its connectivity with visual area V1. On the other hand, only the P1 field and no P2 was found in the New World capuchin monkey. Notably, the similarities in chemoarchitecture contrast with the distinct connectivity patterns and the different visuotopic organizations found across the species.