A predictive model of the cat cortical connectome based on cytoarchitecture and distance

Information processing in the brain is strongly constrained by anatomical connectivity. However, the principles governing the organization of corticocortical connections remain elusive. Here, we tested three models of relationships between the organization of cortical structure and features of connections linking 49 areas of the cat cerebral cortex. Factors taken into account were relative cytoarchitectonic differentiation (‘structural model’), relative spatial position (‘distance model’), or relative hierarchical position (‘hierarchical model’) of the areas. Cytoarchitectonic differentiation and spatial distance (themselves uncorrelated) correlated strongly with the existence of inter-areal connections, whereas no correlation was found with relative hierarchical position. Moreover, a strong correlation was observed between patterns of laminar projection origin or termination and cytoarchitectonic differentiation. Additionally, cytoarchitectonic differentiation correlated with the absolute number of corticocortical connections formed by areas, and varied characteristically between different cortical subnetworks, including a ‘richclub’ module of hub areas. Thus, connections between areas of the cat cerebral cortex can, to a large part, be explained by the two independent factors of relative cytoarchitectonic differentiation and spatial distance of brain regions. As both the structural and distance model were originally formulated in the macaque monkey, their applicability in another mammalian species suggests a general principle of global cortical organization

Functional Brain Organization in Space and Time

The brain is a network functionally organized at many spatial and temporal scales. To understand how the brain processes information, controls behavior and dynamically adapts to an ever-changing environment, it is critical to have a comprehensive description of the constituent elements of this network and how relationships between these elements may change over time. Decades of lesion studies, anatomical tract-tracing, and electrophysiological recording have given insight into this functional organization. Recently, however, resting state functional magnetic resonance imaging (fMRI) has emerged as a powerful tool for whole-brain non-invasive measurement of spontaneous neural activity in humans, giving ready access to macroscopic scales of functional organization previously much more difficult to obtain. This thesis aims to harness the unique combination of spatial and temporal resolution provided by functional MRI to explore the spatial and temporal properties of the functional organization of the brain. First, we establish an approach for defining cortical areas using transitions in correlated patterns of spontaneous BOLD activity (Chapter 2). We then propose and apply measures of internal and external validity to evaluate the credibility of the areal parcellation generated by this technique (Chapter 3). In chapter 4, we extend the study of functional brain organization to a highly sampled individual. We describe the idiosyncratic areal and systems-level organization of the individual relative to a standard group-average description. Further, we develop a model describing the reliability of BOLD correlation estimates across days that accounts for relevant sources of variability. Finally, in Chapter 5, we examine whether BOLD correlations meaningfully vary over the course of single resting-state scans

Anatomical analysis of the feedback projections from extrastriate cortex to area 18 in ferret visual cortex

The purpose of this thesis is to characterize the cortical inputs to area 18 of ferret visual cerebral cortex. Contrary to feedforward connections, feedback connections are presumed to have a modulatory influence on the responses of lower order neurons providing information already processed. Input from feedback connections can supposedly elicit changes in the response to stimuli within the receptive field and may be involved in the role of discriminating objects relative to the background. The aim of our set of experiments was to fully analyze and compare the anatomical characteristics of feedback connections to area 18 from extrastriate areas as opposed to the feedback connections to area 17 in visual cortex. In our analysis, we focus on the overall pattern of retrogradely labeled cells, the proportion of feedback label to area 18, the laminar distribution of these cells, their density and clustering tendencies, and their cortical extent. With this solid base of information we can then make further hypotheses regarding the influence and role extrastriate areas 19, 21, and Suprasylvian cortex provide in modulation. The mean proportion of total cortical input from area 17 is 19.9%, from area 18 (39.5%), from area 19 (27.5%), from area 21 (4%), and from Ssy area (17.1%), from cells undefined in the border covering area 17 and area 18 (3.6%), border cells between area 18 and area 19 (1.5%). The overall feedback proportions when data is pooled for area 19 is 57.2%, for area 21 (8.75%), Ssy area (26.1%), area 18/19 border (6.6%) and area 19/21 border (1.4%). Within each area, there is a significantly larger proportion of feedback connections arising from the infragranular layers (means range between 70 and 88%) than from the supragranular layers (means range between 8% and 25%). After pooling all of our cases together, we measure the grand median of the nearest neighbor distance for each cortical area providing connections to area 18 including area 17 (34.14μm), area 18 (39.48μm), area 19 upper layers (45.61μm), area 19 lower layers (39.55μm), area 21 lower layers (62.48μm), Ssy area upper layers (57.8μm), Ssy area lower layers (44.28μm), borders of area 17/18 (34.58μm), borders of area 18/19 (55.4μm), borders of area 19/21 (41.58μm), and lateral temporal areas (57.74μm). We find the characterization of inputs to area 18 in comparison to the feedback projections to area 17 vary in proportion, anatomical location and cortical extent, which suggest different retinotopic representation in the visual fields

Multiple Transmitter Receptors in Regions and Layers of the Human Cerebral Cortex

We measured the densities (fmol/mg protein) of 15 different receptors of various transmitter systems in the supragranular, granular and infragranular strata of 44 areas of visual, somatosensory, auditory and multimodal association systems of the human cerebral cortex. Receptor densities were obtained after labeling of the receptors using quantitative in vitro receptor autoradiography in human postmortem brains. The mean density of each receptor type over all cortical layers and of each of the three major strata varies between cortical regions. In a single cortical area, the multi-receptor fingerprints of its strata (i.e., polar plots, each visualizing the densities of multiple different receptor types in supragranular, granular or infragranular layers of the same cortical area) differ in shape and size indicating regional and laminar specific balances between the receptors. Furthermore, the three strata are clearly segregated into well definable clusters by their receptor fingerprints. Fingerprints of different cortical areas systematically vary between functional networks, and with the hierarchical levels within sensory systems. Primary sensory areas are clearly separated from all other cortical areas particularly by their very high muscarinic M2 and nicotinic α4β2 receptor densities, and to a lesser degree also by noradrenergic α2 and serotonergic 5-HT2 receptors. Early visual areas of the dorsal and ventral streams are segregated by their multi-receptor fingerprints. The results are discussed on the background of functional segregation, cortical hierarchies, microstructural types, and the horizontal (layers) and vertical (columns) organization in the cerebral cortex. We conclude that a cortical column is composed of segments, which can be assigned to the cortical strata. The segments differ by their patterns of multi-receptor balances, indicating different layer-specific signal processing mechanisms. Additionally, the differences between the strata-and area-specific fingerprints of the 44 areas reflect the segregation of the cerebral cortex into functionally and topographically definable groups of cortical areas (visual, auditory, somatosensory, limbic, motor), and reveals their hierarchical position (primary and unimodal (early) sensory to higher sensory and finally to multimodal association areas).HighlightsDensities of transmitter receptors vary between areas of human cerebral cortex.Multi-receptor fingerprints segregate cortical layers.The densities of all examined receptor types together reach highest values in the supragranular stratum of all areas.The lowest values are found in the infragranular stratum.Multi-receptor fingerprints of entire areas and their layers segregate functional systemsCortical types (primary sensory, motor, multimodal association) differ in their receptor fingerprints

Visual Corticocortical Inputs to Ferret Area 18

Visual cortical areas in the adult mammalian brain are linked by a network of interareal feedforward and feedback circuits. We investigated the topography of feedback projections to ferret (Mustela putorius furo) area 18 from extrastriate areas 19, 21, and Ssy. Our objective was to characterize the anatomical organization of the extrastriate feedback pool to area 18. We also wished to determine if feedback projections to area 18 share similar features as feedback projections to area 17. We injected the tracer cholera toxin B subunit (CTb) into area 18 of adult ferrets to visualize the distribution and pattern of retrogradely labeled cells in extrastriate cortex. We find several similarities to the feedback projection to area 17: (i) Multiple visual cortical areas provide feedback to area 18: areas 19, 21, Ssy, and weaker inputs from posterior parietal and lateral temporal visual areas. Within each area a greater proportion of feedback projections arises from the infragranular than from the supragranular layers. (ii) The cortical area immediately rostral to area 18 provides the greatest proportion of total cortical feedback, and has the greatest peak density of cells providing feedback to area 18. (iii) The spacing (peak cell density and nearest neighbor distances) of cells in extrastriate cortex providing feedback to areas 17 and 18 are similar. However, peak density of feedback cells to area 18 is comparable in the supra- and infragranular layers, whereas peak density of feedback cells to area 17 is higher in the infragranular layers. Another prominent difference is that dorsal area 18 receives a cortical input that area 17 does not: from ventral cortex representing the upper visual field; this appears to be roughly 25% of the feedback input to area 18. Lastly, area 17 receives a greater proportion of cortical feedback from area 21 than from Ssy, whereas area 18 receives more feedback from Ssy than from area 21. While the organization of feedback projections from extrastriate cortex to areas 17 and 18 is broadly similar, the main difference in input topography might arise due to differences in visual field representations of the two areas

Towards a Theory of the Laminar Architecture of Cerebral Cortex: Computational Clues from the Visual System

One of the most exciting and open research frontiers in neuroscience is that of seeking to understand the functional roles of the layers of cerebral cortex. New experimental techniques for probing the laminar circuitry of cortex have recently been developed, opening up novel opportunities for investigating ho1v its six-layered architecture contributes to perception and cognition. The task of trying to interpret this complex structure can be facilitated by theoretical analyses of the types of computations that cortex is carrying out, and of how these might be implemented in specific cortical circuits. We have recently developed a detailed neural model of how the parvocellular stream of the visual cortex utilizes its feedforward, feedback, and horizontal interactions for purposes of visual filtering, attention, and perceptual grouping. This model, called LAMINART, shows how these perceptual processes relate to the mechanisms which ensure stable development of cortical circuits in the infant, and to the continued stability of learning in the adult. The present article reviews this laminar theory of visual cortex, considers how it may be generalized towards a more comprehensive theory that encompasses other cortical areas and cognitive processes, and shows how its laminar framework generates a variety of testable predictions.Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-0409); National Science Foundation (IRI 94-01659); Office of Naval Research (N00014-92-1-1309, N00014-95-1-0657

Studying Brain Organization via Spontaneous fMRI Signal

In recent years, some substantial advances in understanding human (and nonhuman) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the “resting” brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called “resting state.” This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting-state fMRI has been used to delineate aspects of area-level and supra-areal brain organization

The Role of Clustered Organization and Generation of Mixed Properties in Macaque V2

Throughout the mammalian cortex, neurons of similar response characteristics group together into topographic functional domains. The genesis and role of this organization remains in question, but it has been proposed to affect the mixed properties of neurons. These types of neurons possess multiple receptive field preferences, such as a cell responding to a color and an oriented stimulus. To examine the functionality of clustered organization and their effect in generation of neurons possessing mixed properties, this dissertation examined the secondary visual cortex (V2) of the Macaca fasicularis. This particular cortex is comprised of domains organized according to distinct visual stimulus components, specifically clusters of neurons partitioned by color and orientation preferences within a close proximity. In the first series of experiments (Chapter 3), a computer model of a cortical area based upon macaque V2 investigated the effect of clusters of like-preferring neurons on the probability of two different preference terminals synapsing on a particular cell. These results indicate that presence of at least one cluster significantly increases the probability of multiple preferences arriving at a neuron. The second series of experiments (Chapter 4) used single unit electrophysiology to investigate the temporal properties of V2 neurons in response to achromatic and colored oriented stimuli. With the addition of color to the stimulus, an increase in latency, an increase to the time point of the maximum rate of firing, and a decreased initial-phase response with a sustained later-phase response were observed. These studies indicate that functional clusters of neurons significantly increase the joint probability of the co-localization of differing preference terminals, potentially yielding neurons with mixed preferences through these intra-areal connections. Furthermore, the temporal characteristics of V2 neurons, as seen in observed latency and time of maximum spiking, support this idea of domain-enhanced intra-areal integration

Receptor architecture of the macaque monkey superior parietal lobule

The macaque monkey superior parietal lobule (SPL) is part of a neuronal network involved in the integration of information from visual and somatosensory cortices for execution of reaching and grasping movements. The cytoarchitecture of areas V6, V6Ad, V6Av, PE, PEc, PEci and PGm of the SPL has been described, but little is known about their receptor architectonic organization, although receptor analyses not only provide information concerning brain structure, but also crucial insights into its functional organization. Quantitative in vitro receptor autoradiography was applied to analyze the distribution patterns of 15 different receptors for glutamate, GABA, acetylcholine, serotonin, dopamine and adenosine in the SPL of three adult male Macaca fascicularis monkeys. For each area, mean (averaged over all cortical layers) receptor densities were visualized as a receptor fingerprint of each area. Multivariate analyses were conducted to detect clusters of areas according to the degree of (dis)similarity of their receptor organization. Differences in regional and laminar receptor distribution patterns confirm the location and extent of areas V6, V6Ad, V6Av, PE, PEc, PEci and PGm as found in cytoarchitectonical and functional studies. Receptor densities are higher in supra- than in infragranular layers of SPL areas, with the exception of kainate, M2, and adenosine receptors, which reach highest values in layers V-VI. The hierarchical cluster analysis shows a principal segregation of SPL areas from the primary sensory cortices. Areas PEc, PEci and PGm cluster with posterior cingulate area 31. Area V6Av clusters with visual V6, and V6Ad with MIP, while area PE with somatosensory area 2. These results are in accordance with the fact that V6Av contains more cells responsive to visual stimuli than does V6Ad, whereas the opposite holds true for cells responsive to somatosensory stimuli. They further emphasize the special receptor architecture of posterior parietal areas involved in reaching and grasping