Acetylcholine neuromodulation in normal and abnormal learning and memory: vigilance control in waking, sleep, autism, amnesia, and Alzheimer's disease

This article provides a unified mechanistic neural explanation of how learning, recognition, and cognition break down during Alzheimer's disease, medial temporal amnesia, and autism. It also clarifies whey there are often sleep disturbances during these disorders. A key mechanism is how acetylcholine modules vigilance control in cortical layer

Correlated Variability and Adaptation in Orbitofrontal Cortex during Economic Choice

Economic decision-making requires the computation and comparison of subjective values. Several lines of evidence suggest that these processes are mediated by circuits in orbitofrontal cortex (OFC). Neurons in OFC encode the subjective values of choice options and outcomes, and damage to this area leads to selective deficits in value-guided behavior. To understand the nature of choice more thoroughly, it is useful to consider the features of OFC circuits that can limit or enhance information processing. In this document, I present work examining two factors that influence encoding in OFC: noise correlation and value adaptation. In the first study, I show that noise correlations in OFC are small but non-negligible, and that the structure of these correlations constrains the resolution of value representation in OFC. I go on to show that correlation structure predicts a weak relationship between single-neuron variability and decision outcomes in the context of a uniform linear model of decision making. These findings are consistent with empirical data and support the hypothesis that OFC mediates value-based decision-making. In the second study, I investigate how neurons in OFC adapt to changes in the value distribution. I show that neurons adapt to both maximum and minimum available values, but that the dynamic range does not completely remap across conditions. While intermediate adaptation is sub-optimal, it indicates that OFC neurons can partially compensate for changes in the scale of decisions, allowing increased resolution of value encoding in high-magnitude conditions. In summary, decision-making may be limited by correlated noise, but the effect of this constraint is relatively small. Moreover, variability introduced by noise correlation may be partially ameliorated by adaptation to the value range

Visual attention in primates and for machines - neuronal mechanisms

Visual attention is an important cognitive concept for the daily life of humans, but still not fully understood. Due to this, it is also rarely utilized in computer vision systems. However, understanding visual attention is challenging as it has many and seemingly-different aspects, both at neuronal and behavioral level. Thus, it is very hard to give a uniform explanation of visual attention that can account for all aspects. To tackle this problem, this thesis has the goal to identify a common set of neuronal mechanisms, which underlie both neuronal and behavioral aspects. The mechanisms are simulated by neuro-computational models, thus, resulting in a single modeling approach to explain a wide range of phenomena at once. In the thesis, the chosen aspects are multiple neurophysiological effects, real-world object localization, and a visual masking paradigm (OSM). In each of the considered fields, the work also advances the current state-of-the-art to better understand this aspect of attention itself. The three chosen aspects highlight that the approach can account for crucial neurophysiological, functional, and behavioral properties, thus the mechanisms might constitute the general neuronal substrate of visual attention in the cortex. As outlook, our work provides for computer vision a deeper understanding and a concrete prototype of attention to incorporate this crucial aspect of human perception in future systems.:1. General introduction 2. The state-of-the-art in modeling visual attention 3. Microcircuit model of attention 4. Object localization with a model of visual attention 5. Object substitution masking 6. General conclusionVisuelle Aufmerksamkeit ist ein wichtiges kognitives Konzept für das tägliche Leben des Menschen. Es ist aber immer noch nicht komplett verstanden, so dass es ein langjähriges Ziel der Neurowissenschaften ist, das Phänomen grundlegend zu durchdringen. Gleichzeitig wird es aufgrund des mangelnden Verständnisses nur selten in maschinellen Sehsystemen in der Informatik eingesetzt. Das Verständnis von visueller Aufmerksamkeit ist jedoch eine komplexe Herausforderung, da Aufmerksamkeit äußerst vielfältige und scheinbar unterschiedliche Aspekte besitzt. Sie verändert multipel sowohl die neuronalen Feuerraten als auch das menschliche Verhalten. Daher ist es sehr schwierig, eine einheitliche Erklärung von visueller Aufmerksamkeit zu finden, welche für alle Aspekte gleichermaßen gilt. Um dieses Problem anzugehen, hat diese Arbeit das Ziel, einen gemeinsamen Satz neuronaler Mechanismen zu identifizieren, welche sowohl den neuronalen als auch den verhaltenstechnischen Aspekten zugrunde liegen. Die Mechanismen werden in neuro-computationalen Modellen simuliert, wodurch ein einzelnes Modellierungsframework entsteht, welches zum ersten Mal viele und verschiedenste Phänomene von visueller Aufmerksamkeit auf einmal erklären kann. Als Aspekte wurden in dieser Dissertation multiple neurophysiologische Effekte, Realwelt Objektlokalisation und ein visuelles Maskierungsparadigma (OSM) gewählt. In jedem dieser betrachteten Felder wird gleichzeitig der State-of-the-Art verbessert, um auch diesen Teilbereich von Aufmerksamkeit selbst besser zu verstehen. Die drei gewählten Gebiete zeigen, dass der Ansatz grundlegende neurophysiologische, funktionale und verhaltensbezogene Eigenschaften von visueller Aufmerksamkeit erklären kann. Da die gefundenen Mechanismen somit ausreichend sind, das Phänomen so umfassend zu erklären, könnten die Mechanismen vielleicht sogar das essentielle neuronale Substrat von visueller Aufmerksamkeit im Cortex darstellen. Für die Informatik stellt die Arbeit damit ein tiefergehendes Verständnis von visueller Aufmerksamkeit dar. Darüber hinaus liefert das Framework mit seinen neuronalen Mechanismen sogar eine Referenzimplementierung um Aufmerksamkeit in zukünftige Systeme integrieren zu können. Aufmerksamkeit könnte laut der vorliegenden Forschung sehr nützlich für diese sein, da es im Gehirn eine Aufgabenspezifische Optimierung des visuellen Systems bereitstellt. Dieser Aspekt menschlicher Wahrnehmung fehlt meist in den aktuellen, starken Computervisionssystemen, so dass eine Integration in aktuelle Systeme deren Leistung sprunghaft erhöhen und eine neue Klasse definieren dürfte.:1. General introduction 2. The state-of-the-art in modeling visual attention 3. Microcircuit model of attention 4. Object localization with a model of visual attention 5. Object substitution masking 6. General conclusio

Neural dynamics of invariant object recognition: relative disparity, binocular fusion, and predictive eye movements

How does the visual cortex learn invariant object categories as an observer scans a depthful scene? Two neural processes that contribute to this ability are modeled in this thesis. The first model clarifies how an object is represented in depth. Cortical area V1 computes absolute disparity, which is the horizontal difference in retinal location of an image in the left and right foveas. Many cells in cortical area V2 compute relative disparity, which is the difference in absolute disparity of two visible features. Relative, but not absolute, disparity is unaffected by the distance of visual stimuli from an observer, and by vergence eye movements. A laminar cortical model of V2 that includes shunting lateral inhibition of disparity-sensitive layer 4 cells causes a peak shift in cell responses that transforms absolute disparity from V1 into relative disparity in V2. The second model simulates how the brain maintains stable percepts of a 3D scene during binocular movements. The visual cortex initiates the formation of a 3D boundary and surface representation by binocularly fusing corresponding features from the left and right retinotopic images. However, after each saccadic eye movement, every scenic feature projects to a different combination of retinal positions than before the saccade. Yet the 3D representation, resulting from the prior fusion, is stable through the post-saccadic re-fusion. One key to stability is predictive remapping: the system anticipates the new retinal positions of features entailed by eye movements by using gain fields that are updated by eye movement commands. The 3D ARTSCAN model developed here simulates how perceptual, attentional, and cognitive interactions across different brain regions within the What and Where visual processing streams interact to coordinate predictive remapping, stable 3D boundary and surface perception, spatial attention, and the learning of object categories that are invariant to changes in an object's retinal projections. Such invariant learning helps the system to avoid treating each new view of the same object as a distinct object to be learned. The thesis hereby shows how a process that enables invariant object category learning can be extended to also enable stable 3D scene perception

Binocular fusion and invariant category learning due to predictive remapping during scanning of a depthful scene with eye movements

How does the brain maintain stable fusion of 3D scenes when the eyes move? Every eye movement causes each retinal position to process a different set of scenic features, and thus the brain needs to binocularly fuse new combinations of features at each position after an eye movement. Despite these breaks in retinotopic fusion due to each movement, previously fused representations of a scene in depth often appear stable. The 3D ARTSCAN neural model proposes how the brain does this by unifying concepts about how multiple cortical areas in the What and Where cortical streams interact to coordinate processes of 3D boundary and surface perception, spatial attention, invariant object category learning, predictive remapping, eye movement control, and learned coordinate transformations. The model explains data from single neuron and psychophysical studies of covert visual attention shifts prior to eye movements. The model further clarifies how perceptual, attentional, and cognitive interactions among multiple brain regions (LGN, V1, V2, V3A, V4, MT, MST, PPC, LIP, ITp, ITa, SC) may accomplish predictive remapping as part of the process whereby view-invariant object categories are learned. These results build upon earlier neural models of 3D vision and figure-ground separation and the learning of invariant object categories as the eyes freely scan a scene. A key process concerns how an object's surface representation generates a form-fitting distribution of spatial attention, or attentional shroud, in parietal cortex that helps maintain the stability of multiple perceptual and cognitive processes. Predictive eye movement signals maintain the stability of the shroud, as well as of binocularly fused perceptual boundaries and surface representations.Published versio

Sustained Activation of PV+ Interneurons in Core Auditory Cortex Enables Robust Divisive Gain Control for Complex and Naturalistic Stimuli

Sensory cortices must flexibly adapt their operations to internal states and external requirements. Sustained modulation of activity levels in different inhibitory interneuron populations may provide network-level mechanisms for adjustment of sensory cortical processing on behaviorally relevant timescales. However, understanding of the computational roles of inhibitory interneuron modulation has mostly been restricted to effects at short timescales, through the use of phasic optogenetic activation and transient stimuli. Here, we investigated how modulation of inhibitory interneurons affects cortical computation on longer timescales, by using sustained, network-wide optogenetic activation of parvalbumin-positive interneurons (the largest class of cortical inhibitory interneurons) to study modulation of auditory cortical responses to prolonged and naturalistic as well as transient stimuli. We found highly conserved spectral and temporal tuning in auditory cortical neurons, despite a profound reduction in overall network activity. This reduction was predominantly divisive, and consistent across simple, complex, and naturalistic stimuli. A recurrent network model with power-law input–output functions replicated our results. We conclude that modulation of parvalbumin-positive interneurons on timescales typical of sustained neuromodulation may provide a means for robust divisive gain control conserving stimulus representations

Visual Attention and the Role of Normalization

Visual perception can be improved by the intentional allocation of attention to specific visual components. This “top-down” attention can improve perception of specific locations in space, or of specific visual features at all locations in space. Both spatial and feature attention are thought to involve the feedback of attention signals from higher cortical areas to visual cortex, where it modulates the firing rates of specific sensory neurons. However, the mechanisms that determine how top-down attention signals modulate the firing rates of visual neurons are not fully understood. Recently, a sensory mechanism called normalization has been implicated in mediating neuronal modulations by attention. Normalization is a form of gain control that adjusts the dynamic range of neuronal responses, particularly when more than one stimulus lies within a neuron's receptive field. Models of attention propose that this sensory mechanism affects how attention signals modulate the firing rates of sensory neurons, but it remains unclear exactly how normalization is related to the different forms of top-down attention. Here we use single unit electrophysiological recordings from the middle temporal area (MT) of rhesus monkeys to measure the firing rates of sensory neurons. We ask the monkeys to perform a behavioral task that directs their attention to a particular location or feature, allowing us to independently measure modulations to firing rates due to normalization, spatial attention, or feature attention. We report that variations in the strength of normalization across neurons can be explained by an extension of conventional normalization: tuned normalization. Modulation by spatial attention depends greatly on the extent to which the normalization of a neuron is tuned, explaining a neuron-by-neuron correlation between spatial attention and normalization modulation strengths. Tuned normalization also explains a pronounced asymmetry in spatial attention modulations, in which neurons are more modulated by attention to their preferred, versus their non-preferred, stimulus. However, feature attention differs from spatial attention in its relationship to the normalization mechanism. We conclude that while spatial and feature attention appear to be mediated by a common top-down attention mechanism, they are differently influenced by the sensory mechanism of normalization

Unified developmental model of maps, complex cells and surround modulation in the primary visual cortex

For human and animal vision, the perception of local visual features can depend on the spatial arrangement of the surrounding visual stimuli. In the earliest stages of visual processing this phenomenon is called surround modulation, where the response of visually selective neurons is influenced by the response of neighboring neurons. Surround modulation has been implicated in numerous important perceptual phenomena, such as contour integration and figure-ground segregation. In cats, one of the major potential neural substrates for surround modulation are lateral connections between cortical neurons in layer 2/3, which typically contains ”complex” cells that appear to combine responses from ”simple” cells in layer 4C. Interestingly, these lateral connections have also been implicated in the development of functional maps in primary visual cortex, such as smooth, well-organized maps for the preference of oriented lines. Together, this evidence suggests a common underlying substrate the lateral interactions in layer 2/3—as the driving force behind development of orientation maps for both simple and complex cells, and at the same time expression of surround modulation in adult animals. However, previously these phenomena have been studied largely in isolation, and we are not aware of a computational model that can account for all of them simultaneously and show how they are related. In this thesis we resolve this problem by building a single, unified computational model that can explain the development of orientation maps, the development of simple and complex cells, and surround modulation. First we build a simple, single-layer model of orientation map development based on ALISSOM, which has more realistic single cell properties (such as contrast gain control and contrast invariant orientation tuning) than its predecessor. Then we extend this model by adding layer 2/3, and show how the model can explain development of orientation maps of both simple and complex cells. As the last step towards a developmental model of surround modulation, we replace Mexican-hat-like lateral connectivity in layer 2/3 of the model with a more realistic configuration based on long-range excitation and short-range inhibitory cells, extending a simpler model by Judith Law. The resulting unified model of V1 explains how orientation maps of simple and complex cells can develop, while individual neurons in the developed model express realistic orientation tuning and various surround modulation properties. In doing so, we not only offer a consistent explanation behind all these phenomena, but also create a very rich model of V1 in which the interactions between various V1 properties can be studied. The model allows us to formulate several novel predictions that relate the variation of single cell properties to their location in the orientation preference maps in V1, and we show how these predictions can be tested experimentally. Overall, this model represents a synthesis of a wide body of experimental evidence, forming a compact hypothesis for much of the development and behavior of neurons in the visual cortex

A Neural Model of Surface Perception: Lightness, Anchoring, and Filling-in

This article develops a neural model of how the visual system processes natural images under variable illumination conditions to generate surface lightness percepts. Previous models have clarified how the brain can compute the relative contrast of images from variably illuminate scenes. How the brain determines an absolute lightness scale that "anchors" percepts of surface lightness to us the full dynamic range of neurons remains an unsolved problem. Lightness anchoring properties include articulation, insulation, configuration, and are effects. The model quantatively simulates these and other lightness data such as discounting the illuminant, the double brilliant illusion, lightness constancy and contrast, Mondrian contrast constancy, and the Craik-O'Brien-Cornsweet illusion. The model also clarifies the functional significance for lightness perception of anatomical and neurophysiological data, including gain control at retinal photoreceptors, and spatioal contrast adaptation at the negative feedback circuit between the inner segment of photoreceptors and interacting horizontal cells. The model retina can hereby adjust its sensitivity to input intensities ranging from dim moonlight to dazzling sunlight. A later model cortical processing stages, boundary representations gate the filling-in of surface lightness via long-range horizontal connections. Variants of this filling-in mechanism run 100-1000 times faster than diffusion mechanisms of previous biological filling-in models, and shows how filling-in can occur at realistic speeds. A new anchoring mechanism called the Blurred-Highest-Luminance-As-White (BHLAW) rule helps simulate how surface lightness becomes sensitive to the spatial scale of objects in a scene. The model is also able to process natural images under variable lighting conditions.Air Force Office of Scientific Research (F49620-01-1-0397); Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409); Office of Naval Research (N00014-01-1-0624