Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes

BACKGROUND:Recent advances in genome sequencing suggest a remarkable conservation in gene content of mammalian organisms. The similarity in gene repertoire present in different organisms has increased interest in studying regulatory mechanisms of gene expression aimed at elucidating the differences in phenotypes. In particular, a proximal promoter region contains a large number of regulatory elements that control the expression of its downstream gene. Although many studies have focused on identification of these elements, a broader picture on the complexity of transcriptional regulation of different biological processes has not been addressed in mammals. The regulatory complexity may strongly correlate with gene function, as different evolutionary forces must act on the regulatory systems under different biological conditions. We investigate this hypothesis by comparing the conservation of promoters upstream of genes classified in different functional categories.RESULTS:By conducting a rank correlation analysis between functional annotation and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we found a significantly greater conservation of the upstream sequence of genes involved in development, cell communication, neural functions and signaling processes than those involved in more basic processes shared with unicellular organisms such as metabolism and ribosomal function. This observation persists after controlling for G+C content. Considering conservation as a functional signature, we hypothesize a higher density of cis-regulatory elements upstream of genes participating in complex and adaptive processes.CONCLUSION:We identified a class of functions that are associated with either high or low promoter conservation in mammals. We detected a significant tendency that points to complex and adaptive processes were associated with higher promoter conservation, despite the fact that they have emerged relatively recently during evolution. We described and contrasted several hypotheses that provide a deeper insight into how transcriptional complexity might have been emerged during evolution.

Communicable Memory and Lazy Barriers for Bulk Synchronous Parallelism in BSPk

Communication and synchronization stand as the dual bottlenecks in the performance of parallel systems, and especially those that attempt to alleviate the programming burden by incurring overhead in these two domains. We formulate the notions of communicable memory and lazy barriers to help achieve efficient communication and synchronization. These concepts are developed in the context of BSPk, a toolkit library for programming networks of workstations|and other distributed memory architectures in general|based on the Bulk Synchronous Parallel (BSP) model. BSPk emphasizes efficiency in communication by minimizing local memory-to-memory copying, and in barrier synchronization by not forcing a process to wait unless it needs remote data. Both the message passing (MP) and distributed shared memory (DSM) programming styles are supported in BSPk. MP helps processes efficiently exchange short-lived unnamed data values, when the identity of either the sender or receiver is known to the other party. By contrast, DSM supports communication between processes that may be mutually anonymous, so long as they can agree on variable names in which to store shared temporary or long-lived data.

How Does the Cerebral Cortex Work? Developement, Learning, Attention, and 3D Vision by Laminar Circuits of Visual Cortex

A key goal of behavioral and cognitive neuroscience is to link brain mechanisms to behavioral functions. The present article describes recent progress towards explaining how the visual cortex sees. Visual cortex, like many parts of perceptual and cognitive neocortex, is organized into six main layers of cells, as well as characteristic sub-lamina. Here it is proposed how these layered circuits help to realize the processes of developement, learning, perceptual grouping, attention, and 3D vision through a combination of bottom-up, horizontal, and top-down interactions. A key theme is that the mechanisms which enable developement and learning to occur in a stable way imply properties of adult behavior. These results thus begin to unify three fields: infant cortical developement, adult cortical neurophysiology and anatomy, and adult visual perception. The identified cortical mechanisms promise to generalize to explain how other perceptual and cognitive processes work.

Linking Attention to Learning, Expectation, Competition, and Consciousness

The concept of attention has been used in many senses, often without clarifying how or why attention works as it does. Attention, like consciousness, is often described in a disembodied way. The present article summarizes neural models and supportive data and how attention is linked to processes of learning, expectation, competition, and consciousness. A key them is that attention modulates cortical self-organization and stability. Perceptual and cognitive neocortex is organized into six main cell layers, with characteristic sub-lamina. Attention is part of unified design of bottom-up, horizontal, and top-down interactions among indentified cells in laminar cortical circuits. Neural models clarify how attention may be allocated during processes of visual perception, learning and search; auditory streaming and speech perception; movement target selection during sensory-motor control; mental imagery and fantasy; and hallucination during mental disorders, among other processes.

Neural Dynamics of Autistic Behaviors: Cognitive, Emotional, and Timing Substrates

What brain mechanisms underlie autism and how do they give rise to autistic behavioral symptoms? This article describes a neural model, called the iSTART model, which proposes how cognitive, emotional, timing, and motor processes may interact together to create and perpetuate autistic symptoms. These model processes were originally developed to explain data concerning how the brain controls normal behaviors. The iSTART model shows how autistic behavioral symptoms may arise from prescribed breakdowns in these brain processes.

From Working Memory to Long-term Memory and Back: Linked but Distinct

Neural models have proposed how short-term memory (STM) storage in working memory and long-term memory (LTM) storage and recall are linked and interact, but are realized by different mechanisms that obey different laws. The authors' data can be understood in the light of these models, which suggest that the authors may have gone too far in obscuring the differences between these processes.

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.

Learning and Production of Movement Sequences: Behavioral, Neurophysiological, and Modeling Perspectives

A growing wave of behavioral studies, using a wide variety of paradigms that were introduced or greatly refined in recent years, has generated a new wealth of parametric observations about serial order behavior. What was a mere trickle of neurophysiological studies has grown to a more steady stream of probes of neural sites and mechanisms underlying sequential behavior. Moreover, simulation models of serial behavior generation have begun to open a channel to link cellular dynamics with cognitive and behavioral dynamics. Here we summarize the major results from prominent sequence learning and performance tasks, namely immediate serial recall, typing, 2XN, discrete sequence production, and serial reaction time. These populate a continuum from higher to lower degrees of internal control of sequential organization. The main movement classes covered are speech and keypressing, both involving small amplitude movements that are very amenable to parametric study. A brief synopsis of classes of serial order models, vis-à-vis the detailing of major effects found in the behavioral data, leads to a focus on competitive queuing (CQ) models. Recently, the many behavioral predictive successes of CQ models have been joined by successful prediction of distinctively patterend electrophysiological recordings in prefrontal cortex, wherein parallel activation dynamics of multiple neural ensembles strikingly matches the parallel dynamics predicted by CQ theory. An extended CQ simulation model-the N-STREAMS neural network model-is then examined to highlight issues in ongoing attemptes to accomodate a broader range of behavioral and neurophysiological data within a CQ-consistent theory. Important contemporary issues such as the nature of working memory representations for sequential behavior, and the development and role of chunks in hierarchial control are prominent throughout.

SOVEREIGN: A Self-Organizing, Vision, Expectation, Recognition, Emotion, Intelligent, Goal-Oriented Navigation System

Both animals and mobile robots, or animats, need adaptive control systems to guide their movements through a novel environment. Such control systems need reactive mechanisms for exploration, and learned plans to efficiently reach goal objects once the environment is familiar. How reactive and planned behaviors interact together in real time, and arc released at the appropriate times, during autonomous navigation remains a major unsolved problern. This work presents an end-to-end model to address this problem, named SOVEREIGN: A Self-Organizing, Vision, Expectation, Recognition, Emotion, Intelligent, Goal-oriented Navigation system. The model comprises several interacting subsystems, governed by systems of nonlinear differential equations. As the animat explores the environment, a vision module processes visual inputs using networks that arc sensitive to visual form and motion. Targets processed within the visual form system arc categorized by real-time incremental learning. Simultaneously, visual target position is computed with respect to the animat's body. Estimates of target position activate a motor system to initiate approach movements toward the target. Motion cues from animat locomotion can elicit orienting head or camera movements to bring a never target into view. Approach and orienting movements arc alternately performed during animat navigation. Cumulative estimates of each movement, based on both visual and proprioceptive cues, arc stored within a motor working memory. Sensory cues are stored in a parallel sensory working memory. These working memories trigger learning of sensory and motor sequence chunks, which together control planned movements. Effective chunk combinations arc selectively enhanced via reinforcement learning when the animat is rewarded. The planning chunks effect a gradual transition from reactive to planned behavior. The model can read-out different motor sequences under different motivational states and learns more efficient paths to rewarded goals as exploration proceeds. Several volitional signals automatically gate the interactions between model subsystems at appropriate times. A 3-D visual simulation environment reproduces the animat's sensory experiences as it moves through a simplified spatial environment. The SOVEREIGN model exhibits robust goal-oriented learning of sequential motor behaviors. Its biomimctic structure explicates a number of brain processes which are involved in spatial navigation.

Laminar Cortical Dynamics of Visual Form and Motion Interactions During Coherent Object Motion Perception

How do visual form and motion processes cooperate to compute object motion when each process separately is insufficient? A 3D FORMOTION model specifies how 3D boundary representations, which separate figures from backgrounds within cortical area V2, capture motion signals at the appropriate depths in MT; how motion signals in MT disambiguate boundaries in V2 via MT-to-Vl-to-V2 feedback; how sparse feature tracking signals are amplified; and how a spatially anisotropic motion grouping process propagates across perceptual space via MT-MST feedback to integrate feature-tracking and ambiguous motion signals to determine a global object motion percept. Simulated data include: the degree of motion coherence of rotating shapes observed through apertures, the coherent vs. element motion percepts separated in depth during the chopsticks illusion, and the rigid vs. non-rigid appearance of rotating ellipses.

Consciousness CLEARS the Mind

A full understanding of consciouness requires that we identify the brain processes from which conscious experiences emerge. What are these processes, and what is their utility in supporting successful adaptive behaviors? Adaptive Resonance Theory (ART) predicted a functional link between processes of Consciousness, Learning, Expectation, Attention, Resonance, and Synchrony (CLEARS), includes the prediction that "all conscious states are resonant states." This connection clarifies how brain dynamics enable a behaving individual to autonomously adapt in real time to a rapidly changing world. The present article reviews theoretical considerations that predicted these functional links, how they work, and some of the rapidly growing body of behavioral and brain data that have provided support for these predictions. The article also summarizes ART models that predict functional roles for identified cells in laminar thalamocortical circuits, including the six layered neocortical circuits and their interactions with specific primary and higher-order specific thalamic nuclei and nonspecific nuclei. These prediction include explanations of how slow perceptual learning can occur more frequently in superficial cortical layers. ART traces these properties to the existence of intracortical feedback loops, and to reset mechanisms whereby thalamocortical mismatches use circuits such as the one from specific thalamic nuclei to nonspecific thalamic nuclei and then to layer 4 of neocortical areas via layers 1-to-5-to-6-to-4.

Neural Models of Motion Integration, Segmentation, and Probablistic Decision-Making

When brain mechanism carry out motion integration and segmentation processes that compute unambiguous global motion percepts from ambiguous local motion signals? Consider, for example, a deer running at variable speeds behind forest cover. The forest cover is an occluder that creates apertures through which fragments of the deer's motion signals are intermittently experienced. The brain coherently groups these fragments into a trackable percept of the deer in its trajectory. Form and motion processes are needed to accomplish this using feedforward and feedback interactions both within and across cortical processing streams. All the cortical areas V1, V2, MT, and MST are involved in these interactions. Figure-ground processes in the form stream through V2, such as the seperation of occluding boundaries of the forest cover from the boundaries of the deer, select the motion signals which determine global object motion percepts in the motion stream through MT. Sparse, but unambiguous, feauture tracking signals are amplified before they propogate across position and are intergrated with far more numerous ambiguous motion signals. Figure-ground and integration processes together determine the global percept. A neural model predicts the processing stages that embody these form and motion interactions. Model concepts and data are summarized about motion grouping across apertures in response to a wide variety of displays, and probabilistic decision making in parietal cortex in response to random dot displays.

ARTSCENE: A Neural System for Natural Scene Classification

How do humans rapidly recognize a scene? How can neural models capture this biological competence to achieve state-of-the-art scene classification? The ARTSCENE neural system classifies natural scene photographs by using multiple spatial scales to efficiently accumulate evidence for gist and texture. ARTSCENE embodies a coarse-to-fine Texture Size Ranking Principle whereby spatial attention processes multiple scales of scenic information, ranging from global gist to local properties of textures. The model can incrementally learn and predict scene identity by gist information alone and can improve performance through selective attention to scenic textures of progressively smaller size. ARTSCENE discriminates 4 landscape scene categories (coast, forest, mountain and countryside) with up to 91.58% correct on a test set, outperforms alternative models in the literature which use biologically implausible computations, and outperforms component systems that use either gist or texture information alone. Model simulations also show that adjacent textures form higher-order features that are also informative for scene recognition.

Spikes, Synchrony, and Attentive Learning by Laminar Thalamocortical Circuits

This article develops the Synchronous Matching Adaptive Resonance Theory (SMART) neural model to explain how the brain may coordinate multiple levels of thalamocortical and corticocortical processing to rapidly learn, and stably remember, important information about a changing world. The model clarifies how bottom-up and top-down processes work together to realize this goal, notably how processes of learning, expectation, attention, resonance, and synchrony are coordinated. The model hereby clarifies, for the first time, how the following levels of brain organization coexist to realize cognitive processing properties that regulate fast learning and stable memory of brain representations: single cell properties, such as spiking dynamics, spike-timing-dependent plasticity (STDP), and acetylcholine modulation; detailed laminar thalamic and cortical circuit designs and their interactions; aggregate cell recordings, such as current-source densities and local field potentials; and single cell and large-scale inter-areal oscillations in the gamma and beta frequency domains. In particular, the model predicts how laminar circuits of multiple cortical areas interact with primary and higher-order specific thalamic nuclei and nonspecific thalamic nuclei to carry out attentive visual learning and information processing. The model simulates how synchronization of neuronal spiking occurs within and across brain regions, and triggers STDP. Matches between bottom-up adaptively filtered input patterns and learned top-down expectations cause gamma oscillations that support attention, resonance, and learning. Mismatches inhibit learning while causing beta oscillations during reset and hypothesis testing operations that are initiated in the deeper cortical layers. The generality of learned recognition codes is controlled by a vigilance process mediated by acetylcholine.

Task-Irrelevant Perceptual Learning Specific to the Contrast Polarity of Motion Stimuli

Studies of perceptual learning have focused on aspects of learning that are related to early stages of sensory processing. However, conclusions that perceptual learning results in low-level sensory plasticity are of great controversy, largely because such learning can often be attributed to plasticity in later stages of sensory processing or in the decision processes. To address this controversy, we developed a novel random dot motion (RDM) stimulus to target motion cells selective to contrast polarity, by ensuring the motion direction information arises only from signal dot onsets and not their offsets, and used these stimuli in conjunction with the paradigm of task-irrelevant perceptual learning (TIPL). In TIPL, learning is achieved in response to a stimulus by subliminally pairing that stimulus with the targets of an unrelated training task. In this manner, we are able to probe learning for an aspect of motion processing thought to be a function of directional V1 simple cells with a learning procedure that dissociates the learned stimulus from the decision processes relevant to the training task. Our results show learning for the exposed contrast polarity and that this learning does not transfer to the unexposed contrast polarity. These results suggest that TIPL for motion stimuli may occur at the stage of directional V1 simple cells.