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

Why Neurons Have Thousands of Synapses, A Theory of Sequence Memory in Neocortex

Neocortical neurons have thousands of excitatory synapses. It is a mystery how neurons integrate the input from so many synapses and what kind of large-scale network behavior this enables. It has been previously proposed that non-linear properties of dendrites enable neurons to recognize multiple patterns. In this paper we extend this idea by showing that a neuron with several thousand synapses arranged along active dendrites can learn to accurately and robustly recognize hundreds of unique patterns of cellular activity, even in the presence of large amounts of noise and pattern variation. We then propose a neuron model where some of the patterns recognized by a neuron lead to action potentials and define the classic receptive field of the neuron, whereas the majority of the patterns recognized by a neuron act as predictions by slightly depolarizing the neuron without immediately generating an action potential. We then present a network model based on neurons with these properties and show that the network learns a robust model of time-based sequences. Given the similarity of excitatory neurons throughout the neocortex and the importance of sequence memory in inference and behavior, we propose that this form of sequence memory is a universal property of neocortical tissue. We further propose that cellular layers in the neocortex implement variations of the same sequence memory algorithm to achieve different aspects of inference and behavior. The neuron and network models we introduce are robust over a wide range of parameters as long as the network uses a sparse distributed code of cellular activations. The sequence capacity of the network scales linearly with the number of synapses on each neuron. Thus neurons need thousands of synapses to learn the many temporal patterns in sensory stimuli and motor sequences.Comment: Submitted for publicatio

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.National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624

Prediction and memory: A predictive coding account

The hippocampus is crucial for episodic memory, but it is also involved in online prediction. Evidence suggests that a unitary hippocampal code underlies both episodic memory and predictive processing, yet within a predictive coding framework the hippocampal-neocortical interactions that accompany these two phenomena are distinct and opposing. Namely, during episodic recall, the hippocampus is thought to exert an excitatory influence on the neocortex, to reinstate activity patterns across cortical circuits. This contrasts with empirical and theoretical work on predictive processing, where descending predictions suppress prediction errors to ‘explain away’ ascending inputs via cortical inhibition. In this hypothesis piece, we attempt to dissolve this previously overlooked dialectic. We consider how the hippocampus may facilitate both prediction and memory, respectively, by inhibiting neocortical prediction errors or increasing their gain. We propose that these distinct processing modes depend upon the neuromodulatory gain (or precision) ascribed to prediction error units. Within this framework, memory recall is cast as arising from fictive prediction errors that furnish training signals to optimise generative models of the world, in the absence of sensory data

A half century of progress towards a unified neural theory of mind and brain with applications to autonomous adaptive agents and mental disorders

Invited article for the book Artificial Intelligence in the Age of Neural Networks and Brain Computing R. Kozma, C. Alippi, Y. Choe, and F. C. Morabito, Eds. Cambridge, MA: Academic PressThis article surveys some of the main design principles, mechanisms, circuits, and architectures that have been discovered during a half century of systematic research aimed at developing a unified theory that links mind and brain, and shows how psychological functions arise as emergent properties of brain mechanisms. The article describes a theoretical method that has enabled such a theory to be developed in stages by carrying out a kind of conceptual evolution. It also describes revolutionary computational paradigms like Complementary Computing and Laminar Computing that constrain the kind of unified theory that can describe the autonomous adaptive intelligence that emerges from advanced brains. Adaptive Resonance Theory, or ART, is one of the core models that has been discovered in this way. ART proposes how advanced brains learn to attend, recognize, and predict objects and events in a changing world that is filled with unexpected events. ART is not, however, a “theory of everything” if only because, due to Complementary Computing, different matching and learning laws tend to support perception and cognition on the one hand, and spatial representation and action on the other. The article mentions why a theory of this kind may be useful in the design of autonomous adaptive agents in engineering and technology. It also notes how the theory has led to new mechanistic insights about mental disorders such as autism, medial temporal amnesia, Alzheimer’s disease, and schizophrenia, along with mechanistically informed proposals about how their symptoms may be ameliorated

Unsupervised Learning of Visual Structure using Predictive Generative Networks

The ability to predict future states of the environment is a central pillar of intelligence. At its core, effective prediction requires an internal model of the world and an understanding of the rules by which the world changes. Here, we explore the internal models developed by deep neural networks trained using a loss based on predicting future frames in synthetic video sequences, using a CNN-LSTM-deCNN framework. We first show that this architecture can achieve excellent performance in visual sequence prediction tasks, including state-of-the-art performance in a standard 'bouncing balls' dataset (Sutskever et al., 2009). Using a weighted mean-squared error and adversarial loss (Goodfellow et al., 2014), the same architecture successfully extrapolates out-of-the-plane rotations of computer-generated faces. Furthermore, despite being trained end-to-end to predict only pixel-level information, our Predictive Generative Networks learn a representation of the latent structure of the underlying three-dimensional objects themselves. Importantly, we find that this representation is naturally tolerant to object transformations, and generalizes well to new tasks, such as classification of static images. Similar models trained solely with a reconstruction loss fail to generalize as effectively. We argue that prediction can serve as a powerful unsupervised loss for learning rich internal representations of high-level object features.Comment: under review as conference paper at ICLR 201

Higher brain functions served by the lowly rodent primary visual cortex

It has been more than 50 years since the first description of ocular dominance plasticity-the profound modification of primary visual cortex (V1) following temporary monocular deprivation. This discovery immediately attracted the intense interest of neurobiologists focused on the general question of how experience and deprivation modify the brain as a potential substrate for learning and memory. The pace of discovery has quickened considerably in recent years as mice have become the preferred species to study visual cortical plasticity, and new studies have overturned the dogma that primary sensory cortex is immutable after a developmental critical period. Recent work has shown that, in addition to ocular dominance plasticity, adult visual cortex exhibits several forms of response modification previously considered the exclusive province of higher cortical areas. These "higher brain functions" include neural reports of stimulus familiarity, reward-timing prediction, and spatiotemporal sequence learning. Primary visual cortex can no longer be viewed as a simple visual feature detector with static properties determined during early development. Rodent V1 is a rich and dynamic cortical area in which functions normally associated only with "higher" brain regions can be studied at the mechanistic level.National Eye Institute (Grant RO1 EY023037)National Institute of Mental Health (U.S.) (Grant K99 MH09965