Can the banal and transient forgetfulness that we all experience at some point in our lives give us clues about the neural mechanisms underlying the onset of severe dementia, such as Alzheimer´s disease (AD)? The hypothesis we propose suggests an affirmative answer. If access to the memory system (MS) depends on matching key input patterns to appropriate contexts, we postulate that if the matching does not occur, the MS is blocked by a neural gate. From empirical observations, we shift to neural models of memories and their modulation by contexts. Our approach provides a possible explanation for transient memory failures but also suggests that the memory gate (MG) can be a crucial neural module that triggers a cascade of events leading to conditions where AD becomes irreversible and catastrophic. This hypothesis suggests ways to slow down the progression of this disease and may be explored with currently available techniques.

Temporary difficulties in accessing the contents of memories are a common experience in everyday life, for example, when we try to recognize a known person in an unusual context. In addition, recent experiments seem to indicate that retrograde amnesia in the early stages of Alzheimer's disease is due to disorders in accessing memories that were installed normally. These facts suggest the existence of an intermediate step between the stimulus arrival and the associative recognition. In this work, a multimodular neurocomputational model is presented postulating the existence of a neural gate that controls the access of the stimulus with its context to the consolidated memory. If recognition is not achieved, a random search is initiated in a contextual network aroused by the initial context. The search continues until the appropriate context that allows for recognition is found or until the process is turned off because the initial stimulus is no longer maintained in the working memory. The model is based on vector patterns of neural activity and context-dependent matrix memories. Simple Markov chain simulations are presented to exemplify possible search scenarios in the contextual network. Finally, we discuss some of the characteristics of the model and the phenomenon under study.

The skeletal muscle contraction is determined by cross-bridge formation between the myosin heads and the actin active sites. When the muscle contracts, it shortens, increasing its longitudinal shear elastic modulus ([Formula: see text]). Structurally, skeletal muscle can be considered analogous to the molecular receptors that form receptor-ligand complexes and exhibit specific ligand-binding dynamics. In this context, this work aims to apply elastography and the ligand-binding framework to approach the possible intrinsic mechanisms behind muscle synergism. Based on the short-range stiffness principle and the acoustic-elasticity theory, we define the coefficient [Formula: see text], which is directly related to the fraction saturation of molecular receptors and links the relative longitudinal deformation of the muscle to its [Formula: see text]. We show that such a coefficient can be obtained directly from [Formula: see text] estimates, thus calculating it for the biceps brachii, brachioradialis, and brachialis muscles during isometric elbow flexion torque (τ) ramps. The resulting [Formula: see text] curves were analyzed by conventional characterization methods of receptor-ligand systems to study the dynamical behavior of each muscle. The results showed that, depending on muscle, [Formula: see text] exhibits typical ligand-binding dynamics during joint torque production. Therefore, the above indicates that these different behaviors describe the longitudinal shortening pattern of each muscle during load sharing. As a plausible interpretation, we suggested that this could be related to the binding kinetics of the cross-bridges during their synergistic action as torque increases. Likewise, it shows that elastography could be useful to assess contractile processes at different scales related to the change in the mechanical properties of skeletal muscle.

Mechanisms that ensure the stability of dynamical systems are of vital importance, in particular in our globalized and increasingly interconnected world. The so-called connectivity-stability dilemma denotes the theoretical finding that increased connectivity between the components of a large dynamical system drastically reduces its stability. This result has promoted controversies within ecology and other fields of biology, especially, because organisms as well as ecosystems constitute systems that are both highly connected and stable. Hence, it has been a major challenge to find ways to stabilize complex systems while preserving high connectivity at the same time. Investigating the stability of networks that exhibit small-world or scale-free topology is of particular interest, since these topologies have been found in many different types of real-world networks. Here, we use an approach to stabilize recurrent networks of small-world and scale-free topology by increasing the average self-coupling strength of the units of a network. For both topologies, we find that there is a sharp transition from instability to asymptotic stability. Then, most importantly, we find that the average self-coupling strength needed to stabilize a system increases much slower than its size. It appears that the qualitative shape of this relationship is the same for small-world and scale-free networks, while scale-free networks can require higher magnitudes of self-coupling. We further explore the stabilization of networks with Kronecker-Leskovec topology. Finally, we argue that our findings, in particular the stabilization of large recurrent networks through small increases in the unit self-regulation, are of practical importance for the stabilization of diverse types of complex systems.

Laboratory data from conflict tasks, e.g. Simon and Eriksen tasks, reveal differences in response time distributions under different experimental conditions. Only recently have evidence accumulation models successfully reproduced these results, in particular the challenging delta plots with negative slopes. They accomplish this with explicit temporal dependencies in their structure or activation functions. In this work, we introduce an alternative approach to the modeling of decision-making in conflict tasks exclusively based on inhibitory dynamics within a dual-route architecture. We consider simultaneous automatic and controlled drift diffusion processes, with the latter inhibiting the former. Our proposed Dual-Route Evidence Accumulation Model (DREAM) achieves equivalent performance to previous works in fitting experimental response time distributions despite having no time-dependent functions. The model can reproduce conditional accuracy functions and delta plots with positive and negative slopes. The implications of these results, including an interpretation of the parameters and potential links to perceptual representations, are discussed. We provide Python code to fit DREAM to experimental data.

Explaining the foundation of cognitive abilities in the processing of information by neural systems has been in the beginnings of biophysics since McCulloch and Pitts pioneered work within the biophysics school of Chicago in the 1940s and the interdisciplinary cybernetists meetings in the 1950s, inseparable from the birth of computing and artificial intelligence. Since then, neural network models have traveled a long path, both in the biophysical and the computational disciplines. The biological, neurocomputational aspect reached its representational maturity with the Distributed Associative Memory models developed in the early 70 s. In this framework, the inclusion of signal-signal multiplication within neural network models was presented as a necessity to provide matrix associative memories with adaptive, context-sensitive associations, while greatly enhancing their computational capabilities. In this review, we show that several of the most successful neural network models use a form of multiplication of signals. We present several classical models that included such kind of multiplication and the computational reasons for the inclusion. We then turn to the different proposals about the possible biophysical implementation that underlies these computational capacities. We pinpoint the important ideas put forth by different theoretical models using a tensor product representation and show that these models endow memories with the context-dependent adaptive capabilities necessary to allow for evolutionary adaptation to changing and unpredictable environments. Finally, we show how the powerful abilities of contemporary computationally deep-learning models, inspired in neural networks, also depend on multiplications, and discuss some perspectives in view of the wide panorama unfolded. The computational relevance of multiplications calls for the development of new avenues of research that uncover the mechanisms our nervous system uses to achieve multiplication.

Context-dependent computation is a relevant characteristic of neural systems, endowing them with the capacity of adaptively modifying behavioral responses and flexibly discriminating between relevant and irrelevant information in a stimulus. This ability is particularly highlighted in solving conflicting tasks. A long-standing problem in computational neuroscience, flexible routing of information, is also closely linked with the ability to perform context-dependent associations. Here we present an extension of a context-dependent associative memory model to achieve context-dependent decision-making in the presence of conflicting and noisy multi-attribute stimuli. In these models, the input vectors are multiplied by context vectors via the Kronecker tensor product. To outfit the model with a noisy dynamic, we embedded the context-dependent associative memory in a leaky competing accumulator model, and, finally, we proved the power of the model in the reproduction of a behavioral experiment with monkeys in a context-dependent conflicting decision-making task. At the end, we discuss the neural feasibility of the tensor product and made the suggestive observation that the capacities of tensor context models are surprisingly in alignment with the more recent experimental findings about functional flexibility at different levels of brain organization.

Tensor contexts enlarge the performances and computational powers of many neural models of language by generating a double filtering of incoming data. Applied to the linguistic domain, its implementation enables a very efficient disambiguation of polysemous and homonymous words. For the neuro-computational modeling of language, the simultaneous tensor contextualization of inputs and outputs inserts into the models strategic passwords that rout words towards key natural targets, thus allowing for the creation of meaningful phrases. In this work, we present the formal properties of these models and describe possible ways to use contexts to represent plausible neural organizations of sequences of words. We include an illustration of how these contexts generate topographic or thematic organization of data. Finally, we show that double contextualization opens promising ways to explore the neural coding of episodes, one of the most challenging problems of neural computation.

Human brains seem to represent categories of objects and actions as locations in a continuous semantic space across the cortical surface that reflects the similarity among categories. This vision of the semantic organization of information in the brain, suggested by recent experimental findings, is in harmony with the well-known topographically organized somatotopic, retinotopic, and tonotopic maps in the cerebral cortex. Here we show that these topographies can be operationally represented with context-dependent associative memories. In these models, the input vectors and, eventually also, the associated output vectors are multiplied by context vectors via the Kronecker tensor product, which allows a spatial organization of memories. Input and output tensor contexts localize matrices of semantic categories into a neural layer or slice and, at the same time, direct the flow of information arriving at the layer to a specific address, and then forward the output information toward the corresponding targets. Given a neural topographic pattern, the tensor representation will place a set of associative matrix memories within a topographic regionalized host matrix in such way that they reproduce the empirical pattern of patches in the actual neural layer. Progressive approximations to this goal are accomplished by avoiding excessive overlap of memories or the existence of empty regions within the host matrix.

BACKGROUND:One of the central challenges of third millennium medicine is the abatement of medical errors. Among the most frequent and hardiest causes of misdiagnosis are cognitive errors produced by faulty medical reasoning. These errors have been analyzed from the perspectives of cognitive psychology and empirical medical studies. We introduce a neurocognitive model of medical diagnosis to address this issue.METHODS:We construct a connectionist model based on the associative nature of human memory to explore the non-analytical, pattern-recognition mode of diagnosis. A context-dependent matrix memory associates signs and symptoms with their corresponding diseases. The weights of these associations depend on the frequencies of occurrence of each disease and on the different combinations of signs and symptoms of each presentation of that disease. The system receives signs and symptoms and by a second input, the degree of diagnostic uncertainty. Its output is a probabilistic map on the set of possible diseases.RESULTS:The model reproduces different kinds of well-known cognitive errors in diagnosis. Errors in the model come from two sources. One, dependent on the knowledge stored in memory, varies with the accumulated experience of the physician and explains age-dependent errors and effects such as epidemiological masking. The other is independent of experience and explains contextual effects such as anchoring.CONCLUSIONS:Our results strongly suggest that cognitive biases are inevitable consequences of associative storage and recall. We found that this model provides valuable insight into the mechanisms of cognitive error and we hope it will prove useful in medical education.

A central problem concerning the organization of the cognitive semantic web is to understand how different categories of words are stored in the brain with a well-defined topographical organization. This topography is a natural construction that plausibly is strongly related with the syntactic and semantic organization of natural languages. An eloquent experimental evidence of the existence of a continuous semantic representation of object and action categories in the human brain has been published by Huth et al (Neuron 76:1210, 2012). One of the ways to explain the emergence of a topographical organization in the brain cortex using neurocomputational models, is by means of Kohonen’s self-organizing maps. Here we show that these topographies can be operationally represented with associative memories spatially organized by tensor contexts. We illustrate formally and numerically this fact. In addition, we show that, consistently with evidence from pathology, different semantic categories can be specifically damaged.

Every cognitive activity has a neural representation in the brain. When humans deal with abstract mathematical structures, for instance finite groups, certain patterns of activity are occurring in the brain that constitute their neural representation. A formal neurocognitive theory must account for all the activities developed by our brain and provide a possible neural representation for them. Associative memories are neural network models that have a good chance of achieving a universal representation of cognitive phenomena. In this work, we present a possible neural representation of mathematical group structures based on associative memory models that store finite groups through their Cayley graphs. A context-dependent associative memory stores the transitions between elements of the group when multiplied by each generator of a given presentation of the group. Under a convenient election of the vector basis mapping the elements of the group in the neural activity, the input of a vector corresponding to a generator of the group collapses the context-dependent rectangular matrix into a virtual square permutation matrix that is the matrix representation of the generator. This neural representation corresponds to the regular representation of the group, in which to each element is assigned a permutation matrix. This action of the generator on the memory matrix can also be seen as the dissection of the corresponding monochromatic subgraph of the Cayley graph of the group, and the adjacency matrix of this subgraph is the permutation matrix corresponding to the generator.

Numerous cortical disorders affect language. We explore the connection between the observed language behavior and the underlying substrates by adopting a neurocomputational approach. To represent the observed trajectories of the discourse in patients with disorganized speech and in healthy participants, we design a graphical representation for the discourse as a trajectory that allows us to visualize and measure the degree of order in the discourse as a function of the disorder of the trajectories. Our work assumes that many of the properties of language production and comprehension can be understood in terms of the dynamics of modular networks of neural associative memories. Based upon this assumption, we connect three theoretical and empirical domains: (1) neural models of language processing and production, (2) statistical methods used in the construction of functional brain images, and (3) corpus linguistic tools, such as Latent Semantic Analysis (henceforth LSA), that are used to discover the topic organization of language. We show how the neurocomputational models intertwine with LSA and the mathematical basis of functional neuroimaging. Within this framework we describe the properties of a context-dependent neural model, based on matrix associative memories, that performs goal-oriented linguistic behavior. We link these matrix associative memory models with the mathematics that underlie functional neuroimaging techniques and present the “functional brain images” emerging from the model. This provides us with a completely “transparent box” with which to analyze the implication of some statistical images. Finally, we use these models to explore the possibility that functional synaptic disconnection can lead to an increase in connectivity between the representations of concepts that could explain some of the alterations in discourse displayed by patients with schizophrenia.

Cognitive functions rely on the extensive use of information stored in the brain, and the searching for the relevant information for solving some problem is a very complex task. Human cognition largely uses biological search engines, and we assume that to study cognitive function we need to understand the way these brain search engines work. The approach we favor is to study multi-modular network models, able to solve particular problems that involve searching for information. The building blocks of these multimodular networks are the context dependent memory models we have been using for almost 20 years. These models work by associating an output to the Kronecker product of an input and a context. Input, context and output are vectors that represent cognitive variables. Our models constitute a natural extension of the traditional linear associator. We show that coding the information in vectors that are processed through association matrices, allows for a direct contact between these memory models and some procedures that are now classical in the Information Retrieval field. One essential feature of context-dependent models is that they are based on the thematic packing of information, whereby each context points to a particular set of related concepts. The thematic packing can be extended to multimodular networks involving input-output contexts, in order to accomplish more complex tasks. Contexts act as passwords that elicit the appropriate memory to deal with a query. We also show toy versions of several 'neuromimetic' devices that solve cognitive tasks as diverse as decision making or word sense disambiguation. The functioning of these multimodular networks can be described as dynamical systems at the level of cognitive variables.

The role of hippocampal atrophy in the pathogenesis of major depression remains under investigation. Here, we show, within a neural network model, that the incorporation of atrophy reproduces the changes observed in cognitive impairment in depression and could also contribute to the maintenance of the depressed mood. Some other clinical observations, such as treatment resistance and frequent relapses of illness, could also be explained within the framework of the model. We also simulate the action of cognitive therapy and a combined treatment of cognitive therapy and antidepressant drugs. Our findings suggest that, in the presence of hippocampal atrophy, the incorporation of antidepressant drugs would be necessary for the reversal of symptomatology.

Graph-theoretical methods have recently been used to analyze certain properties of natural and social networks. In this work, we have investigated the early stages in the growth of a Uruguayan academic network, the Biology Area of the Programme for the Development of Basic Science (PEDECIBA). This transparent social network is a territory for the exploration of the reliability of clustering methods that can potentially be used when we are confronted with opaque natural systems that provide us with a limited spectrum of observables (happens in research on the relations between brain, thought and language). From our social net, we constructed two different graph representations based on the relationships among researchers revealed by their co-participation in Master's thesis committees. We studied these networks at different times and found that they achieve connectedness early in their evolution and exhibit the small-world property (i.e. high clustering with short path lengths). The data seem compatible with power law distributions of connectivity, clustering coefficients and betweenness centrality. Evidence of preferential attachment of new nodes and of new links between old nodes was also found in both representations. These results suggest that there are topological properties observed throughout the growth of the network that do not depend on the representations we have chosen but reflect intrinsic properties of the academic collective under study. Researchers in PEDECIBA are classified according to their specialties. We analysed the community structure detected by a standard algorithm in both representations. We found that much of the pre-specified structure is recovered and part of the mismatches can be attributed to convergent interests between scientists from different sub-disciplines. This result shows the potentiality of some clustering methods for the analysis of partially known natural systems.

BACKGROUND:The complexity of our contemporary medical practice has impelled the development of different decision-support aids based on artificial intelligence and neural networks. Distributed associative memories are neural network models that fit perfectly well to the vision of cognition emerging from current neurosciences.METHODS:We present the context-dependent autoassociative memory model. The sets of diseases and symptoms are mapped onto a pair of basis of orthogonal vectors. A matrix memory stores the associations between the signs and symptoms, and their corresponding diseases. A minimal numerical example is presented to show how to instruct the memory and how the system works. In order to provide a quick appreciation of the validity of the model and its potential clinical relevance we implemented an application with real data. A memory was trained with published data of neonates with suspected late-onset sepsis in a neonatal intensive care unit (NICU). A set of personal clinical observations was used as a test set to evaluate the capacity of the model to discriminate between septic and non-septic neonates on the basis of clinical and laboratory findings.RESULTS:We show here that matrix memory models with associations modulated by context can perform automatic medical diagnosis. The sequential availability of new information over time makes the system progress in a narrowing process that reduces the range of diagnostic possibilities. At each step the system provides a probabilistic map of the different possible diagnoses to that moment. The system can incorporate the clinical experience, building in that way a representative database of historical data that captures geo-demographical differences between patient populations. The trained model succeeds in diagnosing late-onset sepsis within the test set of infants in the NICU: sensitivity 100%; specificity 80%; percentage of true positives 91%; percentage of true negatives 100%; accuracy (true positives plus true negatives over the totality of patients) 93,3%; and Cohen's kappa index 0,84.CONCLUSION:Context-dependent associative memories can operate as medical expert systems. The model is presented in a simple and tutorial way to encourage straightforward implementations by medical groups. An application with real data, presented as a primary evaluation of the validity and potentiality of the model in medical diagnosis, shows that the model is a highly promising alternative in the development of accuracy diagnostic tools.

Background: The complexity of our contemporary medical practice has impelled the development of different decision-support aids based on artificial intelligence and neural networks. Distributed associative memories are neural network models that fit perfectly well to the vision of cognition emerging from current neurosciences.