A recurrent neural network: Limitations and training

A recurrent, synchronous neural network is treated as a collection of independent perceptrons. The dynamics of the network can be described by a mapping: a finite set of transitions in the state space of the network. We define legal mapping as a mapping that a synchronous neural network is able to perform, and state the necessary and sufficient conditions for a mapping to be legal. A learning algorithm for the network, based on the perceptron's learning algorithm, is guaranteed to converge to a solution when the network is trained to realize a legal mapping. It is shown that the algorithm performs a gradient descent search for a minimum of a cost function that is a certain error measure in the weight space. Performance of the algorithm for the associative memory application and for temporal sequences production is illustrated by numerical simulations. A method is proposed for legalizing any given mapping at the expense of adding a finite number of neurons to the network. It is also shown that when the number of transitions in a random mapping is less than the number of neurons in the network, the probability that such a mapping is legal approaches unity.     

Broca's area and inflectional morphology: evidence from broca's aphasia and computer modeling

In a series of articles Ullman (2001, 2004; Ullman et al., 1997) has proposed that regular inflection is critically subserved by Broca's area. This suggestion is motivated by the finding that English speaking Broca's aphasics show selective deficits with regular inflection. Here we argue that this proposal does not hold cross-linguistically but is based on a confound between inflectional suffix and regularity that is specific to the English language. We present data from two experimental studies of participle inflection with 13 German and 12 Dutch Broca's aphasics. None of these aphasic speakers are selectively impaired for regular inflection but instead most of them show selective deficits with irregular inflection. These data suggest that a selective regular deficit is not a characteristic of Broca's aphasia across languages, and that Broca's area is not critically involved in regular inflection. To investigate the nature and localization of the processes underlying inflection we present a connectionist neural network model that accounts for the deficits of the German aphasic speakers. The model implements the view that the inflection of all verb types is based on a single mechanism with multiple representations that emerge from experience-dependent brain development. We show that global damage to this model results in a selective deficit for irregular inflection that is comparable to that of the German aphasic speakers. This finding suggests that a selective impairment of irregular participles as observed by German and Dutch aphasic speakers does not presuppose two distinctly localized mechanisms or processes that can be selectively affected by brain damage.     

Severe threat in the genesis of panic disorder

The hypothesis that panic disorder is a separate biological disease has attracted a great deal of controversy in recent years. One of the cornerstones of this theory is that panic attacks arise spontaneously, suggesting that the illness is generated by an autonomous physiological process. A number of cases are reported that illustrate Beck's theory that cognitive factors are central to the genesis of acute anxiety. Evidence for a developmental/cognitive theory of anxiety is discussed, and it is concluded that a purely biological model for panic disorder is inadequate.     

Hypnosis: placebo or nonplacebo?

According to Grünbaum's definition of placebo, a therapeutic procedure can be considered a nonplacebo if it can be demonstrated that its effects are produced according to the theory upon which the therapy is based. If the theory is adopted that hypnotic effects depend upon mobilization of the patient's hypnotizability, which is a measurable characteristic, a testable theory is provided. Experimental literature is reviewed that shows that placebo effects are not related to hypnotizability. Clinical outcome studies make it clear that results of hypnotherapy are related to hypnotizability in some disorders such as pain and anxiety, but not in the treatment of addiction or habit disorders. An example of a procedure is given in which hypnosis is nonetheless usefully applied for its placebo value as a method to generate positive expectancies.     

An Anticipatory Circuit Modification That Modifies Subsequent Task Switching

Modulators are generally expected to establish a network configuration that is appropriate for the current circumstances. We characterize a situation where the opposite is apparently observed. A network effect of a peptide modulator is counterproductive in that it tends to impede rather than promote the creation of the configuration that is appropriate when the modulator is released. This raises a question: why does release occur? We present data that strongly suggest that it impacts task switching. Our experiments were conducted in an Aplysia feeding network that generates egestive and ingestive motor programs. Initial experiments focused on egestive activity and the neuron B8. As activity becomes egestive, there is an increase in synaptic drive to B8 and its firing frequency increases (Wang et al., 2019). We show that, as this occurs, there is also a persistent current that develops in B8 that is outward rather than inward. Dynamic clamp introduction of this current decreases excitability. When there is an egestive-ingestive task switch in Aplysia, negative biasing is observed (i.e., a bout of egestive activity has a negative impact on a subsequent attempt to initiate an ingestive response) (Proekt et al., 2004). Using an in vitro analog of negative biasing, we demonstrate that the outward current that develops during egestive priming plays an important role in establishing this phenomenon. Our data suggest that, although the outward current induced as activity becomes egestive is counterproductive at the time, it plays an anticipatory role in that it subsequently impacts task switching.SIGNIFICANCE STATEMENT In this study, we identify a peptide-induced circuit modification (induction of an outward current) that does not immediately promote the establishment of a behaviorally appropriate network configuration. We ask why this might occur, and present data that strongly suggest that it plays an important role during task switching. Specifically, our data suggest that the outward current we characterize plays a role in the negative biasing that is seen in the mollusc Aplysia when there is a transition from egestive to ingestive activity. It is possible that the mechanism that we describe operates in other species. A negative effect of egestion on subsequent ingestion is observed throughout the animal kingdom.     

Factor XII: What does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis

Factor XII (FXII) is a coagulation protein that is essential for surface-activated blood coagulation tests but whose deficiency is not associated with bleeding. For over forty years, investigators in hemostasis have not considered FXII important because its deficiency is not associated with bleeding. It is because there is a dichotomy between abnormal laboratory assay findings due to FXII deficiency and clinical hemostasis that investigators sought explanations for physiologic hemostasis independent of FXII. FXII is a multidomain protein that contains two fibronectin binding consensual sequences, two epidermal growth factor regions, a kringle region, a proline-rich domain, and a catalytic domain that when proteolyzed turns into a plasma serine protease. Recent investigations with FXII deleted mice that are protected from thrombosis indicate that it contributes to the extent of developing thrombus in the intravascular compartment. These findings suggest that it has a role in thrombus formation without influencing hemostasis. Last, FXII has been newly appreciated to be a growth factor that may influence tissue injury repair and angiogenesis. These combined studies suggest that FXII may become a pharmacologic target to reduce arterial thrombosis risk and promote cell repair after injury, without influencing hemostasis.     

Role of taurine uptake on the induction of long-term synaptic potentiation

Taurine application in the CA1 area of rat hippocampal slices induces a long-lasting potentiation of excitatory synaptic transmission that has some mechanistic similitude with the late phase of long-term potentiation (L-LTP). Previous indirect evidence such as temperature and sodium dependence indicated that taurine uptake is one of the primary steps leading to the taurine-induced synaptic potentiation. We show that taurine-induced potentiation is not related to the intracellular accumulation of taurine and is not impaired by 2-guanidinoethanesulphonic acid, a taurine transport inhibitor that is a substrate of taurine transporter. We have found that taurine uptake in hippocampal synaptosomes was inhibited by SKF 89976A, a GABA uptake blocker that is not transportable by GABA transporters. SKF 89976A prevents the induction of synaptic potentiation by taurine application. This effect is neither mimicked by nipecotic acid, a broad inhibitor of GABA transporters that does not affect taurine uptake, nor by NO-711, a specific and potent inhibitor of GABA transporter GAT-1. In addition, L-LTP induced by trains of high-frequency stimulation is also inhibited by SKF 89976A, and taurine, at a concentration that does not change basal synaptic transmission, overcomes such inhibition. We conclude that taurine induces synaptic potentiation through the activation of a system transporting taurine and that taurine uptake is required for the induction of synaptic plasticity phenomena such as L-LTP.     

Neuropsychologic functioning and structural MRI of the brain in patients with schizophrenia

The first episode of schizophrenia represents a transition from a premorbid to a morbid state. Studying the first episode of schizophrenia is useful since it is devoid of the confounds of chronicity and long-term medication. It is also likely to direct us to the core deficits of the illness. Studies on first-episode schizophrenia suggest a generalized neuropsychologic impairment, but that memory, attention and executive function are more severely impaired. Support for a neurodevelopmental model of neuropsychologic impairment in schizophrenia is derived from the findings that much of the neuropsychologic impairment is present by illness onset, that neuropsychologic impairment remains stable over time and that there is a weak relation between duration of untreated psychosis and neuropsychologic impairment. However, neuropsychologic impairment is moderated by neuroleptic treatment, with some evidence that atypical antipsychotics may have some beneficial effects over conventional antipsychotics. The causal mechanisms of brain abnormality in the temporal and frontal lobes appear to be different to that of neuropsychologic impairment in schizophrenia. The observation that there is a brain volume decrement over time and that the rate of change is higher during the first 5 years would be consistent with a neurodegenerative model of schizophrenia. At the same time, the basal ganglia are vulnerable to volumetric increase secondary to neuroleptic medication. Understanding the roles of the neurodevelopmental and neurodegenerative models of schizophrenia is important in deciding intervention strategies.     

Jack Tizard Memorial Lecture: Children's Understanding of Inheritance and Family

It is widely argued that a more general 'genetic literacy' of the public is required so that appropriate use is made of the new human genetic technologies, such as DNA testing, and there is effective public participation in debates about the regulation and development of new technologies. Despite a century of popularisation and school education in Mendelian genetics, public understanding remains very limited. An hypothesis is put forward that suggests that the limited public understanding results from the existence of a lay understanding of inheritance that conflicts with the scientific account of Mendelian genetics and impedes its uptake. It is further proposed that the lay understanding of inheritance is derived by children from a developmentally earlier social understanding of kinship relations. Given that the lay knowledge of inheritance is grounded in social concepts of kinship that are sustained by every day social activities and relationships, it may be particularly resistant to change. A test of the hypothesis is described and evidence relating to the development of concepts of inheritance and family in children is discussed.     

A new view of pain as a homeostatic emotion

Pain is conventionally viewed as a pattern of convergent activity within the somatosensory system that represents the exteroceptive sense of touch. Accumulating functional, anatomical and imaging findings indicate that pain is generated by specific sensory channels that ascend in a central homeostatic afferent pathway. Phylogenetically new thalamocortical projections in primates provide a sensory image of the physiological condition of the body and, in addition, direct activation of limbic motor cortex. These findings indicate that the human feeling of pain is both a distinct sensation and a motivation - that is, a specific emotion that reflects homeostatic behavioral drive, similar to temperature, itch, hunger and thirst.     

Q: Is Addiction a Brain Disease or a Moral Failing? A: Neither

This article uses Marc Lewis’ work as a springboard to discuss the socio-political context of the brain disease model of addiction (BDMA). The claim that promotion of the BDMA is the only way the general public can be persuaded to withhold blame and punishment from addicts is critically examined. After a discussion of public understandings of the disease concept of addiction, it is pointed out that it is possible to develop a scientific account of addiction which is neither a disease nor a moral model but which the public could understand. Evidence is reviewed to suggest that public acceptance of the disease concept is largely lip-service and that the claim the BDMA removes stigma among the public and professionals is unsupported by evidence. Further, there is good evidence that biogenetic explanations of mental/behavioural disorders in general have been counterproductive in the attempt to ally stigma. A model of addiction as a disorder of choice may attract special problems in public-facing communications and risks being misunderstood. However, ways of presenting this model to the public are suggested that may avoid such risks. Lastly, the claim that the BDMA is the only way of ensuring access to treatment and of maintaining research funding for addiction is disputed and a way in which these benefits can be retained under a disorder-of-choice model proposed. The article concludes by enthusiastically endorsing Lewis’ call for a third stage in the governing image of addiction.     

Associative learning in early vision.

Sensory discriminations often improve with practice (perceptual learning). Recent results show that practice does not necessarily lead to the best possible performance on the task. It was shown that learning a task (contrast discrimination) that has already reached saturation could be enabled by a contextual change in the stimulus (the addition of surrounding flankers) during practice. Psychophysical results with varying context show a behavior that is described by a network of local visual processors with horizontal recurrent interactions. We describe a mathematical learning rule for the modification of cortical synapses that is inspired by the experimental results and apply it to recurrent cortical networks that respond to external stimuli. The model predicts that repeated presentation of the same stimulus leads to saturation of synaptic modification, such that the strengths of recurrent connections depend on the configuration of the stimulus but not on its amplitude. When a new stimulus is introduced, the modification is rekindled until a new equilibrium is reached. This effect may explain the saturation of perceptual learning when practicing a certain task repeatedly. We present simulations of contrast discrimination in a simplified model of a cortical column in the primary visual cortex and show that performance of the model is reminiscent of context-dependent perceptual learning.     

The theta/gamma discrete phase code occuring during the hippocampal phase precession may be a more general brain coding scheme

In the hippocampus, oscillations in the theta and gamma frequency range occur together and interact in several ways, indicating that they are part of a common functional system. It is argued that these oscillations form a coding scheme that is used in the hippocampus to organize the readout from long-term memory of the discrete sequence of upcoming places, as cued by current position. This readout of place cells has been analyzed in several ways. First, plots of the theta phase of spikes vs. position on a track show a systematic progression of phase as rats run through a place field. This is termed the phase precession. Second, two cells with nearby place fields have a systematic difference in phase, as indicated by a cross-correlation having a peak with a temporal offset that is a significant fraction of a theta cycle. Third, several different decoding algorithms demonstrate the information content of theta phase in predicting the animal's position. It appears that small phase differences corresponding to jitter within a gamma cycle do not carry information. This evidence, together with the finding that principle cells fire preferentially at a given gamma phase, supports the concept of theta/gamma coding: a given place is encoded by the spatial pattern of neurons that fire in a given gamma cycle (the exact timing within a gamma cycle being unimportant); sequential places are encoded in sequential gamma subcycles of the theta cycle (i.e., with different discrete theta phase). It appears that this general form of coding is not restricted to readout of information from long-term memory in the hippocampus because similar patterns of theta/gamma oscillations have been observed in multiple brain regions, including regions involved in working memory and sensory integration. It is suggested that dual oscillations serve a general function: the encoding of multiple units of information (items) in a way that preserves their serial order. The relationship of such coding to that proposed by Singer and von der Malsburg is discussed; in their scheme, theta is not considered. It is argued that what theta provides is the absolute phase reference needed for encoding order. Theta/gamma coding therefore bears some relationship to the concept of "word" in digital computers, with word length corresponding to the number of gamma cycles within a theta cycle, and discrete phase corresponding to the ordered "place" within a word.     

Purkinje cell vulnerability and autism: a possible etiological connection

Autism is a neurological disorder of unknown etiology. The onset of the abnormal growth and development within the brain is also not known. Current thought by experts in autism is that the time of onset is prenatal, occurring prior to 30 weeks gestation. However, autism comprises a heterogeneous population in that parents report either that their child was abnormal from birth, or that their child was developmentally normal until sometime after birth, at which time the child began to regress or deteriorate. Anecdotal reports suggest that some children with autism have significant illness or clinical events prior to the development of autistic symptoms. Conceivably, these children may become autistic from neuronal cell death or brain damage sometime after birth as result of insult. To support this theory is that marked Purkinje cell loss, the most consistent finding in the autistic disorder, can result from insult. Evidence suggests that the Purkinje cell is selectively vulnerable. This article discusses a theory that the selective vulnerability of the Purkinje cell may play a role in the etiology of autism, and suggests that a future direction in autism research may be to investigate the possibility of neuronal cell loss from insult as a cause of autism. Results of a small pilot survey are also discussed.     

An appraisal of the DSM-III system

DSM-III is a major document in the history of psychiatry. The DSM-III system is here seen as an instrument that promotes the scientific development of psychiatry and the clarity of communication among psychiatrists. However a major theme of this review is that reliability does not ensure validity. While making this point it is recognized that the major defects in the DSM-III system result from scientific inadequacies inherent in present day psychiatry. This review also may be taken as an amplification of the statement in DSM-III-R that it is not a textbook. In particular the data required to arrive at diagnoses in the DSM-III system do not provide sufficient information to arrive at a comprehensive biopsychosocial case formulation, a shortcoming that has relevance for teaching and clinical practice.     

Approximating a solution of the s-t max-cut problem with a deterministic annealing algorithm.

The s-t max-cut problem is an NP-hard combinatorial optimization problem. In this paper an equivalent linearly constrained continuous optimization problem is formulated and an algorithm is proposed for approximating its solution. The algorithm is derived from an application of a logarithmic barrier function, where the barrier parameter behaves as temperature in an annealing procedure and decreases to zero from a sufficiently large positive number satisfying that the barrier function is convex. The algorithm searches for a better solution in a feasible descent direction, which has a desired property that lower and upper bounds are always satisfied automatically if the step length is a number between zero and one. We prove that the algorithm converges to at least a local minimum point if a local minimum point of the barrier problem is generated for a sequence of descending values of the barrier parameter with zero limit. Numerical results show that the algorithm seems effective and efficient.     

Mestizo spirituality: toward an integrated approach to psychotherapy for Latina/OS

Development of culturally syntonic models for treatment that are consistent with belief systems of ethnically diverse populations is at a beginning stage of evolution. This paper is a step toward laying a new conceptual and psychotherapeutic approach with Latina/o clients, specifically those of Mexican American and Mexican backgrounds. It is argued that a psychospiritual belief system is at the base of these populations, and that a culturally consistent framework must appropriately address theory, skills, and practice. Mestizo spirituality is presented and described, and a review of those forces that have impacted this understanding is offered. Key concepts, therapeutic goals, and relationship assumptions of the model, two case examples, application, and limitations of this framework are provided. Lastly, implications for professional practice are given.     

Ambulatory first night sleep effect recording in the elderly

The concept of a first night effect on sleep patterns, specifically in relation to age is a controversial topic in the literature. Our data are obtained during two consecutive 24-h ambulatory home sleep-wake recording in 10 elderly persons with a mean age of 85.5 years. Polysomnographic recordings indicated that a first night effect is present in old age, even using home recording, and that several types of insomnia can be differentiated, stressing that sleep cycle parameters should be taken into account. It is suggested that the first night effect is a 'miniature' replication of a psychophysiological insomnia.     

Evidence for hyperbolic temporal discounting of reward in control of movements

Suppose that the purpose of a movement is to place the body in a more rewarding state. In this framework, slower movements may increase accuracy and therefore improve the probability of acquiring reward, but the longer durations of slow movements produce devaluation of reward. Here we hypothesize that the brain decides the vigor of a movement (duration and velocity) based on the expected discounted reward associated with that movement. We begin by showing that durations of saccades of varying amplitude can be accurately predicted by a model in which motor commands maximize expected discounted reward. This result suggests that reward is temporally discounted even in timescales of tens of milliseconds. One interpretation of temporal discounting is that the true objective of the brain is to maximize the rate of reward-which is equivalent to a specific form of hyperbolic discounting. A consequence of this idea is that the vigor of saccades should change as one alters the intertrial intervals between movements. We find experimentally that in healthy humans, as intertrial intervals are varied, saccade peak velocities and durations change on a trial-by-trial basis precisely as predicted by a model in which the objective is to maximize the rate of reward. Our results are inconsistent with theories in which reward is discounted exponentially. We suggest that there exists a single cost, rate of reward, which provides a unifying principle that may govern control of movements in timescales of milliseconds, as well as decision making in timescales of seconds to years.