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PubMed1991

Variable threshold as a model for selective attention, (de)sensitization, and anesthesia in associative neural networks.

We study the influence of a variable neuronal threshold on fixed points and convergence rates of an associative neural network in the presence of noise. We allow a random distribution in the activity levels of the patterns stored, and a modification to the standard Hebbian learning rule is proposed for this purpose. There is a threshold at which the retrieval ability, including the average final overlap and the convergence rate, is optimized for patterns with a particular activity level at a given noise level. This type of selective attention to one class of patterns with a certain activity level may be obtained at the cost of reducing the retrieval ability of the network for patterns with different activity levels. The effects of a constant threshold independent of noise, time, and pattern are discussed. For high-(low-) activity patterns, the average final overlap is shown to be increased at high noise levels and decreased at low noise levels by a negative (positive) constant threshold, whereas a positive (negative) threshold always reduces the final average overlap. When the magnitude of the constant threshold exceeds a critical value, there is no retrieval. Rates of convergence towards the stored pattern with negative (positive) thresholds are greater than those with positive (negative) thresholds. These results are related to (de)sensitization and anesthesia. For certain threshold values and patterns with certain activity levels, hysteresis appears in the plot of the average final overlap versus the noise level, even for first order interactions. We make the analogy between the pattern-dependent neuronal threshold proposed in the present paper and the "task-related" modulation in neuronal excitability determined by cognitive factors, such as the attentional state of a higher animal. A constant threshold is associated with overall changes in neuronal excitability caused, e.g., by various drugs and physical injuries. Neurophysiological evidence of a dynamically variable neuronal threshold, such as accommodation and potentiation, is presented.

Anesthesia↗
PubMed1976

Drug discrimination in rats: effects of mixtures of ditran and cholinesterase inhibitors.

Groups of rats were trained in a T-shaped maze to discriminate the effects produced by IP injections of ditran (1.60 mg/kg), either when given singly, or when combined with the acetylcholinesterase inhibitors neostigmine (0.25 mg/kg) or physostigmine (0.50 and 1.00 mg/kg), from the nondrug condition (saline). The results from this state-dependency (StD) model indicated that acquisition of the drug discrimination was similar for the 4 groups of rats. After drug discrimination was established the rats were tested with various drug combinations. Physostigmine (0.50 and 1.00 mg/kg) challenge reversed drug discrimination among rats trained with ditran solely or the ditran plus neostigmine combination. There was no antagonism among the ditran plus physostigmine trained rats. Involvement of the C.N.S. is implicated since tests with neostigmine did not upset ditran discrimination. In addition, survival rate of physostigmine treated mice is increased with ditran. In conclusion, this study indicates the usefulness of employing both training and transfer test procedures when evaluating antagonism in this StD model.

Animals↗
PubMedDate not supplied

Neurotransmitters in the regulation of neuronal cytoarchitecture.

Recent experiments in isolated neurons in cell culture have demonstrated that neurotransmitters and associated electrical activity can directly affect neurite outgrowth. The results indicate that neurotransmitters have considerable potential to control the development of the neuronal circuits in which they participate in information coding in the adult. Cellular mechanisms regulating growth cone motility have been found to be similar to those regulating neurotransmitter release at the synapse and involve electrical activity, calcium and other second messengers. These similarities suggest that the morphological changes in connections observed in adult plasticity may involve the transition of synaptic terminals back to a growth mode. Excitatory and inhibitory neurotransmitters can interact to yield a net effect on neuronal morphology. In the intact nervous system a balance between these neurotransmitter inputs is probably important in maintaining circuits. Studies of neurotransmitter involvement in learning and memory processes indicate that brain function can alter brain structure and that neurotransmitters may control these structural changes. The hippocampus is one brain region in which we are beginning to define roles for neurotransmitters as sculptors of neuronal cytoarchitecture. The neurotransmitter glutamate was found to specifically affect the cytoarchitecture of hippocampal pyramidal neuron dendrites in a graded manner which suggests that glutamate may be involved in: establishing hippocampal circuitry during brain development; maintaining and modifying circuitry in the adult; and inducing neurodegeneration in several disorders including epilepsy, Alzheimer's disease, and stroke. Therapeutic approaches to disorders which affect brain cytoarchitecture may now be devised based upon knowledge of the neurotransmitters and their cellular mechanisms in the pertinent brain region.

Animals↗
PubMed2004

Combination treatment of neonatal rats with hypoxia-ischemia and endotoxin induces long-lasting memory and learning impairment that is associated with extended cerebral damage.

OBJECTIVE: We assessed the long-term effects of perinatal hypoxia-ischemia and endotoxin on attention and short- and long-term memory in neonatal rats with the use of behavioral tasks and brain histologic results. STUDY DESIGN: Four hours after injections of lipopolysaccharide (1 mg/kg, intraperitoneally) or saline solution, 7-day-old Wistar rat pups were subjected to unilateral hypoxia-ischemia for 1 hour. We studied 4 groups: controls (n = 43 rats), lipopolysaccharide alone (n = 12 rats), hypoxia-ischemia alone (n = 29 rats), and combined lipopolysaccharide + hypoxia-ischemia treatment (n = 34 rats). Seven to 16 weeks after the treatment, we measured attention with a choice reaction time task, short-term memory with an 8-arm radial maze task, and long-term memory with a water maze task. At 19 weeks of age, the brain was removed, fixed, and sectioned coronally; and the volume of each part was measured. RESULTS: A loss of volume in the hippocampus was observed in the lipopolysaccharide, hypoxia-ischemia, and lipopolysaccharide + hypoxia-ischemia groups; a loss of striatum was observed in the hypoxia-ischemia and lipopolysaccharide + hypoxia-ischemia groups, but loss of cortex was observed only in the lipopolysaccharide + hypoxia-ischemia group. The lipopolysaccharide, hypoxia-ischemia, and lipopolysaccharide + hypoxia-ischemia groups showed significantly poorer performance (attention deficit) than controls in the choice reaction time task. Correct choices decreased, and error increased in the lipopolysaccharide + hypoxia-ischemia group compared with the other groups in the radial maze task, which shows short-term memory impairment. Swimming distance was significantly greater in the hypoxia-ischemia and lipopolysaccharide + hypoxia-ischemia groups than in the other 2 groups in the water maze test, which shows long-term memory impairment. CONCLUSION: Combined lipopolysaccharide and hypoxia-ischemia treatment synergistically induced short-term memory impairment that is associated with loss of cortical volume.

Analysis of Variance↗
PubMed2006

Encoding of time-discounted rewards in orbitofrontal cortex is independent of value representation.

We monitored single-neuron activity in the orbitofrontal cortex of rats performing a time-discounting task in which the spatial location of the reward predicted whether the delay preceding reward delivery would be short or long. We found that rewards delivered after a short delay elicited a stronger neuronal response than those delivered after a long delay in most neurons. Activity in these neurons was not influenced by reward size when delays were held constant. This was also true for a minority of neurons that exhibited sustained increases in firing in anticipation of delayed reward. Thus, encoding of time-discounted rewards in orbitofrontal cortex is independent of the encoding of absolute reward value. These results are contrary to the proposal that orbitofrontal neurons signal the value of delayed rewards in a common currency and instead suggest alternative proposals for the role this region plays in guiding responses for delayed versus immediate rewards.

Action Potentials↗
PubMed1997

Resistance of experientially-induced changes in murine plus-maze behaviour to altered retest conditions.

Prior exposure to the elevated plus-maze results in profound behavioural alterations in rats and mice, with 24 h retest profiles indicative of fear sensitization. The present study was designed to examine the influence of retest cues on this phenomenon in male DBA/2 mice. Results confirmed the potent influence of prior maze experience on subsequent behavioural patterns, and showed that this was not affected by manipulations of extra-maze cues (90 degrees re-orientation of the maze or use of a different laboratory) on Trial 2. Data are discussed in relation to experientially-induced shifts in behavioural strategy and the apparent involvement of simple proximal cues (probably thigmotactic) in this enduring and adaptive form of spatial learning.

Animals↗
PubMed2002

Teaching and learning in a probabilistic prisoner's dilemma.

The prisoner's dilemma is much studied in social psychology and decision-making because it models many real-world conflicts. In everyday terms, the choice to 'cooperate' (maximize reward for the group) or 'defect' (maximize reward for the individual) is often attributed to altruistic or selfish motives. Alternatively, behavior during a dilemma may be understood as a function of reinforcement and punishment. Human participants played a prisoner's-dilemma-type game (for points exchangeable for money) with a computer that employed either a teaching strategy (a probabilistic version of tit-for-tat), in which the computer reinforced or punished participants' cooperation or defection, or a learning strategy (a probabilistic version of Pavlov), in which the computer's responses were reinforced and punished by participants' cooperation and defection. Participants learned to cooperate against both computer strategies. However, in a second experiment which varied the context of the game, they learned to cooperate only against one or other strategy; participants did not learn to cooperate against tit-for-tat when they believed that they were playing against another person; participants did not learn to cooperate against Pavlov when the computer's cooperation probability was signaled by a spinner. The results are consistent with the notion that people are biased not only to cooperate or defect on individual social choices, but also to employ one or other strategy of interaction in a pattern across social choices.

Journal Article↗
PubMed1998

Dynamic On-line Clustering and State Extraction: An Approach to Symbolic Learning.

Although recurrent neural nets have been moderately successful in learning to emulate finite-state machines (FSMs), the continuous internal state dynamics of a neural net are not well matched to the discrete behavior of an FSM. We describe an architecture, called DOLCE, that allows discrete states to evolve in a net as learning progresses. DOLCE consists of a standard recurrent neural net trained by gradient descent and an adaptive clustering technique that quantizes the state space. We describe two implementations of DOLCE. The first implementation, called DOLCE(u), uses an adaptive clustering scheme in an unsupervised mode to determine both the number of clusters and the partitioning of the state space as learning progresses. The second model, DOLCE(s), uses a Gaussian Mixture Model in a supervised learning framework to infer the states of an FSM. DOLCE(s) is based on the assumption that a finite set of discrete internal states is required for the task, and that the actual network state belongs to this set but has been corrupted by noise due to inaccuracy in the weights. DOLCE(s) learns to recover the discrete state with maximum a posteriori probability from the noisy state. Simulations show that both implementations of DOLCE lead to a significant improvement in generalization performance over earlier neural net approaches to FSM induction. The idea of adaptive quantization is not just applicable to DOLCE but can be applied to other domains as well.

Journal Article↗
PubMed2003

Learning in spiking neural networks by reinforcement of stochastic synaptic transmission.

It is well-known that chemical synaptic transmission is an unreliable process, but the function of such unreliability remains unclear. Here I consider the hypothesis that the randomness of synaptic transmission is harnessed by the brain for learning, in analogy to the way that genetic mutation is utilized by Darwinian evolution. This is possible if synapses are "hedonistic," responding to a global reward signal by increasing their probabilities of vesicle release or failure, depending on which action immediately preceded reward. Hedonistic synapses learn by computing a stochastic approximation to the gradient of the average reward. They are compatible with synaptic dynamics such as short-term facilitation and depression and with the intricacies of dendritic integration and action potential generation. A network of hedonistic synapses can be trained to perform a desired computation by administering reward appropriately, as illustrated here through numerical simulations of integrate-and-fire model neurons.

Action Potentials↗
PubMed2002

Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search.

We present a statistical model to estimate the accuracy of peptide assignments to tandem mass (MS/MS) spectra made by database search applications such as SEQUEST. Employing the expectation maximization algorithm, the analysis learns to distinguish correct from incorrect database search results, computing probabilities that peptide assignments to spectra are correct based upon database search scores and the number of tryptic termini of peptides. Using SEQUEST search results for spectra generated from a sample of known protein components, we demonstrate that the computed probabilities are accurate and have high power to discriminate between correctly and incorrectly assigned peptides. This analysis makes it possible to filter large volumes of MS/MS database search results with predictable false identification error rates and can serve as a common standard by which the results of different research groups are compared.

Algorithms↗
PubMed2003

Context change as the mechanism of reinstatement in causal learning.

Four experiments were conducted to explore the mechanism of reinstatement in human causal learning. After a retroactive interference treatment in which a stimulus was first followed by an outcome (A+) and then followed by a different outcome (A*), simple exposure to the original outcome (+) in the interference-test context produced partial reinstatement of the first-learned information (A+). When exposure to the outcome took place in a context different from the interference-test context, reinstatement was not observed (Experiment 1). Equivalent results appeared when the outcome presented during reinstatement was different from the one originally related to the stimulus affected by interference, independent of whether the interfering outcome (Experiments 2, 3, and 4) or a new outcome (Experiments 3 and 4) was presented before the test. These results suggest an interpretation of reinstatement in terms of a context change between interference and testing.

Adolescent↗
PubMed1996

The effects of experience and sexual abuse training on the attitudes of learning disability staff.

Staff employed in three day centres for people with learning disabilities were offered training in sexual abuse. Their knowledge and attitudes about sexual abuse were measured immediately before and after training. Staff were asked about their perceptions of the risks of people with learning disabilities being sexually abused, and their estimations of the probability of the perpetrator being either a member of staff, a client, a person known to the abused person or a stranger. Their responses were found to be influenced by the recent training and their prior personal experience.

Adult↗
PubMed2002

The transition out of medical school - a qualitative study of descriptions of borderline trainee interns.

OBJECTIVE: To describe the characteristics of borderline performance in final year medical students (trainee interns), as judged by their supervisors. DESIGN: Qualitative study based on in-depth interviews followed by validation descriptions of borderline trainee interns identified prospectively over 12 months. SETTING: Christchurch School of Medicine, University of Otago, New Zealand. PARTICIPANTS: Fourteen supervisors of trainee interns chosen because of their experience and/or close contact with trainee interns. MAIN OUTCOME MEASURES: Analysis of supervisors' narratives to identify key themes. RESULTS: Borderline trainee intern performance occurs within a transition period from clinical student to doctor and is characterised by difficulty taking on a professional role. This difficulty may be manifest by not getting involved with the health care team, poor time management and occasionally by interpersonal difficulties or not recognising limits. Taking on a professional role requires ability in the clinical task, including diagnostic ability, which is built on a foundation of basic knowledge and clinical skills. These can be influenced by personal factors such as rigidity, motivation and shyness. Personal illness can affect performance at any stage. CONCLUSIONS: The difficulties faced by borderline trainee interns fit a model of transition from competence as a student to performance as an intern. A sensitive marker of such difficulties is poor time management or not getting involved with the patient care team. Such difficulties may reflect more specific problems such as professional socialization, setting priorities, hypothesis generation, assigning probabilities to identified problems, integrating competing issues, recognising limits and learning when to call for assistance.

Clinical Competence↗
PubMed1982

Cost effectiveness of lead screening.

Lead-screening programs may reduce childhood disabilities, but at what cost? Through a review of the literature, we performed a cost-effectiveness analysis in which the costs, savings, and health benefits of two lead-screening strategies--employing either a free erythrocyte protoporphyrin assay or blood lead measurement--were compared with each other and with a strategy of no screening in a population of three-year-old children. When the prevalence of lead poisoning among the children screened is 7 per cent or more, we estimate that free erythrocyte protoporphyrin screening averts morbidity and results in net savings: It is both better and cheaper than no screening. At prevalences below 7 per cent, the net positive costs from screening and early treatment must be weighed against the noneconomic benefits of improved quality of life and considered in relation to other investments that could be made to benefit society. At all prevalence rates, free erythrocyte protoporphyrin screening is more cost effective than blood lead screening.

Child, Preschool↗