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Ovarian cancer diagnosis by hippocampus and neocortex-inspired learning memory structures.

Early detection and accurate staging of ovarian cancer are the keys to improving survival rate. However, at present there is no single diagnosis modality that is sufficiently sensitive. DNA microarray analysis is an emerging technique that has potential for ameliorating the hardship in early detection and staging of ovarian disease. However, microarray data is ultra-huge and difficult to analyze. Hence, computational intelligence methods are often utilized to assist in the diagnosis and analysis process. Fuzzy Neural Networks (FNN) are more suitable for this task as FNN provides not only the accuracy, but also the interpretability of its reasoning process. Hippocampus-inspired Complementary Learning FNN (CLFNN) is able to rapidly derive fuzzy sets and formulate fuzzy rules. CLFNN uses positive and negative learning, and hence it reduces the effect of the curse of dimensionality and is capable of modeling the dynamics of the problem space with relatively good classification performance. One of its successors, a hybrid of complementary hippocampal learning and associative neocortical learning called Pseudo Associative Complementary Learning (PACL), is a structure that seeks to functionally model the memory consolidation process. Both PACL and CLFNN have human-like reasoning that allows physicians to examine their computation using familiar terms. They can construct intuitive fuzzy rules autonomously to justify their reasoning, which is important to generate trust among the users. Hence, CLFNN and PACL are applied as a diagnostic decision support system in ovarian cancer diagnosis. The experimental results are encouraging.

Algorithms↗

NMDA-antagonism (memantine): an alternative pharmacological therapeutic principle in Alzheimer's and vascular dementia.

Memantine, a non-competitive NMDA antagonist, has been clinically used in the treatment of dementia in Germany for over ten years. The rationale for this indication is strongly related to the physiological and to the pathological role of glutamate in neurotransmission. Physiologically, NMDA receptors mediate synaptic plasticity by acting as a coincidence detector. Only those synapses that show temporally and spatially discrete activation of NMDA receptors undergo plastic changes secondary to Ca++ influx after rapid unblocking of Mg++, thus crucially contributing to memory and learning processes. The voltage-dependency of Mg++ is so pronounced that under pathological conditions it leaves the NMDA channel upon moderate depolarisation, thus interrupting memory and learning. Its pharmacological properties allow memantine to rapidly leave the NMDA channel upon transient physiological activation by synaptic glutamate (restoring significant signal transmission), but to block the sustained activation of low glutamate concentration under pathological conditions, i.e. to protect against excitotoxicity as a pathomechanism of neurodegenerative disorders. Memantine acts as a neuroprotective agent in various animal models based on both neurodegenerative and vascular processes as it ameliorates cognitive and memory deficits. Memantine has shown to be effective and safe in the treatment of dementia, particularly Alzheimer's disease, in controlled clinical trials. Provided that the dose is slowly increased it is generally well tolerated and safe up to 20 and 30 mg per day, with intake preferably in the morning. The compound is completely absorbed after oral intake with Cmax values after 6 hours, undergoes little metabolism and has a terminal elimination half life between 60 and 100 hours. Due to its low potential of interaction, memantine can be combined with acetylcholinesterase inhibitors, the mainstay of current symptomatic treatment of Alzheimer's disease and it is suited in elderly patients receiving multiple drug therapy.

Alzheimer Disease↗

Interpretation of emotion from facial expressions in children with and without learning disabilities.

The accuracy and time required for children with and without learning disabilities to interpret emotions when restricted to information from facial expressions, and the accuracy of those interpretations, were investigated. Ninety-six children participated; an equal number of males and females were included in both learning categories and age levels. Accuracy and response time on a modified version of Pictures of Facial Affect were recorded for the emotions of fear, sadness, surprise, anger, happiness, and disgust, as well as for the entire task. Three-way ANOVAs revealed children with learning disabilities to (a) be less accurate interpreters of emotion and (b) spend more time identifying specific emotions. Both age and sex influenced response time: Younger subjects required more time to interpret the emotions of fear and anger; males spent more time interpreting happiness. Younger females with learning disabilities displayed difficulty in interpretation, and older children with learning disabilities (particularly males) were rapid, but often inaccurate, interpreters of emotion.

Adolescent↗

[Influence of acoustic signal with ultrasonic components on the development of defensive conditioned reflex in Wistar rats].

Short-term (90 s) effects of the complex acoustic signal (CAS) with ultrasonic components on the development of defensive conditioned reflex of two-way active avoidance in a shuttle-box were studied in female Wistar rats. The learning ability of rats was measured on a scale designed in our laboratory. It was shown that CAS stimulation triggered an audiogenic seizure of different strength in 59% of animals. The CAS was extremely stressful for Wistar rats: it prevented the active avoidance learning in early terms after its application (the first training session in 4 or 6 days). This effect did not depend on the presence or intensity of audiogenic seizures during CAS. In the second training session in 9 days (the first session was in 4 days), learning was impaired as compared to control without CAS. However, during repeated training procedure 1.5 months after the CAS (the first session in 6 days), rats rapidly reached the criterion of learning (10 consecutive avoidance reactions). On the other hand, if the CAS was presented with different time lags (immediately, in 3 or in 45 days) after the first training session, the ability of animals to learn during the second session was not impaired both in early and late terms after exposure to the stressor. The results suggest that exposure to CAS prevents development of short-term memory but does not affect consolidation process and long-term memory.

Acoustic Stimulation↗

Learning in mammalian sensory cortex.

The improvement of perceptual capabilities with training can offer important insight into the physiological basis of learning in the cerebral cortex. The rapid time course and ease with which some perceptual capabilities can improve suggest that learning is an integral part of normal perception. Electrophysiological and neuroimaging studies of sensory systems in the cortex suggest that the changes underlying perceptual learning can occur in a variety of areas and are likely to involve multiple mechanisms. In particular, recent psychological and physiological studies suggest that perceptual learning might often involve the task-specific suppression of signals that interfere with performance.

Action Potentials↗

Response-reinforcer relationships and improved learning in autistic children.

In order to affect more rapid response acquisition for autistic children, researchers have recently begun to investigate the functional relationships of reinforcers to other components of the operant conditioning paradigm. Previous research suggested that functional relationships between target behaviors and reinforcers might be especially effective. For example, locating a reward inside a container might be a more efficient way to teach a child to open the container than by handling the child a reward for opening an empty container. The present experiment assessed, within a multiple baseline design, the possibility of improving autistic children's learning by changing arbitrary response-reinforcer relationships (while holding target behaviors and reinforcers constant) so that the target behaviors became functional (i.e., a direct part of the response chain required for the child to procure the reinforcer). The results showed that: (1) arranging functional response-reinforcer relationships produced immediate improvement in the children's learning, and resulted in rapid acquisition of criterion level responding; and (2) high levels of correct responding initially produced by functional response-reinforcer relationships were continued even when previously ineffective arbitrary response-reinforcer conditions were reinstated. The results are discussed in terms of understanding and improving autistic children's learning.

Autistic Disorder↗

Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats.

Relationships were examined between spatial learning and hippocampal concentrations of the alpha, beta2, and gamma isoforms of protein kinase C (PKC), an enzyme implicated in neuronal plasticity and memory formation. Concentrations of PKC were determined for individual 6-month-old (n = 13) and 24-month-old (n = 27) male Long-Evans rats trained in the water maze on a standard place-learning task and a transfer task designed for rapid acquisition. The results showed significant relationships between spatial learning and the amount of PKC among individual subjects, and those relationships differed according to age, isoform, and subcellular fraction. Among 6-month-old rats, those with the best spatial memory were those with the highest concentrations of PKCgamma in the particulate fraction and of PKCbeta2 in the soluble fraction. Aged rats had increased hippocampal PKCgamma concentrations in both subcellular fractions in comparison with young rats, and memory impairment was correlated with higher PKCgamma concentrations in the soluble fraction. No age difference or correlations with behavior were found for concentrations of PKCgamma in a comparison structure, the neostriatum, or for PKCalpha in the hippocampus. Relationships between spatial learning and hippocampal concentrations of calcium-dependent PKC are isoform-specific. Moreover, age-related spatial memory impairment is associated with altered subcellular concentrations of PKCgamma and may be indicative of deficient signal transduction and neuronal plasticity in the hippocampal formation.

Aging↗

Anatomical correlates of learning novel speech sounds.

We examined the relationship between brain anatomy and the ability to learn nonnative speech sounds, as well as rapidly changing and steady-state nonlinguistic sounds, using voxel-based morphometry in 59 healthy adults. Faster phonetic learners appeared to have more white matter in parietal regions, especially in the left hemisphere. The pattern of results was similar for the rapidly changing but not for the steady-state nonlinguistic stimuli, suggesting that morphological correlates of phonetic learning are related to the ability to process rapid temporal variation. Greater asymmetry in the amount of white matter in faster learners may be related to greater myelination allowing more efficient neural processing, which is critical for the ability to process certain speech sounds.

Acoustic Stimulation↗

Fuzzy lattice neurocomputing (FLN) models.

In this work it is shown how fuzzy lattice neurocomputing (FLN) emerges as a connectionist paradigm in the framework of fuzzy lattices (FL-framework) whose advantages include the capacity to deal rigorously with: disparate types of data such as numeric and linguistic data, intervals of values, 'missing' and 'don't care' data. A novel notation for the FL-framework is introduced here in order to simplify mathematical expressions without losing content. Two concrete FLN models are presented, namely 'sigma-FLN' for competitive clustering, and 'FLN with tightest fits (FLNtf)' for supervised clustering. Learning by the sigma-FLN, is rapid as it requires a single pass through the data, whereas learning by the FLNtf, is incremental, data order independent, polynomial theta(n3), and it guarantees maximization of the degree of inclusion of an input in a learned class as explained in the text. Convenient geometric interpretations are provided. The sigma-FLN is presented here as fuzzy-ART's extension in the FL-framework such that sigma-FLN widens fuzzy-ART's domain of application to (mathematical) lattices by augmenting the scope of both of fuzzy-ART's choice (Weber) and match functions, and by enhancing fuzzy-ART's complement coding technique. The FLNtf neural model is applied to four benchmark data sets of various sizes for pattern recognition and rule extraction. The benchmark data sets in question involve jointly numeric and nominal data with 'missing' and/or 'don't care' attribute values, whereas the lattices involved include the unit-hypercube, a probability space, and a Boolean algebra. The potential of the FL-framework in computing is also delineated.

Fuzzy Logic↗

Neuroinflammation alters the hippocampal pattern of behaviorally induced Arc expression.

Neuroinflammation is associated with a variety of neurological and pathological diseases, such as Alzheimer's disease (AD), and is reliably detected by the presence of activated microglia. In early AD, the highest degree of activated microglia is observed in brain regions involved in learning and memory. To investigate whether neuroinflammation alters the pattern of rapid de novo gene expression associated with learning and memory, we studied the expression of the activity-induced immediate early gene Arc in the hippocampus of rats with experimental neuroinflammation. Rats were chronically infused with lipopolysaccharide (LPS) (0.25 mug/h) into the fourth ventricle for 28 d. On day 29, the rats explored twice a novel environment for 5 min, separated by 45 or 90 min. In the dentate gyrus and CA3 regions of LPS-infused rats, Arc and OX-6 (specific for major histocompatibility complex class II antigens) immunolabeling and Arc fluorescence in situ hybridization revealed both activated microglia (OX-6 immunoreactivity) and elevated exploration-induced Arc expression compared with control-infused rats. In contrast, in the CA1 of LPS-infused rats, where there was no OX-6 immunostaining, exploration-induced Arc mRNA and protein remained similar in both LPS- and control-infused rats. LPS-induced neuroinflammation did not affect basal levels of Arc expression. Behaviorally induced Arc expression was altered only within the regions showing activated microglia (OX-6 immunoreactivity), suggesting that neuroinflammation may alter the coupling of neural activity with macromolecular synthesis implicated in learning and plasticity. This activity-related alteration in Arc expression induced by neuroinflammation may contribute to the cognitive deficits found in diseases associated with inflammation, such as AD.

Animals↗

Scaling down motor memories: de-adaptation after motor learning.

Although adaptation to novel motor tasks is sometimes a very slow process, de-adaptation is usually extremely rapid. Such rapid de-adaptation is seen in dynamic learning in which subjects can take hundreds of movements to learn a novel force environment but only a few movements to de-adapt back to a normal or "null" force environment. We investigated whether this effect is unique to the null environment or reveals a more general rapid adaptation mechanism by studying how subjects behave when their dynamic environment changes. We observed that after learning a dynamic force field, subjects took longer to de-adapt when the forces were turned off than to adapt to a novel scaled-down version of the experienced field. This demonstrates that rapid adaptation is not unique to the "null" force environment. Moreover, we examined subjects' ability to adapt from a learned field to either a scaled down field or to a field in which the sign of the forces changed. Even though in both conditions the required change in force output was identical, subjects were significantly faster at adapting to the scaled down field. The result suggests that rapid de-adaptation reflects a capacity to scale down the relative contribution of existing control modules to the motor output.

Adaptation, Physiological↗

Rapid reshaping of human motor generalization.

People routinely learn how to manipulate new tools or make new movements. This learning requires the transformation of sensed movement error into updates of predictive neural control. Here, we demonstrate that the richness of motor training determines not only what we learn but how we learn. Human subjects made reaching movements while holding a robotic arm whose perturbing forces changed directions at the same rate, twice as fast, or four times as fast as the direction of movement, therefore exposing subjects to environments of increasing complexity across movement space. Subjects learned all three environments and learned the low- and medium-complexity environments equally well. We found that subjects lessened their movement-by-movement adaptation and narrowed the spatial extent of generalization to match the environmental complexity. This result demonstrated that people can rapidly reshape the transformation of sense into motor prediction to best learn a new movement task. We then modeled this adaptation using a neural network and found that, to mimic human behavior, the modeled neuronal tuning of movement space needed to narrow and reduce gain with increased environmental complexity. Prominent theories of neural computation have hypothesized that neuronal tuning of space, which determines generalization, should remained fixed during learning so that a combination of neuronal outputs can underlie adaptation simply and flexibly. Here, we challenge those theories with evidence that the neuronal tuning of movement space changed within minutes of training.

Adaptation, Physiological↗

Elevated dynorphin in the hippocampal formation of aged rats: relation to cognitive impairment on a spatial learning task.

Radioimmunoassay revealed increased dynorphin A(1-8)-like immunoreactivity [dynA(1-8)LI] in the aged rat brain. Among a number of brain regions examined, an age-related dynA(1-8)LI elevation was found only in the hippocampal formation and frontal cortex. Moreover, the increase in dynA(1-8)LI in the aged hippocampus was associated with a decline in spatial learning ability: dynA(1-8)LI distinguished aged rats that were behaviorally impaired from aged cohorts that learned the spatial task as rapidly as younger animals. Northern blot hybridization using a 32P-labeled complementary RNA probe encoding rat prodynorphin indicated that the abundance of prodynorphin mRNA was also significantly increased in the hippocampal formation of aged rats with identified spatial learning impairments.

Aging↗

Objective assessment of gynecologic laparoscopic skills using the LapSimGyn virtual reality simulator.

BACKGROUND: Safe realistic training and unbiased quantitative assessment of technical skills are required for laparoscopy. Virtual reality (VR) simulators may be useful tools for training and assessing basic and advanced surgical skills and procedures. This study aimed to investigate the construct validity of the LapSimGyn VR simulator, and to determine the learning curves of gynecologists with different levels of experience. METHODS: For this study, 32 gynecologic trainees and consultants (juniors or seniors) were allocated into three groups: novices (0 advanced laparoscopic procedures), intermediate level (>20 and <60 procedures), and experts (>100 procedures). All performed 10 sets of simulations consisting of three basic skill tasks and an ectopic pregnancy program. The simulations were carried out on 3 days within a maximum period of 2 weeks. Assessment of skills was based on time, economy of movement, and error parameters measured by the simulator. RESULTS: The data showed that expert gynecologists performed significantly and consistently better than intermediate and novice gynecologists. The learning curves differed significantly between the groups, showing that experts start at a higher level and more rapidly reach the plateau of their learning curve than do intermediate and novice groups of surgeons. CONCLUSION: The LapSimGyn VR simulator package demonstrates construct validity on both the basic skills module and the procedural gynecologic module for ectopic pregnancy. Learning curves can be obtained, but to reach the maximum performance for the more complex tasks, 10 repetitions do not seem sufficient at the given task level and settings. LapSimGyn also seems to be flexible and widely accepted by the users.

Clinical Competence↗

Rapid identification of closely related muscle foods by vibrational spectroscopy and machine learning.

Muscle foods are an integral part of the human diet and during the last few decades consumption of poultry products in particular has increased significantly. It is important for consumers, retailers and food regulatory bodies that these products are of a consistently high quality, authentic, and have not been subjected to adulteration by any lower-grade material either by accident or for economic gain. A variety of methods have been developed for the identification and authentication of muscle foods. However, none of these are rapid or non-invasive, all are time-consuming and difficulties have been encountered in discriminating between the commercially important avian species. Whilst previous attempts have been made to discriminate between muscle foods using infrared spectroscopy, these have had limited success, in particular regarding the closely related poultry species, chicken and turkey. Moreover, this study includes novel data since no attempts have been made to discriminate between both the species and the distinct muscle groups within these species, and this is the first application of Raman spectroscopy to the study of muscle foods. Samples of pre-packed meat and poultry were acquired and FT-IR and Raman measurements taken directly from the meat surface. Qualitative interpretation of FT-IR and Raman spectra at the species and muscle group levels were possible using discriminant function analysis. Genetic algorithms were used to elucidate meaningful interpretation of FT-IR results in (bio)chemical terms and we show that specific wavenumbers, and therefore chemical species, were discriminatory for each type (species and muscle) of poultry sample. We believe that this approach would aid food regulatory bodies in the rapid identification of meat and poultry products and shows particular potential for rapid assessment of food adulteration.

Algorithms↗

The control of sequential goal-directed movement: learning to use feedback or central planning?

Fifteen participants practiced a two-target sequential aiming movement with either full vision of the movement environment, vision during flight, or vision while in contact with the first target. After 100 acquisition trials, participants performed a retention test in their own condition and then were transferred to each of the other two vision conditions. Both performance and kinematic data indicated that rather than becoming less dependent on visual information with practice, subjects learned to adjust their movement trajectories to use the visual information available in their particular vision condition. Although transfer to a degraded vision condition disrupted performance, when vision was augmented participants quickly adjusted their aiming trajectories to use the added information. The findings suggest that at least part of learning involves the development of rapid and efficient procedures for processing afferent information, including visual response-produced feedback.

Adolescent↗

Perceptual learning in visual search generalizes over tasks, locations, and eyes.

In a visual search task, targets containing elementary features are detected in parallel, while a serial search is necessary for the detection of a target without a feature, or for targets containing conjunctions of features. In this study, we re-investigated the role of practice in visual search tasks, using an uncued visual search paradigm. Under some circumstances, initially serial tasks can become parallel with practice. Perceptual learning of feature search tasks is rapid (a few hundreds of trials are sufficient to transform serial into parallel search), long-lasting (a learned task is retained over several months), but far less specific than learning of other visual tasks (see also Sireteanu & Rettenbach, 1995a [Vision Research, 35, 2037-2043]). Learning transfers from one task to another, from one location in the visual field to another, and between the two eyes of a given subject, even if the subject has reduced stereopsis. Search for a conjunction of orientation and colour becomes more efficient, suggesting that a different search strategy emerges after prolonged practice. These results suggest that learning of visual search tasks modifies neural structures located at a high level in the visual pathway, involving different, presumably more central neural circuits, than the learning of visual discriminations and hyperacuity.

Analysis of Variance↗

The orbitofrontal cortex and reward.

The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. The orbitofrontal cortex also receives information about the sight of objects and faces from the temporal lobe cortical visual areas, and neurons in it learn and reverse the visual stimulus to which they respond when the association of the visual stimulus with a primary reinforcing stimulus (such as a taste reward) is reversed. However, the orbitofrontal cortex is involved in representing negative reinforcers (punishers) too, such as aversive taste, and in rapid stimulus-reinforcement association learning for both positive and negative primary reinforcers. In complementary neuroimaging studies in humans it is being found that areas of the orbitofrontal cortex (and connected subgenual cingulate cortex) are activated by pleasant touch, by painful touch, by rewarding and aversive taste, and by odor. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus- reinforcement associations, and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. This evidence thus shows that the orbitofrontal cortex is involved in decoding and representing some primary reinforcers such as taste and touch; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and in controlling and correcting reward-related and punishment-related behavior, and thus in emotion.

Afferent Pathways↗