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A computational principle for hippocampal learning and neurogenesis.

In the three decades since Marr put forward his computational theory of hippocampal coding, many computational models have been built on the same key principles proposed by Marr: sparse representations, rapid Hebbian storage, associative recall and consolidation. Most of these models have focused on either the CA3 or CA1 fields, using "off-the-shelf" learning algorithms such as competitive learning or Hebbian pattern association. Here, we propose a novel coding principle that is common to all hippocampal regions, and from this one principal, we derive learning rules for each of the major pathways within the hippocampus. The learning rules turn out to have much in common with several models of CA3 and CA1 in the literature, and provide a unifying framework in which to view these models. Simulations of the complete circuit confirm that both recognition memory and recall are superior relative to a hippocampally lesioned model, consistent with human data. Further, we propose a functional role for neurogenesis in the dentate gyrus (DG), namely, to create distinct memory traces for highly similar items. Our simulation results support our prediction that memory capacity increases with the number of dentate granule cells, while neuronal turnover with a fixed dentate layer size improves recall, by minimizing interference between highly similar items.

Action Potentials↗

Lexical neighborhoods and the word-form representations of 14-month-olds.

The degree to which infants represent phonetic detail in words has been a source of controversy in phonology and developmental psychology. One prominent hypothesis holds that infants store words in a vague or inaccurate form until the learning of similar-sounding neighbors forces attention to subtle phonetic distinctions. In the experiment reported here, we used a visual fixation task to assess word recognition. We present the first evidence indicating that, infact, the lexical representations of 14- and 15-month-olds are encoded in fine detail, even when this detail is not functionally necessary for distinguishing similar words in the infant's vocabulary. Exposure to words is sufficient for well-specified lexical representations, even well before the vocabulary spurt. These results suggest developmental continuity in infants' representations of speech: As infants begin to build a vocabulary and learn word meanings, they use the perceptual abilities previously demonstrated in tasks testing the discrimination and categorization of meaningless syllables.

Attention↗

Visual and proprioceptive representations in spatial memory.

It has been shown that spatial information can be acquired from both visual and nonvisual modalities. The present study explored how spatial information from vision and proprioception was represented in memory, investigating orientation dependence of spatial memories acquired through visual and proprioceptive spatial learning. Experiment 1 examined whether visual learning alone and proprioceptive learning alone yielded orientation-dependent spatial memory. Results showed that spatial memories from both types of learning were orientation dependent. Experiment 2 explored how different orientations of the same environment were represented when they were learned visually and proprioceptively. Results showed that both visually and proprioceptively learned orientations were represented in spatial memory, suggesting that participants established two different reference systems based on each type of learning experience and interpreted the environment in terms of these two reference systems. The results provide some initial clues to how different modalities make unique contributions to spatial representations.

Adolescent↗

Integrating RNA sequencing with deep learning-based metabolic toxicity prediction: A new perspective on screening prioritized liquid crystal monomers.

Nearly 99 % of liquid crystal monomers (LCMs) toxicological data remains gaps, especially to aquatic organisms. Herein, this study proposes a rapid and high-throughput screening method for identifying priority LCMs in natural water. Using six fluorinated LCMs (LCMsF) with significant enrichment characteristics in zebrafish as examples, RNA sequencing revealed that LCMsF-induced metabolic disturbances are predominant, including 28 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway abnormalities attributed to 498 differentially expressed genes. Notably, the intricate sequencing process resulted in the inability to rapid identify additional 857 LCMsF that may induce metabolic disturbances. To address this, LCMsT-MTP, a predictive deep learning model based on RNA sequencing, was developed. This model integrates a comprehensive representation of LCMsF structures and metabolic toxicity target sequences. LCMsT-MTP improves upon traditional methods that are limited to single targets and mechanisms by facilitating the simultaneous identification of 21 metabolic toxicities induced by LCMsF. In addition, the LCMsT-MTP model was further applied to non-fluorinated LCMs (LCMsNone F) that satisfy the applicability domains test. Accordingly, a metabolic toxicity priority list of LCMs was proposed, with ∼95 % of LCMs classified as high or medium risk. Priority list validation by molecular dynamics confirmed that the interactions of LCMsF/LCMsNone F and metabolic toxicity targets in representative KEGG pathways were distinct.

Animals↗

Cued recall from image and sentence memory: a shift from episodic to identical elements representation.

The applicability of the identical elements (IE) model of arithmetic fact retrieval (T. C. Rickard, A. F. Healy, & L. E. Bourne, 1994) to cued recall from episodic (image and sentence) memory was explored in 3 transfer experiments. In agreement with results from arithmetic, speedup following even minimal practice recalling a missing word from an episodically bound word triplet did not transfer positively to other cued recall items involving the same triplet. The shape of the learning curve further supported a shift from episode-based to IE-based recall, extending some models of skill learning to cued recall practice. In contrast with previous findings, these results indicate that a form of representation that is independent of the original episodic memory underlies cued-recall performance following minimal practice.

Cues↗

Hippocampal participation in navigational map learning in young homing pigeons is dependent on training experience.

The homing pigeon navigational map is perhaps one of the most striking examples of a naturally occurring spatial representation of the environment used to guide navigation. In a previous study, it was found that hippocampal lesions thoroughly disrupt the ability of young homing pigeons held in an outdoor aviary to learn a navigational map. However, since that study an accumulation of anecdotal data has hinted that hippocampal-lesioned young pigeons allowed to fly during their first summer could learn a navigational map. In the present study, young control and hippocampal-lesioned homing pigeons were either held in an outdoor aviary or allowed to fly during the time of navigational map learning. At the end of their first summer, the birds were experimentally released to test for navigational map learning. Independent of training experience, control pigeons oriented homeward during the experimental releases demonstrating that they learned a navigational map. Surprisingly, while the aviary-held hippocampal-lesioned pigeons failed to learn a navigational map as reported previously, hippocampal-lesioned birds allowed flight experience learned a navigational map indistinguishable from the two control groups. A subsequent experiment revealed that the navigational map learned by the three groups was based on atmospheric odours. The results demonstrate that hippocampal participation in navigational map learning depends on the type of experience a young bird pigeon has, and presumably, the type of navigational map learned.

Animals↗

Learning in Stochastic Bit Stream Neural Networks.

This paper presents learning techniques for a novel feedforward stochastic neural network. The model uses stochastic weights and the "bit stream" data representation. It has a clean analysable functionality and is very attractive with its great potential to be implemented in hardware using standard digital VLSI technology. The design allows simulation at three different levels and learning techniques are described for each level. The lowest level corresponds to on-chip learning. Simulation results on three benchmark MONK's problems and handwritten digit recognition with a clean set of 500 16 x 16 pixel digits demonstrate that the new model is powerful enough for the real world applications. Copyright 1996 Elsevier Science Ltd

Journal Article↗

Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle.

The orbitofrontal cortex (OFC) has been implicated in the representation of emotional stimuli, assignment of emotional valence/salience to stimuli, stimulus-reinforcement association learning, motivation, and socio-emotional control. Using functional magnetic resonance imaging in female subjects without premenstrual mood symptoms, we found that OFC activity to emotional linguistic stimuli varies depending on the menstrual cycle phase. Specifically, anterior-medial OFC activity for negative vs. neutral stimuli was increased premenstrually and decreased postmenstrually. The inverse pattern was seen in the lateral OFC. These findings suggest that specific subregional OFC activity to emotional stimuli is modulated across the menstrual cycle. The data also demonstrate that menstrual cycle phase is an important consideration in further studies attempting to elucidate the neural substrates of affective representation.

Adult↗

Text processing and feedback: what have we learned?

In studies on the effects of feedback on text comprehension, it was determined that text content interacts differentially with the feedback provided. Specifically, the types of memorial representations sought must be considered in terms of type of text, feedback timing, frequency, and modality.

Feedback↗

Separating style and content with bilinear models.

Perceptual systems routinely separate "content" from "style," classifying familiar words spoken in an unfamiliar accent, identifying a font or handwriting style across letters, or recognizing a familiar face or object seen under unfamiliar viewing conditions. Yet a general and tractable computational model of this ability to untangle the underlying factors of perceptual observations remains elusive (Hofstadter, 1985). Existing factor models (Mardia, Kent, & Bibby, 1979; Hinton & Zemel, 1994; Ghahramani, 1995; Bell & Sejnowski, 1995; Hinton, Dayan, Frey, & Neal, 1995; Dayan, Hinton, Neal, & Zemel, 1995; Hinton & Ghahramani, 1997) are either insufficiently rich to capture the complex interactions of perceptually meaningful factors such as phoneme and speaker accent or letter and font, or do not allow efficient learning algorithms. We present a general framework for learning to solve two-factor tasks using bilinear models, which provide sufficiently expressive representations of factor interactions but can nonetheless be fit to data using efficient algorithms based on the singular value decomposition and expectation-maximization. We report promising results on three different tasks in three different perceptual domains: spoken vowel classification with a benchmark multi-speaker database, extrapolation of fonts to unseen letters, and translation of faces to novel illuminants.

Algorithms↗

Long-lasting perceptual priming and semantic learning in amnesia: a case experiment.

An investigation of perceptual priming and semantic learning in the severely amnesic subject K.C. is reported. He was taught 64 three-word sentences and tested for his ability to produce the final word of each sentence. Despite a total lack of episodic memory, he exhibited (a) strong perceptual priming effects in word-fragment completion, which were retained essentially in full strength for 12 months, and (b) independent of perceptual priming, learning of new semantic facts, many of which were also retained for 12 months. K.C.'s semantic learning may be at least partly attributable to repeated study trials and minimal interference during learning. The findings suggest that perceptual priming and semantic learning are subserved by two memory systems different from episodic memory and that both systems (perceptual representation and semantic memory) are at least partially preserved in some amnesic subjects.

Adult↗

Comparison of normal and learning disabled children on a nonverbal short-term memory serial position task.

A serial recall task was used to compare performance of 15 normal and 15 learning disabled elementary school children matched on CA, IQ, and sex with two and three dimensional representations of nonverbal eight-point shapes. Two a priori assumptions were not supported: (a) no differences in recall were found between groups and (b) no differences in recall were found for either group using two or three dimensional stimuli. Three dimensional stimuli did facilitate visual rehearsal at the primacy position for both groups. Learning disabled children's performance was consistent with the mediation deficiency hypothesis found with normal children.

Child↗

Olfactory coding in the mammalian olfactory bulb.

There have been a number of recent approaches to the study of olfactory coding, each of which has its advantages and disadvantages. In the present review, we discuss our own work on this topic, which has involved mapping uptake of [14C]2-deoxyglucose across the entire glomerular layer of the rat main olfactory bulb in response to systematically selected pure odorant molecules. Our strategy to understand the olfactory code has involved four approaches. In the first, we determined whether the system encodes odorants in their entirety, or whether it encodes odorants by representing combinations of molecular features that add together to comprise a neural picture of each odorant. Multiple odorant features appeared to be coded by multiple receptors. Our second strategy examined the ways that such features are represented. We stimulated rats with odorants that differed greatly in their molecular structure to be able to identify a set of odorant feature response domains. Our third approach asked how odorants with very small differences in molecular structure are coded, and we found systematic differences in the representation of such features within response domains. Finally, we were able to predict odor perception from the neural representations of odorants that differed in only a single aspect of their structure. Using these strategies, we have been able to learn some of the rules by which the olfactory code operates. These rules have allowed us to predict where previously unmapped molecules would be represented and how differences in molecular representations affect olfactory perceptions.

Animals↗

Computer-assisted learning using a dialogue system for virtual teacher-student communication.

Over the past decade, computer-assisted learning in the field of chemistry has given rise to a large number of systems that approach this objective from different viewpoints: static courses aimed at specific concepts, tutorial systems, 2D and 3D virtual environments, and so on. Correct structuring and representation of the knowledge to be taught, the building of a suitable student interface, and the adaptation of the learning process to the knowledge of the student are but a few of the challenges to be faced in the development of efficient computer-assisted learning systems. The present study tackles the use of computerized dialogue systems as a viable alternative for the simulation of teacher-student interaction and proposes an ontology for the characterization of such interaction, employing the object-oriented paradigm in the modeling of both the knowledge to be taught and the actual level of the student. The proposed solution is based on the representation of the knowledge to be taught through a network of multiconnected knowledge frames (chunks), where each chunk may be specialized in more specific frames (prerequisites and subobjectives), contain associated explanations of varying complexity and with a range of explanatory models, and be associated with one or a set of possible questions the student might ask; to this end, a constantly evolving knowledge model is maintained throughout the explanatory process. Based on the proposed model, Java was used to develop and manage an explanatory system that could be used in any type of teaching system based on student-dominated dialogues. Here, the system has been applied to the teaching of chemistry laboratory practice by its integration into the Virtual Chemistry Laboratory (VCL), a system designed by the authors to simulate chemistry techniques in a virtual 3D world.

Journal Article↗

Development of interocular equivalence of place learning in the rat requires convergence sites established prior to training.

Interocular equivalence for spatial-navigation learning requires that the neural pathways originating in each eye converge on common memory sites. Rats fail to display interocular equivalence if they are trained and tested on the Morris (1981) place-navigation task when they are 22 days old, but they succeed if they are trained and tested when they are 28 days old (Rudy & Stadler-Morris, 1987). This delay suggests that there is a period in development when the interhemispheric connections necessary for convergence are immature and rats behave temporarily as split-brain organisms. In the present experiment, rats completed training when they were 22 days old but were not tested for interocular equivalence until they were 28 days old. Nevertheless, these subjects failed to demonstrate equivalence. Thus, for interocular equivalence to be observed, the neural pathways from each eye must converge on common neural sites that are functional at the time the memory representation is established.

Animals↗

Learning-induced physiological memory in adult primary auditory cortex: receptive fields plasticity, model, and mechanisms.

It is well established that the functional organization of adult sensory cortices, including the auditory cortex, can be modified by deafferentation, sensory deprivation, or selective sensory stimulation. This paper reviews evidence establishing that the adult primary auditory cortex develops physiological plasticity during learning. Determination of frequency receptive fields before and at various times following aversive classical conditioning and instrumental avoidance learning in the guinea pig reveals increased neuronal responses to the pure tone frequency used as a conditioned stimulus (CS). In contrast, responses to the pretraining best frequency and other non-CS frequencies are decreased. These opposite changes are often sufficient to shift cellular tuning toward or even to the frequency of the CS. Learning-induced receptive field (RF) plasticity (i) is associative (requires pairing tone and shock), (ii) highly specific to the CS frequency (e.g., limited to this frequency +/- a small fraction of an octave), (iii) discriminative (specific increased response to a reinforced CS+ frequency but decreased response to a nonreinforced CS- frequency), (iv) develops extremely rapidly (within 5 trials, the fewest trials tested), and (v) is retained indefinitely (tested to 8 weeks). Moreover, RF plasticity is robust and not due to arousal, but can be expressed in the deeply anesthetized subject. Because learning- induced RF plasticity has the major characteristics of associative memory, it is therefore referred to as "physiological memory". We developed a model of RF plasticity based on convergence in the auditory cortex of nucleus basalis cholinergic effects acting at muscarinic receptors, with lemniscal and nonlemniscal frequency information from the ventral and magnocellular divisions of the medial geniculate nucleus, respectively. In the model, the specificity of RF plasticity is dependent on Hebbian rules of covariance. This aspect was confirmed in vivo using microstimulation techniques. Further, the model predicts that pairing a tone with activation of the nucleus basalis is sufficient to induce RF plasticity similar to that obtained in behavioral learning. This prediction has been confirmed. Additional tests of the model are described. RF plasticity is thought to translate the acquired significance of sound into an increased frequency representation of behaviorally important stimuli.

Adult↗

Frontal networks for learning and executing arbitrary stimulus-response associations.

Flexible rule learning, a behavior with obvious adaptive value, is known to depend on an intact prefrontal cortex (PFC). One simple, yet powerful, form of such learning consists of forming arbitrary stimulus-response (S-R) associations. A variety of evidence from monkey and human studies suggests that the PFC plays an important role in both forming new S-R associations and in using learned rules to select the contextually appropriate response to a particular stimulus cue. Although monkey lesion studies more strongly implicate the ventrolateral PFC (vlPFC) in S-R learning, clinical data and neurophysiology studies have implicated both the vlPFC and the dorsolateral region (dlPFC) in associative rule learning. Previous human imaging studies of S-R learning tasks, however, have not demonstrated involvement of the dlPFC. This may be because of the design of previous imaging studies, which used few stimuli and used explicitly stated one-to-one S-R mapping rules that were usually practiced before scanning. Humans learn these rules very quickly, limiting the ability of imaging techniques to capture activity related to rule acquisition. To address these issues, we performed functional magnetic resonance imaging while subjects learned by trial and error to associate sets of abstract visual stimuli with arbitrary manual responses. Successful learning of this task required discernment of a categorical type of S-R rule in a block design expected to yield sustained rule representation. Our results show that distinct components of the dorsolateral, ventrolateral, and anterior PFC, lateral premotor cortex, supplementary motor area, and the striatum are involved in learning versus executing categorical S-R rules.

Adult↗

Integrating behavioral and physiological models of hippocampal function.

In recent modeling of hippocampal function, we have attempted to integrate formal behavioral analyses of classical conditioning with psychobiological data on brain lesions (Gluck and Myers [1993] Hippocampus 3:491-516; Myers and Gluck [1994] Behav Neurosci 108(5):835-847). Based on comparative behavioral analyses, we have argued that animals with hippocampal region damage are unable to alter stimulus similarity based on experience. While hippocampal-damaged animals can still learn whether to respond to an individual stimulus, they are notably impaired at many tasks involving learning relationships between stimuli-especially in the absence of explicit reinforcement. These analyses lead to a computational theory which identifies two representational recoding processes-predictive differentiation and redundancy compression-which alter stimulus similarity relationships in intact animals but are dependent on intact hippocampal region processing. More recent, and ongoing, modeling aims to broaden this model of hippocampal region function in classical conditioning, with an emphasis on physiological and anatomical constraints, including the role of the fornix and subcortical modulation, preprocessing in sensory cortices, and localization of the proposed representational functions within more precisely identified hippocampal region substrates (Myers et al. [1995] Psychology 23(2):116-138; Myers and Gluck [1996] Behav Neurosci; Myers et al. [1996] Neurobiol Learning Memory). Working to bridge between behavioral and physiological levels of analysis, we ultimately hope to develop a more complete understanding of hippocampal region function in memory across a wider range of behavioral paradigms, elucidating how this functionality emerges from underlying physiological and anatomical substrates.

Amnesia↗