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At least 1,603 records · Page 89Linked to original sources
PubMed1995

Differential modulation of brain immediate early genes by intraperitoneal LiCl.

We have used in situ hybridization to investigate the modulation of expression of the immediate early genes (IEGs) c-fos, fos-B, zif/268 and CREM in rat brain following oral administration of saccharin, i.p. injection of LiCl, and conditioned taste aversion (CTA) training in which these stimuli are used as the conditioned stimulus (CS) and the unconditioned stimulus (UCS), respectively. Modulation of c-fos, zif/268 and CREM was detected in the NTS, PBN, hypothalamic PVN and central nucleus of the amygdala after the administration of the UCS but not the CS. Our data are consonant with the hypothesis that differential and combinatorial expression of IEGs plays a role in encoding the representation of LiCl-induced malaise in the brain.

Animals↗
PubMed2025

STRUMP-I: Structure-based machine learning approach to pMHC-I binding prediction using force field energy features.

The adaptive immune system monitors cellular integrity by recognizing short peptides from intracellular proteins presented on Major Histocompatibility Complex class I (MHC-I) molecules, collectively termed peptide-MHC complexes (pMHC), enabling detection of foreign or mutated proteins. With the rising importance of immunotherapies targeting neoantigens in cancers, the ability to accurately predict which peptides will bind to the diverse population of MHC alleles is critically important. Current computational methods for pMHC-I prediction fall broadly into sequence-based methods, which rely heavily on large training datasets, and structure-based methods that leverage structural modeling and energetics of pMHC binding. While sequence-based methods have been popularly used, their performance is dependent on the size and quality of training data. On the other hands, while structure-based approaches can generalize better across diverse MHC alleles, they traditionally depend on identifying a single global minimum energy conformation, an assumption that often fails due to the inherent binding promiscuity of MHC-I molecules. To address these limitations, we developed a STRUMP-I (STRUcture-based pMHC Prediction (for class I)), a novel pMHC binding prediction tool that directly leverages a broad set of force-field-derived energy terms as machine-learning features. STRUMP-I achieves performance comparable to state-of-the-art sequence-based models while significantly outperforming them on MHC alleles with limited representation in training data. Furthermore, STRUMP-I demonstrates strong synergy when integrated with sequence-based methods, notably enhancing prediction precision. The robustness and generalizability of STRUMP-I were confirmed by evaluating its predictive performance on independent, previously unseen datasets, including an experimentally validated cancer neoantigen dataset. This combined approach advances our capability to reliably identify clinically relevant neoantigen targets. The source code and trained models are available at https://github.com/yoonjoolab/STRUMP-I.

energy optimization↗
PubMed1993

Sexual approach conditioning: tests of unconditioned stimulus devaluation using hormone manipulations.

Contents of learning that result from conditioned-unconditioned stimulus pairings in sexual approach conditioning were explored with male Japanese quail (Coturnix coturnix japonica). Sexual motivation of subjects conditioned to approach an arbitrary stimulus in a Pavlovian sexual conditioning paradigm was reduced by exposing them to a short photoperiod. Decreased sexual motivation resulted in a decline in sexually conditioned approach behavior (Experiments 1 and 2). Responding was restored when subjects were returned to a long photoperiod (Experiment 1) and when exogenous testosterone was administered (Experiment 2). Decreased sexual motivation did not affect food-conditioned approach behavior (Experiment 3). These results suggest that sexually conditioned approach behavior is mediated by a representation of the unconditioned stimulus, which is activated by the conditioned stimulus.

Animals↗
PubMedDate not supplied

Some recalcitrant views on the role of noncognitive S-R factors in human Pavlovian autonomic conditioning. Some facts still haunt us.

Either implicitly or explicity, most workers in the last two decades have adopted the (imperialistic) view that conditioning is simply the learning of (cognitive) S-S relationships, and that (noncognitive) S-R factors are irrelevant. I shall remind us of some contrary evidence from human Pavlovian autonomic conditioning (HPAC), consideration of which may spoil our neat cognitive picture (representation?) of the world, but may also lead both to a better understanding of the conditioning phenomenon and to more genuinely useful applications of conditioning principles to behavioral (including psychophysiological) problems.

Arousal↗
PubMedDate not supplied

Spatial visualization, visual imagery, and mathematical problem solving of students with varying abilities.

The purpose of this study was to investigate students' use of visual imagery and its relationship to spatial visualization ability while solving mathematical word problems. Students with learning disabilities (LD), average achievers, and gifted students in sixth grade (N = 66) participated in this study. Students were assessed on measures of mathematical problem solving, visual imagery representation, and spatial visualization ability. The results indicated that gifted students performed better on both spatial visualization measures than students with LD and average-achieving students. Use of visual images was positively correlated with higher mathematical word-problem-solving performance. Furthermore, the use of schematic imagery was significantly and positively correlated with higher performance on each spatial visualization measure; conversely, it was negatively correlated with the use of pictorial images.

Demography↗
PubMed1991

Remembering facial configurations.

Eight experiments are reported showing that subjects can remember rather subtle aspects of the configuration of facial features to which they have earlier been exposed. Subjects saw several slightly different configurations (formed by altering the relative placement of internal features of the face) of each of ten different faces, and they were asked to rate the apparent age and masculinity-femininity of each. Afterwards, subjects were asked to select from pairs of faces the configuration which was identical to one previously rated. Subjects responded strongly to the central or "prototypical" configuration of each studied face where this was included as one member of each test pair, whether or not it had been studied (Experiments 1, 2 and 4). Subjects were also quite accurate at recognizing one of the previously encountered extremes of the series of configurations that had been rated (Experiment 3), but when unseen prototypes were paired with seen exemplars subjects' performance was at chance (Experiment 5). Prototype learning of face patterns was shown to be stronger than that for house patterns, though both classes of patterns were affected equally by inversion (Experiment 6). The final two experiments demonstrated that preferences for the prototype could be affected by instructions at study and by whether different exemplars of the same face were shown consecutively or distributed through the study series. The discussion examines the implications of these results for theories of the representation of faces and for instance-based models of memory.

Adolescent↗
PubMed2005

Motor control and learning in altered dynamic environments.

Dynamic perturbations of reaching movements are an important technique for studying motor learning and adaptation. Adaptation to non-contacting, velocity-dependent inertial Coriolis forces generated by arm movements during passive body rotation is very rapid, and when complete the Coriolis forces are no longer sensed. Adaptation to velocity-dependent forces delivered by a robotic manipulandum takes longer and the perturbations continue to be perceived even when adaptation is complete. These differences reflect adaptive self-calibration of motor control versus learning the behavior of an external object or 'tool'. Velocity-dependent inertial Coriolis forces also arise in everyday behavior during voluntary turn and reach movements but because of anticipatory feedforward motor compensations do not affect movement accuracy despite being larger than the velocity-dependent forces typically used in experimental studies. Progress has been made in understanding: the common features that determine adaptive responses to velocity-dependent perturbations of jaw and limb movements; the transfer of adaptation to mechanical perturbations across different contact sites on a limb; and the parcellation and separate representation of the static and dynamic components of multiforce perturbations.

Animals↗
PubMed2002

Differential muscarinic and NMDA contributions to visuo-spatial paired-associate learning in rhesus monkeys.

RATIONALE: Early, accurate detection of degenerative neurological disorders such as Alzheimer's disease (AD) is essential for therapies designed to slow disease progression. Performance of a touch-screen mediated visuo-spatial paired-associates learning (vsPAL) task predicts neurocognitive decline in elderly populations presenting with mild cognitive impairment and distinguishes AD patients from elderly depressed individuals. Translation of this cognitive task to a non-human model may therefore provide an improved tool for study of the etiology and treatment of dementia. OBJECTIVE: The goal of the current study was to contrast cholinergic and glutamatergic contributions to performance of this AD-sensitive task by challenging rhesus monkeys performing vsPAL with muscarinic antagonist and non-competitive NMDA antagonist drugs. METHODS: Seven monkeys were trained to perform vsPAL and then serially challenged with acute doses of scopolamine (3, 10, 17 microg/kg, IM) and ketamine (0.3, 1.0, 1.78 mg/kg, IM). RESULTS: Scopolamine produced a dosexdifficulty related impairment of both recognition memory and incremental acquisition aspects of task performance. In contrast, ketamine administration resulted in a dose-dependent impairment of recognition memory but not incremental acquisition. CONCLUSIONS: Monkeys' performance of a task sensitive to AD in humans was impaired by two classic pharmacological models of cognitive impairment, therefore supporting the use of this nonhuman model to explore mechanisms of AD-associated cognitive decline. The differential pattern of impairment observed is consistent with a hypothesis that muscarinic mechanisms are required for linking external events with an existing internal representation, whereas NMDA mechanisms are required for the formation/strengthening of such an internal representation.

Animals↗
PubMed2004

Neural foundations of emerging route knowledge in complex spatial environments.

Behavioral evidence suggests that spatial knowledge derived from ground-level navigation can consist of both route and survey knowledge. Neuroimaging and lesion studies aiming to identify the neural structures responsible for topographical learning in humans have yielded partially inconsistent results, probably due to the lack of an effective behavioral parameter allowing for a reliable distinction between different representations. Therefore, we employed a novel virtual reality environment that provides accuracy and reaction time measures precisely indicating the emergence of route vs. survey knowledge. Functional magnetic resonance imaging (fMRI) was used to localize brain regions involved in the acquisition of pure route knowledge in the form of associations between consecutive landmark views and the direction of intermediate movements. Participants were scanned during repeated encoding of the complex environment from a first-person, ground-level perspective. Behavioral data revealed emerging route knowledge in 11 out of 14 subjects. Overall comparisons between encoding and control conditions identified activation in medial frontal gyrus, retrosplenial cortex and posterior inferior parietal cortex. Most importantly, only posterior inferior parietal regions showed increasing activation across sessions, thus paralleling behavioral measures of route expertise. Given the established role of the posterior parietal cortex in spatial processing, this area is thought to provide the pivotal spatial link between two landmarks encountered in immediate temporal succession.

Adult↗
PubMed1998

Navigation and acquisition of spatial knowledge in a virtual maze.

Spatial behavior in humans and animals includes a wide variety of behavioral competences and makes use of a large number of sensory cues. Here we studied the ability of human subjects to search locations, to find shortcuts and novel paths, to estimate distances between remembered places, and to draw sketch maps of the explored environment; these competences are related to goal-independent memory of space, or cognitive maps. Information on spatial relations was restricted to two types: a visual motion sequence generated by simulated movements in a virtual maze and the subject's own movement decisions defining the path through the maze. Visual information was local (i.e., no global landmarks or compass information was provided). Other position and movement information (vestibular or proprioceptive) was excluded. The amount of visual information provided was varied over four experimental conditions. The results indicate that human subjects are able to learn a virtual maze from sequences of local views and movements. The information acquired is local, consisting of recognized positions and movement decisions associated to them. Although simple associations of this type can be shown to be present in some subjects, more complete configurational knowledge is acquired as well. The results are discussed in a view-based framework of navigation and the representation of spatial knowledge by means of a view graph.

Adolescent↗
PubMed1999

Emergence of symmetric, modular, and reciprocal connections in recurrent networks with Hebbian learning.

While learning and development are well characterized in feedforward networks, these features are more difficult to analyze in recurrent networks due to the increased complexity of dual dynamics - the rapid dynamics arising from activation states and the slow dynamics arising from learning or developmental plasticity. We present analytical and numerical results that consider dual dynamics in a recurrent network undergoing Hebbian learning with either constant weight decay or weight normalization. Starting from initially random connections, the recurrent network develops symmetric or near-symmetric connections through Hebbian learning. Reciprocity and modularity arise naturally through correlations in the activation states. Additionally, weight normalization may be better than constant weight decay for the development of multiple attractor states that allow a diverse representation of the inputs. These results suggest a natural mechanism by which synaptic plasticity in recurrent networks such as cortical and brainstem premotor circuits could enhance neural computation and the generation of motor programs.

Animals↗
PubMed1999

Brain responses reveal the learning of foreign language phonemes.

Learning to speak a new language requires the formation of recognition patterns for the speech sounds specific to the newly acquired language. The present study demonstrates the dynamic nature of cortical memory representations for phonemes in adults by using the mismatch negativity (MMN) event-related potential. We studied Hungarian and Finnish subjects, dividing the Hungarians into a naive (no knowledge of Finnish) and a fluent (in Finnish) group. We found that the MMN for a contrast between two Finnish phonemes was elicited in the fluent Hungarians but not in the naive Hungarians. This result indicates that the fluent Hungarians developed cortical memory representations for the Finnish phoneme system that enabled them to preattentively categorize phonemes specific to this language.

Adult↗
PubMed2026

EvoSNR-Prom: Predicting promoters at single-nucleotide resolution with label-aware transfer learning of the pretrained EVO model.

The precise identification of promoters is crucial for understanding gene regulation. Deep learning methods have achieved considerable success in promoter prediction, yet most operate at the sequence level with coarse-grained labels. This means they label an entire DNA segment as either a "promoter" or "non-promoter," which results in a lack of the nucleotide-level resolution in prediction. In this study, we propose EvoSNR-Prom, a model designed for promoter prediction at single-nucleotide resolution. EvoSNR-Prom is built on the Evo foundation model and formulates promoter identification as a token-level sequence labeling problem, analogous to named entity recognition in natural language processing. To address the limited contextual information available in single-nucleotide tokenization, we introduce a lexicon-enhanced embedding strategy that incorporates biologically meaningful DNA lexicons, enriching contextual representations and improving the model's ability to capture complex sequence motifs. Furthermore, to enhance predictive performance on small size datasets, we integrate a label-aware transfer learning framework to leverage knowledge from well-annotated source species to a target organism. The results across various prokaryotic datasets show that EvoSNR-Prom achieves excellent performance. This work provides a valuable computational framework for the high-precision analysis of gene regulatory elements, contributing to the advancement of promoter prediction at single-nucleotide resolution.

Promoter Regions, Genetic↗
PubMed2007

Modelling memory functions with recurrent neural networks consisting of input compensation units: I. Static situations.

Humans are able to form internal representations of the information they process -- a capability which enables them to perform many different memory tasks. Therefore, the neural system has to learn somehow to represent aspects of the environmental situation; this process is assumed to be based on synaptic changes. The situations to be represented are various as for example different types of static patterns but also dynamic scenes. How are neural networks consisting of mutually connected neurons capable of performing such tasks? Here we propose a new neuronal structure for artificial neurons. This structure allows one to disentangle the dynamics of the recurrent connectivity from the dynamics induced by synaptic changes due to the learning processes. The error signal is computed locally within the individual neuron. Thus, online learning is possible without any additional structures. Recurrent neural networks equipped with these computational units cope with different memory tasks. Examples illustrate how information is extracted from environmental situations comprising fixed patterns to produce sustained activity and to deal with simple algebraic relations.

Humans↗
PubMed1997

Information and viewpoint dependence in face recognition.

How we recognize faces despite rotations in depth is of great interest to psychologists, computer scientists and neurophysiologists because of the accuracy of human performance despite the intrinsic difficulty of the task. Three experiments are reported here which used three-dimensional facial surface representations to investigate the effects of rotations in depth on a face recognition task. Experiment 1, using "shape only" representations, showed that all the views used (full-face, three-quarter and profile) were equally well recognized when all had been learned. Performance was better when the same views were presented in an animated sequence rather than at random, suggesting that structure-from-motion provides useful information for recognition. When stimuli were presented inverted, performance was worse and there were differences in the recognizability of views, demonstrating that the familiarity of upright faces affects generalization across views. Experiments 2 and 3 investigated generalization from single views and found performance to be dependent on learned view. In both experiments, generalization from learned full-face fell off with increasing angle of rotation. With shape only stimuli, three-quarter views generalized well to each other, even when inverted but for profiles generalization was equally bad to all unlearned views. This difference may be explained because of the particular relationship of the profile to the axis of symmetry. In Experiment 3, addition of information about superficial properties including color and texture facilitated performance, but patterns of generalization remained substantially the same, emphasizing the importance of underlying shape information. However, generalization from the three-quarter view became viewpoint invariant and there was some evidence for better generalization between profiles. The results are interpreted as showing that three-dimensional shape information is fundamental for recognition across rotations in depth although superficial information may also be used to reduce viewpoint dependence.

Adult↗
PubMed2002

Focal enhancement of motor cortex excitability during motor imagery: a transcranial magnetic stimulation study.

OBJECTIVES: In order to learn more about the physiology of the motor cortex during motor imagery, we evaluated the changes in excitability of two different hand muscle representations in the primary motor cortex (M1) of both hemispheres during two imagery conditions. MATERIALS AND METHODS: We applied focal transcranial magnetic stimulation (TMS) over each M1, recording motor evoked potentials (MEPs) from the contralateral abductor pollicis brevis (APB) and first dorsal interosseus (FDI) muscles during rest, imagery of contralateral thumb abduction (C-APB), and imagery of ipsilateral thumb abduction (I-APB). We obtained measures of motor threshold (MT), MEP recruitment curve (MEP-rc) and F waves. RESULTS: Motor imagery compared with rest significantly decreased the MT and increased MEPs amplitude at stimulation intensities clearly above MT in condition C-APB, but not in condition I-APB. These effects were not significantly different between right and left hemisphere. MEPs simultaneously recorded from the FDI, which was not involved in the task, did not show facilitatory effects. There were no significant changes in F wave amplitude during motor imagery compared with rest. CONCLUSIONS: Imagery of unilateral simple movements is associated with increased excitability only of a highly specific representation in the contralateral M1 and does not differ between hemispheres.

Adult↗