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PubMed1999

Preserved negative patterning and impaired spatial learning in pigeons (Columba livia) with lesions of the hippocampus.

Pigeons (Columba livia) with bilateral electrolytic lesions of the hippocampus and area parahippocampalis were compared with control pigeons on 2 tasks: negative patterning and delayed spatial alternation. Negative patterning demands configural stimulus representations for its successful solution. The only effect of hippocampal lesions on this task was an increased response rate to the rewarded stimuli. On the delayed spatial alternation task, hippocampal birds showed deficits relative to controls. Differences in the results of prior studies on negative patterning appear to be due to different response requirements to the nonreinforced stimuli. These results are consistent with prior work with rats and suggest that the avian hippocampus is essential for spatial memory and response inhibition but is not involved in configural learning.

Animals↗
PubMed1983

Graphical representation of multidimensional EEG data and classificatory aspects.

EEG data are intrinsically multidimensional and this applies also to a set of broad band spectral parameters (6 parameters per derivation). Non-metric multidimensional scaling (MDS) and principal component analysis (PCA) are compared with respect to their capacity to achieve an adequate few-dimensional representation for the graphical comparison of groups and the identification of subgroups. In an application to neurophysiological aspects of mental retardation and learning disability, MDS proved to be somewhat superior to PCA. Both methods profited from the introduction of (1-p)-convex hulls to define a normative region.

Adolescent↗
PubMed1984

Neural substrates for tone-conditioned bradycardia demonstrated with 2-deoxyglucose. I. Activation of auditory nuclei.

The 2-deoxyglucose (2-DG) autoradiographic method was used to map the metabolic activity of auditory nuclei before, during and after conditioning. The experiment involved freely behaving rats in a Pavlovian conditioning paradigm in which a 4-5 kHz frequency modulated tone (CS) was paired with aversive electrical stimulation of the midbrain reticular formation (US). The unconditioned response was a rapid decrease in heart rate evoked by the US. Eight groups of rats were subjected to: (1) the tone CS before conditioning; (2) the US alone; (3) the paired CS-US (acquisition); (4) the tone CS after conditioning (extinction); (5) the US prior to the CS (sensitization); (6) the unpaired CS-US (pseudoconditioning); (7) the CS after pseudoconditioning; and (8) no stimulation. The major finding was the differential effect produced by the same tone before and after conditioning. The results showed that: (a) reticular mechanisms interact with incoming acoustic stimuli and modulate the response of auditory nuclei; (b) within each auditory nucleus the region of overlap of the spatial representations of CS and US developed an enhanced metabolic response during conditioning; and (c) the CS representation within the neuronal space of the tonotopic maps in all auditory nuclei, with the exception of the medial geniculate, reflected the learned behavioral value of the CS. The changes revealed by the 2-DG method represent the first anatomical demonstration of the activating effects of reticular sensitization and conditioning on a sensory system. The observations support the conclusion that auditory responses are dependent on the physical as well as on the behavioral parameters of a stimulus.

Animals↗
PubMed1992

Using sound to solve syntactic problems: the role of phonology in grammatical category assignments.

One ubiquitous problem in language processing involves the assignment of words to the correct grammatical category, such as noun or verb. In general, semantic and syntactic cues have been cited as the principal information for grammatical category assignment, to the neglect of possible phonological cues. This neglect is unwarranted, and the following claims are made: (a) Numerous correlations between phonology and grammatical class exist, (b) some of these correlations are large and can pervade the entire lexicon of a language and hence can involve thousands of words, (c) experiments have repeatedly found that adults and children have learned these correlations, and (d) explanations for how these correlations arose can be proposed and evaluated. Implications of these phenomena for language representation and processing are discussed.

Humans↗
PubMed2005

Androgen mediation of conditioned rhythmic cloacal sphincter movements in Japanese Quail (Coturnix japonica).

Demonstrations of increased reproductive success due to sexual conditioning in Japanese quail (Coturnix japonica) have been reported, although the mechanisms that underlie these effects have remained elusive. One possible mechanism is conditioned rhythmic cloacal sphincter movements (RCSM). Two experiments were conducted with male quail to determine whether associations between a conditioned stimulus (CS) and a hen would result in the ability of the CS to elicit RCSM, and to explore the androgen mediation of conditioned RCSM. The results suggest that a focal CS paired with visual access to a female will elicit RCSM via a representation of the hen activated by the CS. Further, the available evidence indicates that conditioned RCSM is androgen mediated and that this learning may transfer across breeding seasons.

Anal Canal↗
PubMed1993

Speaker-independent consonant classification in continuous speech with distinctive features and neural networks.

This paper provides experimental evidence to the assertion that the design of appropriate neural networks (NN) for speech recognition should be inspired by acoustic and phonetic knowledge, and not only by knowledge in pattern recognition. Rather than investigating the NN learning paradigm, the paper is focused on the influence of the input parameters, of the internal structure, and of the desired output representation on the classification performance of recurrent multilayer perceptrons. As an instructive example, the paper analyzes the problem of classifying ten stop and nasal consonants in continuous speech independently of the speaker. Experiments are reported for the TIMIT database, using 343 speakers in the training set and 77 different speakers in the test set. Comparative experiments show that good performance is obtained when many input acoustic parameters are used, including a time/frequency gradient operator related to transitions of the second formant, and when the desired outputs represent context-dependent articulatory features. Classification is performed by principal component analysis of the NN outputs. Refinement of the design parameters yield increasingly better performance on the test set, ranging from 45% errors for a perceptron without hidden nodes to 23.3% errors for the best NN.

Female↗
PubMed2006

JColorGrid: software for the visualization of biological measurements.

BACKGROUND: Two-dimensional data colourings are an effective medium by which to represent three-dimensional data in two dimensions. Such "color-grid" representations have found increasing use in the biological sciences (e.g. microarray 'heat maps' and bioactivity data) as they are particularly suited to complex data sets and offer an alternative to the graphical representations included in traditional statistical software packages. The effectiveness of color-grids lies in their graphical design, which introduces a standard for customizable data representation. Currently, software applications capable of generating limited color-grid representations can be found only in advanced statistical packages or custom programs (e.g. micro-array analysis tools), often associated with steep learning curves and requiring expert knowledge. RESULTS: Here we describe JColorGrid, a Java library and platform independent application that renders color-grid graphics from data. The software can be used as a Java library, as a command-line application, and as a color-grid parameter interface and graphical viewer application. Data, titles, and data labels are input as tab-delimited text files or Microsoft Excel spreadsheets and the color-grid settings are specified through the graphical interface or a text configuration file. JColorGrid allows both user graphical data exploration as well as a means of automatically rendering color-grids from data as part of research pipelines. CONCLUSION: The program has been tested on Windows, Mac, and Linux operating systems, and the binary executables and source files are available for download at http://jcolorgrid.ucsf.edu.

Biology↗
PubMed2004

Putting fear in its place: remapping of hippocampal place cells during fear conditioning.

We recorded hippocampal place cells in two spatial environments: a training environment in which rats underwent fear conditioning and a neutral control environment. Fear conditioning caused many place cells to alter (or remap) their preferred firing locations in the training environment, whereas most cells remained stable in the control environment. This finding indicates that aversive reinforcement can induce place cell remapping even when the environment itself remains unchanged. Furthermore, contextual fear conditioning caused significantly more remapping of place cells than auditory fear conditioning, suggesting that place cell remapping was related to the rat's learned fear of the environment. These results suggest that one possible function of place cell remapping may be to generate new spatial representations of a single environment, which could help the animal to discriminate among different motivational contexts within that environment.

Animals↗
PubMed2003

An automated apparatus for presenting depth-rotated three-dimensional objects in human and animal object recognition research.

For practical reasons, research on the recognition of objects from different viewpoints has relied almost exclusively on the use of two-dimensional representations of three-dimensional objects. We describe an apparatus that enables the presentation of three-dimensional objects in a discrimination learning paradigm. Three chambers positioned on a movable table allow each of two objects to be presented on either the left or the right side; a viewing window exposes only two of the objects at a time. The objects can be arbitrarily designated as either an S+ or an S-. In addition, they can be placed precisely in any arbitrary start position and rotated in depth in 100 steps of 3.6 degrees each. We have successfully used this apparatus to investigate recognition of depth-rotated objects by both pigeons and humans. By varying the stimuli, number of stimulus chambers, and software programs, the apparatus can be used for other types of tasks and to investigate other types of processes.

Animals↗
PubMed1999

[Transmission of binding by mothers and their children in the preschool age].

A new method is presented in order to assess attachment representations in preschoolers. Using the symbolic medium of doll play and story completions the internal representations of attachment in children beyond infancy can be assessed. Additionally the thesis of transmission of attachment across generations was tested empirically in a sample of 28 German families from middle class socioeconomic background as part of longitudinal study. Transmission of attachment means that parents transmit their different attachment representations to preschool-aged children. Secure and insecure attachment representation in mothers assessed with the Adult Attachment Interview, are associated systematically with their childrens' attachment representations coded from the doll play. In the present study the Adult Attachment Interview was conducted with mothers during the fifth year post delivery. Their first-born children, 17 boys and 11 girls with a mean age of 6;4 years participated in the story completion session. Using a two-fold distinction (secure and insecure) as well as a converted 4-level scale of attachment security, results revealed a correspondence between maternal and child attachment representations. According to psychometric indicaters the story completion procedure demonstrates satisfying reliability and convergent validity with the Separation Anxiety Test. Finally, reasons for the high match of mothers' and childrens' attachment representations are discussed. Maternal sensitive behavior, maternal reflection of their own childhood triggered by the observation of their own child, and various learning processes may operate as mediating factors in this case.

Adult↗
PubMed1998

Abstract and effector-specific representations of motor sequences identified with PET.

Positron emission tomography was used to identify neural systems involved in the acquisition and expression of sequential movements produced by different effectors. Subjects were tested on the serial reaction time task under implicit learning conditions. In the initial acquisition phase, subjects responded to the stimuli with keypresses using the four fingers of the right hand. During this phase, the stimuli followed a fixed sequence for one group of subjects (group A) and were randomly selected for another group (group B). In the transfer phase, arm movements were used to press keys on a substantially larger keyboard, and for both groups, the stimuli followed the sequence. Behavioral indices provided clear evidence of learning during the acquisition phase for group A and transfer when switched to the large keyboard. Sequence acquisition was associated with learning-related increases in regional cerebral blood flow (rCBF) in a network of areas in the contralateral left hemisphere, including sensorimotor cortex, supplementary motor area, and rostral inferior parietal cortex. After transfer, activity in inferior parietal cortex remained high, suggesting that this area had encoded the sequence at an abstract level independent of the particular effectors used to perform the task. In contrast, activity in sensorimotor cortex shifted to a more dorsal locus, consistent with motor cortex somatotopy. Thus, activity here was effector-specific. An increase in rCBF was also observed in the cingulate motor area at transfer, suggesting a role linking the abstract sequential representations with the task-relevant effector system. These results highlight a network of areas involved in sequence encoding and retrieval.

Adult↗
PubMed2005

Preserved spatial memory after hippocampal lesions: effects of extensive experience in a complex environment.

Damage to the hippocampus typically impairs spatial learning and memory in animals, but humans with hippocampal lesions retain spatial memories of premorbidly familiar environments. We showed that, like humans, normal rats reared in a complex environment and then given hippocampal lesions retained allocentric spatial memory for that environment. These results, which ruled out dependency on single cues, landmarks or specific routes, suggest that extensive premorbid experience leads to spatial representations that are independent of the hippocampus.

Animals↗
PubMed2001

Neurobiologic responses to speech in noise in children with learning problems: deficits and strategies for improvement.

OBJECTIVES: Some children with learning problems (LP) experience speech-sound perception deficits that worsen in background noise. The first goal was to determine whether these impairments are associated with abnormal neurophysiologic representation of speech features in noise reflected at brain-stem and cortical levels. The second goal was to examine the perceptual and neurophysiological benefits provided to an impaired system by acoustic cue enhancements. METHODS: Behavioral speech perception measures (just noticeable difference scores), auditory brain-stem responses, frequency-following responses and cortical-evoked potentials (P1, N1, P1', N1') were studied in a group of LP children and compared to responses in normal children. RESULTS: We report abnormalities in the fundamental sensory representation of sound at brain-stem and cortical levels in the LP children when speech sounds were presented in noise, but not in quiet. Specifically, the neurophysiologic responses from these LP children displayed a different spectral pattern and lacked precision in the neural representation of key stimulus features. Cue enhancement benefited both behavioral and neurophysiological responses. CONCLUSIONS: Overall, these findings contribute to our understanding of the preconscious biological processes underlying perception deficits and may assist in the design of effective intervention strategies.

Adolescent↗
PubMed1995

Mapping of stimulus features and meaning in gerbil auditory cortex with 2-deoxyglucose and c-Fos antibodies.

The basic functional organization of gerbil auditory cortex was previously mapped with unit recording of best frequency and with the fluoro-2-deoxyglucose mapping (FDG) technique. Among at least seven subfields in this cortex the primary auditory cortex (AI) and the anterior auditory field (AAF) showed prominent tonotopic organization with parallel dorsoventral iso-frequency contours (electrophysiology) in correspondence to FDG labelling of frequency band laminae. In an approach to mechanisms of learning aversive tone conditioning paradigms were found to reshape frequency receptive fields of single units in AI and also produced spatial shifts of tone representation in the tonotopic maps of AI and AAF. Both results suggest that spectral features as well as aspects of behavioural meaning of sounds may be represented even in primary auditory cortex. General meaningfulness in terms of occurrence of novel and salient stimuli may be reflected by expression of immediate early genes. Mapping with an antibody against the immediate early gene product c-Fos was performed in order to identify the spatial distribution of neurons in auditory cortex which change metabolism as a result of stimulation with auditory signals in a new environment. Very short e.g. less than 3 min repetitive stimulation with a tone led to frequency-specific columnar expression of c-Fos in AI and to spare non-tonotopic expression in other fields. Longer stimulation or longer aversive conditioning with the same tone led to spreading of expression, i.e. to accessory non-tonotopic labelling in AI and other fields, particularly pronounced in the output layers V and VI. It is assumed that this spreading relates to the formation of output schemes from auditory cortex in terms of implicit behavioural meaning of stimuli.

Animals↗
PubMed2025

Anticancer drug response prediction integrating multi-omics pathway-based difference features and multiple deep learning techniques.

Individualized prediction of cancer drug sensitivity is of vital importance in precision medicine. While numerous predictive methodologies for cancer drug response have been proposed, the precise prediction of an individual patient's response to drug and a thorough understanding of differences in drug responses among individuals continue to pose significant challenges. This study introduced a deep learning model PASO, which integrated transformer encoder, multi-scale convolutional networks and attention mechanisms to predict the sensitivity of cell lines to anticancer drugs, based on the omics data of cell lines and the SMILES representations of drug molecules. First, we use statistical methods to compute the differences in gene expression, gene mutation, and gene copy number variations between within and outside biological pathways, and utilized these pathway difference values as cell line features, combined with the drugs' SMILES chemical structure information as inputs to the model. Then the model integrates various deep learning technologies multi-scale convolutional networks and transformer encoder to extract the properties of drug molecules from different perspectives, while an attention network is devoted to learning complex interactions between the omics features of cell lines and the aforementioned properties of drug molecules. Finally, a multilayer perceptron (MLP) outputs the final predictions of drug response. Our model exhibits higher accuracy in predicting the sensitivity to anticancer drugs comparing with other methods proposed recently. It is found that PARP inhibitors, and Topoisomerase I inhibitors were particularly sensitive to SCLC when analyzing the drug response predictions for lung cancer cell lines. Additionally, the model is capable of highlighting biological pathways related to cancer and accurately capturing critical parts of the drug's chemical structure. We also validated the model's clinical utility using clinical data from The Cancer Genome Atlas. In summary, the PASO model suggests potential as a robust support in individualized cancer treatment. Our methods are implemented in Python and are freely available from GitHub (https://github.com/queryang/PASO).

Deep Learning↗
PubMed2005

Learning to like: a role for human orbitofrontal cortex in conditioned reward.

A great deal of human behavior and motivation is based on the intrinsic emotional significance of rewarding or aversive events, as well as on the associations formed between such emotional events and concurrent environmental stimuli. Recent functional neuroimaging studies have implicated the ventral striatum, orbitofrontal cortex (OFC), and amygdala in the representation of reward values and/or in the anticipation of rewarding events. Here, we use functional magnetic resonance imaging to compare brain activation during the presentation of reward with that during presentation of (conditioned) stimuli that have been paired previously with reward. Specifically, we aimed to investigate conditioned reward in the absence of explicit reward anticipation. Twenty-two healthy volunteers were scanned while monochrome visual patterns were incidentally associated with reward or negative feedback in the context of a simple card game. In the subsequent session, visual patterns, including the conditioned stimuli, were presented without reward or negative feedback, and the affective valence of these stimuli was assessed behaviorally. The presentation of reward compared with negative feedback activated the ventral striatum and OFC. Activation in the same OFC region was observed when, in the subsequent session, subjects passively viewed the stimuli that had been paired with reward, without the administration of reward and with subjects being essentially unaware of the conditioning manipulation. These findings suggest that the OFC in humans plays an important role in the representation of both rewarding stimuli and conditioned stimuli that have acquired reward value.

Adolescent↗
PubMed1994

Inter-subject variability of cerebral activations in acquiring a motor skill: a study with positron emission tomography.

Cerebral structures activated during sequential right-hand finger movements were mapped with regional cerebral blood flow (rCBF) measurements by positron emission tomography (PET) in individual subjects. Nine healthy volunteers were examined twice; after initial learning and after practicing the finger movement sequence for more than 1 h. Task-specific activation sites were identified by statistical distributions of maximal activity and region size in rCBF subtraction images. A consistent task-specific activation in all nine subjects was detected in the contralateral sensorimotor cortex at an average movement rate of 3.2 Hz reached after practice. This corresponded to a significant increase of the mean rCBF in the left primary sensorimotor cortex in spatially standardised and averaged PET images. Additional task-specific activation sites detected by individual analysis were found in the lateral and medial premotor, parietal, and cingulate areas, and in subcortical structures including the basal ganglia of both cerebral hemispheres. These activations showed no or little spatial overlap from subject to subject, thus being obscured in the analysis of pooled data. The observed activity patterns were related to movement rate and accuracy in individual subjects. It is suggested that the rCBF changes associated with acquisition of a motor skill in individual humans may correspond to plasticity of sensorimotor representations reported in monkeys.

Adult↗
PubMed2006

The dynamics of hippocampal activation during encoding of overlapping sequences.

Sequence disambiguation, the process by which overlapping sequences are kept separate, has been proposed to underlie a wide range of memory capacities supported by the hippocampus, including episodic memory and spatial navigation. We used functional magnetic resonance imaging (fMRI) to explore the dynamic pattern of hippocampal activation during the encoding of sequences of faces. Activation in right posterior hippocampus, only during the encoding of overlapping sequences but not nonoverlapping sequences, was found to correlate robustly with a subject-specific behavioral index of sequence learning. Moreover, our data indicate that hippocampal activation in response to elements common to both sequences in the overlapping sequence pair, may be particularly important for accurate sequence encoding and retrieval. Together, these findings support the conclusion that the human hippocampus is involved in the earliest stage of sequence disambiguation, when memory representations are in the process of being created, and provide empirical support for contemporary computational models of hippocampal function.

Adult↗