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PubMed2002

Effects of cortical lesions on saccadic: eye movements in humans.

Our knowledge of the cortical control of saccadic eye movements (saccades) in humans has recently progressed mainly because of lesion and transcranial magnetic stimulation (TMS) studies, but also because of functional imaging. It is now well known that the frontal eye field is involved in the control of intentional saccades, the parietal eye field in that of reflexive saccades, the supplementary eye field (SEF) in the initiation of motor programs comprising saccades, the pre-SEF in the learning of these programs, and the dorsolateral prefrontal cortex (DLPFC) in saccade inhibition, prediction and spatial working memory. Saccades may also be used as a convenient model of motricity to study general cognitive processes such as motivation and spatial memory. Thus, it has been shown that the posterior part of the anterior cingulate cortex, called the cingulate eye field, is involved in motivation and the preparation of all intentional saccades, but not in reflexive saccades. Recently, our understanding of the cortical control of spatial memory has noticeably progressed by using the simple visuo-oculomotor model represented by the memory-guide saccade paradigm, in which a single saccade is made to the remembered position of a unique visual item presented a while before. Transcranial magnetic stimulation studies have determined that after a brief stage of spatial integration in the posterior parietal cortex (inferior to 300 ms), short-term spatial memory (i.e., up to 15-20 seconds) is controlled by the DLPFC. Behavioral and lesion studies have shown that medium-term spatial memory (between 15 and 20 seconds and a few minutes) is specifically controlled by the parahippocampal cortex, before long-term memorization (i.e., after a few minutes) in the hippocampal formation. These different but complementary study methods used in humans have thus contributed to a better understanding of both eye movement physiology and general cognitive processes preparing motricity as whole.

Cerebral Cortex↗

PubMed1997

Optimal, unsupervised learning in invariant object recognition.

A means for establishing transformation-invariant representations of objects is proposed and analyzed, in which different views are associated on the basis of the temporal order of the presentation of these views, as well as their spatial similarity. Assuming knowledge of the distribution of presentation times, an optimal linear learning rule is derived. Simulations of a competitive network trained on a character recognition task are then used t highlight the success of this learning rule in relation to simple Hebbian learning and to show that the theory can give accurate quantitative predictions for the optimal parameters for such networks.

Animals↗

PubMed2024

Combination of computational techniques and RNAi reveal targets in Anopheles gambiae for malaria vector control.

Increasing reports of insecticide resistance continue to hamper the gains of vector control strategies in curbing malaria transmission. This makes identifying new insecticide targets or alternative vector control strategies necessary. CLassifier of Essentiality AcRoss EukaRyote (CLEARER), a leave-one-organism-out cross-validation machine learning classifier for essential genes, was used to predict essential genes in Anopheles gambiae and selected predicted genes experimentally validated. The CLEARER algorithm was trained on six model organisms: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and employed to identify essential genes in An. gambiae. Of the 10,426 genes in An. gambiae, 1,946 genes (18.7%) were predicted to be Cellular Essential Genes (CEGs), 1716 (16.5%) to be Organism Essential Genes (OEGs), and 852 genes (8.2%) to be essential as both OEGs and CEGs. RNA interference (RNAi) was used to validate the top three highly expressed non-ribosomal predictions as probable vector control targets, by determining the effect of these genes on the survival of An. gambiae G3 mosquitoes. In addition, the effect of knockdown of arginase (AGAP008783) on Plasmodium berghei infection in mosquitoes was evaluated, an enzyme we computationally inferred earlier to be essential based on chokepoint analysis. Arginase and the top three genes, AGAP007406 (Elongation factor 1-alpha, Elf1), AGAP002076 (Heat shock 70kDa protein 1/8, HSP), AGAP009441 (Elongation factor 2, Elf2), had knockdown efficiencies of 91%, 75%, 63%, and 61%, respectively. While knockdown of HSP or Elf2 significantly reduced longevity of the mosquitoes (p<0.0001) compared to control groups, Elf1 or arginase knockdown had no effect on survival. However, arginase knockdown significantly reduced P. berghei oocytes counts in the midgut of mosquitoes when compared to LacZ-injected controls. The study reveals HSP and Elf2 as important contributors to mosquito survival and arginase as important for parasite development, hence placing them as possible targets for vector control.

Animals↗

PubMed2001

Disinhibition and expectancy in risk for alcohol use: comparing black and white college samples.

OBJECTIVE: This study tested several predictions of the "acquired preparedness" model in both black and white samples of college students. The acquired preparedness model holds that trait disinhibition affects alcohol-related learning and, ultimately, alcohol use. This model maintains that the reward focus typical of disinhibited individuals increases the likelihood of forming overly positive expectancies about the effects of alcohol. Alcohol expectancy, then, acts as a mediator of the relationship of disinhibition and drinking behavior. METHOD: Participants (N = 479, 341 women) were 279 white and 200 black college students. Self-reported alcohol expectancy, disinhibition and drinking behavior were assessed. Covariance structure analysis was used to test hypotheses separately for each sample, controlling for socioeconomic status. RESULTS: Black participants scored significantly lower on disinhibition, expectancy and drinking. However, invariance testing indicated that the relationships between these variables were not different across groups. Results were consistent with the stated hypotheses in both samples--alcohol expectancy functioned as a mediator of the disinhibition-drinking relationship. Results did not differ across expectancy content. CONCLUSIONS: These results provide support for the validity of the acquired preparedness model. Despite mean differences in risk and drinking levels between black and white samples, psychosocial learning appears to mediate the influence of disinhibition on drinking for both groups.

Adolescent↗

PubMed1976

Imitative modeling as a theoretical base for instructing language-disordered children.

A modification of Bandura's social learning theory (imitative modeling) was employed as a theoretical base for language instruction. This approach was experimentally compared to an alternative technique which required the subject to literally match each stimulus statement made by che clinician (mimicry). The results support the prediction that modeling is more effective in teaching the subject the appropriate grammatical rule, which he or she initially lacked. Moreover, subjects in the modeling condition exhibited both greater retention of the rule and a more successful generalization of it to novel contexts. The results are explained in terms of an "interference hypothesis," which suggests that a client's overt verbalization may interfere with the cognitive processing necessary to learn an abstract language rule.

Child↗

PubMed2004

N-Terminal myristoylation predictions by ensembles of neural networks.

N-terminal myristoylation is a post-translational modification that causes the addition of a myristate to a glycine in the N-terminal end of the amino acid chain. This work presents neural network (NN) models that learn to discriminate myristoylated and nonmyristoylated proteins. Ensembles of 25 NNs and decision trees were trained on 390 positive sequences and 327 negative sequences. Experiments showed that NN ensembles were more accurate than decision tree ensembles. Our NN predictor evaluated by the leave-one-out procedure, obtained a false positive error rate equal to 2.1%. That was better than the PROSITE pattern for myristoylation for which the false positive error rate was 22.3%. On a recent version of Swiss-Prot (41.2), the NN ensemble predicted 876 myristoylated proteins, while 1150 proteins were predicted by the PROSITE pattern for myristoylation. Finally, compared to the well-known NMT predictor, the NN predictor gave similar results. Our tool is available under http://www.expasy.org/tools/myristoylator/myristoylator.html.

Amino Acid Sequence↗

PubMedDate not supplied

Models of receptive-field dynamics in visual cortex.

The position, size, and shape of the receptive field (RF) of some cortical neurons change dynamically, in response to artificial scotoma conditioning (Pettet & Gilbert, 1992) and to retinal lesions (Chino et al., 1992; Darian-Smith & Gilbert, 1995) in adult animals. The RF dynamics are of interest because they show how visual systems may adaptively overcome damage (from lesions, scotomas, or other failures), may enhance processing efficiency by altering RF coverage in response to visual demand, and may perform perceptual learning. This paper presents an afferent excitatory synaptic plasticity rule and a lateral inhibitory synaptic plasticity rule--the EXIN rules (Marshall, 1995)--to model persistent RF changes after artificial scotoma conditioning and retinal lesions. The EXIN model is compared to the LISSOM model (Sirosh et al., 1996) and to a neuronal adaptation model (Xing & Gerstein, 1994). The rules within each model are isolated and are analyzed independently, to elucidate their roles in adult cortical RF dynamics. Based on computer simulations, the EXIN lateral inhibitory synaptic plasticity rule and the LISSOM lateral excitatory synaptic plasticity rule produced the best fit with current neurophysiological data on visual cortical plasticity in adult animals (Chino et al., 1992; Pettet & Gilbert, 1992; Darian-Smith & Gilbert, 1995) including (1) the retinal position and shape of the expanding RFs; (2) the corticotopic direction in which responsiveness returns to the silenced cortex; (3) the direction of RF shifts; (4) the amount of change in response to blank stimuli; and (5) the lack of dynamic RF changes during conditioning with a retinal lesion in one eye and the unlesioned eye kept open, in adult animals. The effects of the LISSOM lateral inhibitory synaptic plasticity rule during artificial scotoma conditioning are in conflict with those of the other two LISSOM synaptic plasticity rules. A novel "complementary scotoma" conditioning experiment, in which stimulation of two complementary regions of visual space alternates repeatedly, is proposed to differentiate the predictions of the EXIN and LISSOM rules.

Adaptation, Physiological↗

PubMed2004

Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model.

BACKGROUND: Sentinel lymph node (SLN) biopsy allows surgeons to identify patients with subclinical nodal involvement who may benefit from lymphadenectomy and, possibly, adjuvant therapy. Several factors have been variably, and sometimes discordantly, reported to have predictive value for SLN metastasis to best select which patients require SLN biopsy. METHODS: We reviewed 419 patients who underwent SLN biopsy for melanoma from a prospectively collected melanoma database. To derive a probabilistic model for the occurrence of a positive SLN, a multivariate logistic model was fit by using a stepwise variable selection method. The accuracy of each model was evaluated by using receiver operator characteristic curves. RESULTS: On univariate analysis, the number of mitoses per square millimeter, increasing Breslow depth, decreasing age, ulceration, and melanoma on the trunk showed a significant relationship to a positive SLN. Multivariate analysis revealed that once age, mitotic rate, and Breslow thickness were included, no other factor, including ulceration, was significantly associated with a positive SLN. The data suggest that younger patients with tumors <1 mm may still have a substantial risk for a positive SLN, especially if the mitotic rate is high. CONCLUSIONS: In addition to Breslow depth, mitoses per square millimeter and younger age were factors identified as independent predictors of a positive SLN. This model may identify patients with thin melanoma at sufficient risk for metastases to justify SLN biopsy.

Adult↗

PubMed2005

Surprise and change: variations in the strength of present and absent cues in causal learning.

It is said that "absence makes the heart grow fonder." But, when and why does an absent event become salient to the heart or to the brain? An absent event may become salient when its nonoccurrence is surprising. Van Hamme and Wasserman (1994) found that a nonpresented but expected stimulus can actually change its associative status-and in the opposite direction from a presented stimulus. Associative models like that of Rescorla and Wagner (1972) focus only on presented cues; so, they cannot explain this result. However, absent cues can be permitted to change their value by assigning different learning parameters to present and absent cues. Van Hamme and Wasserman revised the Rescorla-Wagner model so that the a parameter is positive for present cues, but negative for absent cues; now, changes in the associative strength of absent cues move in the opposite direction as presented ones. This revised Rescorla-Wagner model can thus explain such otherwise vexing empirical findings as backward blocking, recovery from overshadowing, and backward conditioned inhibition. Moreover, the revised model predicts new effects. For example, explicit information about the absence of nonpresented cues should increase their salience (that is, their negative a value should be larger), leading to stronger associative changes than when no explicit mention is made of cue absence. Support for this prediction is detailed in a new causal judgment experiment in which participants rated the effectiveness of different foods' triggering a patient's allergic reaction. Overall, these and other findings encourage us to view human causal learning from an associative perspective.

Adult↗

PubMed1996

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↗

PubMed1996

Prediction of probable Alzheimer's disease in memory-impaired patients: A prospective longitudinal study.

We determined whether a battery of neuropsychological tests could predict who would develop Alzheimer's disease (AD) in a group of 123 memory-impaired nondemented patients. Patients were followed longitudinally for 2 years with a research battery of neuropsychological tests. After 2 years, 29 developed probable AD, and 94 did not develop dementia. We used logistic regression analyses to examine the classification accuracy of subjects' performance at entry to the study on the research battery. The logistic regression model was significant with an accuracy of 89%, sensitivity of 76%, and specificity of 94%. Two tests contributed significantly to this model: the delayed recall from the Rey Auditory Verbal Learning Test and the Mental Control subtest of the Wechsler Memory Scale. These two tests alone produced the same accuracy, sensitivity, and specificity as the larger model. These results demonstrate that probable AD can be predicted with a high degree of accuracy and with a relatively brief battery of neuropsychological tests.

Alzheimer Disease↗

PubMed1989

Effects of relative position and shape relation on gap detection with geometric form pairs.

A letter presented parafoveally is better identified when flanked by a letter to its foveal side than when flanked by a letter to its peripheral side if the letters are different in shape. If the letters are similar, relative position does not affect identifiability. Whereas some articles in the literature suggest that this effect may not extend to geometric forms, results of the first experiment showed that it does. Results of the second experiment revealed that the strength of the significant interaction between relative position and shape relation remains constant over a range of eccentricities (2-20 deg were tested) extending above and below as well as to the left and right of fixation. Results are compared with predictions from a model that can account for the relative position-shape relation interaction.

Adult↗

PubMed1991

Apparent extended body motions in depth.

Five experiments were designed to investigate the influence of three-dimensional (3-D) orientation change on apparent motion. Projections of an orientation-specific 3-D object were sequentially flashed in different locations and at different orientations. Such an occurrence could be resolved by perceiving a rotational motion in depth around an axis external to the object. Consistent with this proposal, it was found that observers perceived curved paths in depth. Although the magnitude of perceived trajectory curvature often fell short of that required for rotational motions in depth (3-D circularity), judgments of the slant of the virtual plane on which apparent motions occurred were quite close to the predictions of a model that proposes circular paths in depth.

Adult↗

PubMed2006

Retrieval experience in prospective memory: strategic monitoring and spontaneous retrieval.

According to the multi-process model of prospective memory (McDaniel & Einstein, 2000), performance in a prospective memory task may be due to spontaneous retrieval processes or due to strategic monitoring. Spontaneous retrieval is typically accompanied by a pop up experience and strategic monitoring by a search experience. In this study we report two experiments with young adults in which we systematically investigated whether retrieval experience differed across experimental conditions. In Experiment 1 some prospective memory targets were preceded by associated primes. We expected that presenting primes would enhance performance by an automatic activation of the intention and hence lead to an increase in pop up experiences. In Experiment 2 half of the participants received instructions containing information about the specific context in which the prospective memory task would occur, whereas the other half of the participants received no such information. We expected that specific context instructions would enhance performance by legitimate anticipation of the prospective memory task and hence would lead to an increase in search experiences. The results confirmed these expectations. They indicate that the assessment of retrieval experience can provide valuable insights into the processes underlying prospective memory performance. They also suggest that retrieval experience can vary systematically across experimental situations as predicted by the multi-process model.

Adult↗

PubMed1994

Avoidant attachment as a risk factor for health.

A style of coping with stress is described which has been observed in cancer patients and in highly dependent, insecurely attached individuals. This coping style includes the suppression of negative emotions and avoidance of support seeking. It is suggested that this pattern of responses is potentially dysfunctional insofar as it tends to perpetuate distress and may increase vulnerability to a broad range of illnesses. These considerations provide the basis for a provisional conceptual model, which links avoidant attachment style to the regulation of negative affect and to symptoms of psychological and physical ill-health. This is tested on a sample of young adults under stress and predictions from the model are largely supported.

Adaptation, Psychological↗

PubMed2002

Effects of D-amphetamine in a temporal discrimination procedure: selective changes in timing or rate dependency?

Two experiments evaluated rate dependency and a neuropharmacological model of timing as explanations of the effects of amphetamine on behavior under discriminative control by time. Four pigeons pecked keys during 60-trial sessions. On each trial, the houselight was lit for a particular duration (5 to 30 s), and then the key was lit for 30 s. In Experiment 1, the key could be lit either green or blue. If the key was lit green and the sample was 30 s, or if the key was lit blue and the sample was 5 s, pecks produced food on a variable-interval 20-s schedule. The rate of key pecking increased as a function of sample duration when the key was green and decreased as a function of sample duration when the key was blue. Acute d-amphetamine (0.1 to 3.0 mg/kg) decreased higher rates of key pecking and increased lower rates of key pecking as predicted by rate dependency, but did not shift the timing functions leftward (toward overestimation) as predicted by the neuropharmacological model. These results were replicated in Experiment 2, in which the key was lit only one color during sessions, indicating that the effects were not likely due to disruption of discriminative control by key color. These results are thus consistent with rate dependency but not with the predictions of the neuropharmacological model.

Animals↗

PubMed1998

A computational role for dopamine delivery in human decision-making.

Recent work suggests that fluctuations in dopamine delivery at target structures represent an evaluation of future events that can be used to direct learning and decision-making. To examine the behavioral consequences of this interpretation, we gave simple decision-making tasks to 66 human subjects and to a network based on a predictive model of mesencephalic dopamine systems. The human subjects displayed behavior similar to the network behavior in terms of choice allocation and the character of deliberation times. The agreement between human and model performances suggests a direct relationship between biases in human decision strategies and fluctuating dopamine delivery. We also show that the model offers a new interpretation of deficits that result when dopamine levels are increased or decreased through disease or pharmacological interventions. The bottom-up approach presented here also suggests that a variety of behavioral strategies may result from the expression of relatively simple neural mechanisms in different behavioral contexts.

Cerebral Cortex↗

PubMed1991

Predictors for infection following open-heart surgery.

A large open-heart surgery unit dealing with approximately 1000 elective patients per annum and housed in a dedicated suite, including a specialized intensive therapy unit, has provided a unique model for the study of predictors of infections and related phenomena. Over more than 10 years a series of studies has shown: the powerful effect of antibiotic usage on the colonization/infection rates with Gram-negative bacilli; the predictive relationships between preoperative chest status and the development of postoperative chest problems; an important correlation between preoperative peak urine flow rates and susceptibility to postoperative urinary tract infections; and the predictive significance of preoperative antibodies to enteric Gram-negative bacilli in relation to postoperative pyrexia and Gram-negative infection. The lessons learned from this easily studied group of patients may have important applications in other surgical settings.

Anti-Bacterial Agents↗