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PubMed2004

Do current connectionist learning models account for reading development in different languages?

Learning to read a relatively irregular orthography, such as English, is harder and takes longer than learning to read a relatively regular orthography, such as German. At the end of grade 1, the difference in reading performance on a simple set of words and nonwords is quite dramatic. Whereas children using regular orthographies are already close to ceiling, English children read only about 40% of the words and nonwords correctly. It takes almost 4 years for English children to come close to the reading level of their German peers. In the present study, we investigated to what extent recent connectionist learning models are capable of simulating this cross-language learning rate effect as measured by nonword decoding accuracy. We implemented German and English versions of two major connectionist reading models, Plaut et al.'s (Plaut, D. C., McClelland, J. L., Seidenberg, M. S., & Patterson, K. (1996). Understanding normal and impaired word reading: computational principles in quasi-regular domains. Psychological Review, 103, 56-115) parallel distributed model and Zorzi et al.'s (Zorzi, M., Houghton, G., & Butterworth, B. (1998a). Two routes or one in reading aloud? A connectionist dual-process model. Journal of Experimental Psychology: Human Perception and Performance, 24, 1131-1161); two-layer associative network. While both models predicted an overall advantage for the more regular orthography (i.e. German over English), they failed to predict that the difference between children learning to read regular versus irregular orthographies is larger earlier on. Further investigations showed that the two-layer network could be brought to simulate the cross-language learning rate effect when cross-language differences in teaching methods (phonics versus whole-word approach) were taken into account. The present work thus shows that in order to adequately capture the pattern of reading acquisition displayed by children, current connectionist models must not only be sensitive to the statistical structure of spelling-to-sound relations but also to the way reading is taught in different countries.

Child↗

PubMed1998

Identification of structural features and associated mechanisms of action for carcinogens in rats.

A set of chemicals tested for carcinogenicity in rats that have been analyzed in the Carcinogenic Potency Database (CPDB) was subjected to CASE/MULTICASE (a computer-automated structure evaluation system) structure-activity relationship (SAR) analyses. This SAR system identifies structural features of chemicals in a learning set that are associated with a predefined activity and produces an SAR model based on these characteristics. The rat CPDB used in this study consisted of 745 chemicals, 383 of which are carcinogens, 14 marginally active carcinogens (i.e., chemicals that require a relatively high dose to induce carcinogenesis) and 348 are non-carcinogens. In an internal prediction analysis where CASE/MULTICASE 'predicted' the activity of chemicals in the learning set, the system was able to achieve a concordance between experimental and predicted results of 95%. This indicates that the program is able to adequately assess the chemicals in the database. In a 10-fold cross-validation study where 10 disjoint sets of 10% of the chemicals were removed from the database and the remaining 90% of the chemicals were used as a learning set, CASE/MULTICASE was able to achieve a concordance between experimental and predicted results of 64%. Using a modified validation process designed to investigate the predictivity of a more focused SAR model, the system was able to achieve a concordance of 71% between experimental and predicted results. Among the major biophores identified by CASE/MULTICASE as associated with cancer causation in rats, several are derived from electrophilic or potentially electrophilic compounds (e.g., aromatic amines, nitrogen mustards, isocyanates, epoxides). Other biophores however are derived from chemicals seemingly devoid of actual or potential DNA-reactivity and as such may represent structural features of non-genotoxic carcinogens.

Animals↗

PubMed2026

Biallelic loss of RB1 in hepatocellular carcinoma as synthetic lethal target for artificial intelligence-guided therapy.

The retinoblastoma (RB1) gene is a critical tumor suppressor that regulates cell cycle progression and genomic stability. Although RB1 alterations have been reported in hepatocellular carcinoma (HCC), the biological and clinical consequences of biallelic RB1 inactivation (RB1-Bi) remain poorly defined. We performed a comprehensive allele-specific genomic analysis of HCC patients from the TCGA-LIHC (n = 355) and in-house AMC (n = 206) cohorts, collectively comprising the AMC-TCGA discovery cohort. In this combined cohort, RB1-Bi was identified in 14.6% of tumors, was enriched in poorly differentiated HCCs and was independently associated with significantly reduced overall survival (adjusted hazard ratio 3.32, 95% CI 1.93-5.72, p < 0.001). Additionally, a deep learning-based histopathology model using hematoxylin and eosin-stained slides (i.e., FR-MIL model) accurately predicted RB1-Bi status (F1 score 84.39% [95% CI, ±0.02]), making it readily identifiable in routine clinical practice. The prevalence and prognostic impact of RB1-Bi, as well as FR-MIL model performance, were consistent across independent validation cohorts, including advanced-stage tumors and external institutions. High-throughput drug screening in isogenic HCC models revealed that RB1-Bi HCC cells were particularly sensitive to inhibitors targeting mitotic regulators (e.g., AURKA, PLK1, KSP) and DNA damage response pathways (e.g., PARP inhibitors). Synthetic lethal interactions between RB1-Bi and these compounds were demonstrated in vitro and in vivo, and combination treatment with mitotic and PARP inhibitors had synergistic effects with acceptable tolerability. We conclude that RB1-Bi represents a clinically actionable biomarker that identifies a high-risk HCC subtype with specific therapeutic vulnerabilities, offering new opportunities for precision medicine.

Humans↗

PubMed2005

Learned helplessness: validity and reliability of depressive-like states in mice.

The learned helplessness paradigm is a depression model in which animals are exposed to unpredictable and uncontrollable stress, e.g. electroshocks, and subsequently develop coping deficits for aversive but escapable situations (J.B. Overmier, M.E. Seligman, Effects of inescapable shock upon subsequent escape and avoidance responding, J. Comp. Physiol. Psychol. 63 (1967) 28-33 ). It represents a model with good similarity to the symptoms of depression, construct, and predictive validity in rats. Despite an increased need to investigate emotional, in particular depression-like behaviors in transgenic mice, so far only a few studies have been published using the learned helplessness paradigm. One reason may be the fact that-in contrast to rats (B. Vollmayr, F.A. Henn, Learned helplessness in the rat: improvements in validity and reliability, Brain Res. Brain Res. Protoc. 8 (2001) 1-7)--there is no generally accepted learned helplessness protocol available for mice. This prompted us to develop a reliable helplessness procedure in C57BL/6N mice, to exclude possible artifacts, and to establish a protocol, which yields a consistent fraction of helpless mice following the shock exposure. Furthermore, we validated this protocol pharmacologically using the tricyclic antidepressant imipramine. Here, we present a mouse model with good face and predictive validity that can be used for transgenic, behavioral, and pharmacological studies.

Animals↗

PubMed2003

Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study.

We recently reported 3 risk factors (RFs) at diagnosis of chronic graft-versus-host disease (cGVHD) that were significantly associated with increased nonrelapse mortality. These included extensive skin involvement (ESI), thrombocytopenia (TP), and progressive type of onset (PTO). The hazard ratio (HR) for mortality of the patients with prognostic score (PS) between 0 and 2 (intermediate-risk; 1 RF) compared to those with PS 0 (favorable-risk; 0 RF) was 3.7 (95% CI, 1.4, 9.3); the HR for patients with PS equal to or more than 2 (high-risk; > 1 RF) compared with intermediate-risk group was 6.9 (3.8, 12.4). A rare presentation of TP and PTO without ESI yielded a PS of 1.8 (intermediate-risk). This paper reports the performance of the prognostic model and the individual RFs using data from an additional 1105 patients from University of Nebraska (n = 60), International Bone Marrow Transplantation Registry (n = 708), Fred Hutchinson Cancer Research Center (n = 188), and University of Minnesota (n = 149). The extent of skin involvement was quantified in 3 cohorts using the available data collected in different formats before the analysis. Although the HR for mortality of the patients in the intermediate-risk group versus those in the favorable-risk group ranged from 2.3 to 8.9 across the centers, it was between 1.6 to 6.9 for patients in the high-risk group versus those in the intermediate-risk group. Although TP itself was uniformly associated with increased risk of mortality across all test samples, ESI and PTO showed statistically significant associations with mortality in 1 and 2 cohorts, respectively. In conclusion, the model was predictive of cGVHD-specific survival, but the mortality hazard associated with ESI was lower in each of these test samples compared with the learning sample. Although the new clinical grading based on the model is promising because of its utility across multiple independent data sets, prospective validation is needed.

Adolescent↗

PubMed2001

Learning related modulation of functional retrieval networks in man.

The medial temporal lobe has been implicated in studies of episodic memory tasks involving spatio-temporal context and object-location conjunctions. We have previously demonstrated that an increased level of practice in a free-recall task parallels a decrease in the functional activity of several brain regions, including the medial temporal lobe, the prefrontal, the anterior cingulate, the anterior insular, and the posterior parietal cortices, that in concert demonstrate a move from elaborate controlled processing towards a higher degree of automaticity. Here we report data from two experiments that extend these initial observations. We used a similar experimental approach but probed for effects of retrieval paradigms and stimulus material. In the first experiment we investigated practice related changes during recognition of object-location conjunctions and in the second during free-recall of pseudo-words. Learning in a neural network is a dynamic consequence of information processing and network plasticity. The present and previous PET results indicate that practice can induce a learning related functional restructuring of information processing. Different adaptive processes likely subserve the functional re-organisation observed. These may in part be related to different demands for attentional and working memory processing. It appears that the role(s) of the prefrontal cortex and the medial temporal lobe in memory retrieval are complex, perhaps reflecting several different interacting processes or cognitive components. We suggest that an integrative interactive perspective on the role of the prefrontal and medial temporal lobe is necessary for an understanding of the processing significance of these regions in learning and memory. It appears necessary to develop elaborated and explicit computational models for prefrontal and medial temporal functions in order to derive detailed empirical predictions, and in combination with an efficient use and development of functional neuroimaging approaches, to further the understanding of the processing significance of these regions in memory.

Adult↗

PubMed2001

Competitive Hebbian learning and the hippocampal place cell system: modeling the interaction of visual and path integration cues.

The hippocampus has long been thought essential for implementing a cognitive map of the environment. However, almost 30 years since place cells were found in rodent hippocampal field CA1, it is still unclear how such an allocentric representation arises from an ego-centrically perceived world. By means of a competitive Hebbian learning rule responsible for coding visual and path integration cues, our model is able to explain the diversity of place cell responses observed in a large set of electrophysiological experiments with a single fixed set of parameters. Experiments included changes observed in place fields due to exploration of a new environment, darkness, retrosplenial cortex inactivation, and removal, rotation, and permutation of landmarks. To code for visual cues for each landmark, we defined two perceptual schemas representing landmark bearing and distance information over a linear array of cells. The information conveyed by the perceptual schemas is further processed through a network of adaptive layers which ultimately modulate the resulting activity of our simulated place cells. In path integration terms, our system is able to dynamically remap a bump of activity coding for the displacement of the animal in relation to an environmental anchor. We hypothesize that path integration information is computed in the rodent posterior parietal cortex and conveyed to the hippocampus where, together with visual information, it modulates place cell activity. The resulting network yields a more direct treatment of partial remapping of place fields than other models. In so doing, it makes new predictions regarding the nature of the interaction between visual and path integration cues during new learning and when the system is challenged with environmental changes.

Animals↗

PubMed2000

Risk analysis for thoracoscopic lung volume reduction: a multi-institutional experience.

OBJECTIVE: Most reports of thoracoscopic lung volume reduction (TLVR) are relatively small and early experiences from a single institution, factors which limit both the statistical validity and the applicability to the population at large. In order to address these shortcomings we undertook an analysis of the TLVR experience at five separate institutions to assess operative morbidity and identify predictors of mortality. METHODS: Questionnaires were sent to four groups of surgical investigators at five institutions actively performing TLVR. Data was requested regarding preoperative, operative and postoperative parameters. Twenty-five potential predictors of mortality were analyzed and seven proved to be at least marginally significant (P<0.10). These parameters were entered into a stepwise logistic regression analysis to identify independent predictors. RESULTS: The 682 patients (415 males, 267 females, mean age 64.0 years) underwent unilateral (410) or bilateral (272) TLVRs. Overall, operative mortality was 6% with half of the deaths resulting from respiratory causes. The remaining patients were discharged to home (88%), a rehabilitation facility (4%) or a ventilator facility (2%). There were 25 perioperative factors chosen representing clinically important indices such as spirometry, oxygenation, functional status, clinical and demographic variables. Univariate analysis identified seven variables as predictors of mortality (P<0.10) and these were entered into a stepwise logistic regression analysis. Only age, 6-min walk, gender (male 8%, female 3% mortality) and the procedure performed (unilateral 4.6%, bilateral 8%) were independent predictors while preoperative steroid therapy, preoperative oxygen administration, and time since smoking cessation dropped out of the model. The specific institution, learning curve (early vs. late experience), type of lung disease, spirometric indices and predicted maximum VO(2) were not significant predictors. CONCLUSION: This experience suggests that unilateral and bilateral lung volume reduction procedure can be performed with acceptable morbidity and mortality. Although age, gender, exercise capacity and the procedure performed are all independent predictors of mortality, the risk of operative death did not appear excessive in this fragile patient subset.

Adult↗

PubMed1995

Anticonvulsant tolerance and withdrawal characteristics of benzodiazepine receptor ligands in different seizure models in mice. Comparison of diazepam, bretazenil and abecarnil.

The use of benzodiazepines (BDZs) in the long-term treatment of epilepsy is greatly restricted by their capacity to induce tolerance and dependence. Thus, the development of new BDZ-related therapeutic agents should be directed by strategies that minimize tolerance- and dependence-inducing properties. Experimental procedures used to determine the success of such strategies often rely on a single assay procedure (e.g., one seizure model), which might lead to false predictions. Furthermore, the different types of tolerance, i.e., "pharmacological" (metabolic or functional) and "behavioral" ("learned" or "contingent"), are often not dealt with in such studies. This prompted us to compare the chronic anticonvulsant efficacy and withdrawal characteristics of diazepam and two novel BDZ receptor ligands, i.e., the partial agonist bretazenil and the subtype-selective agonist abecarnil, in different seizure models in mice. Myoclonic, clonic and tonic seizures were induced by i.v. infusion of pentylenetetrazol and by transcorneal or transauricular application of electrical stimuli. Prolonged administration of diazepam (5 mg/kg twice daily for 6 days) resulted in marked anticonvulsant effects on myoclonic, clonic and tonic seizure thresholds at the onset of treatment, but pronounced tolerance developed rapidly during subsequent treatment. The time course and extent of tolerance was similar with most seizure models. Tolerance characteristics were not affected by study design, i.e., use of separate or the same animals for each seizure induction, indicating that learned or contingent tolerance was not significantly involved under these experimental conditions. After termination of treatment with diazepam, significant seizure threshold decreases were determined, indicating withdrawal hyperexcitability in response to physical dependence. During prolonged administration of abecarnil (10 mg/kg twice daily for 6 days), some anticonvulsant tolerance was seen with electroshock seizures, but not with pentylenetetrazol seizures; no withdrawal hyperexcitability was determined upon termination of treatment. Bretazenil (10 mg/kg twice daily for 6 days) produced no tolerance in any of the seizure models, but a significant decrease in electroshock seizure threshold was seen in the withdrawal period. The data indicate that tolerance and withdrawal characteristics of BDZ receptor partial and subtype-selective agonists in mice depend on the experimental model used, whereas the influence of the experimental protocol is less critical in the case of a full BDZ receptor agonist such as diazepam.

Animals↗

PubMed2002

Modeling cerebellar flocculus and paraflocculus involvement in complex predictive smooth eye pursuit in monkeys.

The role of flocculus and paraflocculus neurons in the cerebellar control of predictive eye movements was examined using two modeling techniques. The first study characterized the dependence of individual Purkinje-cell firing patterns on oculomotor output, visual input, and response timing using multilinear regression techniques. Interestingly, no dependence on visual input was detected. Purkinje cell firing was explained by sensitivities to eye position and eye velocity alone. However, complex responses occurred when sensitivity vectors pointed in different directions. For example, some neurons showed a preference for circular pursuit in a particular rotation direction. Responses also tended to lead the eye during predictable pursuit and to lag during unpredictable, visually driven pursuit. This suggests that flocculus and paraflocculus neurons played a stronger role during predictive pursuit than visually driven pursuit. A second modeling study demonstrated how the flocculus/paraflocculus system might generate predictive pursuit. A biologically realistic neural network was simulated based on the known anatomy and physiology of this cerebellar system. It included mossy and climbing fibers with realistic responses, Purkinje cells acting on well-characterized brain-stem circuits, and granule, Golgi, basket, and stellate cells with appropriate connections. The network was able to learn new pursuit trajectories based on long-term alterations in synaptic connectivity at parallel-to-Purkinje synapses. Interestingly, this model was able to generate predictive pursuit without visual input based only on eye-motion input. Thus, both models provide complementary evidence for the generation of nonvisual predictive control by flocculus and paraflocculus neurons.

Animals↗

PubMed1999

Prediction of prostatic cancer progression after radical prostatectomy using artificial neural networks: a feasibility study.

OBJECTIVE: To report a methodological feasibility study in a small series of patients with node-negative organ-confined prostatic cancer, using artificial neural networks to predict tumour progression after radical prostatectomy and thus help to identify high-risk patients who would benefit from adjuvant treatment. PATIENTS AND METHODS: A group of 20 patients with pT2N0 prostatic cancer and postoperative tumour progression was compared with a control group of 20 patients with no progression, matched for age, duration of follow-up and preoperative serum prostate-specific antigen level. Histopathological data were obtained from the radical prostatectomy specimens, i.e. the Gleason score, World Health Organisation (WHO) grade and maximum diameter of the tumour transects. The volume and surface area of the epithelial tumour component and of the lumina of the neoplastic glands per unit tissue volume were estimated by morphometric methods. To predict recurrence, multilayer feedforward networks with backpropagation (MLFF-BP), two implementations of learning vector quantization (LVQ), and linear discriminant analysis (LDA) were applied. The ability of these models to correctly classify new cases was tested using the 'leave-one-out' technique. RESULTS: Progression was predicted correctly in 85% of newly presented cases from the three routine histopathological variables alone. On the basis of the four morphometric variables alone progression was predicted correctly in 93% of cases. The use of all seven variables as input data only slightly improved the quality of prediction. The best results were obtained by the LVQ networks and LDA, followed by MLFF-BP networks. CONCLUSIONS: In this methodological feasibility study, the progression of pT2N0 prostatic cancer after radical prostatectomy could be predicted with good accuracy, sensitivity and specificity from routine variables or morphometric texture variables using artificial neural networks. These results suggest that this approach should be assessed in a prospective study with more cases.

Biopsy↗

PubMed1993

Prediction of protein secondary structure by the hidden Markov model.

The purpose of this paper is to introduce a new method for analyzing the amino acid sequences of proteins using the hidden Markov model (HMM), which is a type of stochastic model. Secondary structures such as helix, sheet and turn are learned by HMMs, and these HMMs are applied to new sequences whose structures are unknown. The output probabilities from the HMMs are used to predict the secondary structures of the sequences. The authors tested this prediction system on approximately 100 sequences from a public database (Brookhaven PDB). Although the implementation is 'without grammar' (no rule for the appearance patterns of secondary structure) the result was reasonable.

Algorithms↗

PubMed2001

Predictive versus diagnostic causal learning: evidence from an overshadowing paradigm.

Causal directionality belongs to one of the most fundamental aspects of causality that cannot be reduced to mere covariation. This paper is part of a debate between proponents of associative theories, which claim that learners are insensitive to the causal status of cues and outcomes, and proponents of causal-model theory, which postulates an interaction of assumptions about causal directionality and learning. Some researchers endorsing the associationist view have argued that evidence for the interaction between cue competition and causal directionality may be restricted to two-phase blocking designs. Furthermore, from the viewpoint of causal-model theory, blocking designs carry the potential problem that the predicted asymmetries of cue competition are partly dependent on asymmetries of retrospective inferences. The present experiments use a one-phase overshadowing paradigm that does not allow for retrospective inferences and therefore represents a more unambiguous test of sensitivity to causal directionality. The results strengthen causal-model theory by clearly demonstrating the influence of causal directionality on learning. However, they also provide evidence for boundary conditions for this effect by highlighting the role of the semantics of the learning task.

Adult↗

PubMed2002

Bayesian probabilistic network modeling of remifentanil and propofol interaction on wakeup time after closed-loop controlled anesthesia.

OBJECTIVE: Until now, the knowledge of combining anesthetics to obtain an adequate level of anesthesia and to economize wakeup time has been empirical and difficult to represent in quantitative models. Since there is no reason to expect that the effect of non-opioid and opioid anesthetics can be modeled in a simple linear manner, the use of a new computational approach with Bayesian belief network software is demonstrated. METHODS: A data set from a pharmacodynamic study was used where remifentanil was randomly given in three fixed target concentrations (2, 4, and 8 ng/ml) to 62 subjects. Target concentrations of propofol were controlled according to the closed-loop system feedback of the auditory evoked potential index to render modeling unbiased by the level of anesthesia. Time to open eyes was measured to represent wakeup time after surgery. The NETICA version 1.37 software was used on a personal computer for network building, validation, and prediction. RESULTS: After the learning phase, the network was used to generate a series of random cases whose probability distribution matches that of the compiled network. The sampling algorithms used are precise, so that the frequencies of the simulated cases will exactly approach the probabilities of the network and that of the data learned. The graphical display of the predicted wakeup time shows less variability but a more complex interaction pattern than with the unadjusted original data. CONCLUSIONS: Model building and evaluation with Bayesian networks does not depend on underlying linear relationships. Bayesian relationships represent true features of the represented data sample. Data may be sparse, uncertain, stochastic, or imprecise. Multiple platform software that is easy to use is increasingly available. Bayesian networks promise to be versatile tools for building valid, nonlinear, predictive instruments to further gain insight into the complex interaction of anesthetics.

Anesthesia Recovery Period↗

PubMedDate not supplied

Associative learning in early vision.

Sensory discriminations often improve with practice (perceptual learning). Recent results show that practice does not necessarily lead to the best possible performance on the task. It was shown that learning a task (contrast discrimination) that has already reached saturation could be enabled by a contextual change in the stimulus (the addition of surrounding flankers) during practice. Psychophysical results with varying context show a behavior that is described by a network of local visual processors with horizontal recurrent interactions. We describe a mathematical learning rule for the modification of cortical synapses that is inspired by the experimental results and apply it to recurrent cortical networks that respond to external stimuli. The model predicts that repeated presentation of the same stimulus leads to saturation of synaptic modification, such that the strengths of recurrent connections depend on the configuration of the stimulus but not on its amplitude. When a new stimulus is introduced, the modification is rekindled until a new equilibrium is reached. This effect may explain the saturation of perceptual learning when practicing a certain task repeatedly. We present simulations of contrast discrimination in a simplified model of a cortical column in the primary visual cortex and show that performance of the model is reminiscent of context-dependent perceptual learning.

Computer Simulation↗

PubMed2004

The role of neuromuscular properties in determining the end-point of a movement.

How does the activation of several muscles combine to produce reliable multijoint movements? To study this question, we stimulated up to six sites in muscles, nerves, and the spinal cord. Flexion and extension of the hip, knee, and ankle were elicited in anesthetized and decerebrate cats. The movements occurred largely in the sagittal plane against a constant spring load and covered most of the passive range of motion of the cat's limb. The movements of the end-point (foot) were compared with predictions based on vectorial summation of end-point movements elicited by stimulating single electrodes. The lengths of the movements produced by stimulating more than one site exceeded what was expected from linear summation for small movements (<3 cm) and showed a less than linear summation for large movements (>11 cm). The data were compared with muscle and limb models. Since the deviations from linearity were predictable as a function of distance, adjustments might easily be learned by trial and error. The summation was less complete for spinal stimulation, compared to nerve and muscle stimulation, so spinal circuits do not appear to compensate for the nonlinearities. Movements were elicited from positions of the limb not only in a neutral position, but also in front and behind the neutral position. A degree of convergence was seen, even with stimulation of some individual muscles, but the convergence increased as more muscles were stimulated and more joints were actively involved. This suggests that convergence to an equilibrium-point arises at least partly from muscle properties. In conclusion, there are deviations from linear vectorial summation, and these deviations increase when more muscles are stimulated. The convergence to an equilibrium-point may simplify the computations needed to produce movements involving many muscles.

Anesthesia↗

PubMed1999

Does urge to drink predict relapse after treatment?

The urge to drink, also often referred to as craving, is an emotional state in which a person is motivated to seek and use alcohol. In abstinent alcoholics, this urge may contribute to the risk of relapse. Researchers have developed several models--including the conditioned withdrawal model, conditioned appetitive motivational model, social learning model, and information-processing model--to describe the role of urges in relapse. Several studies have evaluated the role of urges in predicting alcoholism treatment outcome and relapse. Some findings indicate that the degree of urge an alcoholic experiences when confronted with a simulated high-risk situation at the end of alcoholism treatment can predict subsequent drinking. Other studies, however, show inconsistent results regarding the role of urges in predicting treatment outcome. Overall, the study results suggest that urges do not necessarily increase the risk of relapse but may actually protect some drinkers against further drinking.

Alcoholism↗

PubMed1988

Effects of lesions of the dorsal noradrenergic bundle on successive discrimination in the rat.

Male Sprague-Dawley rats were trained to bar-press for food reward on a successive discrimination involving periods of reward on a variable-interval (VI) 18-s schedule interspersed with periods of extinction. The two components of the schedule were signaled by a steady or a flashing light, counterbalanced between VI and extinction components. Confirming previous findings, the discrimination was easier when the flashing light signaled VI and the steady light signaled extinction, than with the reverse allocation of stimuli. This pattern of results is consistent with a dynamogenic effect of flashing light relative to steady light, facilitating discrimination when the flashing light signals the occasion to respond but impairing discrimination when this stimulus signals the occasion to withhold responding. Given this interpretation of performance in the successive discrimination task, it may be used to test three different hypotheses of the functions of the dorsal noradrenergic bundle (DB): that this subserves learning, selective attention, or behavioral inhibition plus arousal. To examine these hypotheses sham-operated animals were compared to animals in which hippocampal noradrenaline levels had been reduced by 98% and hypothalamic levels by 48% after injection into the DB of the catecholamine-specific neurotoxin, 6-hydroxy-dopamine. The lesioned animals responded more slowly than controls in VI components when these were signaled by the flashing light, and more rapidly than controls in extinction components when these were signaled by the steady light. In consequence, the discrimination was impaired only in the condition (flashing light signaling VI, steady light signaling extinction) which controls found easier. These results are in conflict with predictions from the learning and attentional hypotheses of DB function. They are consistent, however, with a model that attributes behavioral inhibitory functions to the DB projection to the septohippocampal system, and arousing functions to the DB projection to the hypothalamus.

Animals↗