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Biomedical subjects

W Schultz

Publications and source records attributed to W Schultz.

At least 19 recordsLinked to original sources
PubMed2001

Dopamine responses comply with basic assumptions of formal learning theory.

According to contemporary learning theories, the discrepancy, or error, between the actual and predicted reward determines whether learning occurs when a stimulus is paired with a reward. The role of prediction errors is directly demonstrated by the observation that learning is blocked when the stimulus is paired with a fully predicted reward. By using this blocking procedure, we show that the responses of dopamine neurons to conditioned stimuli was governed differentially by the occurrence of reward prediction errors rather than stimulus-reward associations alone, as was the learning of behavioural reactions. Both behavioural and neuronal learning occurred predominantly when dopamine neurons registered a reward prediction error at the time of the reward. Our data indicate that the use of analytical tests derived from formal behavioural learning theory provides a powerful approach for studying the role of single neurons in learning.

Animals↗
PubMed2001

[Hemialloarthroplasty of the knee joint. Results of 2 different gliding prosthesis models].

The outcome of 2 different unicompartimental knee arthroplasty procedures (St. Georg, Link AG, and Wessinghage, Sulzer Medica AG) is presented. The clinical results were evaluated by use of the Insall Score (Knee Society Rating System). According to this system, the subjective opinion of the patients are presented as a "Function Score" and the clinical evaluations is shown as a "Knee Score". In this study, the median follow-up for the St. Georg implant was 7 years and 6 months with good results reported by both scores. The median follow-up for the Wessinghage implant was 3 years and 2 months and it also showed good results. Despite the high average age of the patients in this study as well as the high percentage of female patients, both types of prostheses produced good results. If any, partial or complete radioluciencies were mainly observed in the tibial component. However, they had no clinical consequence. It should be noted, however, that arthritis in the compartment not receiving arthroplasty surgery progressed in almost 2/3 of the patients. By implantation of both implants a physiological axis of the leg could be achieved. The survivorship of the St. Georg implant was 88.92% (10 years survivorship). For the Wessinghage implant it was 98.35% (5 years survivorship).

Aged↗
PubMed2001

Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study.

Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.

Adult↗
PubMed2001

The small proteoglycans decorin and biglycan in human articular cartilage of late-stage osteoarthritis.

OBJECTIVE: Disturbances in proteoglycan metabolism of hyaline cartilage play an essential role in the pathology of degenerative joint disease. We investigated the relation between transcript expression, protein synthesis and the ultrastructural localization of the matrix-organizing proteoglycans decorin and biglycan within intra- and extracellular compartments of late-stage osteoarthritic human articular cartilage. METHODS: Human cartilage samples of a macroscopically intact area, the adjoining area and an area of the main defect from knee joints of 10 patients with late stage osteoarthritis were investigated. In situ hybridization and immunogold histochemistry were carried out separately and in combination at the light and electron microscopic level. RESULTS: Ultrastructurally, three main chondrocyte types were identified. The highest levels of mRNA of decorin and biglycan were produced by elongated secretory type 2 cells, already known to synthesize type I collagen. Cells with high levels of mRNA also translated the corresponding proteins to be found in the extracellular compartment. The highest production rate of decorin and biglycan was seen in the tissue area adjoining the main defect. CONCLUSION: The results indicate that at late stages of osteoarthritis the levels of transcription and translation for decorin and biglycan are up-regulated, probably in an effort to compensate for the general proteoglycan loss, characteristic of this disease stage.

Aged↗
PubMed2001

Influence of expectation of different rewards on behavior-related neuronal activity in the striatum.

This study investigated how different expected rewards influence behavior-related neuronal activity in the anterior striatum. In a spatial delayed-response task, monkeys reached for a left or right target and obtained a small quantity of one of two juices (apple, grenadine, orange, lemon, black currant, or raspberry). In each trial, an initial instruction picture indicated the behavioral target and predicted the reward. Nonmovement trials served as controls for movement relationships. Consistent preferences in special reward choice trials and differences in anticipatory licks, performance errors, and reaction times indicated that animals differentially expected the rewards predicted by the instructions. About 600 of >2,500 neurons in anterior parts of caudate nucleus, putamen, and ventral striatum showed five forms of task-related activations, comprising responses to instructions, spatial or nonspatial activations during the preparation or execution of the movement, and activations preceding or following the rewards. About one-third of the neurons showed different levels of task-related activity depending on which liquid reward was predicted at trial end. Activations were either higher or lower for rewards that were preferred by the animals as compared with nonpreferred rewards. These data suggest that the expectation of an upcoming liquid reward may influence a fraction of task-related neurons in the anterior striatum. Apparently the information about the expected reward is incorporated into the neuronal activity related to the behavioral reaction leading to the reward. The results of this study are in general agreement with an account of goal-directed behavior according to which the outcome should be represented already at the time at which the behavior toward the outcome is performed.

Animals↗
PubMed2001

Temporal difference model reproduces anticipatory neural activity.

Anticipatory neural activity preceding behaviorally important events has been reported in cortex, striatum, and midbrain dopamine neurons. Whereas dopamine neurons are phasically activated by reward-predictive stimuli, anticipatory activity of cortical and striatal neurons is increased during delay periods before important events. Characteristics of dopamine neuron activity resemble those of the prediction error signal of the temporal difference (TD) model of Pavlovian learning (Sutton & Barto, 1990). This study demonstrates that the prediction signal of the TD model reproduces characteristics of cortical and striatal anticipatory neural activity. This finding suggests that tonic anticipatory activities may reflect prediction signals that are involved in the processing of dopamine neuron activity.

Algorithms↗
PubMed2001

Reward signaling by dopamine neurons.

Dopamine projections from the midbrain to the striatum and frontal cortex are involved in behavioral reactions controlled by rewards, as inferred from deficits in parkinsonism, schizophrenia, and drug addiction. Recent experiments have shown that dopamine neurons are not directly modulated in relation to movements. Rather, they appear to code the rewarding aspects of environmental stimuli. They show short, phasic increases of activity following primary food and liquid rewards ("unconditioned stimuli") and conditioned, reward-predicting stimuli of visual, auditory, and somatosensory modalities. They also display smaller activation-depression sequences after stimuli resembling rewards and after novel or particularly intense stimuli. Rewards are only reported as far as they occur differently than predicted. According to learning theories, a "prediction error" message may constitute a powerful teaching signal for behavior and learning. The phasic reward message is different from the more tonic enabling function of dopamine that is deficient in Parkinson's disease, indicating that dopamine neurons subserve different functions at different time scales. Neurons in other brain structures, such as the striatum, orbitofrontal cortex, and amygdala, code the quality, quantity, and preference of rewards. The dopamine reward prediction error signal may cooperate with these reward perception signals during the learning and performance of behavioral reactions to motivating environmental stimuli.

Animals↗
PubMed2000

Reduced reward processing in the brains of Parkinsonian patients.

Regional cerebral blood flow (rCBF) in healthy controls and non-demented, non-depressed Parkinsonian patients was measured using H2(15)O PET while subjects performed a prelearned pattern recognition task with delayed response. To investigate differences between the two groups in response to reward, the experimental design consisted of three reinforcement conditions: no reinforcement consisting of nonsense feedback, positive symbolic reinforcement and monetary reward. In the controls, monetary reward activated bilaterally the striatum and anterior cingulate gyrus, as well as unilaterally the left cerebellum, midbrain and medial frontal gyrus. Symbolic reinforcement revealed a similar pattern of activation, except that the striatum and left midbrain showed no activation. The Parkinsonian patients responded to monetary reward with increased activation bilaterally in the cerebellum, medial frontal gyrus, and anterior cingulate gyrus as well as unilaterally in the right fusiform gyrus and midbrain and left caudate nucleus and precentral gyrus. Symbolic reinforcement induced significantly increased rCBF in the right cerebellum only. Compared with symbolic reinforcement, monetary reward produced extended activation of temporoparietal association cortex. The pattern observed in the controls demonstrates the role in reward processing of dopaminergic mesolimbic pathways in the healthy human brain, whereas the pattern in the Parkinsonian patients suggests the involvement of compensatory cortical loops in the diseased brain.

Arousal↗
PubMed2000

Involvement of basal ganglia and orbitofrontal cortex in goal-directed behavior.

An impressive array of neural processing appears to be dedicated to the extraction of reward-related information from environmental stimuli and use of this information in the generation of goal-directed behaviors. While other structures are certainly involved in these processes, the characteristics of activations seen in mesencephalic dopamine neurons, striatal neurons and neurons of the orbitofrontal cortex provide distinct examples of the different ways in which reward-related information is processed. In addition, the differences in activations seen in these three regions demonstrate the different roles they may play in goal-directed behavior. A principal role played by dopamine neurons is that of a detector of an error in reward prediction. The homogeneity of responsiveness across the population of dopamine neurons indicates that this error signal is widely broadcast to dopamine terminal regions where it could provide a teaching signal for synaptic modifications underlying the learning of goal-directed appetitive behaviors. The responses of these same neurons to conditioned stimuli associated with reward could also serve as a signal of prediction error useful for the learning of sequences of environmental stimuli leading to reward. Dopamine neuron responses to both rewards and conditioned stimuli are not contingent on the behavior executed to obtain the reward and thus appear to reflect a relatively pure signal of a reward prediction error. It is not yet clear whether these activations, and responses to novel stimuli, have an additional function in engaging neural systems involved in the representation and execution of goal-directed behaviors. This representation of goal-directed behaviors may involve the striatal regions studied, where processing of reward-related information appears to be much more heterogeneous. Different subpopulations of striatal neurons are activated at different stages in the course of goal-directed behaviors, with largely separate populations activated following presentation of conditioned stimuli, preceding reinforcers, and following reinforcers. Neurons exhibiting each of these types of activation appear to differentiate between rewarding and non-rewarding outcomes of behavioral acts and, as a population, appear to be biased towards processing reward vs. non-reward. These activations observed in the striatum were often contingent on the behavioral act associated with obtaining reward, reflecting an integration of information not observed in dopamine neurons. Another difference between reward processing in striatal neurons and dopamine neurons is the influence of predictability on neuronal responsiveness. Unlike dopamine neurons, many striatal neurons respond to predicted rewards, although at least some may reflect the relative degree of predictability in the magnitude of the responses to reward. Thus, striatal processing of reward-related information is in some ways more complex than that observed in dopamine neurons, incorporating information on behavior and potentially providing more detailed information regarding predictability. These activations could serve as a component of the neural representation of the goal, and/or the behavioral aspects of goal-directed behaviors. As such they would be of use for the execution of appropriate goal-directed behaviors in response to known environmental stimuli, as well as for generating behaviors in response to novel stimuli that may be associated with desirable goals. Neuronal activations in the orbitofrontal cortex appear to involve less integration of behavioral and reward-related information, but rather incorporate another aspect of reward, the relative motivational significance of different rewards. These activations would serve a function similar to those striatal neurons that encode exclusively reward-related information in situations in which only a single outcome is obtainable. (ABSTRACT TRUNCATED)

Animals↗
PubMed2000

Multiple reward signals in the brain.

The fundamental biological importance of rewards has created an increasing interest in the neuronal processing of reward information. The suggestion that the mechanisms underlying drug addiction might involve natural reward systems has also stimulated interest. This article focuses on recent neurophysiological studies in primates that have revealed that neurons in a limited number of brain structures carry specific signals about past and future rewards. This research provides the first step towards an understanding of how rewards influence behaviour before they are received and how the brain might use reward information to control learning and goal-directed behaviour.

Animals↗
PubMed2000

Massive intraosseous ganglion of the talus: reconstruction of the articular surface of the ankle joint.

We report on the outcome after autologous chondrocyte and spongiosal bone transplantation in a case of a massive intraosseous ganglion of the talus in a young patient. A 24-year-old man suffered from decreased ankle joint motion, recurrent swelling, and pain. Diagnostic evaluation by plain radiographs, computed tomography, and magnetic resonance imaging revealed cystic lesions in the head and the body of the talus with additional involvement of the cartilage surface. Operative treatment consisted primarily of an initial diagnostic arthroscopy, which established grade VI articular damage according to the arthroscopic classification of Bauer and Jackson. Pathological examination of intralesional biopsy tissue revealed the existence of an intraosseous ganglion. Additionally, healthy cartilage biopsy specimens were obtained and sent for chondrocyte extraction and cultivation with 60 mL of autologous serum. To retain the function of the ankle joint and to minimize the number of necessary operative interventions, 3 weeks after the initial arthroscopic operation, we performed a simultaneous curettage of the cystic lesion followed by autologous spongiosal bone and cultivated chondrocytes transplantation of the talus. Continuous passive motion was applied postoperatively and full weight bearing was allowed after 8 weeks. There were no complications. The clinical result after 18 months was excellent, with a fully functional, pain-free, and weight-bearing ankle joint. The postoperative evaluation score of Finsen (modified Weber score) of 2/6 = 0.3 showed an improvement comparison with the preoperative value of of 21/6 = 3.5 (0 = normal, 4 = pathologic). We encountered no complications postoperatively. Clinical success was achieved by this method of treatment on a patient too young to be treated through arthrodesis.

Adult↗
PubMed2000

Reward processing in primate orbitofrontal cortex and basal ganglia.

This article reviews and interprets neuronal activities related to the expectation and delivery of reward in the primate orbitofrontal cortex, in comparison with slowly discharging neurons in the striatum (caudate, putamen and ventral striatum, including nucleus accumbens) and midbrain dopamine neurons. Orbitofrontal neurons showed three principal forms of reward-related activity during the performance of delayed response tasks, namely responses to reward-predicting instructions, activations during the expectation period immediately preceding reward and responses following reward. These activations discriminated between different rewards, often on the basis of the animals' preferences. Neurons in the striatum were also activated in relation to the expectation and detection of reward but in addition showed activities related to the preparation, initiation and execution of movements which reflected the expected reward. Dopamine neurons responded to rewards and reward-predicting stimuli, and coded an error in the prediction of reward. Thus, the investigated cortical and basal ganglia structures showed multiple, heterogeneous, partly simultaneous activations which were related to specific aspects of rewards. These activations may represent the neuronal substrates of rewards during learning and established behavioral performance. The processing of reward expectations suggests an access to central representations of rewards which may be used for the neuronal control of goaldirected behavior.

Animals↗
PubMed2000

Neuronal coding of prediction errors.

Associative learning enables animals to anticipate the occurrence of important outcomes. Learning occurs when the actual outcome differs from the predicted outcome, resulting in a prediction error. Neurons in several brain structures appear to code prediction errors in relation to rewards, punishments, external stimuli, and behavioral reactions. In one form, dopamine neurons, norepinephrine neurons, and nucleus basalis neurons broadcast prediction errors as global reinforcement or teaching signals to large postsynaptic structures. In other cases, error signals are coded by selected neurons in the cerebellum, superior colliculus, frontal eye fields, parietal cortex, striatum, and visual system, where they influence specific subgroups of neurons. Prediction errors can be used in postsynaptic structures for the immediate selection of behavior or for synaptic changes underlying behavioral learning. The coding of prediction errors may represent a basic mode of brain function that may also contribute to the processing of sensory information and the short-term control of behavior.

Animals↗
PubMed2000

Reward-related neuronal activity during go-nogo task performance in primate orbitofrontal cortex.

The orbitofrontal cortex appears to be involved in the control of voluntary, goal-directed behavior by motivational outcomes. This study investigated how orbitofrontal neurons process information about rewards in a task that depends on intact orbitofrontal functions. In a delayed go-nogo task, animals executed or withheld a reaching movement and obtained liquid or a conditioned sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed (movement vs. nonmovement) and the reinforcer to be obtained (liquid vs. sound) after a subsequent trigger stimulus. We found task-related activations in 188 of 505 neurons in rostral orbitofrontal area 13, entire area 11, and lateral area 14. The principal task-related activations consisted of responses to instructions, activations preceding reinforcers, or responses to reinforcers. Most activations reflected the reinforcing event rather than other task components. Instruction responses occurred either in liquid- or sound-reinforced trials but rarely distinguished between movement and nonmovement reactions. These instruction responses reflected the predicted motivational outcome rather than the behavioral reaction necessary for obtaining that outcome. Activations preceding the reinforcer began slowly and terminated immediately after the reinforcer, even when the reinforcer occurred earlier or later than usually. These activations preceded usually the liquid reward but rarely the conditioned auditory reinforcer. The activations also preceded expected drops of liquid delivered outside the task, suggesting a primary appetitive rather than a task-reinforcing relationship that apparently was related to the expectation of reward. Responses after the reinforcer occurred in liquid- but rarely in sound-reinforced trials. Reward-preceding activations and reward responses were unrelated temporally to licking movements. Several neurons showed reward responses outside the task but instruction responses during the task, indicating a response transfer from primary reward to the reward-predicting instruction, possibly reflecting the temporal unpredictability of reward. In conclusion, orbitofrontal neurons report stimuli associated with reinforcers are concerned with the expectation of reward and detect reward delivery at trial end. These activities may contribute to the processing of reward information for the motivational control of goal-directed behavior.

Animals↗
PubMed2000

Modifications of reward expectation-related neuronal activity during learning in primate orbitofrontal cortex.

This study investigated how neuronal activity in orbitofrontal cortex related to the expectation of reward changed while monkeys repeatedly learned to associate new instruction pictures with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or a conditioned auditory reinforcer. When novel instruction pictures were presented, animals learned according to a trial-and-error strategy. After experience with a large number of novel pictures, learning occurred in a few trials, and correct performance usually exceeded 70% in the first 60-90 trials. About 150 task-related neurons in orbitofrontal cortex were studied in both familiar and learning conditions and showed two major forms of changes during learning. Quantitative changes of responses to the initial instruction were seen as appearance of new responses, increase of existing responses, or decrease or complete disappearance of responses. The changes usually outlasted initial learning trials and persisted during subsequent consolidation. They often modified the trial selectivities of activations. Increases might reflect the increased attention during learning and induce neuronal changes underlying the behavioral adaptations. Decreases might be related to the unreliable reward-predicting value of frequently changing learning instructions. The second form of changes reflected the adaptation of reward expectations during learning. In initial learning trials, animals reacted as if they expected liquid reward in every trial type, although only two of the three trial types were rewarded with liquid. In close correspondence, neuronal activations related to the expectation of reward occurred initially in every trial type. The behavioral indices for reward expectation and their neuronal correlates adapted in parallel during the course of learning and became restricted to rewarded trials. In conclusion, these data support the notion that neurons in orbitofrontal cortex code reward information in a flexible and adaptive manner during behavioral changes after novel stimuli.

Adaptation, Psychological↗
PubMed2000

[Para-articular knee osteotomies].

Osteotomy close to the knee is an established method to treat degenerative osteoarthritis of the knee with varus or valgus deformity. However, indications, surgical techniques and results are discussed controversially. This article gives an overview of those surgical procedures most commonly used for correcting valgus and varus deformities. Supported by our results it is shown that osteotomy of the tibia for degenerative osteoarthritis together with operative arthroscopy in the same operative session gives better results compared to osteotomy alone. Despite the success of arthroplasty of the knee, osteotomy has it's place in the treatment of osteoarthritis.

Arthroscopy↗
PubMed1999

Relative reward preference in primate orbitofrontal cortex.

The orbital part of prefrontal cortex appears to be crucially involved in the motivational control of goal-directed behaviour. Patients with lesions of orbitofrontal cortex show impairments in making decisions about the expected outcome of actions. Monkeys with orbitofrontal lesions respond abnormally to changes in reward expectations and show altered reward preferences. As rewards constitute basic goals of behaviour, we investigated here how neurons in the orbitofrontal cortex of monkeys process information about liquid and food rewards in a typical frontal task, spatial delayed responding. The activity of orbitofrontal neurons increases in response to reward-predicting signals, during the expectation of rewards, and after the receipt of rewards. Neurons discriminate between different rewards, mainly irrespective of the spatial and visual features of reward-predicting stimuli and behavioural reactions. Most reward discriminations reflect the animals' relative preference among the available rewards, as expressed by their choice behaviour, rather than physical reward properties. Thus, neurons in the orbitofrontal cortex appear to process the motivational value of rewarding outcomes of voluntary action.

Animals↗