Search PubMed⌕ Search

Biomedical subjects

W Schultz

Publications and source records attributed to W Schultz.

At least 37 records · Page 2Linked to original sources

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↗

[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↗

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↗

Articular cartilage regeneration of the knee joint after proximal tibial valgus osteotomy: a prospective study of different intra- and extra-articular operative techniques.

In this prospective study high tibial osteotomy for medial gonarthrosis was performed in 95 patients (105 knee joints). The patients underwent simultaneously diagnostic and operative arthroscopic surgery of the knee joint. A follow-up arthroscopic examination could be performed in 75 patients (85 knee joints) at the time of implant removal. In group 1 (20 knee joints), the osteotomy was performed after diagnostic arthroscopy without arthroscopic operation of the knee joint. The fixation of the osteotomy was accomplished by staples, postoperative plaster fixation and physiotherapy. In group 2 (20 knee joints), osteotomy was performed without additional operative arthroscopy after diagnostic arthroscopy, internal fixation by AOT-plate, no external fixation postoperatively and physiotherapy. In group 3 (22 knee joints), osteotomy was performed with additional operative arthroscopy (Pridie drilling), internal fixation by AOT-plate no external fixation postoperatively no external fixation, physiotherapy and continuous passive motion. In group 4 (23 knee joints), osteotomy was performed with additional operative arthroscopy (abrasio-arthroplasty), internal fixation by AOT-plate, no external fixation postoperatively, physiotherapy and continuous passive motion. All patients underwent arthroscopic examination of the knee with cartilage biopsies taken from three different regions of the femoral condyle during the same operative session as the osteotomy. At follow-up arthroscopy cartilage biopsies were taken from the same regions. There was no great difference in clinical outcome after 1 year between all groups. Arthroscopy as well as routine and electron microscopy showed better cartilage regeneration in groups 3 and 4. Groups 1 and 2 showed only regeneration isles, sometimes not well fixed to the underlying bone, while in groups 3 and 4 cartilage regeneration was thicker and more stable, sometimes covering all of the pre-existing erosions. Therefore, we recommend osteotomy of the tibia for osteoarthritis together with operative arthroscopy in the same operative session.

Adult↗

A neural network model with dopamine-like reinforcement signal that learns a spatial delayed response task.

This study investigated how the simulated response of dopamine neurons to reward-related stimuli could be used as reinforcement signal for learning a spatial delayed response task. Spatial delayed response tasks assess the functions of frontal cortex and basal ganglia in short-term memory, movement preparation and expectation of environmental events. In these tasks, a stimulus appears for a short period at a particular location, and after a delay the subject moves to the location indicated. Dopamine neurons are activated by unpredicted rewards and reward-predicting stimuli, are not influenced by fully predicted rewards, and are depressed by omitted rewards. Thus, they appear to report an error in the prediction of reward, which is the crucial reinforcement term in formal learning theories. Theoretical studies on reinforcement learning have shown that signals similar to dopamine responses can be used as effective teaching signals for learning. A neural network model implementing the temporal difference algorithm was trained to perform a simulated spatial delayed response task. The reinforcement signal was modeled according to the basic characteristics of dopamine responses to novel stimuli, primary rewards and reward-predicting stimuli. A Critic component analogous to dopamine neurons computed a temporal error in the prediction of reinforcement and emitted this signal to an Actor component which mediated the behavioral output. The spatial delayed response task was learned via two subtasks introducing spatial choices and temporal delays, in the same manner as monkeys in the laboratory. In all three tasks, the reinforcement signal of the Critic developed in a similar manner to the responses of natural dopamine neurons in comparable learning situations, and the learning curves of the Actor replicated the progress of learning observed in the animals. Several manipulations demonstrated further the efficacy of the particular characteristics of the dopamine-like reinforcement signal. Omission of reward induced a phasic reduction of the reinforcement signal at the time of the reward and led to extinction of learned actions. A reinforcement signal without prediction error resulted in impaired learning because of perseverative errors. Loss of learned behavior was seen with sustained reductions of the reinforcement signal, a situation in general comparable to the loss of dopamine innervation in Parkinsonian patients and experimentally lesioned animals. The striking similarities in teaching signals and learning behavior between the computational and biological results suggest that dopamine-like reward responses may serve as effective teaching signals for learning behavioral tasks that are typical for primate cognitive behavior, such as spatial delayed responding.

Animals↗

Learning of sequential movements by neural network model with dopamine-like reinforcement signal.

Dopamine neurons appear to code an error in the prediction of reward. They are activated by unpredicted rewards, are not influenced by predicted rewards, and are depressed when a predicted reward is omitted. After conditioning, they respond to reward-predicting stimuli in a similar manner. With these characteristics, the dopamine response strongly resembles the predictive reinforcement teaching signal of neural network models implementing the temporal difference learning algorithm. This study explored a neural network model that used a reward-prediction error signal strongly resembling dopamine responses for learning movement sequences. A different stimulus was presented in each step of the sequence and required a different movement reaction, and reward occurred at the end of the correctly performed sequence. The dopamine-like predictive reinforcement signal efficiently allowed the model to learn long sequences. By contrast, learning with an unconditional reinforcement signal required synaptic eligibility traces of longer and biologically less-plausible durations for obtaining satisfactory performance. Thus, dopamine-like neuronal signals constitute excellent teaching signals for learning sequential behavior.

Algorithms↗

Dopamine neurons report an error in the temporal prediction of reward during learning.

Many behaviors are affected by rewards, undergoing long-term changes when rewards are different than predicted but remaining unchanged when rewards occur exactly as predicted. The discrepancy between reward occurrence and reward prediction is termed an 'error in reward prediction'. Dopamine neurons in the substantia nigra and the ventral tegmental area are believed to be involved in reward-dependent behaviors. Consistent with this role, they are activated by rewards, and because they are activated more strongly by unpredicted than by predicted rewards they may play a role in learning. The present study investigated whether monkey dopamine neurons code an error in reward prediction during the course of learning. Dopamine neuron responses reflected the changes in reward prediction during individual learning episodes; dopamine neurons were activated by rewards during early trials, when errors were frequent and rewards unpredictable, but activation was progressively reduced as performance was consolidated and rewards became more predictable. These neurons were also activated when rewards occurred at unpredicted times and were depressed when rewards were omitted at the predicted times. Thus, dopamine neurons code errors in the prediction of both the occurrence and the time of rewards. In this respect, their responses resemble the teaching signals that have been employed in particularly efficient computational learning models.

Animals↗

Light and electron microscopic in-situ hybridization of collagen type I and type II mRNA in the fibrocartilaginous tissue of late-stage osteoarthritis.

OBJECTIVE: Biochemical analysis indicates the presence of collagen type I in fibrocartilaginous tissue of osteoarthritic cartilage, whereas normal hyaline cartilage contains only collagen type II produced by normal chondrocytes. Fibrocartilaginous tissue of late-stage osteoarthritis also exhibits irregularly shaped type 2b secretory chondrocytes as described in the literature. We have attempted to elucidate the type of cell which produces each type of collagen in late-stage osteoarthritis. DESIGN: We carried out in-situ hybridization at the light and electron microscopic level on the same tissue embedded in LR-Gold applying silver enhancement for gold-coupled anti-DIG antibodies. We correlated the types of cells with the expression of transcripts for type I and type II collagen. RESULTS: We found that cells resembling type 2b secretory chondrocytes of deep zones of fibrocartilaginous tissue expressed collagen type I mRNA and almost no collagen type II mRNA. The amount of collagen type I mRNA was as high as the amount produced in normal human skin fibroblasts. CONCLUSION: Some of the collagen type I in osteoarthritic human cartilage of late-stage disease is produced by cells resembling type 2b secretory chondrocytes of the deep zone.

Adult↗

Predictive reward signal of dopamine neurons.

The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest that midbrain dopamine systems are involved in processing reward information and learning approach behavior. Most dopamine neurons show phasic activations after primary liquid and food rewards and conditioned, reward-predicting visual and auditory stimuli. They show biphasic, activation-depression responses after stimuli that resemble reward-predicting stimuli or are novel or particularly salient. However, only few phasic activations follow aversive stimuli. Thus dopamine neurons label environmental stimuli with appetitive value, predict and detect rewards and signal alerting and motivating events. By failing to discriminate between different rewards, dopamine neurons appear to emit an alerting message about the surprising presence or absence of rewards. All responses to rewards and reward-predicting stimuli depend on event predictability. Dopamine neurons are activated by rewarding events that are better than predicted, remain uninfluenced by events that are as good as predicted, and are depressed by events that are worse than predicted. By signaling rewards according to a prediction error, dopamine responses have the formal characteristics of a teaching signal postulated by reinforcement learning theories. Dopamine responses transfer during learning from primary rewards to reward-predicting stimuli. This may contribute to neuronal mechanisms underlying the retrograde action of rewards, one of the main puzzles in reinforcement learning. The impulse response releases a short pulse of dopamine onto many dendrites, thus broadcasting a rather global reinforcement signal to postsynaptic neurons. This signal may improve approach behavior by providing advance reward information before the behavior occurs, and may contribute to learning by modifying synaptic transmission. The dopamine reward signal is supplemented by activity in neurons in striatum, frontal cortex, and amygdala, which process specific reward information but do not emit a global reward prediction error signal. A cooperation between the different reward signals may assure the use of specific rewards for selectively reinforcing behaviors. Among the other projection systems, noradrenaline neurons predominantly serve attentional mechanisms and nucleus basalis neurons code rewards heterogeneously. Cerebellar climbing fibers signal errors in motor performance or errors in the prediction of aversive events to cerebellar Purkinje cells. Most deficits following dopamine-depleting lesions are not easily explained by a defective reward signal but may reflect the absence of a general enabling function of tonic levels of extracellular dopamine. Thus dopamine systems may have two functions, the phasic transmission of reward information and the tonic enabling of postsynaptic neurons.

Animals↗

Influence of reward expectation on behavior-related neuronal activity in primate striatum.

Rewards constitute important goals for voluntary behavior. This study aimed to investigate how expected rewards influence behavior-related neuronal activity in the anterior striatum. In a delayed go-nogo task, monkeys executed or withheld a reaching movement and obtained liquid or sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed and the reinforcer to be obtained after a subsequent trigger stimulus. Movements varied according to the reinforcers predicted by the instructions, suggesting that animals differentially expected the two outcomes. About 250 of nearly 1,500 neurons in anterior parts of caudate nucleus, putamen, and ventral striatum showed typical task-related activations that reflected the expectation of instructions and trigger, and the preparation, initiation, and execution of behavioral reactions. Strikingly, most task-related activations occurred only when liquid reward was delivered at trial end, rather than the reinforcing sound. Activations close to the time of reward showed similar preferences for liquid reward over the reinforcing sound, suggesting a relationship to the expectation or detection of the motivational outcome of the trial rather than to a "correct" or "end-of-trial" signal. By contrast, relatively few activations in the present task occurred irrespective of the type of reinforcement. In conclusion, many of the behavior-related neurons investigated in the anterior striatum were influenced by an upcoming primary liquid reward and did not appear to code behavioral acts in a motivationally neutral manner. Rather, these neurons incorporated information about the expected outcome into their behavior-related activity. The activations influenced by reward several seconds before its occurrence may constitute a neuronal basis for the retrograde effects of rewards on behavioral reactions.

Animals↗

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

This study investigated neuronal activity in the anterior striatum while monkeys repeatedly learned to associate new instruction stimuli 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 not. During learning, new instruction pictures were presented, and animals guessed and performed one of the trial types according to a trial-and-error strategy. Learning of a large number of pictures resulted in a learning set in which learning took place in a few trials and correct performance exceeded 80% in the first 60-90 trials. About 200 task-related striatal neurons studied in both familiar and learning conditions showed three forms of changes during learning. Activations related to the preparation and execution of behavioral reactions and the expectation of reward were maintained in many neurons but occurred in inappropriate trial types when behavioral errors were made. The activations became appropriate for individual trial types when the animals' behavior adapted to the new task contingencies. In particular, reward expectation-related activations occurred initially in both rewarded and unrewarded movement trials and became subsequently restricted to rewarded trials. These changes occurred in parallel with the visible adaptation of reward expectations by the animals. The second learning change consisted in decreases of task-related activations that were either restricted to the initial trials of new learning problems or persisted during the subsequent consolidation phase. They probably reflected reductions in the expectation and preparation of upcoming task events, including reward. The third learning change consisted in transient or sustained increases of activations. These might reflect the increased attention accompanying learning and serve to induce synaptic changes underlying the behavioral adaptations. Both decreases and increases often induced changes in the trial selective occurrence of activations. In conclusion, neurons in anterior striatum showed changes related to adaptations or reductions of expectations in new task situations and displayed activations that might serve to induce structural changes during learning.

Animals↗

Activation of the human brain by monetary reward.

With the purpose of studying neural activation associated with reward processing in humans, we measured regional cerebral blood flow in 10 right-handed healthy subjects performing a delayed go-no go task in two different reinforcement conditions. Correct responses were either rewarded by money or a simple "ok' reinforcer. Behaviour rewarded by money, as compared with the "ok' reinforcement, was most significantly associated with activation of dorsolateral and orbital frontal cortex and also involved the midbrain and thalamus. These results may reflect the processing of reward information, although arousal effects cannot be completely excluded. It is suggested that the observed foci are implicated in the assessment of consequences in goal-directed behaviour which agrees with research in non-human primates.

Adult↗

A neural substrate of prediction and reward.

The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.

Algorithms↗

Dopamine neurons and their role in reward mechanisms.

Information related to rewards is processed by a limited number of brain structures. Recent studies have demonstrated that dopamine neurons respond to appetitive events, such as primary rewards and reward-predicting stimuli. Rather than responding unconditionally, these neurons signal deviations from the prediction of future appetitive events. These reward-related responses correspond formally to concepts of behavioral and computational learning theories and may thus constitute teaching signals for appetitive learning.

Animals↗

Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli.

Midbrain dopamine systems are crucially involved in motivational processes underlying the learning and execution of goal-directed behaviour. Dopamine neurons in monkeys are uniformly activated by unpredicted appetitive stimuli such as food and liquid rewards and conditioned, reward-predicting stimuli. By contrast, fully predicted stimuli are ineffective, and the omission of predicted reward depresses their activity. These characteristics follow associative-learning rules, suggesting that dopamine responses report an error in reward prediction. Accordingly, neural network models are efficiently trained using a dopamine-like reinforcement signal. However, it is unknown whether the responses to environmental stimuli concern specific motivational attributes or reflect more general stimulus salience. To resolve this, we have compared dopamine impulse responses to motivationally opposing appetitive and aversive stimuli. In contrast to appetitive events, primary and conditioned non-noxious aversive stimuli either failed to activate dopamine neurons or, in cases of close resemblance with appetitive stimuli, induced weaker responses than appetitive stimuli. Thus, dopamine neurons preferentially report environmental stimuli with appetitive rather than aversive motivational value.

Animals↗

[Differential indications for so-called "lateral release" in treatment of chondropathia patellae].

The success rate of the operation of lateral release for pain caused by the patella is reported as being between 14% and 99%. The choice between arthroscopic or open procedures does not seem to affect the results. The wide ranges of results probably reflects differences in patients selection or the method and investigations of follow up. The early term outcome usually show better results than long term follow up. This study evaluates the indications for the operation of lateral releases and discusses the result of 36 out of a total of 42 patients who were follow up for 3 years later surgery. We found that an insufficiency of dysplasia of the vastus medialis, the laxity of the capsule and soft ligaments, and a strong lateral retinaculum were important factors in the indication for this procedure. The quadriceps angle was also of prime importance, but the minor forms of patellar dysplasia played only a minor role. In the so-called hyperpression syndrome, where the patella has a strong tendency to move laterally, the simple lateral release is the single most successful operation. The indication for procedures additionally to the lateral release is examined. We found that in a case with an insufficiently guided patella, a weak capsule and ligaments, an additional capsule roughing should be performed. The presence of early degenerative changes in the joint predisposes to poor results in operations such as abrasion and pride drilling. The results in our study were assessed using the Lysholm score. Our results show that the most successful technique was the combination of an arthroscopy and an extraarticular open operation controlled by arthroscopic means. This technique was not associated with major complications such as haemarthrosis and consecutive prolonged postoperative rehabilitation. Overall we achieved a rate of 83% of good or satisfactory results at more than 3 years using the indications and techniques described above.

Adult↗