Timing Of Conditioned Responses Research Articles

Pharmacological analysis of cerebellar contributions to the timing and expression of conditioned eyelid responses

Contradictory results have been reported regarding the effects of cerebellar cortex lesions on the expression of conditioned eyelid responses—either no effect, partial to complete abolition of responses, or disruption of response timing. This uncertainty is increased by debates regarding the region(s) of cerebellar cortex that are involved, by the likelihood that cortex lesions can inadvertently include damage to the interpositus nucleus or other pathways necessary for response expression, and by potential confounds from the degeneration of climbing fibers produced by cerebellar cortex lesions. We have addressed these issues by reversibly blocking cerebellar cortex output via infusion of the GABA antagonist picrotoxin into the interpositus nucleus. After picrotoxin infusion, conditioned responses are spared but their timing is disrupted and their amplitude diminished. In the same animals, conditioned responses were abolished by infusion of the GABA agonist muscimol and were unaffected by infusion of saline vehicle. These results are consistent with the hypothesis that (i) plasticity in the interpositus nucleus contributes to the expression of conditioned responses, as suggested by the responses seen with the cortex disconnected, and (ii) plasticity in the cerebellar cortex also contributes to conditioned response expression, as suggested by disruption of response timing.

Conditioned response timing and integration in the cerebellum.

Classical conditioning procedures instill knowledge about the temporal relationships between events. The unconditioned stimulus (US) is the event to be timed. The conditioned response (CR) is viewed as a prediction of the imminence of the US. Knowledge of the elapsed time between conditioned stimuli (CSs) and US delivery is expressed in the topological features of the CR. The peak amplitude of the CR coincides with the timing of the US. A simple connectionist network based on Sutton and Barto's Time Derivative (TD) Model of Pavlovian Reinforcement provides a mechanism that can account for and simulate CR timing in a variety of protocols. This article describes extensions of the model to predictive timing under temporal uncertainty. The model is expressed in terms of equations that operate in real time according to a competitive learning rule. The unfolding of time from the onsets and offsets of events such as CSs is represented by the propagation of activity along a sequence of time-tagged elements. The model can be aligned with anatomical circuits of the cerebellum and brain stem that are essential for learning and performance of conditioned eye-blink responses.

Extinction of conditioned eyelid responses requires the anterior lobe of cerebellar cortex

We test the hypothesis that the cerebellar cortex is required for the extinction of conditioned eyelid responses in rabbits trained using standard Pavlovian delay procedures. Following 10 daily training sessions during which rabbits achieved asymptotic performance, lesions of the ipsilateral hemisphere of the cerebellar cortex were made by aspiration. The target of these lesions was the anterior lobe, as suggested by previous observations that this region is necessary for the learning-dependent timing of conditioned eyelid responses (Perrett et al., 1993). We report that anterior lobe damage, as indicated by disrupted response timing and confirmed by tissue analysis, produces severe deficits in conditioned response extinction. Postlesion responses show no significant decline over ten training sessions, whereas response timing and extinction are unaffected by lesions that do not include the anterior lobe. These conditioned responses that do not extinguish display stimulus specificity, excluding the possibility that they are unlearned responses unmasked by cerebellar cortex lesions. These observations suggest that Pavlovian eyelid conditioning is mediated by synaptic plasticity in at least two sites and the anterior lobe of the cerebellar cortex influences one of these sites during extinction. Based on these and previous data, we propose the hypothesis that eyelid conditioning can involve plasticity in both the cerebellar cortex and interpositus nucleus and that plasticity in the nucleus is controlled by input from Purkinje cell activity in the cortex. This hypothesis is consistent with observations that the cerebellar cortex may not always be required for the expression of conditioned responses, but it is necessary for response timing and for extinction.

A reliability model for real-time rule-based expert systems

This paper uses two modeling tools to analyze the reliability of real-time expert systems: (1) a stochastic Petri net (SPN) for computing the conditional response time distribution given that a fixed number of expert system match-select-act cycles are executed, and (2) a simulation search tree for computing the distribution of expert system match-select-act cycles for formulating a control strategy in response to external events. By modeling the intrinsic match-select-act cycle of expert systems and associating rewards rates with markings of the SPN, the response time distribution for the expert system to reach a decision can be computed as a function of design parameters, thereby facilitating the assessment of reliability of expert systems in the presence of real-time constraints. The utility of the reliability model is illustrated with an expert system characterized by a set of design conditions under a real-time constraint. This reliability model allows the system designers to: (1) experiment with a range of selected parameter values; and (2) observe their effects on system reliability.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Connections to cerebellar cortex (Larsell's HVI) in the rabbit: a WGA-HRP study with implications for classical eyeblink conditioning.

Conditioned eyeblink responses are presumably learned in the cerebellum and relayed to motoneurons by way of the red nucleus. Projections from the red nucleus to cerebellar cortex (Larsell's lobule HVI) could be important for shaping temporally adaptive features of the conditioned response. Rabbits that had pipettes containing wheat germ agglutinated horseradish peroxidase (WGA-HRP) implanted unilaterally into HVI showed retrograde labeling of neurons within subregions of the contralateral red nucleus implicated in eyeblink conditioning by lesioning and recording studies. Retrogradely labeled neurons were also observed in the pontine nuclei, inferior olive, and spinal trigeminal nucleus pars oralis. Projections to HVI provide a possible neural substrate for implementing time-derivative computational models of learning in the cerebellum. Time-derivative models are capable of describing the timing and topography of conditioned responses.

Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses

Among the many issues surrounding the involvement of the cerebellum in motor learning, the relative roles of the cerebellar cortex and cerebellar nuclei in Pavlovian conditioning have been particularly difficult to assess. While previous studies have investigated the effects of cerebellar cortex lesions on the acquisition and retention of conditioned movements, we have examined the effects of these lesions on the timing of Pavlovian eyelid responses. The rationale for this approach arises from previous studies indicating that this timing is a component of Pavlovian eyelid responses that is learned and that involves temporal discrimination. To permit within-animal comparisons, rabbits were trained to produce differently timed responses to high- and low-frequency auditory conditioned stimuli (CSs). Before the lesion the conditioned responses to both CSs were appropriately timed--each peaked near the time at which the unconditioned stimulus was presented for that CS. However, after the lesion both CSs could elicit similarly timed conditioned responses that peaked inappropriately at very short latencies. The changes in responses timing were sensitive to the size of the lesion, particularly its rostral-caudal extent. Similar results were obtained in animals trained with one CS, indicating that the disruption of response timing is not related to impaired auditory discrimination. Because response timing is learned and therefore requires synaptic plasticity, these data suggest that there are at least two sites of plasticity involved in the motor expression of Pavlovian eyelid responses. Plasticity at one site is necessary for the learned timing of conditioned responses, while plasticity at another site is revealed by the inappropriately timed responses observed following removal of the cerebellar cortex. This lesion-induced dissociation of the expression of motor responses and their learned timing supports a synthesis of competing views by suggesting that motor learning involves both the cerebellar cortex and cerebellar nuclei. We hypothesize that motor learning involves a decrease in strength of the granule cell-Purkinje cell synapses (e.g., Ito and Kano, 1982) in the cerebellar cortex and an increase in strength of the mossy fiber-cerebellar nuclei synapses (e.g., Racine et al., 1986). Finally, these data suggest that the cerebellar cortex may mediate the temporal discriminations that are necessary for the learned timing of conditioned responses.

An execution/sleep scheduling policy for serving an additional job in priority queueing systems

In a priority-based computer system, besides the regular jobs, an additional job (refereed to as job A ) is invoked infrequently but requires a significant amount of CPU time. To avoid CPU hogging, job A receives (up to) a fixed amount of CPU time whenever it is served. When the time expires, job A immediately relinquishes the CPU and puts itself to sleep for a period of time. By doing so, jobs with low priority may be processed in a timely manner. When the sleep time is over, job A is awakened and waits to resume service according to its priority. Then, the whole process is repeated until job A service is completed. In this paper, such an execution/sleep (ES) scheduling policy is analyzed for serving job A in a nonpreemptive priority queuing system. The Laplace Transforms are derived for: (i) the conditional response time of job A and (ii) the response time for jobs with priorities higher and lower than job A. This work is motivated by the ES policy in a switching system in which job A is invoked in response to the failure of signaling links. The proposed model is applicable to other real-time computer systems, and the modeling techniques can be applied or generalized to analyzing other scheduling policies in which timers are involved.

Learning-dependent timing of Pavlovian eyelid responses: differential conditioning using multiple interstimulus intervals.

This study demonstrates that individual animals can concurrently acquire differently timed conditioned eyelid responses using a differential conditioning procedure in which distinctive conditioned stimuli (CSs) are individually paired with an unconditioned stimulus, with each using a different interstimulus interval (ISI). This promotes robust conditioning, and the timing of the conditioned responses is appropriate for the respective ISIs, differs for each CS to the extent that the ISIs are dissimilar, and is apparent in individual trials. This procedure was used to demonstrate that response timing is not a function of associative strength. These data suggest response timing is mediated by an ability to make temporal discriminations during the CS. The within-animals comparisons made possible by this differential conditioning should facilitate lesion and unit recording analyses of the neural basis of response timing.

Approximations for moments of response times in time sharing queues with limited number of service positions

A time sharing system consisting of a single processor with a limited number of service positions and unlimited waiting line is studied, in equilibrium, under a FIFO waiting line regime. A spectral method is applied to the calculation of the conditional response time moments in the case of state dependent arrival and service rates. The numerical results show that for the M/M/1 case the expected conditional response time is approximately a straight line, when presented as a function of the processing requirement length, in the region of interest. Thus in that region the behavior of the subsystem consisting of the service positions is similar to that of a symmetric queue. Based on this observation a linear approximation for the expected conditional response time in the M/G/1 case is obtained. The linear approximation is men compared to simulated results.

Temporal specificity in cross-modal transfer of the rabbit nictitating membrane response.

Two experiments examine cross-modal transfer of response features specific to the interstimulus interval (ISI) between a conditioned stimulus (CS) and an unconditioned stimulus. Rabbits were given initial training with a stimulus (CSA) in one modality (e.g., tone) at a designated ISI (e.g., 600 ms). Training was then shifted to a new stimulus (CSB) in another modality (e.g., light) at a new ISI (e.g., 400 ms). The timing of early conditioned responses (CRs) to CSB reflected the ISI of CSA. Ultimately, CRs to CSB shifted to a temporal location conforming to the ISI of CSB. When the ISI of CSB was shorter than that of CSA, CRs to CSA also shifted to a locus conforming to the ISI of CSB. The present results confirmed previous findings that training in one CS modality accelerates CR acquisition to a CS in another modality. The findings are compared with the transfer of response patterns in instrumental learning sets and are discussed regarding their implications for theories of cross-modal transfer.

On Finite Capacity Processor-Shared Queues

A processor-sharing queueing system is considered that can accommodate a finite number K of customers. In a processor-shared queue, every customer gets an equal fraction of the server (processor). The main quantity of interest in such a system is a customer’s response time (time spent in system) conditioned on that customer’s total required service and the number of other customers present at the arrival time. Using singular perturbation methods, we construct asymptotic expansions for the first two moments of the conditional response time for systems where the capacity K is large.

Stationary increments in the accumulated work process in processor-sharing queues

We present a new approach to the processor-sharing queue that allows us to study the accumulated work process of a job that requires an amount of processing time x. Our approach simplifies the proofs of some earlier results on expected conditional response times and extends them to the M/G/φ (·) class. The approach illuminates some of the paradoxical features of these systems.

Stationary increments in the accumulated work process in processor-sharing queues

We present a new approach to the processor-sharing queue that allows us to study the accumulated work process of a job that requires an amount of processing time x. Our approach simplifies the proofs of some earlier results on expected conditional response times and extends them to the M/G/φ (·) class. The approach illuminates some of the paradoxical features of these systems.

A single server queue with gated processor-sharing discipline

In this paper we consider a single server queue in which arrivals occur according to a Poisson process and each customer's service time is exponentially distributed. The server works according to the gated process-sharing discipline. In this discipline, the server provides service to a batch of at mostm customers at a time. Once a batch of customers begins service, no other waiting customer can receive service until all members of the batch have completed their service. For this queue, we derive performance characteristics, such as waiting time distribution, queue length distribution etc. For this queue, it is possible to obtain the mean conditional response time for a customer whose service time is known. This conditional response time is a nonlinear function (as opposed to the linear case for the ordinary processor-sharing queue). A special case of the queue (wherem=∞) has an interesting and unusual solution. For this special case, the size of the batch for service is a Markov chain whose steady state distribution can be explicitly written down. Apart from the contribution to the theory of Markov chains and queues, the model may be applicable to scheduling of computer and communication systems.

Temporal patterns of the rabbit's nictitating membrane response to compound and component stimuli under mixed CS-US intervals.

The acquisition of the rabbit's nictitating membrane response to a tone and light compound and to its components was examined when compound presentations were reinforced at one conditioned stimulus-unconditioned stimulus (CS-US) interval and individual component presentations were reinforced at another CS-US interval. Examination of the time course of the CRs revealed that (a) despite the mixture of CS-US intervals, conditioned response (CR) timing remained accurate, that is, CRs reached their peaks at the alternative points of US delivery; (b) the momentary magnitude of the CR to the compound was predominantly an additive function of the CR magnitude to the individual components; but (c) there was modest evidence of differentiation between the compound as a unit and the individual components. The results are discussed in terms of their implications for the study of the neural substrates of temporal and sensory integration as they modulate CR acquisition.

Reliability Bounds for Fault-Tolerant Systems with Competing Responses to Component Failures

Bounds are established for the probability of failure of fault-tolerant systems. The underlying failure and recovery process is assumed to follow a semi-Markov model in which the potential sojourn times of component failures have exponential distributions and those of system responses have general distributions. A product form of the bounds is derived from a model which provides for competing responses to component failures. Bounds are calculated in terms of integral factors which depend on component failure rates and the actual distributions of response times. Bounds are also calculated in terms of percentiles, conditional mean response times, and certain transition probabilities. Besides providing a computationally efficient method of estimating reliability from a flexible model, the bounds seem reasonably tight for a fairly wide range of cases. An example is given to illustrate calculating the bounds for a model with competing system responses.

A Conditional Response Time of the M/M/1 Processor-Sharing Queue

In this paper we examine the distribution of the response time of an arriving customer conditioned on the number of customers present in an M/M/1 processor-sharing queue. We show that the rth moment of the distribution is a polynomial in the number of customers present, and obtain a recursion for its determination. The Laplace-Stieltjes transform of the conditional distribution is also obtained. We find an expansion in powers of the arrival rate, which permits accurate computation when the utilization is not too close to one, and also give an asymptotic expansion when the number of customers in the system is large. This permits assessment of response time in a heavily loaded system. We present numerical results using these methods and discuss their relative merits.

Conditional expected sojourn times in insensitive queueing systems and networks

We consider queueing systems where the stationary state probabilities are insensitive with respect to the distribution of certain basic random variables such as service requirements, interarrival times, repair times, etc. The conditional expected sojourn times are stated as Radon–Nikodym densities of the stationary distribution at jump points of the queueing system. The conditions are the given values of such basic random variables for which the insensitivity is valid. We use stationary point processes as our main tool. This means that dependences between certain basic random variables are permitted. Conditional expected real service times, conditional mean response times in closed queueing networks, and similar conditional expected values, are dealt with as special cases.

Conditional expected sojourn times in insensitive queueing systems and networks

We consider queueing systems where the stationary state probabilities are insensitive with respect to the distribution of certain basic random variables such as service requirements, interarrival times, repair times, etc. The conditional expected sojourn times are stated as Radon–Nikodym densities of the stationary distribution at jump points of the queueing system. The conditions are the given values of such basic random variables for which the insensitivity is valid. We use stationary point processes as our main tool. This means that dependences between certain basic random variables are permitted. Conditional expected real service times, conditional mean response times in closed queueing networks, and similar conditional expected values, are dealt with as special cases.

Conditional response times in the M/G/1 processor-sharing system

The expected response time of a job that requires processing time t and meets n jobs on arrival in the M/G/1 processor-sharing system is derived.