A Local Circuit Model of Learned Straitial and Dopamine Cell Responses under Probabilistic Schedules of Reward

Before choosing, it helps to know both the expected value signaled by a predictive cue and the associated uncertainty that the reward will be forthcoming. Recently, Fiorillo et al. (2003) found the dopamine (DA) neurons of the SNc exhibit sustained responses related to the uncertainty that a cure will be followed by reward, in addition to phasic responses related to reward prediction errors (RPEs). This suggests that cue-dependent anticipations of the timing, magnitude, and uncertainty of rewards are learned and reflected in components of the DA signals broadcast by SNc neurons. What is the minimal local circuit model that can explain such multifaceted reward-related learning? A new computational model shows how learned uncertainty responses emerge robustly on single trial along with phasic RPE responses, such that both types of DA responses exhibit the empirically observed dependence on conditional probability, expected value of reward, and time since onset of the reward-predicting cue. The model includes three major pathways for computing: immediate expected values of cures, timed predictions of reward magnitudes (and RPEs), and the uncertainty associated with these predictions. The first two model pathways refine those previously modeled by Brown et al. (1999). A third, newly modeled, pathway is formed by medium spiny projection neurons (MSPNs) of the matrix compartment of the striatum, whose axons co-release GABA and a neuropeptide, substance P, both at synapses with GABAergic neurons in the SNr and with the dendrites (in SNr) of DA neurons whose somas are in ventral SNc. Co-release enables efficient computation of sustained DA uncertainty responses that are a non-monotonic function of the conditonal probability that a reward will follow the cue. The new model's incorporation of a striatal microcircuit allowed it to reveals that variability in striatal cholinergic transmission can explain observed difference, between monkeys, in the amplitutude of the non-monotonic uncertainty function. Involvement of matriceal MSPNs and striatal cholinergic transmission implpies a relation between uncertainty in the cue-reward contigency and action-selection functions of the basal ganglia. The model synthesizes anatomical, electrophysiological and behavioral data regarding the midbrain DA system in a novel way, by relating the ability to compute uncertainty, in parallel with other aspects of reward contingencies, to the unique distribution of SP inputs in ventral SN.

Integration of relational and hierarchical network information for protein function prediction

BACKGROUND:In the current climate of high-throughput computational biology, the inference of a protein's function from related measurements, such as protein-protein interaction relations, has become a canonical task. Most existing technologies pursue this task as a classification problem, on a term-by-term basis, for each term in a database, such as the Gene Ontology (GO) database, a popular rigorous vocabulary for biological functions. However, ontology structures are essentially hierarchies, with certain top to bottom annotation rules which protein function predictions should in principle follow. Currently, the most common approach to imposing these hierarchical constraints on network-based classifiers is through the use of transitive closure to predictions.RESULTS:We propose a probabilistic framework to integrate information in relational data, in the form of a protein-protein interaction network, and a hierarchically structured database of terms, in the form of the GO database, for the purpose of protein function prediction. At the heart of our framework is a factorization of local neighborhood information in the protein-protein interaction network across successive ancestral terms in the GO hierarchy. We introduce a classifier within this framework, with computationally efficient implementation, that produces GO-term predictions that naturally obey a hierarchical 'true-path' consistency from root to leaves, without the need for further post-processing.CONCLUSION:A cross-validation study, using data from the yeast Saccharomyces cerevisiae, shows our method offers substantial improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor) and more refined Markov random field methods, whether in their original form or when post-processed to artificially impose 'true-path' consistency. Further analysis of the results indicates that these improvements are associated with increased predictive capabilities (i.e., increased positive predictive value), and that this increase is consistent uniformly with GO-term depth. Additional in silico validation on a collection of new annotations recently added to GO confirms the advantages suggested by the cross-validation study. Taken as a whole, our results show that a hierarchical approach to network-based protein function prediction, that exploits the ontological structure of protein annotation databases in a principled manner, can offer substantial advantages over the successive application of 'flat' network-based methods.

Statistic Rate Monotonic Scheduling

In this paper we present Statistical Rate Monotonic Scheduling (SRMS), a generalization of the classical RMS results of Liu and Layland that allows scheduling periodic tasks with highly variable execution times and statistical QoS requirements. Similar to RMS, SRMS has two components: a feasibility test and a scheduling algorithm. The feasibility test for SRMS ensures that using SRMS' scheduling algorithms, it is possible for a given periodic task set to share a given resource (e.g. a processor, communication medium, switching device, etc.) in such a way that such sharing does not result in the violation of any of the periodic tasks QoS constraints. The SRMS scheduling algorithm incorporates a number of unique features. First, it allows for fixed priority scheduling that keeps the tasks' value (or importance) independent of their periods. Second, it allows for job admission control, which allows the rejection of jobs that are not guaranteed to finish by their deadlines as soon as they are released, thus enabling the system to take necessary compensating actions. Also, admission control allows the preservation of resources since no time is spent on jobs that will miss their deadlines anyway. Third, SRMS integrates reservation-based and best-effort resource scheduling seamlessly. Reservation-based scheduling ensures the delivery of the minimal requested QoS; best-effort scheduling ensures that unused, reserved bandwidth is not wasted, but rather used to improve QoS further. Fourth, SRMS allows a system to deal gracefully with overload conditions by ensuring a fair deterioration in QoS across all tasks---as opposed to penalizing tasks with longer periods, for example. Finally, SRMS has the added advantage that its schedulability test is simple and its scheduling algorithm has a constant overhead in the sense that the complexity of the scheduler is not dependent on the number of the tasks in the system. We have evaluated SRMS against a number of alternative scheduling algorithms suggested in the literature (e.g. RMS and slack stealing), as well as refinements thereof, which we describe in this paper. Consistently throughout our experiments, SRMS provided the best performance. In addition, to evaluate the optimality of SRMS, we have compared it to an inefficient, yet optimal scheduler for task sets with harmonic periods.

Multiplexing VBR Traffic Flows with Guaranteed Application-level QoS Using Statistical Rate Monotonic Scheduling

Quality of Service (QoS) guarantees are required by an increasing number of applications to ensure a minimal level of fidelity in the delivery of application data units through the network. Application-level QoS does not necessarily follow from any transport-level QoS guarantees regarding the delivery of the individual cells (e.g. ATM cells) which comprise the application's data units. The distinction between application-level and transport-level QoS guarantees is due primarily to the fragmentation that occurs when transmitting large application data units (e.g. IP packets, or video frames) using much smaller network cells, whereby the partial delivery of a data unit is useless; and, bandwidth spent to partially transmit the data unit is wasted. The data units transmitted by an application may vary in size while being constant in rate, which results in a variable bit rate (VBR) data flow. That data flow requires QoS guarantees. Statistical multiplexing is inadequate, because no guarantees can be made and no firewall property exists between different data flows. In this paper, we present a novel resource management paradigm for the maintenance of application-level QoS for VBR flows. Our paradigm is based on Statistical Rate Monotonic Scheduling (SRMS), in which (1) each application generates its variable-size data units at a fixed rate, (2) the partial delivery of data units is of no value to the application, and (3) the QoS guarantee extended to the application is the probability that an arbitrary data unit will be successfully transmitted through the network to/from the application.

Design and Implementation of Statistical Rate Monotonic Scheduling in KURT Linux

Statistical Rate Monotonic Scheduling (SRMS) is a generalization of the classical RMS results of Liu and Layland [LL73] for periodic tasks with highly variable execution times and statistical QoS requirements. The main tenet of SRMS is that the variability in task resource requirements could be smoothed through aggregation to yield guaranteed QoS. This aggregation is done over time for a given task and across multiple tasks for a given period of time. Similar to RMS, SRMS has two components: a feasibility test and a scheduling algorithm. SRMS feasibility test ensures that it is possible for a given periodic task set to share a given resource without violating any of the statistical QoS constraints imposed on each task in the set. The SRMS scheduling algorithm consists of two parts: a job admission controller and a scheduler. The SRMS scheduler is a simple, preemptive, fixed-priority scheduler. The SRMS job admission controller manages the QoS delivered to the various tasks through admit/reject and priority assignment decisions. In particular, it ensures the important property of task isolation, whereby tasks do not infringe on each other. In this paper we present the design and implementation of SRMS within the KURT Linux Operating System [HSPN98, SPH 98, Sri98]. KURT Linux supports conventional tasks as well as real-time tasks. It provides a mechanism for transitioning from normal Linux scheduling to a mixed scheduling of conventional and real-time tasks, and to a focused mode where only real-time tasks are scheduled. We overview the technical issues that we had to overcome in order to integrate SRMS into KURT Linux and present the API we have developed for scheduling periodic real-time tasks using SRMS.

Neuropeptide Co-Release with Gaba May Explain Functional Non-Monotonic Uncertainty Responses in Dopamine Neurons

Co-release of the inhibitory neurotransmitter GABA and the neuropeptide substance-P (SP) from single axons is a conspicuous feature of the basal ganglia, yet its computational role, if any, has not been resolved. In a new learning model, co-release of GABA and SP from axons of striatal projection neurons emerges as a highly efficient way to compute the uncertainty responses that are exhibited by dopamine (DA) neurons when animals adapt to probabilistic contingencies between rewards and the stimuli that predict their delivery. Such uncertainty-related dopamine release appears to be an adaptive phenotype, because it promotes behavioral switching at opportune times. Understanding the computational linkages between SP and DA in the basal ganglia is important, because Huntington's disease is characterized by massive SP depletion, whereas Parkinson's disease is characterized by massive DA depletion.