2001 — 2002 |
Buhusi, Catalin V. |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Dopaminergic Mechanisms of Interval Timing &Drug Abuse
DESCRIPTION (provided by applicant): The main goal of this proposal is to evaluate the impact of the characteristics of conditioned stimuli on the effects of abuse drugs in the context of a class of behaviors that was shown to accurately reflect the degree of intoxication: timing in the seconds-to-minutes range. While fundamental behavioral processes such as learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals, drugs of abuse result in distortions of time perception. Dopamine (DA) agonists (e.g., methamphetamine, AMP) result in behavior consistent with a speeding up of the internal clock, while DA antagonists (e.g., haloperidol, HAL) result in behavior consistent with a slowing of the clock. While there is the possibility that some reinforcing and addiction properties of DA agonists might be related to their effects on the internal clock, evidence suggests that DA might also serve attentional or predictive functions. It is therefore possible that besides clock-related effects, DA drugs might distort time perception indirectly by affecting the filtering or prediction of events. The experiments described in this proposal aim at dissociating the memory effects, clock-effects, and attentional effects of DA drugs on interval timing in the rat animal model, because DA neuropsychopharmacology is very similar in rats and humans. The main goals of the project are as follows: (1) To develop a set of procedures to evaluate the impact of the characteristics of conditioned stimuli on timing and memory for timing. By contrasting the timing of "empty" and "filled" intervals one can dissociate attentional from clock and memory effects. The modality bias will be examined by using auditory or visual timed cues. (2) To dissociate the attentional and clock effects of AMP and HAL by evaluating their effect on timing "empty" and "filled" intervals in rats. There are no studies of the effects of DA drugs on timing "empty" intervals. Dose response curves will be established for both AMP and HAL (three drug doses for each drug). (3) To dissociate the clock and attentional effects of AMP and HAL on interval timing, by studying the interruption of the timed interval by another event (gap). The experiments will dissociate the clock (shift left/right) and attentional (reset/stop) effects of AMP and HAL. There are no studies of the effects of DA drugs on memory for timing "empty" intervals or intervals with gaps. Together, the studies will inform current models of timing, time perception, and DA psychopharmacology. They will help elucidate the pharmacological basis of interval timing and understand the impact of the characteristics of the attentional cues on the distortions of time perception by drugs of abuse.
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0.97 |
2002 — 2013 |
Buhusi, Catalin V. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Attentional Processing of Temporal Information
DESCRIPTION (provided by applicant): Fundamental behavioral processes such as associative learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals in the seconds-to-minutes range (interval timing). One of the underlying assumptions of most timing theories is that subjects are able to readily abstract from the input stimulus the temporal information, and to tune their behavior according to this cue, irrespective of non-temporal properties the real timed event. In contrast, evidence suggests that both animal and human timing is highly sensitive to properties of the timed signal thus supporting the notion of an "attentional switch/gate" interval timing mechanism. The objective of this proposal is to study attentional processing of temporal information in the seconds-to-minutes range (interval timing) using a multi-level, behavioral, neuropharmacological, and computational approach. Behaviorally, the investigator will study a newly developed interval timing procedure shown to engage attentional processing of temporal cues. Within this procedure, the investigator proposes to evaluate the impact of the characteristics of stimuli on timing and memory for timing. Pharmacologically, the investigator proposes to dissociate the clock effects and attentional effects of specific dopamine agonists and antagonists on interval timing. We also propose to investigate the neural substrates involved in the attentional switch/gate mechanism of timing. Computationally, the investigator proposes to develop a model of the attentional switch/gate mechanism of interval timing in order to address the effect of behavioral and pharmacological manipulations on attentional processing of temporal information. The studies will inform current models of timing, time perception, and neuropharmacology of interval timing. They will provide new means for understanding the impact of attentional factors on complex cognitive mechanisms that require temporal processing. They will help elucidate the pharmacological and neural basis of attentional processing of temporal information
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1 |
2006 — 2009 |
Buhusi, Catalin V. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Representation of Temporal Information
[unreadable] DESCRIPTION (provided by applicant): Fundamental processes such as associative learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals. These processes are disrupted in Parkinson's disease, Huntington's disease, and Schizophrenia. This project will further our understanding of the disruptions of cognitive processes in these disorders by investigating neural activity in the neural substrates showed by imaging studies to be dysregulated in these disorders. The major objective of this proposal is to study the neural representation of temporal information in the seconds-to-minutes range using a multi-level approach involving electrophysiology, behavior, and computational modeling. The neural representation of temporal information will be investigated by multi-site, multi-electrode neural recordings; the behavioral representation of time will be examined in freely behaving rats performing interval timing tasks; the computational elements and operations required to perform these behavioral tasks will be investigated by computer modeling. First, at the electrophysiology level, the investigator will examine the neural representation of temporal information by multi-site, ensemble recordings in a network of substrates including striatum, frontal cortex, substantia nigra, and the hippocampus in freely behaving normal rats as well as in rats in which some of these substrates are temporarily inactivated. Notably, from the couple of electrophysiological studies currently addressing the substrates of interval timing, one was performed by our research group. Second, rats' behavior will be examined while performing two behavioral tasks (involving time estimation and reproduction) in which Parkinson, Huntington, and Schizophrenic patients are known to be impaired. Third, at the computational level the investigator will study a biologically plausible model of interval timing and will compare the predictions of the model with data collected in the behavioral studies. The project will help elucidate the behavioral and neural coding of time, and our understanding of the role of specific neural substrates in disorders like Parkinson, Huntington, and Schizophrenia. The results of the project can be used to devise behavioral measures for the early assessment of such disorders, and to understand the cognitive processes disrupted when these substrates are dysfunctional. This information is crucial to assessing the value/efficiency of potential treatment strategies in animal models of such disorders. [unreadable] [unreadable] [unreadable]
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1 |