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). 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 the impact of characteristics of events on the ability to keep track of time. 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. Such data support a resource allocation theory which posits that attentional and memory resources dedicated to interval timing may be re-allocated for other cognitive processes, which in turn may hinder timing. The main objective of this proposal is to study attentional processing of temporal information in the seconds-to-minutes range (interval timing) using combined behavioral, physiological, and computational approaches. Behaviorally, we will study the effects of non-temporal features of events on the re-allocation of attentional and memory resources when subjects time one or multiple durations. At the physiological level, we propose to dissect the neural circuits involved in the interaction between the internal clock and the resource allocation mechanisms using neuropsychopharmacological methods, specifically by local infusions of specific agonist and antagonists in key sites of the neural circuit in order to manipulate it and gain knowledge of its functioning. Computationally, we propose to evaluate two models of re-allocation of resources, in order to address the effect of behavioral and pharmacological manipulations on attentional processing of temporal information, and to arrive at predictions that warrant further experimental investigation. The studies will help elucidate the behavioral, neural, and computational mechanisms involved when we pay attention to timed stimuli, and will improve our understanding of the impact of attentional factors on complex cognitive processes that require temporal information, processes which may be disrupted 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.

Public Health Relevance

Keeping track of when events occur, and their duration, is fundamental for learning, rate estimation, and decision making. These processes are impaired in patients with Parkinson's disease, Huntington's disease, Schizophrenia and Dyslexia. By studying the impact of attentional factors on cognitive mechanisms that require temporal processing, the present project will (a) allow the development of easy to use criteria for early diagnose of these disorders, (b) enhance our understanding of the brain circuits involved in these disorders, (c) help the assessment of the value/efficiency of potential treatment strategies in animal models of such disorders, which is crucial for developing clinical treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH065561-09
Application #
8266286
Study Section
Special Emphasis Panel (ZRG1-BBBP-C (02))
Program Officer
Rossi, Andrew
Project Start
2002-02-04
Project End
2012-08-06
Budget Start
2012-04-01
Budget End
2012-08-06
Support Year
9
Fiscal Year
2012
Total Cost
$191,031
Indirect Cost
$61,518
Name
Medical University of South Carolina
Department
Neurosciences
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Buhusi, Catalin V; Oprisan, Sorinel A; Buhusi, Mona (2016) Clocks within Clocks: Timing by Coincidence Detection. Curr Opin Behav Sci 8:207-213
Oprisan, Sorinel A; Buhusi, Catalin V (2014) What is all the noise about in interval timing? Philos Trans R Soc Lond B Biol Sci 369:20120459
Reyes, Marcelo Bussotti; Buhusi, Catalin V (2014) What is learned during simultaneous temporal acquisition? An individual-trials analysis. Behav Processes 101:32-7
Oprisan, Sorinel A; Dix, Steven; Buhusi, Catalin V (2014) Phase resetting and its implications for interval timing with intruders. Behav Processes 101:146-53
Buhusi, Catalin V; Matthews, Alexander R (2014) Effect of distracter preexposure on the reset of an internal clock. Behav Processes 101:72-80
Buhusi, Catalin V; Oprisan, Sorinel A (2013) Time-scale invariance as an emergent property in a perceptron with realistic, noisy neurons. Behav Processes 95:60-70
Oprisan, Sorinel A; Buhusi, Catalin V (2013) How noise contributes to time-scale invariance of interval timing. Phys Rev E Stat Nonlin Soft Matter Phys 87:052717
Oprisan, Sorinel A; Buhusi, Catalin V (2013) Why noise is useful in functional and neural mechanisms of interval timing? BMC Neurosci 14:84
Matthews, Alexander R; He, Olivia H; Buhusi, Mona et al. (2012) Dissociation of the role of the prelimbic cortex in interval timing and resource allocation: beneficial effect of norepinephrine and dopamine reuptake inhibitor nomifensine on anxiety-inducing distraction. Front Integr Neurosci 6:111
Buhusi, Catalin V (2012) Time-sharing in rats: effect of distracter intensity and discriminability. J Exp Psychol Anim Behav Process 38:30-9

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