A Mathematical Index of Performance on Fixed‐interval Schedules of Reinforcement

Fry, William; Kelleher, Roger T.; Cook, Leonard

doi:10.1901/jeab.1960.3-193

Cited by 243 publications

(168 citation statements)

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“…This index ranges between −1 and 1 and measures the deviation from the cumulative response record of a straight line, with 0 indicating a constant response rate throughout the interval. The curvature index has been used as a measure of timing during fixed-interval timing (20,21) that is independent of overall response rate, because animals' curvature indices are close to zero (meaning they respond equally through the interval) before they learn to time but curvature indices increase (meaning they respond more at the end of the interval) as responses are controlled in time (21). Second, we measured postreinforcement pauses (20), which examined the delay between the last reinforcer and the next response, which also have been used extensively as a measure of timing independent of overall response rate.…”

Section: Resultsmentioning

confidence: 99%

“…Locomotion was measured by calculating the elapsed time between nosepokes on one side of the chamber and reward collection on the opposite chamber wall. Time-response histograms were normalized to maximum response rate to investigate timing independent of response rate, and curvature statistics were calculated from smoothed timeresponse histograms (21). Response rates were compared between experimental sessions via t tests; for optogenetics experiments, paired t tests were used within subjects between sessions with and without photostimulation.…”

Section: Methodsmentioning

confidence: 99%

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Prefrontal D1 dopamine signaling is required for temporal control

Narayanan

Land

Solder

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

112

152

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Temporal control, or how organisms guide movements in time to achieve behavioral goals, depends on dopamine signaling. The medial prefrontal cortex controls many goal-directed behaviors and receives dopaminergic input primarily from the midbrain ventral tegmental area. However, this system has never been linked with temporal control. Here, we test the hypothesis that dopaminergic projections from the ventral tegmental area to the prefrontal cortex influence temporal control. Rodents were trained to perform a fixed-interval timing task with an interval of 20 s. We report several results: first, that decreasing dopaminergic neurotransmission using virally mediated RNA interference of tyrosine hydroxylase impaired temporal control, and second that pharmacological disruption of prefrontal D1 dopamine receptors, but not D2 dopamine receptors, impaired temporal control. We then used optogenetics to specifically and selectively manipulate prefrontal neurons expressing D1 dopamine receptors during fixed-interval timing performance. Selective inhibition of D1-expressing prefrontal neurons impaired fixed-interval timing, whereas stimulation made animals more efficient during task performance. These data provide evidence that ventral tegmental dopaminergic projections to the prefrontal cortex influence temporal control via D1 receptors. The results identify a critical circuit for temporal control of behavior that could serve as a target for the treatment of dopaminergic diseases.T emporal control, or guiding movements in time to achieve behavioral goals, is a crucial function of mammalian nervous systems. This process depends on the integrated activity of corticostriatal systems (1-3) and requires intact dopaminergic signaling (4). Patients with Parkinson disease with depleted dopamine have dramatically impaired temporal control (5). Despite these data, the neural circuitry influenced by dopamine during temporal computations is not understood.Temporal control can be carefully studied using an intervaltiming task (Fig. 1) (6), in which participants estimate a discrete interval of time. In rodents, disrupting nigrostriatal dopamine (7) in the dorsal, but not the ventral, striatum (8) impairs temporal control. Overexpression of D2 receptors in the striatum also diminished temporal control of behavior (9). A brain region that organizes goal-directed behavior is the medial prefrontal cortex (10, 11). In metabolic imaging studies, hypoactivity in this area is correlated with impaired executive function in Parkinson disease (12). Medial prefrontal regions are activated during human brain imaging of fixed-interval timing tasks (13). In rodents, the medial prefrontal cortex has single neurons that encode the passage of time (14) and exerts topdown control over other brain areas to control movements in time (11). Medial prefrontal regions receive prominent dopaminergic input from the midbrain ventral tegmental region (8), which loses dopamine neurons in Parkinson disease (15)(16)(17). Dysfunction of this system may contribute to cog...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Prefrontal D1 dopamine signaling is required for temporal control

Narayanan

Land

Solder

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

112

152

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“…To assess quantitatively the extent and direction of the cannabinoid-induced change in the temporal response pattern, we applied a previously characterized mathematical analysis known as the index of curvature (Fry et al, 1960;Narayanan et al, 2012). In the index of curvature analysis, a premature acceleration of responding will produce a negative index, while a slower acceleration of responding will produce a positive index.…”

Section: Resultsmentioning

confidence: 99%

“…In the index of curvature analysis, a premature acceleration of responding will produce a negative index, while a slower acceleration of responding will produce a positive index. The index of curvature is calculated by dividing the difference between the area under a hypothetical linear response pattern (A ¼ area of OYX) and the area under the observed temporal response pattern (A 0 ¼ area of Oa 0 b 0 c 0 YX) by the area under the hypothetical linear response pattern (I ¼ (A À A 0 )/A; Figure 5a; Fry et al, 1960). WIN 55 212-2 significantly changed the index of curvature (F (5,29) ¼ 9.361; po0.01), with dosages of 0.6 mg/kg (p ¼ 0.01) and 1 mg/kg (po0.01) inducing a negative curvature index in comparison to vehicle.…”

Section: Resultsmentioning

confidence: 99%

Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

Oleson

Cachope

Fitoussi

et al. 2013

Neuropsychopharmacol

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The ability to discern temporally pertinent environmental events is essential for the generation of adaptive behavior in conventional tasks, and our overall survival. Cannabinoids are thought to disrupt temporally controlled behaviors by interfering with dedicated brain timing networks. Cannabinoids also increase dopamine release within the mesolimbic system, a neural pathway generally implicated in timing behavior. Timing can be assessed using fixed-interval (FI) schedules, which reinforce behavior on the basis of time. To date, it remains unknown how cannabinoids modulate dopamine release when responding under FI conditions, and for that matter, how subsecond dopamine release is related to time in these tasks. In the present study, we hypothesized that cannabinoids would accelerate timing behavior in an FI task while concurrently augmenting a temporally relevant pattern of dopamine release. To assess this possibility, we measured subsecond dopamine concentrations in the nucleus accumbens while mice responded for food under the influence of the cannabinoid agonist WIN 55 212-2 in an FI task. Our data reveal that accumbal dopamine concentrations decrease proportionally to interval duration-suggesting that dopamine encodes time in FI tasks. We further demonstrate that WIN 55 212-2 dose-dependently increases dopamine release and accelerates a temporal behavioral response pattern in a CB1 receptor-dependent manner-suggesting that cannabinoid receptor activation modifies timing behavior, in part, by augmenting time-engendered patterns of dopamine release. Additional investigation uncovered a specific role for endogenous cannabinoid tone in timing behavior, as elevations in 2-arachidonoylglycerol, but not anandamide, significantly accelerated the temporal response pattern in a manner akin to WIN 55 212-2.

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“…The shape of these functions was quantified using the index of curvature, a measure devised to describe non-linear response patterns on time-based reinforcement schedules (see Fry et al 1960). Any negatively accelerating curve produces a negative curvature index; any positively accelerating curve produces a positive index (Fry et al 1960).…”

Section: Data Analysesmentioning

confidence: 99%

Marijuana Effects on Sensitivity to Reinforcement in Humans

Lane

Cherek

2002

Neuropsychopharmacology

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Administration of marijuana has consistently been shown to disrupt behavioral and CNS functions, including acquisition and choice discrimination learning, short-term memory, and time perception (Adams and Barratt 1976;Chait and Pierri 1992;Darley et al. 1973;Heishman et al. 1990;Kelly et al. 1993;Schulze et al. 1989;Vachon et al. 1974). These acute effects-which are evident in rats, monkeys, and humans-are presumably related to the disruptive action of ⌬ 9 THC in the brain. With regard to learning processes, some laboratory tasks like repeated acquisition and match to sample are shaped and maintained by reinforcement, e.g., food, money, or positive feedback (Kelly et al. 1993;Schulze et al. 1989). However, studies of acute marijuana effects on reinforcement-based learning have focused on the acquisition of response patterns rather than sensitivity to reinforcer frequency or magnitude, and less is known about the interaction between acute marijuana intoxication and behavioral sensitivity to reinforcement frequency.Two questions logically precede an inquiry into the effects of marijuana on sensitivity to reinforcement. Why would one expect any relationship? Why would such a relationship be important? At the behavioral level, acute administration of ⌬ 9 THC has repeatedly been shown to impair performance on learning tasks shaped and maintained by reinforcement Balster 1980, Kelly et al. 1993;Kamien et al. 1994;Schulze et al. 1989). Furthermore, on simulated tasks in which subjects could work to earn money, acute marijuana smoking decreased rates of working (and earnings)-an effect presumably mediated by changes in From the Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center -Houston.Address correspondence to: Scott D. Lane, Ph.D., Dept of Psychiatry and Behavioral Sciences, UTSHC-Houston, 1300 Moursund St., Houston, TX 77030, Tel.: (713) 500-2620, Fax: (713) NO . 4 Marijuana and Sensitivity to Reinforcement 521 reinforcement or "motivational" processes (Foltin et al. 1989;Haney et al. 1997, Kagel et al. 1980Miles et al. 1974;Pihl and Sigal 1978). While the present study was not intended to address specific mechanisms, activity at the biochemical level provides a plausible rationale for disruptive effects of ⌬ 9 THC on reinforcement processes. Marijuana impacts both dopamine (DA) and cannabinoid (CB) receptor systems. Administration of ⌬ 9 THC modifies DA release in the "reward pathway", or mesolimbic DA system, projecting from the ventral tegmental area to the nucleus accumbens and into prefrontal cortex (Chen et al. 1990, Gardner and Lowinson 1991, Tanda et al. 1997. Since this pathway is a primary site involved in reinforcement processes (Fibiger and Phillips 1988;Koob and Swerdlow 1988;Wise and Rompre 1989), it follows that marijuana may have acute effects on behavioral sensitivity to reinforcement (see also Loeber and Yurgelun-Todd 1999). ⌬ 9 THC also directly modifies CB receptor function, including sites in the amygdala and hippocampus (Herkenham 1995;Heyser e...

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A Mathematical Index of Performance on Fixed‐interval Schedules of Reinforcement

Cited by 243 publications

References 1 publication

Prefrontal D1 dopamine signaling is required for temporal control

Prefrontal D1 dopamine signaling is required for temporal control

Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

Marijuana Effects on Sensitivity to Reinforcement in Humans

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