Effects of quinolinic acid-induced lesions of the orbital prefrontal cortex on inter-temporal choice: a quantitative analysis (original) (raw)
Related papers
Psychopharmacology, 2002
Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size, delay and/ or probability) has been proposed as a model of "impulsive choice" in animals. Objective: The effect of lesions of the OPFC on rats' inter-temporal choice behaviour was examined in two experiments: (1) rats chose between a smaller immediate reinforcer and a larger delayed reinforcer; (2) rats chose between a smaller certain reinforcer and a larger probabilistic reinforcer. Methods: Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC (0.1 M, 0.5 µl, two injections in each hemisphere), or sham lesions (injections of vehicle). They were trained to press two levers (A and B) for food-pellet reinforcers in discrete-trials schedules. In free-choice trials, a press on A resulted in immediate delivery of one food pellet; a press on B resulted in delivery of two pellets, either following a delay (d) (experiment 1), or with a probability (p) <1 (experiment 2). The values of d and p were manipulated across phases of the experiments. The locations of the lesions were verified histologically at the end of the experiment. Results: In experiment 1, both groups showed declining choice of lever B as a function of d. The lesioned rats showed significantly shorter indifference delays (D 50 : the value of d corresponding to 50% choice of lever B) than the sham-lesioned rats. In experiment 2, both groups showed declining choice of lever B as a function of the odds against delivery of the twopellet reinforcer, θ (θ=[1/p]-1). The lesioned rats showed lower indifference odds (θ 50 : the value of θ corresponding to 50% choice of lever B) than the sham-lesioned rats. In both experiments, the lesioned rats showed extensive atrophy of the OPFC, with sparing of the dorsolateral prefrontal cortex. Conclusions: The results show that lesions of the OPFC can promote preference for the smaller and more immediate, and the smaller and more certain of two reinforcers. The results are consistent with two interpretations: the lesion may have altered (i) the rates of delay and odds discounting, and/or (ii) sensitivity to the ratio of the sizes of the two reinforcers.
Psychopharmacology
Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size, delay and/ or probability) has been proposed as a model of "impulsive choice" in animals. Objective: The effect of lesions of the OPFC on rats' inter-temporal choice behaviour was examined in two experiments: (1) rats chose between a smaller immediate reinforcer and a larger delayed reinforcer; (2) rats chose between a smaller certain reinforcer and a larger probabilistic reinforcer. Methods: Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC (0.1 M, 0.5 µl, two injections in each hemisphere), or sham lesions (injections of vehicle). They were trained to press two levers (A and B) for food-pellet reinforcers in discrete-trials schedules. In free-choice trials, a press on A resulted in immediate delivery of one food pellet; a press on B resulted in delivery of two pellets, either following a delay (d) (experiment 1), or with a probability (p) <1 (experiment 2). The values of d and p were manipulated across phases of the experiments. The locations of the lesions were verified histologically at the end of the experiment. Results: In experiment 1, both groups showed declining choice of lever B as a function of d. The lesioned rats showed significantly shorter indifference delays (D 50 : the value of d corresponding to 50% choice of lever B) than the sham-lesioned rats. In experiment 2, both groups showed declining choice of lever B as a function of the odds against delivery of the twopellet reinforcer, θ (θ=[1/p]-1). The lesioned rats showed lower indifference odds (θ 50 : the value of θ corresponding to 50% choice of lever B) than the sham-lesioned rats. In both experiments, the lesioned rats showed extensive atrophy of the OPFC, with sparing of the dorsolateral prefrontal cortex. Conclusions: The results show that lesions of the OPFC can promote preference for the smaller and more immediate, and the smaller and more certain of two reinforcers. The results are consistent with two interpretations: the lesion may have altered (i) the rates of delay and odds discounting, and/or (ii) sensitivity to the ratio of the sizes of the two reinforcers.
Behavioural Processes, 2003
Inter-temporal choice' refers to choice between two or more outcomes that differ with respect to their sizes, delays, and/or probabilities of occurrence. According to the multiplicative hyperbolic model of inter-temporal choice, the value of a reinforcer increases as a hyperbolic function of its size, and decreases as a hyperbolic function of its delay and the odds against its occurrence. These functions, each of which contains a single discounting parameter, are assumed to combine multiplicatively to determine the overall value of the reinforcer. The model gives rise to a quantitative methodology for analysing inter-temporal choice, based on a family of linear null equations which describe performance under conditions of indifference, when the values of the reinforcers are assumed to be equal. This approach was used to examine the effect of lesions of the orbital prefrontal cortex (OPFC) on inter-temporal choice in rats. Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC or sham lesions. They were trained to press two levers (A and B) for food-pellet reinforcers in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of a pellet after a delay d A with a probability P = 0.5; a press on B resulted in delivery of a pellet with a probability P = 1 after a delay d B. d B was increased progressively across successive blocks of six trials in each session, while d A was manipulated systematically across phases of the experiment. The indifference delays, d B(50) (value of d B corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of d B(50) versus d A were derived, and the parameters of the function compared between the groups. In both groups, d B(50) increased linearly with d A. The slope of the linear function was significantly steeper in the lesioned group than in the sham-lesioned group, whereas the intercept did not differ significantly between the groups. Analysis based on the relevant null equation indicated that the lesion of the OPFC increased the rate of both delay and odds discounting. Possible implications of the results for interpreting the effects of OPFC lesions on inter-temporal choice behaviour in man are discussed.
Psychopharmacology, 2007
Rationale-There is evidence that lesions of the nucleus accumbens core (AcbC) promote preference for smaller earlier reinforcers over larger delayed reinforcers in inter-temporal choice paradigms. It is not known whether this reflects an effect of the lesion on the rate of delay discounting, on sensitivity to reinforcer magnitude, or both. Aim-We examined the effect of AcbC lesions on inter-temporal choice using a quantitative method that allows effects on delay discounting to be distinguished from effects on sensitivity to reinforcer size. Method-16 rats received bilateral quinolinic acid-induced lesions of the AcbC; 14 received sham lesions. They were trained under a discrete-trials progressive delay schedule to press two levers (A and B) for a sucrose solution. Responses on A delivered 50 μl of the solution after a delay d A ; responses on B delivered 100 μl after d B. d B increased across blocks of trials, while d A was manipulated across phases of the experiment. Indifference delay d B(50) (value of d B corresponding to 50% choice of B) was estimated in each phase, and linear indifference functions (d B(50) vs. d A) derived. Results-d B(50) increased linearly with d A (r 2 >0.95 in each group). The intercept of the indifference function was lower in the lesioned than the sham-lesioned group; slope did not differ between groups. The lesioned rats had extensive neuronal loss in the AcbC. Conclusions-The results confirm that lesions of the AcbC promote preference for smaller, earlier reinforcers and suggest that this reflects an effect of the lesion on the rate of delay discounting.
Psychopharmacology, 2004
Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size and delay) has been proposed as a model of "impulsive choice" in animals. We recently found that destruction of the OPFC disrupted inter-temporal choice in rats. It is not known whether the dopaminergic projection to the OPFC contributes to the regulation of inter-temporal choice. Objective: A quantitative method was used to compare intertemporal choice in rats whose OPFC had been depleted of dopamine with that of sham-lesioned control rats. Methods: Under halothane anaesthesia, rats received injections of 6-hydroxydopamine into the OPFC (2 mg ml 1 , 0.5 ml, two injections in each hemisphere), or sham lesions (injections of the vehicle). They were trained to press two levers (A and B) for sucrose reinforcement (0.6 M) in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of 50 ml of the sucrose solution after a delay d A ; a press on B resulted in delivery of 100 ml of the same solution after a delay d B. d B was increased progressively across successive blocks of six trials in each session, while d A was manipulated systematically across phases of the experiment. The indifference delay, d B(50) (value of d B corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of d B(50) versus d A were derived, and the parameters of the function compared between the groups. Concentrations of monoamines in the OPFC were determined by highperformance liquid chromatography at the end of the experiment. Results: In both groups, d B(50) increased linearly with d A (r 2 >0.9 in each case). The slope of the function was significantly steeper in the lesioned group than the sham-lesioned group, whereas the intercept did not differ significantly between the groups. When delays of 4 or 8 s were imposed on the smaller reinforcer, the lesioned rats showed greater tolerance of delay to the larger reinforcer (i.e. they exhibited longer values of d B(50)) than the sham-lesioned rats. Dopamine, noradrenaline and 5-hydroxytryptamine levels in the OPFC of the lesioned group were 20, 75 and 98% of those of the shamlesioned group. Conclusions: The results indicate that dopaminergic afferents to the OPFC contribute to the regulation of inter-temporal choice behaviour due to their role in determining organisms' sensitivity both to reinforcer size and to delay of reinforcement.
Dissociable effects of lesions to orbitofrontal cortex subregions on impulsive choice in the rat
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011
The orbitofrontal cortex (OFC) is implicated in a variety of adaptive decision-making processes. Human studies suggest that there is a functional dissociation between medial and lateral OFC (mOFC and lOFC, respectively) subregions when performing certain choice procedures. However, little work has examined the functional consequences of manipulations of OFC subregions on decision making in rodents. In the present experiments, impulsive choice was assessed by evaluating intolerance to delayed, but economically optimal, reward options using a delay-discounting paradigm. Following initial delay-discounting training, rats received bilateral neurotoxic or sham lesions targeting whole OFC (wOFC) or restricted to either mOFC or lOFC subregions. A transient flattening of delay-discounting curves was observed in wOFC-lesioned animals relative to shams--differences that disappeared with further training. Stable, dissociable effects were found when lesions were restricted to OFC subregions; mO...
The neurobiology of intertemporal choice: insight from imaging and lesion studies
2011
People are frequently faced with intertemporal choices, i.e., choices differing in the timing of their consequences, preferring smaller rewards available immediately over larger rewards delivered after a delay. The inability to forgo sooner gratification to favor delayed reward (e.g., impulsivity) has been related to several pathological conditions characterized by poor self-control, including drug addiction and obesity. Comparative and functional human studies have implicated a network of brain areas involved in intertemporal choice, including the medial portion of the orbitofrontal cortex (mOFC). Moreover, damage to this cortical area increases preference for immediate gratification in intertemporal decisions. Here, we review recent neuroscientific studies concerning intertemporal choice, suggesting that the mOFC contributes to preference for delayed rewards, either by computing the value of future outcomes (i.e., valuation), or by enabling people to imagine and represent future rewards and their consequences (e.g., prospection).
Effect of orbitofrontal cortex lesions on temporal discounting in rats
Behavioural Brain Research, 2013
Temporal discounting of the rat was studied using a novel inter-temporal choice task. Rat's choices were better explained by hyperbolic than exponential discount functions. Two-parameter discount functions were superior to single-parameter discount functions. Orbitofrontal cortex lesions did not alter rat's inter-temporal choice behavior.
Synapse, 2012
Interest is rising for animal modeling of impaired behavioral inhibition. Impulsivity and risk proneness, key symptoms of impulse-control disorders, are classically measured by Intolerance to Delay (ID) and Probabilistic Delivery (PD) tasks, requiring choice between a ''Small & Soon'' or ''Sure'' (SS) versus a ''Large & Late'' or ''Luck-Linked'' (LL or LLL, respectively) reinforcer. Several temporal parameters shall be set, which are not always explicit. Here, we focused on duration of timeout (TO; three groups: 15, 30, or 45 s; Exp. 1) and on session length (SL; three groups: 60, 90, or 120 min; Exp. 2) to determine whether these parameters may affect rats' performance in ID and PD tasks, respectively. In Exp. 1, rats' reaction to increasing experimental delays (absolute values 0-90 s, delay-equivalent odds 0 to 1.94 6 0.11) was critically affected by TO duration: a steeper impulsivity curve was found in subjects tested with the longest TO, while random performance was elicited with too short TO. In Exp. 2, a specific ''gambling'' part was presented (LLL probability lower than 20%). Subjects tested with the shortest session length (60 min), who had a low number of gambling opportunities (performed trials 5 84.33 6 1.91), exhibited a profile of risk proneness, with sustained LLL preference despite high uncertainty and low payoff. Present data demonstrate that TO and SL crucially influence rats' performance in these operant tasks. Their methodological refinement is highly relevant to validate preclinical models for inhibitory-control impairments. Synapse 00:000-000, 2012. V V C 2012 Wiley Periodicals, Inc.