Kheramin S, Body S, Mobini S, Ho M-Y, Velázquez-Martinez D N, Bradshaw C M, Szabadi E, Deakin J F W, Anderson I M
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Room B109, Medical School, Queen's Medical Centre, UK.
Psychopharmacology (Berl). 2002 Dec;165(1):9-17. doi: 10.1007/s00213-002-1228-6. Epub 2002 Oct 12.
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.
A quantitative method was used to analyse inter-temporal choice in rats with lesions of the OPFC and sham-lesioned control rats.
Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC (0.1 M, 0.5 micro l; 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 micro l of the sucrose solution after a delay d (A); a press on B resulted in delivery of 100 micro l 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. The locations of the lesions were verified histologically at the end of the experiment.
In both groups, d (B(50)) increased linearly with d (A) ( r(2)>0.98 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. The brains of the lesioned rats showed extensive atrophy/gliosis of the OPFC, with sparing of the dorsolateral prefrontal cortex.
The results indicate that lesions of the OPFC can alter inter-temporal choice, either promoting or suppressing "impulsive choice", depending upon the relative sizes and delays of the two choice alternatives. Theoretical analysis based on a quantitative model of inter-temporal choice indicates that the pattern of effect of the OPFC lesion is likely to reflect two actions: (i) an increase in the rate of time discounting; (ii) an increase in sensitivity to the ratio of the sizes of two reinforcers.
眶额前皮质（OPFC）损伤可导致人类出现病理性冲动行为。跨期选择行为（在大小和延迟不同的强化物之间进行选择）已被提议作为动物“冲动选择”的模型。
采用定量方法分析OPFC损伤大鼠和假损伤对照大鼠的跨期选择。
在氟烷麻醉下，给大鼠在OPFC注射兴奋性毒素喹啉酸（0.1 M，0.5 μl；每侧半球注射两次），或进行假损伤（注射溶剂）。训练它们在离散试验程序中按压两个杠杆（A和B）以获得蔗糖强化物（0.6 M）。在自由选择试验中，按压A会在延迟d（A）后给予50 μl蔗糖溶液；按压B会在延迟d（B）后给予100 μl相同溶液。在每个实验环节的连续六个试验块中，d（B）逐渐增加，而d（A）在实验阶段进行系统调整。估计每只大鼠在每个阶段的无差异延迟d（B(50)）（对应50%选择B时的d（B）值）。得出d（B(50)）与d（A）的线性函数，并比较两组函数的参数。实验结束时通过组织学方法验证损伤位置。
两组中，d（B(50)）均随d（A）线性增加（每组r(2)>0.98）。损伤组函数的斜率显著陡于假损伤组，而两组的截距无显著差异。损伤大鼠的大脑显示OPFC广泛萎缩/胶质增生，背外侧前额叶皮质未受影响。
结果表明，OPFC损伤可改变跨期选择，根据两种选择选项的相对大小和延迟，要么促进要么抑制“冲动选择”。基于跨期选择定量模型的理论分析表明，OPFC损伤的效应模式可能反映两种作用：（i）时间折扣率增加；（ii）对两种强化物大小比例的敏感性增加。
