Perseverative interference with object-in-place scene learning in rhesus monkeys with bilateral ablation of ventrolateral prefrontal cortex

Abstract

Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with bilateral ablations of ventrolateral prefrontal cortex in object-in-place scene learning. These monkeys were mildly impaired in scene learning relative to their own preoperative performance, similar in severity to that of monkeys with bilateral ablation of orbital prefrontal cortex. An analysis of response types showed that the monkeys with lesions were specifically impaired in responding to negative feedback during learning: The post-operative increase in errors was limited to trials in which the first response to each new problem, made on the basis of trial and error, was incorrect. This perseverative pattern of deficit was not observed in the same analysis of response types in monkeys with bilateral ablations of the orbital prefrontal cortex, who were equally impaired on trials with correct and incorrect first responses. This may represent a specific signature of ventrolateral prefrontal involvement in episodic learning and memory.

Figure 1.

Areas of damage in the five monkeys with ventrolateral prefrontal lesions are plotted onto schematic coronal brain sections from a standard atlas of the rhesus monkey brain (Szwarcbart 2005). Large numerals indicate millimeters anterior to the interaural plane. The lesions are illustrated as the extent to which damage is present in one, two, three, four, or all five of the lesion cases, indicated by color going from light gray to black (the scale is represented at the top of the figure). The ventrolateral prefrontal cortex is extensively damaged in all five cases (occupying much of the inferior frontal convexity), although the lateral borders of the lesions vary from case to case.

Figure 2.

Lesions of VLPFC in cases VL1-VL5. The intended lesion is shown in red on coronal sections of a normal rhesus monkey in the leftmost column, at five stereotaxic levels through the prefrontal cortex, moving from rostral to caudal from the top to the bottom of the figure. Photomicrographs of brain sections from cases VL1-VL5 at corresponding stereotaxic levels are shown in the other columns.

Figure 3.

Three examples of scenes are shown, illustrating the background elements and the two foreground stimuli (small alphanumeric characters, e.g., F and W in the scene on the left).

Figure 4.

(A) Learning curves across trials 1–8 for new scene learning in pre- and post-operative performance tests in control monkeys and monkeys with bilateral ventrolateral prefrontal ablation. Monkeys with ventrolateral prefrontal lesions show slower learning post-operatively. (B) Individual performance on object-in-place scene learning for each monkey (CON1–CON4, controls; VL1–VL5, monkeys with bilateral ablations of ventrolateral prefrontal cortex). The measure plotted is mean performance (percentage error) across trials 2–8 of lists of new scenes learned pre- and post-operatively. The monkeys with ventrolateral lesions are mildly impaired in scene learning post-operatively.

Figure 5.

Performance on trials 2–8 of learning new scene problems divided by whether the initial response to each scene was correct (1C) or wrong (1W), according to each monkey’s choice for each problem. (Trial 1 is omitted because, by definition, it is 0 for 1C scenes and 100 for 1W scenes.) All monkeys make more errors in learning scenes to which their initial response is incorrect. The performance of control monkeys is indistinguishable between their two performance tests (before and after a rest period equivalent to the post-operative recovery time of monkeys that receive surgery). Ablation of ventrolateral prefrontal cortex does not significantly increase the errors monkeys make in learning 1C scenes, but it substantially impairs learning of 1W scenes. Data from monkeys with bilateral ablation of orbital prefrontal cortex are shown for comparison (Baxter et al. 2007). These lesions produce a similar overall deficit in scene learning in terms of total errors on trials 2–8, but this effect is due to a mild impairment in learning in both 1C and 1W trials. Left and right panels were replotted with permission from the Society for Neuroscience © 2007, Figure 5 of Baxter et al. 2007.