Neurotoxic lesions of ventrolateral prefrontal cortex impair object-in-place scene memory

Abstract

Disconnection of the frontal lobe from the inferotemporal cortex produces deficits in a number of cognitive tasks that require the application of memory-dependent rules to visual stimuli. The specific regions of frontal cortex that interact with the temporal lobe in performance of these tasks remain undefined. One capacity that is impaired by frontal-temporal disconnection is rapid learning of new object-in-place scene problems, in which visual discriminations between two small typographic characters are learned in the context of different visually complex scenes. In the present study, we examined whether neurotoxic lesions of ventrolateral prefrontal cortex in one hemisphere, combined with ablation of inferior temporal cortex in the contralateral hemisphere, would impair learning of new object-in-place scene problems. Male macaque monkeys learned 10 or 20 new object-in-place problems in each daily test session. Unilateral neurotoxic lesions of ventrolateral prefrontal cortex produced by multiple injections of a mixture of ibotenate and N-methyl-D-aspartate did not affect performance. However, when disconnection from inferotemporal cortex was completed by ablating this region contralateral to the neurotoxic prefrontal lesion, new learning was substantially impaired. Sham disconnection (injecting saline instead of neurotoxin contralateral to the inferotemporal lesion) did not affect performance. These findings support two conclusions: first, that the ventrolateral prefrontal cortex is a critical area within the frontal lobe for scene memory; and second, the effects of ablations of prefrontal cortex can be confidently attributed to the loss of cell bodies within the prefrontal cortex rather than to interruption of fibres of passage through the lesioned area.

Fig. 1

(a) Maximum intended extent of unilateral ventrolateral prefrontal neurotoxic lesions (light grey), showing lateral and ventral views. (b) Intended extent of unilateral inferotemporal ablations (dark grey), also showing lateral and ventral views.

Fig. 2

Coronal cresyl violet-stained sections through the frontal lobe in the three cases (S1, S2 and S3) that received injections of neurotoxin into the left ventrolateral frontal cortex. The most anterior section in each case is at the top of the figure and the most posterior at the bottom. Compare the left, lesioned hemisphere of each section with the right, intact hemisphere; arrows indicate the extent of the lesions. Scale bar, 5 mm (applies to all sections).

Fig. 3

Higher power images at the midpoint of the frontal lobe in three cases. (A) Case S3, illustrating cell loss in the inferior convexity, ventral bank of principal sulcus, and a focus of cell loss in the lateral orbital gyrus. (B) Case S1, illustrating a similar extent of cell loss in the inferior convexity and ventral bank of principal sulcus to case S3. (C) Case S4, which received saline injections into the frontal cortex. No cell loss is evident but a needle track is visible. Scale bars, 1 mm.

Fig. 4

Coronal cresyl violet-stained sections through the temporal lobe in all four cases, illustrating the extent of the inferotemporal ablation. The most anterior section in each case is at the top of the figure and the most posterior at the bottom. Compare the right, lesioned hemisphere of each section with the left, intact hemisphere. Damage to the parietal cortex, apparent in the left hemisphere in the most posterior section for case S4, was sustained in a surgery performed after the data reported in the present paper were collected. Scale bar, 5 mm (applies to all sections).

Fig. 5

Learning curves for the eight repetitions of lists of new scenes before surgery, after unilateral ventrolateral frontal (vFL) lesions (Postop 1), and after disconnection from inferotemporal cortex (IT) was complete (Postop 2). Data presented are the mean percentage error for each repetition of lists of new scenes for cases S1–S3. There was no effect of unilateral frontal lobe damage on scene learning but a severe impairment is evident after the disconnection of IT from the vFL is completed in the second postoperative phase.

Fig. 6

Comparison of neurotoxic ventrolateral frontal lesions, saline injections and full disconnection of frontal lobe from inferotemporal cortex. Data presented are the mean percentage error on trials 2–8 of lists of new scene problems. ‘Pre’ represents performance after unilateral lesions of either the frontal lobe (FL) or temporal lobe (subjects A, B and C in group FL × IT, data from figure 4 of Browning et al., 2005) or after unilateral injections into the ventrolateral frontal cortex (subjects S1–S4, groups vFL, present study). ‘Post’ represents performance after frontal–temporal disconnection in all three groups. The impairment in group FL × IT appears to be more severe than that in group vFL (neurotoxic) × IT, although comparison is complicated because of differences in baseline performance. ‘Sham’ disconnection as a result of saline injections into vFL (case S4) was without effect on scene learning.

Fig. 7

Phase–space plot comparing the current data with those presented in Browning et al. (2005). Data are plotted as mean preoperative percentage error against mean percentage error following the second surgeries in the disconnection procedure, or the only surgery in group Bilateral PFC. Each point represents the mean pre- vs. postoperative performance on a given repetition of lists of new scenes. The central diagonal line represents performance that is identical prior to and after surgery. As such, points below this line represent an improvement from pre- to postoperative performance tests, and points above it represent an impairment in performance from pre to post. Group vFL(saline) × IT shows a small improvement, whereas impairments are clear in groups Bilateral PFC, vFL(neurotoxic) × IT, and FL × IT. The impairment in group vFL(neurotoxic) × IT was mildly less severe than that of group FL × IT. FL, frontal lobe; IT, inferotemporal cortex; PFC, prefrontal cortex; vFL, ventrolateral frontal cortex.