Neuronal Modulation in the Prefrontal Cortex in a Transitive Inference Task: Evidence of Neuronal Correlates of Mental Schema Management

Abstract

When informed that A > B and B > C, humans and other animals can easily conclude that A > C. This remarkable trait of advanced animals, which allows them to manipulate knowledge flexibly to infer logical relations, has only recently garnered interest in mainstream neuroscience. How the brain controls these logical processes remains an unanswered question that has been merely superficially addressed in neuroimaging and lesion studies, which are unable to identify the underlying neuronal computations. We observed that the activation pattern of neurons in the prefrontal cortex (PFC) during pair comparisons in a highly demanding transitive inference task fully supports the behavioral performance of the two monkeys that we tested. Our results indicate that the PFC contributes to the construction and use of a mental schema to represent premises. This evidence provides a novel framework for understanding the function of various areas of brain in logic processes and impairments to them in degenerative, traumatic, and psychiatric pathologies.

Significance statement: In cognitive neuroscience, it is unknown how information that leads to inferential deductions are encoded and manipulated at the neuronal level. We addressed this question by recording single-unit activity from the dorsolateral prefrontal cortex of monkeys that were performing a transitive inference (TI) task. The TI required one to choose the higher ranked of two items, based on previous, indirect experience. Our results demonstrated that single-neuron activity supports the construction of an abstract, mental schema of ordered items in solving the task and that this representation is independent of the reward value that is experienced for the single items. These findings identify the neural substrates of abstract mental representations that support inferential thinking.

Keywords: monkey; prefrontal cortex; single-unit activity; transitive inference.

Figure 1.

TI task and behavioral performance. A, Time sequence of the task during the learning and test blocks. The gray bars indicate the analysis epochs. Top, Sample of rank-ordered stimuli at the beginning of a daily experimental session. B, Schematic of all 15 possible combinations of item pairs, labeled as learned (white boxes) or novel (filled boxes). C, Average performance on all pairs during the test phase for both animals in all sessions. The gray region highlights data referring to novel pairs. Error bars are SE.

Figure 2.

Monkeys' performance on linked chains of items. A, Schematic of the behavioral sessions with two-chain learning. The learning of each chain included blocks of 20 trials, during which each pair of items of a chain was presented (e.g., AB, BC for Chain 1; A–C). Once the monkeys performed well above chance levels [threshold: p(correct) >80%] on each pair, they performed blocks of 20 trials with the two pairs randomly presented, until their performance in the block reached at least 60% of correct choices. The same procedure was used to learn Chain 2 (D–F). Subsequently, the monkeys performed 20 trials with the CD pair to link the two chains of items. B, Average performance of both monkeys during the test phase, expressed as a function of SPE (left) and overall symbolic distance (right). Inset, The average performance for pairs that included the second item (i.e., B) in the series. C, Performance for the first presentation of all pairs in the test phase after learning the two chains in 11 sessions. D, Percentage of reinforced choices for each item presentation during learning. The extreme items A and F are always and never reinforced when touched, respectively. Each line indicates the percentage of rewarded choices for the seven learning sessions analyzed. Error bars in B are SE.

Figure 3.

Eye movement behavior in a sample session of Monkey 1, with the target item always on the right. A, Distribution of horizontal eye positions. Each trial is organized according to the symbolic distance and aligned to the pair onset. Early delay epoch is highlighted (orange). The value of the saccade direction IDX for each symbolic distance is reported. B, Distribution of eye positions throughout the working space during the early delay epoch. The value of the eye position IDX for each symbolic distance is reported.

Figure 4.

Recording area and neural modulation in the test phase. A, Electrode tracks for both animals. AS, Arcuate sulcus; PS, principal sulcus. The relative proportion of SPE- and SDE-related activity is indicated for each entry point. Entry points located posteriorly to the arcuate sulcus are indicated by black dots only. B, Activity histograms (aligned to the pair onset; vertical bar) for all comparisons during the test phase with the target item presented in the preferred location for a task-related neuron. The average neural activity and the activity during the first trial of the test phase in the early delay epoch are indicated by black dots and red triangles, respectively. Filled gray squares denote the average neural activity for groups of pairs organized by symbolic distance.

Figure 5.

Neural and behavioral modulation for SPE and SDE. Mean and SEM for the performance of Monkey 1 (top, black lines) and Monkey 2 (top, red lines) and normalized population neural activity in the early (bottom, black) and late (bottom, gray) delays for each serial position (left) and symbolic distance (right). A, data related to SPE. B, data related to SDE.

Figure 6.

Discriminability analysis for task-modulated neurons. A, Time evolution of accuracy (auROC) in discriminating between middle and extreme items from SP3 aligned to the pair onset (color plots) and time at which the accuracy value reached 0.65 (starting time of discrimination; top histograms; vertical arrows indicate median values). B, Time evolution of accuracy in discriminating between symbolic distances (color plots) and the start time of the discrimination (top histograms; vertical arrows indicate median values). C, Average (shaded areas indicate SEM) value across population aligned at the start of discrimination for serial position (left) and symbolic distance (right). The differences between conditions over time are indicated (horizontal black segment). Insets, Values obtained using only neurons with significant values. Horizontal bars in C, time of significant difference. *p < 0.05.

Figure 7.

Distribution of choice probability. Distribution of choice probability across the task-related neurons in the early (left) and late (right) delays. Dark points indicate values that are significantly different from chance after permutation. Average values of the distributions (vertical arrows) were significantly >0.5 (t test: p < 0.01).

Figure 8.

Behavioral performance and neural modulation for SPE and SDE in the first test trial. A, Top, Behavioral performance for the first trials of pairs organized according to the serial position of the target (rewarded) item. Middle, Corresponding neural modulation for task-related neurons. B, Top, Behavioral performance for the first trials of pairs organized according to the symbolic distance of items forming the pair. Middle, Corresponding neural modulation for task-related neurons. C, Top, Behavioral performance for comparisons of adjacent pairs (learned) in the first test trial and the corresponding neuronal modulation (middle). D, Behavioral (top) and neural modulation (middle) for the symbolic distance for item B. The lower part of the figure shows the pairs used for data in A and B (lower left) and for data in C and D (lower right).

Figure 9.

Estimated neural representation of rank order supporting the observed SPE and SDE. A, Estimated neural representations (n = 720) of a rank-ordered set of items that could model the observed neural responses during all pair comparisons in B (observed; black dots). Colored lines are for curves with R-square > 0.1 when tested as in B. The thick red curve is for the highest R-square value in the group. B, Comparison between the observed (black) and modeled (empty dots; obtained from best fit in A) responses of a neuron during pair comparisons. A measure of the goodness of fit (R-square) is reported. C, Distribution of R-square values obtained for all task-related neurons. The gray bar indicates the proportion of neurons with R-square <0.1. The average R-square is indicated (black arrow). D, Distribution of the estimated families of curves sorted by frequency of observation. The thickness of the lines and the size of the dots increase with the proportion of the curve belonging to the same group.