Medial-lateral organization of the orbitofrontal cortex

Abstract

Emerging evidence suggests that specific cognitive functions localize to different subregions of OFC, but the nature of these functional distinctions remains unclear. One prominent theory, derived from human neuroimaging, proposes that different stimulus valences are processed in separate orbital regions, with medial and lateral OFC processing positive and negative stimuli, respectively. Thus far, neurophysiology data have not supported this theory. We attempted to reconcile these accounts by recording neural activity from the full medial-lateral extent of the orbital surface in monkeys receiving rewards and punishments via gain or loss of secondary reinforcement. We found no convincing evidence for valence selectivity in any orbital region. Instead, we report differences between neurons in central OFC and those on the inferior-lateral orbital convexity, in that they encoded different sources of value information provided by the behavioral task. Neurons in inferior convexity encoded the value of external stimuli, whereas those in OFC encoded value information derived from the structure of the behavioral task. We interpret these results in light of recent theories of OFC function and propose that these distinctions, not valence selectivity, may shed light on a fundamental organizing principle for value processing in orbital cortex.

Figure 1. Recording locations and behavioral task

A) Top panel: Schematic of the ventral view of the macaque brain grossly distinguishing mOFC (green), OFC (cyan) and IC (dark blue). Bottom panel: Coronal MRI image corresponding to the level of the gray line in the top panel. Yellow lines depict electrode tracks and shaded regions are areas from which we recorded. B) Task sequence for a positive (left) and negative (right) picture trial. The reward bar is in blue at the bottom of the screen and remains visible throughout the trial. On each trial, the length of the reward bar could increase (left), decrease (right) or remain the same size (not shown). The size of the bar carries over until the next trial within every block of six trials. C) Behavioral effects of positive and negative stimuli for each subject. Plots show the mean percentage of trials in which a correct joystick response is executed (top) or the median RT to make a response (bottom), separately for positive and negative pictures, and right and left joystick movements. D) Mean percent correct (± SE, top) and median RT (± SE, bottom) for 6 different levels of reward bar size or number of trials completed within each block, shown separately for positive and negative pictures. E) AIC weights averaged across both subjects for each of 15 models of behavior. Model numbers refer to Table 1. O = weights for Subject C. X = weights for Subject M. Model 12 was the best fitting model for both subjects.

Figure 2. Neuronal responses during the sample period

A–D) Spike density histograms for two neurons encoding picture valence (A and B) and two neurons encoding response direction (C and D) during the sample epoch. Firing rates are aligned to stimulus onset (gray line). Neurons A and C were recorded from IC, B and D from OFC. E) The top panel shows the percentage of neurons in each region encoding the picture valence (gray) or response direction (black) during the sample epoch. The bottom panel shows mean CPDs (± SE) for valence and response during the sample epoch. Mean CPDs are low, as they are population averages that included non-selective neurons (* = p < 0.05, Wilcoxon rank sum test). F) Plots show the cumulative number of neurons significantly encoding picture valence or response in mOFC (blue), OFC (red) and IC (black) across time.

Figure 3. Neural encoding of valence during sample epochs

A) The top panel shows the percentage of neurons encoding positive or negative valences, and the bottom panel shows mean CPDs (± SE) for picture valence during the sample epoch. CPDs were averaged over all neurons with positive or negative beta coefficients in a multiple regression. B) Heat plots show significant beta coefficients among neurons responding to positive or negative pictures. Each horizontal line corresponds to the data from an individual neuron, and the color indicates the absolute value of the beta coefficient at that time point. Neurons were sorted by latency to encode each variable. Yellow lines indicate picture onset, and gray lines show the median encoding latency for each group. C) Flattened maps of the orbital surface outlining the LOS and MOS (shaded gray), averaged across subjects, and locations of neurons responding to positive (blue) and negative (red) pictures during the sample epoch. Gray lines indicate the lateral (top) and medial (bottom) convexities, where the orbital surface terminates and curves around onto the lateral and medial surfaces of the frontal lobe. Anterior-posterior (AP) positions are relative to the inter-aural line, and medial-lateral (ML) positions are relative to the LOS. For display, AP positions were jittered by ± 0.2-mm and offset 0.2-mm. Circle diameters represent strength of encoding, and are proportional to the absolute value of the beta coefficient for picture valence. Inset boxplots show the median (central line), 25^th and 75^th percentile (box top and bottom) ML position of neurons responding to positive (blue) and negative (red) pictures during the sample epoch (Wilcoxon rank-sum test, p > 0.1). Whiskers show the data spread, and ‘+’ points identify outliers. The flatmap on the right shows labeled anatomical landmarks. Each ‘×’ indicates the location of a recorded neuron. Sulci are shaded gray; convexities are marked by a gray line. Inset is a schematic of the orbital region of a single coronal slice, demarcating landmarks shown on the flatmap.

Figure 4. Neural encoding of feedback valence

A–F) Spike density histograms show four neurons encoding feedback (FB) in different ways. Firing rates are aligned to feedback onset (gray line). Blue = positive feedback trials, cyan = no feedback following a positive picture, orange = no feedback following a negative picture, red = negative feedback trials. Neurons A, C, E and F were recorded from IC, B and D from OFC. G) Scatter plots show the distribution of feedback-related responses. Each point represents a selective neuron, and its position on the y-axis is determined by the beta coefficient. Positive and negative betas indicate that the neuron’s response consisted of an increase or decrease in firing rate respectively. H) Percent of neurons with higher firing rates for positive or negative outcomes. I) Percent of neurons that encode expected or unexpected outcomes. Expected outcomes include positive feedback following a positive picture and no feedback following a negative picture (e.g. A and E). Unexpected outcomes include negative feedback or no feedback following a positive picture (e.g. B and D). * = p < 0.05, χ² test

Figure 5. Consistent and inconsistent valence coding across epochs

Percentage of neurons showing A) the same valence encoding for sample pictures and feedback or B) opposite valence encoding between these two epochs. The x-axis the percentage of neurons in each region expected to respond to sample pictures and feedback of the same or different valence if coding in each epoch were independent, and the y-axis is the percentage of neurons observed. Shapes indicate data from different brain areas, and color indicates the valence of encoding during the sample presentation (blue = positive, red = negative). * = p < 0.05, binomial test.

Figure 6. Neurons encoding other sources of value in the task

Spike density histograms for single neurons whose firing rate during the fixation epoch correlated with either A) the size of the reward bar in IC or B) the number of trials completed in OFC. The same neuron’s activity was sorted by reward bar size (left panels), or number of trials completed (right panels), with colors indicating size or number respectively. Bar sizes of 0 and >=6 consisted of very few trials, and were therefore excluded from plots. C) Scatterplots of beta coefficients for bar size (x-axes) versus trial number (y-axes) from a multiple regression that included both parameters. Each point represents a neuron selective for either bar size (purple) or trial number (green). Positive beta coefficients indicate that the neurons activity was positively correlated with value, while negative values indicated an anti-correlation. Data were taken from the fixation epoch. D) Percent of neurons encoding either reward bar size or trial number during fixation (Fix) and sample (S) epochs. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, χ² test. E) Flattened orbital map outlining the lateral and medial orbital sulci (shaded gray) as in Figure 3. Circles show the location of neurons encoding bar size (purple) and trial number (green) during the fixation epoch. AP positions were jittered within ± 0.2-mm and offset 0.2-mm for display. Circle diameters represent strength of encoding and are proportional to the absolute value of the beta coefficient for bar size or trial number respectively. Inset boxplots show ML distributions of neurons in orbital areas encoding bar size (purple) or trials completed (green). The central line shows the median, box top and bottom show the 25^th and 75^th percentile, whiskers show the data spread, and ‘+’ points identify outliers. **= p<0.01, Wilcoxon rank-sum test.

Figure 7. Comparison of neurons encoding value during feedback and juice delivery

Scatterplot shows the absolute values of beta coefficients from a linear regression of reward bar size (which corresponded to juice volume) and neuron firing rates during feedback (x-axis) and juice delivery (y-axis). Each point represents a neuron that was selective during at least one epoch. Red=IC, Blue=OFC, Green=mOFC. Inset bar plots show the overall percent of neurons that were selective during each epoch (FB=feedback, juice=juice delivery). * = p <.05 χ² test.