Processing in Lateral Orbitofrontal Cortex Is Required to Estimate Subjective Preference during Initial, but Not Established, Economic Choice

Abstract

The orbitofrontal cortex (OFC) is proposed to be critical to economic decision making. Yet one can inactivate OFC without affecting well-practiced choices. One possible explanation of this lack of effect is that well-practiced decisions are codified into habits or configural-based policies not normally thought to require OFC. Here, we tested this idea by training rats to choose between different pellet pairs across a set of standard offers and then inactivating OFC subregions during choices between novel offers of previously experienced pairs or between novel pairs of previously experienced pellets. Contrary to expectations, controls performed as well on novel as experienced offers yet had difficulty initially estimating their subjective preference on novel pairs, difficulty exacerbated by lateral OFC inactivation. This pattern of results indicates that established economic choice reflects the use of an underlying model or goods space and that lateral OFC is only required for normal behavior when the established framework must incorporate new information.

Figure 1.. General Task Design and Description of the Novel Offer and Novel Pairs Experiments

(A) Schematic of a single trial on the economic choice task. Rats must nosepoke at a central port following onset of an auditory stimulus. The rats must then maintain the nosepoke hold for 2 s, which is indicated by cessation of the auditory cue. After the first second of the hold, visual stimuli are presented on the screens indicating the current offer. After completing the hold, rats can make a decision by pressing one of the screens. (B) The set of visual stimuli used in the experiment. Rats were trained to associate the symbol (row) of each visual stimulus with a specific type of food pellet and the number of segmentations within the stimulus (column) with the number of pellets available. Visual symbol - food pellet associations remained constant throughout the experiment. The bottom two stimuli were used for only the novel pairs experiment. (C) Design for the novel offers experiment. One pair of the 10 possible symbol-pellet pairs was randomly chosen, and the 11 standard offers rats experienced during training (black circles) were given for a warm-up session. On the subsequent experimental session, rats were given two additional novel offer types (orange circles), in which the numbers of each pellet offered had never been chosen between before. To assess the contribution of the lateral and medial portions of the OFC, brain regions were either inactivated or not during all trials (during the choice period) of an experimental session. An example set of offers presented during an experimental session is shown with the standard offers (gray) and two novel offers (orange). (D) Design for the novel pairs experiment. Rats were tested on up to 8 food pellet comparisons that they had never previously experienced (dotted lines). On the first day of experiencing a “novel pair,” brain regions were either inactivated or not on every trial (during the choice period) for 16 trials of each of the 11 standard offers for 176 total trials. Rats were then tested on a second day in which no inactivation occurred in order to be used as a reference for stable behavior. An example set of offers is shown for an experimental session. Unlike the “novel offer” experiment, the rats never had any previous experience with any of the offers because the two food pellets had never been included in the same session.

Figure 2.. Histological Verification of Fiber Placements and Viral Expression in Lateral and Medial Orbitofrontal Cortex

(A) Schematic histological assessment of the extent of viral expression (middle) and the terminal fiber placement (left) for each of the rats in the lateral OFC inactivation group at ~3.0 mm anterior of bregma. Example of NpHR3.0-eYFP expression (green) and DAPI (blue; right) is shown. (B) Same as (A) but for the medial OFC inactivation group, ~4.7 mm anterior of bregma.

Figure 3.. Choices for Novel Offers Are Consistent with Established Preferences and Do Not Require OFC

(A) Single session examples in which offer types rats had never previously experienced were given. Standard offers (black circles) are plotted alongside the two novel offer types (shown in red) for control sessions (first column), lateral OFC inactivation sessions (second column), and medial OFC inactivation sessions (third column). The percentage of trials in which the non-preferred pellet (pellet B) was chosen is plotted for each of the offer ratios (x axis; log scale). (B) Histograms of the residuals for standard offers adjacent to the novel offer types (adjacent, dark color) and novel offer types (novel, lighter color). Residuals were based on a sigmoidal fit (probit analysis) using a leave-one-out approach. Columns are the same as in (A). (C) Mean residuals for the different offer types are shown for each group, as well as the mean residuals of the potential range of disruption for the novel offer types. Columns are the same as in (B). (D) The average paired difference in residuals between the standard adjacent and novel offers (left) and corresponding histograms (right) for each group (gray, controls; blue, lateral OFC inactivation; magenta, medial OFC inactivation). Error bars are plotted as SEM.

Figure 4.. Decisions for Novel Pairs Require Learning for Accurate Reflection of Subjective Preferences

(A) Example sessions of behavior for experienced pellet pairs (left, yellow) and novel orfirst-time pairs (right, gray). First day choice behavior on a pair is split into quarters (44 trials bins), with the corresponding sigmoidal fits displayed from light (first quarter) to dark (last quarter) colors. Behavior including all trials on the second day of the novel pairs is displayed (black circles) as well as the associated sigmoidal fit (black). The percentage of times the rat chose pellet B (y axis) is plotted for the different offer types (x axis, log scale). (B) Scatterplots of the behavioral measures, indifference point (IP) (x axis), and inverse slope (y axis) for each quarter of day 1 (large circles) linked (by black lines) to behavior on day 2 (small circles, dark gray) for experienced pairs (left) and novel pairs (right). Colors are the same as in (A). Oval area plots (gray, background) show the mean ± 2 standard deviations of the data shown for day 1. Sessions for the experienced pairs were downsampled for display purposes to match the number of novel pair sessions. (C) The change in behavior across the first day on a pellet pair referenced to the second day on the pair using a 44-trial moving window stepped by 11 trials. Bins are plotted from light, first 44 trials of day 1, to dark, last 44 trials of day 1. x axis, absolute change in the IP (log scale) from the 44 trial bins on day 1 to all trials of day 2; y axis, corresponding change of the inverse slope. Columns are the same as in (B). (D) Same data as in (C) plotted across the 11 trial steps of the moving window for the absolute change in IP (left) and the change in inverse slope (right) for both the experienced (yellow) and novel (gray) pairs. For (C) and (D), both axes are referenced to the experienced pair differences for day 1. Error bars are plotted as SEM.

Figure 5.. Accurate Updating of Subjective Preferences for Novel Pairs Relies on Lateral, but Not Medial, OFC

(A) Example sessions of behavior for control novel pellet pairs (left, gray), for lateral OFC inactivation (middle, blue), and for medial OFC inactivation (right, magenta). Choice behavior for the first day on a pair is split into quarters (44 trials bins), with the corresponding sigmoidal fits displayed from light (first quarter) to dark (last quarter). Behavior including all trials on the second day of the novel pairs is displayed (black circles) as well as the associated sigmoidal fit (black). The percentage of times the rat chose pellet B (y axis) is plotted for the different offer types (x axis, log scale). (B) Scatterplots of the behavioral measures, IP (x axis), and inverse slope (y axis) for each quarter of day 1 (large circles, colors same as in A linked [by black lines] to behavior on day 2 [small circles, dark gray] for controls [left], lateral OFC inactivation [middle], and medial OFC inactivation [right]). Oval area plots (gray, background) show the mean ± 2 standard deviations of the data shown for day 1. (C) The change in behavior across the first day on a pellet pair referenced to the second day on the pair using a 44-trial moving window stepped by 11 trials. Bins are plotted from light, first 44 trials of day 1, to dark, last 44 trials of day 1. x axis, absolute change in the IP (log scale) from the 44 trial bins on day 1 to all trials of day 2; y axis, corresponding change of the inverse slope. Columns are the same as in (B). (D) Same data as in (C) plotted across the 11 trial steps of the moving window for the absolute change in IP (left) and the change in inverse slope (right) for the control (gray), lateral OFC inactivation (blue), and medial OFC inactivation (magenta) groups. For (C) and (D), both axes are referenced to the experienced pair differences for day 1. Error bars are plotted as SEM.

Figure 6.. Mild Experience with Food Pairs Removes Dependence of Choice Behavior on Lateral OFC

(A) The change in behavior across the first day on a pellet pair referenced to the second day on the pair using a 44-trial moving window stepped by 11 trials. Bins are plotted from light, first 44 trials of day 1, to dark, last 44 trials of day 1. x axis, absolute change in the IP (log scale) from the 44 trial bins on day 1 to all trials of day 2; y axis, corresponding change of the inverse slope. Left, control novel pairs, gray; middle, control mild-experienced pairs, red; right, lateral OFC inactivation mild-experienced pairs, green. (B) Same data as in (A) plotted across the 11 trial steps of the moving window for the absolute change in IP (left) and the change in inverse slope (right) for the control (gray), mild-experienced controls (red), and lateral OFC inactivation mild-experience (green) groups. Both axes are referenced to the experienced pair differences for day 1. Error bars are plotted as SEM.