Real-Time Value Integration during Economic Choice Is Regulated by Orbitofrontal Cortex

Abstract

Neural correlates implicate the orbitofrontal cortex (OFC) in value-based or economic decision making [1-3]. Yet inactivation of OFC in rats performing a rodent version of the standard economic choice task is without effect [4, 5], a finding more in accord with ideas that the OFC is primarily necessary for behavior when new information must be taken into account [6-9]. Neural activity in the OFC spontaneously updates to reflect new information, particularly about outcomes [10-16], and the OFC is necessary for adjustments to learned behavior only under these conditions [4, 16-26]. Here, we merge these two independent lines of research by inactivating lateral OFC during an economic choice that requires new information about the value of the predicted outcomes to be incorporated into an already established choice. Outcome value was changed by pre-feeding the rats one of two food options before testing. In control rats, this pre-feeding resulted in divergent changes in choice behavior that depended on the rats' prior preference for the pre-fed food. Optogenetic inactivation of the OFC disrupted this bi-directional effect of pre-feeding without affecting other measures that describe the underlying choice behavior. This finding unifies the role of the OFC in economic choice with its role in a host of other behaviors, causally demonstrating that the OFC is not necessary for economic choice per se-unless that choice incorporates new information about the outcomes.

Keywords: decision-making; economic; optogenetics; orbitofrontal; revaluation; satiety.

Figure 1.. Description of the Economic Choice Task and Design for Optogenetic Inactivation of OFC Following Exposure to One of the Pellets.

A, Description of a single trial on the economic choice task. Rats are required to nosepoke at a central port following onset of a white noise auditory stimulus. After a 1 second hold, the current offer is presented by displaying the appropriate visual stimuli on either screen. Rats must maintain the nosepoke hold for another second before termination of the white noise stimulus, after which the rats can make a decision by pressing one of the screens. An illustrative example of a single trial on the choice task is shown in A. B, All visual stimuli used in the experiment. All rats were trained to associate the shape of each visual stimulus with a specific type of food pellet and the number of segmentations within the visual stimulus with the number of pellets available. Visual symbol → food pellet associations were randomly assigned and remained constant throughout the experiment. C, Design for the experiment. On the first day, one pair of the 10 possible symbol-pellet pairs was randomly chosen and tested in order to determine a baseline measurement of the indifference point (IP) for the chosen pellets. On the second day, rats were pre-exposed to one of the two pellets that were experienced on the prior day in order to revalue that pellet before being tested on the choice task on a limited set of offers around the IP. D, Histological verification of viral expression (middle) and fiber placement (left) for each of the rats at ~3.0 mm anterior of bregma. Example of NpHR3.0-eYFP expression (green) and DAPI (blue) (right). E, Three representative examples of behavior for the control (Blocked Fiber) condition. Symbols (black circles: baseline – day 1 and blue crosses: probe test – day 2) and lines show choice behavior for each of the 11 offers (x-axis) and the GLM probit regression, respectively. Percent choice on the y-axis is plotted for pellet B, the pellet-type which was pre-fed before the probe test on day 2. A shift of behavior to the right from the baseline indicates a devaluation effect for pre-feeding.

Figure 2.. OFC Inactivation Disrupts the Dependence of Pellet Revaluation Induced by Pre-Feeding on Baseline Preference.

A, Scatter plots of the IP shift from day 1 to day 2 (y-axis, log ratio of IP day 2 : day 1) plotted against the IP measured during the baseline session (x-axis) for the control (blocked-fiber) sessions. Filled circles represent significant preferences (IPs) determined from the GLM regression either for the prefed pellet (grey) or for the non-prefed pellet (magenta). Box plots of the change in IP for each of the groups are shown to the right of the scatterplots. Red line: linear regression of the IP Shift as a function of the Baseline Preference. B, Same as in A, but for the inactivation (patent-fiber) sessions. Yellow: pre-fed pellet and green: non-pre-fed pellet. See Figure S1 for scatterplots identifying individual subjects. A linear regression comparing the two conditions revealed a significant coefficient for the interaction of Fiber-Type*Baseline Preference (β = 0.66, t₃₁ = 2.10, p = 0.043), and no other significant coefficients: (Preference: β = −0.11, t₃₁ = 1.07, p = 0.29, Fiber: β = 0.13, t₃₁ = 1.07, p = 0.29, y-intercept: β = 0.011, t₃₁ = 0.23, p = 0.96, Subjects: t₃₁ <= 1.34, p >= 0.19). The estimated variance of the shifts in preference was similar across the two conditions, see Figure S2A. C, Cumulative distributions of the change in IPs (blocked-fiber sessions) determined using a moving window (20 trials, see Figure S2B for window size selection) beginning at trial 20 (thick line) over 10 trial intervals until trial 60 (dark to light violet indicates early to late trials). C Inset, The median change in IP (solid line) for each of the 20 trial steps plotted with the 25% and 75% percentiles (dotted lines). D, same as in C for the patent-fiber sessions. * p < 0.05 and n.s. not significant.

Figure 3.. OFC Inactivation Does not Affect the Slope of the Choice Curve.

A, Scatter plot showing the inverse slope (σ, probit regression) on the baseline day (x-axis) and test day (y-axis) for the blocked fiber sessions. Red line: linear regression of the test day σ as a function of the Baseline σ (y-intercept: β = −0.42, t₂₂ = 1.33, p = 0.20; Baseline: β = 1.73, t₂₂ = 2.02, p = 0.055 – tested against the idenitity line; R = 0.71). Filled circles represent significant preferences (IPs) determined from the GLM regression either for the prefed pellet (B) (grey) or for the non-prefed pellet (A) (magenta). B, Same as in A for the inactivation (patent fiber) sessions. Sessions with significant baseline preferences for the prefed pellet (B) (yellow) and for the non-prefed pellets (A) (green). Linear regression results: (y-intercept: β = −0.41, t₂₁ = 1.07, p = 0.71; Baseline: β = 2.10, t₂₁ = 1.06, p = 0.31 – tested against the idenitity line; R = 0.40) C, Boxplots of the change in σ from the baseline to test day. A two-way repeated mesures ANOVA (Day X Fiber) revealed a significant main effect of Day (F_1,78 = 4.34, p = 0.041) but no other significant effect (Fiber: F_1,78 = 0.78, p = 0.38; Fiber*Day: F_1,78 = 1.19, p = 0.28; Subject: F12,78 = 1.37, p = 0.20). See Table S2 for linear regression including Preference as a factor. n.s. not significant.

Figure 4.. Effects of OFC Inactivation on Choice Behavior and Choice Latencies Following Pre-Feeding.

A, Average behavior for the first (light grey, preferred and non-preferred conditions combined) and second day of the test for both the preferred (grey) and non-preferred (magenta) pre-feeding conditions of the control (blocked fiber) sessions. Behavior was realigned to the IP for each session to allow for appropriate alignment of the psychometric curves. A subset of offers around the IP on the second day were experienced by the rats in order to minimize the number of trials for the test session. An ANOVA performed on the choice behavior treating preference as a categorical factor revealed a significant interaction of Fiber*Preference (F_1,43 = 6.64, p = 0.013), see Table S4 for full results. C, Average choice latencies for each of the offers for day 1 (light grey) and test day (grey/magenta). B and D, same as in A and C, respectively, for the inactivation (patent-fiber) sessions (preferred pre-fed: yellow, non-preferred prefed: green). A two-way repeated mesures ANOVA (Day X Fiber) revealed a significant main effect of Day (F_1,78 = 17.6, p = 1.0×10⁻⁴) yet no significant effects of Fiber (F_1,78 = 0.15, p = 0.70) or Fiber*Day (F_1,78 = 0.30, p = 0.58). There was a significant effect of Subject: F12,78 = 12.9, p < 10⁻⁵). See Table S3 for linear regression including Preference as a factor. All data is plotted in log scale. Error bars represent standard error. * p < 0.05 and n.s. not significant.