Reward-Based Decision-Making Engages Distinct Modes of Cross-Frequency Coupling

Abstract

Prefrontal cortex exerts control over sensory and motor systems via cross-frequency coupling. However, it is unknown whether these signals play a role in reward-based decision-making and whether such dynamic network configuration is altered in a major depressive episode. We recruited men and women with and without depression to perform a streamlined version of the Expenditure of Effort for Reward Task during recording of electroencephalography. Goal-directed behavior was quantified as willingness to exert physical effort to obtain reward, and reward-evaluation was the degree to which the decision to exert effort was modulated by incentive level. We found that the amplitude of frontal-midline theta oscillations was greatest in participants with the greatest reward-evaluation. Furthermore, coupling between frontal theta phase and parieto-occipital gamma amplitude was positively correlated with reward-evaluation. In addition, goal-directed behavior was positively correlated with coupling between frontal delta phase to motor beta amplitude. Finally, we performed a factor analysis to derive 2 symptom dimensions and found that mood symptoms positively tracked with reward-evaluation and motivation symptoms negatively tracked with goal-directed behavior. Altogether, these results provide evidence that 2 aspects of reward-based decision-making are instantiated by different modes of prefrontal top-down control and are modulated in different symptom dimensions of depression.

Keywords: cross-frequency coupling; depression; goal-directed behavior; reward-evaluation; symptom dimensions.

Figure 1

Streamlined Expenditure of Effort for Reward Task (S-EEfRT). (A) The task consisted of 5 epochs. Participants decided between performing a HARD task with a high or low incentive (presented) or an EASY task with a minimal incentive (fixed and not presented). After a countdown, participants pressed a button with their pinky finger at 70% of their maximum rate for the HARD task or index finger at 40% for the EASY task. After a brief fixation, participants received notification of a probabilistic monetary reward. (B) Histogram of goal-directed behavior (N = 79) revealed a bimodal distribution bisected at 85% (dashed red vertical line). Mean and standard deviation for participants that engaged reward-based decision-making (black; N = 53) and those with performance at ceiling (red; N = 26). Gaussian curves are superimposed on the histogram for visualization purposes only and do not represent fitted data. (C) Reward-evaluation was quantified as the slope of a linear fit between the percent HARD decision and the incentive level. Error bars are within-participant standard error of mean. (D) Goal-directed behavior and reward-evaluation showed a low correlation value (Pearson, N = 53) suggesting that the behavioral metrics were dissociable. A dashed line is P > 0.05. Shaded area is 95% confidence interval.

Figure 2

Individual differences analysis of neural oscillations in prefrontal electrodes. (A) Time–frequency analysis of electrodes over anterior prefrontal cortex (aPFC), defined as Fz and its adjacent electrodes (topographic insert), shows a significant increase in the amplitude of theta oscillations immediately following the presentation of the incentive at time zero (black vertical line). N = 53. Thin gray outline is P < 0.0001 and permutation-based cluster correction. The early and late windows for analysis are depicted with a black rectangle. Spectral amplitude (% from baseline) from 100 ms to 400 ms, early, shows a clear theta peak; and from 800 ms to 1500 ms, late, shows a clear delta peak. Shaded area is standard error of mean. (B) Individual differences analysis of spectral amplitude in prefrontal electrodes with reward-evaluation revealed a single significant cluster in the theta band (3–6 Hz). Black outline for significant time–frequency cluster. Asterisk represents P < 0.05 and permutation-based cluster correction. (C) Topographic individual differences analysis of the canonical theta band (4–7 Hz) from 100 ms to 600 ms after stimulus presentation to reward-evaluation found a significant positive correlation in frontal-midline, left lateral frontal, and posterior-midline electrodes. Dot represents P < 0.05 in topographic plots. This analysis identified a region of interest, left prefrontal cortex (L-PFC) that was used for phase-amplitude coupling analysis (purple outline). aPFC is overlaid for comparison. Electrodes from the 10–20 system are label in relevant regions. (D) An individual differences correlation analysis of the spectrogram in aPFC during the decision epoch of the S-EEfRT with goal-directed behavior (%HARD) did not reveal any significant time–frequency clusters. n.s. is not significant.

Figure 3

Theta–gamma phase-amplitude coupling during reward-evaluation. The phase of theta oscillations (3–6 Hz, 100–600 ms after incentive presentation) was estimated for the left prefrontal cortex (L-PFC) region of interest localized from time–frequency analysis (purple outline) and coupling was calculated to gamma amplitude (35–58 Hz) across the scalp. (A) Theta–gamma phase-amplitude coupling (PAC) between L-PFC phase and posterior-midline electrodes was significantly present in the high incentive condition. Black dot represents P < 0.05. (B) There was no region that displayed theta–gamma coupling as a function of incentive. Significant region defined as a contiguous cluster of at least 3 electrodes at P < 0.05. (C) Theta–gamma PAC as a function of incentive level (high minus low) was positively correlated with reward-evaluation between L-PFC and right parieto-occipital electrodes (R-ParOcc; dashed circle is post hoc significant region). (D) There was no relationship between theta–gamma PAC and goal-directed behavior. n.s. is not significant. Electrodes from the 10–20 system in relevant regions are labeled.

Figure 4

Delta–beta coupling during decision-making. (A) Electrodes over left motor cortex (L-M1), defined a priori as C3 and its adjacent electrodes (see insert), displayed a prolonged modulation of beta amplitude (15–30 Hz). All conditions, N = 53. Vertical line at 0 ms is presentation of the incentive stimulus. Outlined square highlights the a priori time-window analyzed by delta–beta phase-amplitude coupling (PAC) analysis (100–1500 ms after decision epoch onset) and the range of the beta band (15–25 Hz). Thin gray outline is P < 0.0001 and permutation-based cluster correction. (B) The topography of beta modulation after spatial normalization was concentrated to the left and right motor cortex (black circles). L-M1 region is depicted. Electrodes from the 10–20 system are labeled. (C) With a high incentive, delta phase in anterior prefrontal cortex electrodes (aPFC; depicted; Fz and its adjacent electrodes) was coupled with beta amplitude in L-M1 during the decision period. Outline was significant at P < 0.05 and permutation-based cluster correction. (D) With a low incentive for the HARD task, delta–beta coupling between aPFC and L-M1 did not significantly increase. Negative values were set to 0 as PAC can only be positive. (E). As a function of monetary incentive (high vs. low), the phase of delta oscillations (2–3 Hz) in aPFC was coupled to the amplitude of beta oscillations (15–25 Hz) in L-M1 and posterior-midline electrodes. Dot represents P < 0.05 in topographic plots. (F) Individual differences analysis (Pearson correlation) revealed that goal-directed behavior (%HARD) across all incentive levels was positively correlated with coupling between delta phase in aPFC and beta amplitude in L-M1. Dots represent P < 0.05. The aPFC and L-M1 regions are depicted in black for amplitude modulation and in green when associated with delta–beta coupling.

Figure 5

Motivation and mood symptoms track goal-directed behavior and reward-evaluation. (A) 2D factor analysis of clinical assessments for participants in a current major depressive episode (MDE) with at least mild depression severity (HAM-D ≥ 12). N = 38. Dotted line is a priori inclusion criteria set at 10% explained variance. (−) is reverse-scored. Metrics that met inclusion criteria (^*) were normalized and combined into a composite metric for motivation (green) and mood (purple) symptoms (Sx). (B–E) Correlation analysis (Pearson) for behavioral metrics, goal-directed behavior and reward-evaluation, with motivation and mood symptoms. ~P < 0.1, ^*P < 0.05. Dashed line is not significant. Shaded area is 95% confidence interval. See Methods for the acronyms used for each assessment subscore. Correlation analyses were performed on participants that engaged reward-based decision-making processes (N = 53).

Figure 6

Delta–beta and theta–gamma coupling as distinct modes of cognitive control that become impaired in depression. (A) We propose a model by which the amplitude of theta and gamma oscillations is modulated during perception including memory processes, and the amplitude of delta and beta oscillations is modulated during action including decision-making. Arrows reflect top–down control via phase-amplitude coupling. Gamma oscillations depicted with a dashed line as we did not find direct evidence of increased gamma amplitude. (B) Prefrontal cortex provides top–down control via cross-frequency coupling in 2 distinct modes. Delta–beta coupling between prefrontal and motor cortex coordinates action during decision-making, and theta–gamma coupling between prefrontal and visual processing regions guides perception including the evaluation of potential rewards. These cognitive control modes are differentially impacted by symptoms of depression with increased theta–gamma coupling with symptoms of anxiety and decreased delta–beta coupling with symptoms of anhedonia.