Neuronal activity in primate dorsal anterior cingulate cortex signals task conflict and predicts adjustments in pupil-linked arousal

Abstract

Whether driving a car, shopping for food, or paying attention in a classroom of boisterous teenagers, it's often hard to maintain focus on goals in the face of distraction. Brain imaging studies in humans implicate the dorsal anterior cingulate cortex (dACC) in regulating the conflict between goals and distractors. Here we show that single dACC neurons signal conflict between task goals and distractors in the rhesus macaque, particularly for biologically relevant social stimuli. For some neurons, task conflict signals predicted subsequent changes in pupil size-a peripheral index of arousal linked to noradrenergic tone-associated with reduced distractor interference. dACC neurons also responded to errors, and these signals predicted adjustments in pupil size. These findings provide the first neurophysiological endorsement of the hypothesis that dACC regulates conflict, in part, via modulation of pupil-linked processes such as arousal.

Figure 1

Social interference task. A) Distractors were briefly flashed (67 ms) during performance of a simple visually-guided saccade task. Distractors could be in 3 spatial locations relative to the target-congruent, incongruent, or a neutral position outside the plane of possible targets. In addition, distractors could be flashed in 1 of these 3 locations during the ITI. B) Distractor images could either be rhesus monkey faces or phase-scrambled versions of the same images. C) Distractors interfered with response times according to both target congruence and social content.

Figure 2

Baseline pupil size is modulated by last-trial distractor type and predicts task performance. A) Example traces of pupil size measurements during trials. Baseline pupil size was determined by taking the mean pupil size over the first 350 ms following fixation acquisition (gray shaded region). The transient change in pupil size at fixation acquisition is due to the saccade toward the fixation spot and the depression in pupil size after fixation is due to the pupil light response to distractors (see supplemental information). B) The presence and location of distractors predicts subsequent adjustments in pupil size, normalized to the no-distractor (absent) baseline for each session. C) Baseline pupil size predicted increased frequency of errant saccades. As baseline pupil size increased, so did the frequency of errant saccades following distractors. Bars ± SEM.

Figure 3

The dACC population signals task conflict. A) Recording sites (in gray) on a flattened, midline view of the cingulate sulcus. Neurons were recorded on the dorsal and ventral banks of the cingulate sulcus, dorsal to the genu of the corpus callosum. B) Grand average population PSTH, aligned to task, ITI, or sham distractor onset. Shading ± SEM. C) Proportion of cells that responded to only task distractors (light red), only ITI distractors (dark red), both task and ITI distractors (bright red), or did not respond to any distractors (dark gray). Among the large minority of cells that responded to both task and ITI distractors (38/94 cells, 40%), different effect sizes were observed for task and ITI distractors (scatter plot of Cohen’s d’ for the difference between distractor present and distractor absent responses in each condition). Inset is the distribution of effect size differences.

Figure 4

dACC neurons signal task conflict. A) Population average PSTH shows differences in the population response to distractors in different locations. B) Distractor location effect sizes. Top panel: Several individual neurons encoded distractor congruency (different responses to congruent and incongruent distractors, 18 cells, in red). However, the sign of these effects was heterogeneous within the congruency-selective population (mean, red arrow) and across the whole population (mean, gray arrow), indicating that action conflict did not increase dACC firing rate. Bottom panel: Task conflict signals. Same as in top panel, but for congruent and incongruent versus neutral. Significant neurons selectively increased firing rate for both incongruent and congruent distractors, which induced task conflict, compared to neutral distractors, which did not affect task performance (Wilcoxon sign-rank, p < 0.05). C) Histogram of response latencies to task distractors. Latencies were heterogeneous across the population of responsive cells, apart from one population of early-responsive cells in green. D) Early-responding cells encoded task conflict. Left: social distractors, which had a greater impact on response time than nonsocial distractors, elicited more activity in these neurons than did nonsocial distractors (p < 0.04, z(15) = 2. 12). Right: Activity was enhanced following both incongruent and congruent distractors compared to neutral distractors (p < 0.001, Wilcoxon signed rank, z(15) = 3.31), indicating that early-responding neurons signaled task conflict. No effect of distractor congruence (action conflict) was observed in these cells (p > 0.6, z(15) = 0.46).

Figure 5

Relationship between distractor responses and pupil size. A-D) Example neurons that signaled distractor presence and predicted future pupil size. Traces are sorted by pupil size quantile bin on the next trial, separately for distractor present (shades of red) and distractor absent (shades of gray) trials. Lighter shades reflect smaller pupil sizes on subsequent trials, while darker shades reflect larger pupils. E) Distribution of distractor and pupil signaling in the dACC population F) For neurons that both responded to distractors and tracked pupil size, responses to distractors and adjustment in future pupil size were correlated. Line indicates least squares fit. G) Population tuning for reductions in pupil size. Across all recorded neurons, whole trial activity tended to be increased in advance of decreasing adjustments in pupil size (Pearson’s r is illustrated). Individual cells that had significant correlations between mean firing rate and adjustment in pupil size in either the Spearman (19 cells) or Pearson (14 cells) correlations are in blue. Overlay: nonparametric kernel density estimate.

Figure 6

Causal modeling of the relationship between dACC activity and adjustments in pupil size. The depicted model is the moderated mediation model. The inherited signal model fixed the regression coefficients b1 and b2 to 0. Large arrows are regressions, double-headed arrows are covariances. Paths are labeled with estimated coefficients, +/− robust standard errors. Additional coefficients for current pupil size, random effects of cell identity, and disturbance terms for each measured variable were included in the model, but not shown here for clarity.

Figure 7

An overlapping population of single neurons responds to errors and signals pupil size. A) On trials immediately following error commission, baseline pupil size was reduced, mirroring the effects found on trials following distractor presentation. B) The majority of single neurons responded to errors (69%, 65/94, in red and purple), however only a minority of this group had pure error responses (26%, 24/94, in red). Instead, 44% (41/94) of all recorded cells signaled both errors and either current or future pupil size (purple). Other populations of cells were not classified in this analysis (11% 10/94, in gray), or signaled only current or future pupil size (20%, 19/94 in blue). Significance thresholds were corrected for multiple comparisons. C) Error responses and pupil size adjustment signals were correlated within the neurons that both responded to errors and scaled with pupil size (Pearson’s r = 0.32, p < 0.05). Line reflects least squares fit.