Figure 1. Experimental set-up: behavioral task, pharmacological manipulation, and physiological responses.

(A) Schematic representation of the behavioral task. Participants responded to the orientation (clockwise/counterclockwise [CW/CCW]) of unilaterally presented Gabor stimuli that were embedded in noise (bilaterally presented). The likely location of the Gabor stimulus was cued (horizontal dash presented 0.33° left/right from fixation) with 80% validity before stimulus onset. (B) Schematic overview of experimental sessions. Participants came to the lab on four occasions: one intake session and three experimental sessions. On the experimental sessions, participants received either placebo (PLC, data in orange), donepezil (DNP, 5 mg, data in green), or atomoxetine (ATX, 40 mg, data in blue). Drug order was counterbalanced across participants. (C) Time schedule of experimental sessions. Participants received a pill on two moments in each session, one at the beginning of the session and a second pill 2 hr later. The first pill contained either placebo (PLC and ATX session) or donepezil (DNP session), the second pill was either a placebo (PLC and DNP session) or atomoxetine (ATX session). Behavioral testing started 4 hr after administration of the first pill. (D) Baseline pupil diameter was measured before onset of the behavioral task. Participants fixated while the background luminance of the monitor was dimmed (for 15 s) and then brightened (for 15 s) to establish the pupil size in dark and bright circumstances. Shading indicates standard error of the mean (SEM). (E–J) Effects of drug on pupil diameter during the dark (P_max, E) and bright (P_min, F) measurement windows, heart rate (HR, G), mean arterial blood pressure (MAP, H, see Materials and methods), and subjective ratings (visual analogue scale [VAS]; see Materials and methods) of alertness (panel I) and calmness (J). All measurements except pupil diameter were baseline-corrected to the first measurement taken right before ingestion of the first pill.

Figure 1—figure supplement 1. Late effects of drug on subjective and bodily measures of arousal.

(A) Heart rate was modulated by drug condition at the end of the experimental session (F_2,54=5.44, p=0.01, ${\displaystyle {\eta }_p^2}$ = 0.17) and post hoc tests showed that this effect was driven by increased heart rates under ATX vs. PLC (t(27)=3.11, p=0.004, ${\eta }_p^2$ = 0.26) but not DNP vs. PLC t(27)=0.80, p=0.43, ${\eta }_p^2$ = 0.02, BF₀₁=3.72. (B–D) We observed no late effects of drug condition on (B) mean arterial blood pressure (F_2,54=0.23, p=0.80, ${\eta }_p^2$ = 0.01), (C) subjective ratings of alertness (F_2,54=0.37, p=0.69, ${\eta }_p^2$ = 0.01), and (D) calmness (F_2,54=0.03, p=0.97, ${\eta }_p^2$ = 0.00). Error bars around the means indicate SEM. Abbr.: ATX: atomoxetine, PLC: placebo, DNP: donepezil.