Fig. 1.

(A) Subjects encoded four or two (not shown; see Methods) circle locations and, after a delay, indicated whether the circle was presented at that location or not (probe). Subjects also completed a control task where four gray circles appeared but were explicitly asked not to encode the circles. During the probe phase, another gray circle was shown, requiring a motor response but no recall. (B) Second-level conjunction fMRI analysis strategy: (i) we computed a main effect of task (i.e., WM vs. control condition) type I error corrected at the whole-brain level (Fig. 2); and (ii) we computed a task × infusion interaction, revealing regions differentially modulated by ketamine across task conditions. Regions identified this way are not guaranteed to be involved in WM. That is, regions showing a task × infusion interaction may not show engagement during WM (i.e., main effect of task). Thus, we computed a conjunction (logical AND) between these effects. The surviving regions were ensured to show both a task main effect and modulation of this effect by ketamine (Fig. 3A and Fig. S2). (C) Percentage drop in accuracy (% correct) is shown for the control (white bar) and WM (black bar) tasks following ketamine vs. placebo infusion (difference plotted). ****P < 0.0001 (see SI Text, Behavioral Results for complete behavioral analysis). Error bars reflect ±1 SEM.