Exploring Ketamine’s Impact on Self- and Other-Trait Attributions: Behavioural and Neural Insights

Ketamine, a rapid-acting NMDA receptor antagonist with antidepressant properties, has been suggested to alter emotional and cognitive biases. This study investigated whether a single infusion of S(+)-ketamine modulates self- and other-referential processing of positive and negative trait adjectives. Using a double-blind, within-subjects crossover design, 28 healthy participants completed two sessions receiving either ketamine (20 mg/h, weight-adjusted) or placebo (saline). During each session, participants performed a Trait Adjective Task (TAT) involving self- or other-referential judgments of positive and negative adjectives while EEG was recorded. Reaction times (RTs), endorsement rates, mood ratings (Affect Grid), dose guess, expectancy, and event-related potentials (ERPs; N300, N400, and Late Positive Component [LPC] at fronto-central electrodes) were analyzed. Ketamine significantly slowed RTs compared to placebo (p < .001) and interacted with response type (p= .042), with...Show moreKetamine, a rapid-acting NMDA receptor antagonist with antidepressant properties, has been suggested to alter emotional and cognitive biases. This study investigated whether a single infusion of S(+)-ketamine modulates self- and other-referential processing of positive and negative trait adjectives. Using a double-blind, within-subjects crossover design, 28 healthy participants completed two sessions receiving either ketamine (20 mg/h, weight-adjusted) or placebo (saline). During each session, participants performed a Trait Adjective Task (TAT) involving self- or other-referential judgments of positive and negative adjectives while EEG was recorded. Reaction times (RTs), endorsement rates, mood ratings (Affect Grid), dose guess, expectancy, and event-related potentials (ERPs; N300, N400, and Late Positive Component [LPC] at fronto-central electrodes) were analyzed. Ketamine significantly slowed RTs compared to placebo (p < .001) and interacted with response type (p= .042), with greater slowing of “No” responses. Repeated-measures ANOVAs revealed main effects of drug and referent, as well as drug × referent and referent × valence interactions (all ps < .05), indicating that ketamine influenced response speed and its dependence on self- versus other-evaluations, but did not differentially affect positive versus negative adjectives (p > .40). Endorsement rates and pre-task mood ratings did not differ between drug conditions (all ps > .12). Participants endorsed more positive than negative traits, but these effects were not altered by ketamine. ERP analyses showed main effects of drug on N300 (p < .001) and N400 (p= .012) amplitudes, as well as electrode- and valence-related effects, but no drug × valence or drug × referent interactions (all ps > .23). In summary, ketamine slowed behavioral responses and influenced ERP amplitudes but did not specifically alter positive versus negative or self- versus other-referential processing. Participants were able to guess the drug condition above chance, indicating compromised blinding, and expectancy effects were high. These findings suggest that ketamine’s acute effects on self-referential trait evaluation are subtle in healthy individuals and may reflect broader cognitive changes rather than targeted modulation of self-related biases. Future work should test whether stronger or more specific effects emerge in clinical populations with pronounced negative self-bias, clarifying ketamine’s antidepressive mechanisms.emvShow less

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Exploring Ketamine’s Impact on Self- and Other-Trait Attributions: Behavioural and Neural Insights