Ketamine increases fronto-posterior functional connectivity during meta-perceptual confidence ratings

• Published in: Behavioural brain research Vol. 430; p. 113925
• Main Authors: Lehmann, Mirko, Neumann, Claudia, Wasserthal, Sven, Delis, Achilles, Schultz, Johannes, Hurlemann, René, Ettinger, Ulrich
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 26-07-2022
• Subjects: Confidence; Functional connectivity; Glutamate; Ketamine; Metacognition; Perceptual decision-making; Functional connectivity; Ketamine; Glutamate; Confidence; Perceptual decision-making; Metacognition; Perceptual Decision-Making
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2022.113925

Recent advances in the neuropsychopharmacology of metacognition indicate a constituent role of glutamate for the integrity of metamnestic processes. However, the extent to which previous results can be generalized across functional domains to characterize the relationship between glutamate and metacognition remains unclear. Here, in a randomized, double-blind, placebo-controlled, preregistered fMRI study, we tested the effects of a psychotomimetic dose (target plasma concentration 100 ng/mL) of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine on metacognition in a perceptual decision-making framework. We collected trial-by-trial metacognitive reports as participants performed a two-alternative forced-choice perceptual task during functional magnetic resonance imaging (fMRI). Results indicated ketamine-induced deterioration in metacognitive performance, whereas no significant effects were observed for perceptual performance, response times and – unexpectedly – metacognitive bias. Whilst there were no detectable ketamine effects on mean BOLD activation, exploratory psychophysiological interaction (PPI) analysis revealed alterations in functional connectivity during metacognitive confidence ratings under ketamine. Specifically, there was increased task-specific connectivity for ketamine compared to placebo between right anterior dorsolateral prefrontal cortex and left middle temporal, supramarginal and precentral gyrus, as well as between right insula/inferior frontal gyrus and left lingual gyrus, possibly indicating re-representations of object-level features supplied for metacognitive evaluations. Overall, these findings contribute towards the emerging picture of the substructures underlying metacognitive operations at the neurotransmitter level and may shed light on a neural pattern characteristic of pharmacologically challenged metacognition.
•We explored the role of glutamate in perceptual metacognition by applying ketamine.•The psychotomimetic drug significantly impaired metacognitive sensitivity.•We observed fronto-posterior increases in task-specific connectivity for ketamine.•This may indicate re-representations of object-level features for metacognition.