Dopamine is a double-edged sword: Enhancing memory retrieval performance at the expense of metacognition

Abstract

While memory encoding and consolidation processes have been linked with dopaminergic signaling for a long time, the role of dopamine in episodic memory retrieval remained mostly unexplored. Based on previous observations of striatal activity during memory retrieval, we used pharmacological fMRI to investigate the effects of dopamine on retrieval performance and metacognitive memory confidence in healthy humans. Dopaminergic modulation by the D2 antagonist haloperidol administered acutely during the retrieval phase improved recognition accuracy of previously learned pictures significantly and was associated with increased activity in the SN/VTA, locus coeruleus, hippocampus and amygdala during retrieval. In contrast, confidence for new-decisions was impaired by unsystematically increased activity of the striatum across confidence levels and restricted range of responsiveness in frontostriatal networks under haloperidol. These findings offer new insights into the mechanisms underlying memory retrieval and metacognition and provide a broader perspective on the presence of memory problems in dopamine-related diseases and the treatment of memory disorders.

Enhanced transformation of incidentally learned knowledge into explicit memory by dopaminergic modulation

“…The majority of that sample also took part in the current behavioural study, which allows us to evaluate the effects of increased dopamine on the emergence of explicit memory during incidental learning in the SRT task. This increase in dopamine level was further corroborated by re-analysing the fMRI data [ 19 ] for the current participant sample to confirm group differences in striatal activity observed in the larger participant sample [ 19 ].…”

“…Moreover, doses of 0.03 mg/kg in rats (corresponding to 2.1 mg for 70 kg) were associated with increased locomotion behaviour clearly indicative of postsynaptic activation (rather than inhibition) of dopamine receptors. In line with this, we previously provided evidence for an increased dopamine level in the larger participant sample under 2 mg haloperidol based on fMRI activations [ 19 ]. The majority of that sample also took part in the current behavioural study, which allows us to evaluate the effects of increased dopamine on the emergence of explicit memory during incidental learning in the SRT task.…”

“…We used a double-blind, placebo-controlled between-group design with 54 participants in total which were randomly assigned to the haloperidol or control group as part of a larger study [ 19 ]. 42 of these participants (14 males, age 23.8±3.0 years; 20 haloperidol and 22 placebo) took part in the SRTT paradigm.…”

“…Blood pressure and pulse measurements together with questionnaires on adverse medication effects and current mood were repeated 0.5h, 2h and 4.5h after drug/placebo administration. The SRT paradigm was preceded by the fMRI task [ 19 ] also described below and started approximately 4.5h after drug/placebo administration outside the fMRI scanner on a PC. At the end of the study all participants were asked to indicate the substance (haloperidol or placebo) they thought they had received and how certain they were of this guess.…”

“…To directly test this hypothesis we here manipulated dopamine levels using 2 mg of the D2-receptor antagonist haloperidol in a randomized placebo-controlled between group design as part of a larger study [ 19 ] and assessed the emergence of explicit memory during incidental learning within a modified version of the classical serial reaction time task (SRTT) [ 20 ].…”