Agency as a bridge to form associative memories.

The perception of agency can influence memory when individuals feel their decisions exert control over their environment. While perceived agency has been shown to increase memory for items, most real-life situations are much more complex. Here, we examined how an individual's agency to influence the outcome of a situation affects their ability to learn associations between items that occur prior to and after a decision is made. In our paradigm, participants were told they were playing a game show where they had to help a trial unique cue, a "contestant," choose between three doors. On "agency" trials, participants were allowed to pick any door they wanted. On "forced-choice" trials, participants were instructed to select a door that was highlighted. They then saw the outcome, a "prize" that was behind the selected door. Across multiple studies, we find evidence for agency-related memory enhancements for contestants, a pattern that extended to contestant-prize, contestant-door, and door-prize associations. Additionally, we found that agency benefits for inferred cue-outcome relationships (i.e., door-prize) were limited to situations when choices were motivated by an explicit goal. Finally, we found that agency acts indirectly to influence cue-outcome binding by enhancing processes akin to inferential reasoning which associate information across item pairs containing overlapping information. Together, these data suggest having agency over a situation leads to enhanced memory for all items in that situation. This enhanced binding for items may be occurring by the formation of causal links when an individual has agency over their learning environment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cholinergic modulation of hippocampally mediated attention and perception.

Attention to the relations between visual features modulates hippocampal representations. Moreover, hippocampal damage impairs discrimination of spatial relations. We explore a mechanism by which this might occur: modulation by the acetylcholine system. Acetylcholine enhances afferent input to the hippocampus and suppresses recurrent connections within it. This biases hippocampal processing toward environmental input, and should improve externally oriented, hippocampally mediated attention and perception. We examined cholinergic modulation on an attention task that recruits the hippocampus. On each trial, participants viewed two images (rooms with paintings). On "similar room" trials, they judged whether the rooms had the same spatial layout from a different perspective. On "similar art" trials, they judged whether the paintings could have been painted by the same artist. On "identical" trials, participants simply had to detect identical paintings or rooms. We hypothesized that cholinergic modulation would improve performance on the similar room task, given past findings that hippocampal representations predicted, and hippocampal damage impaired, behavior on this task. To test this, nicotine cigarette smokers took part in two sessions: one before which they abstained from nicotine for 12 hours, and one before which they ingested nicotine in the past hour. Individual differences in expired breath carbon monoxide levels-a measure of how recently or how much someone smoked-predicted performance improvements on the similar room task. This finding provides novel support for computational models that propose that acetylcholine enhances externally oriented attentional states in the hippocampus. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Medial Temporal Lobe Is Critical for Spatial Relational Perception.

The medial temporal lobe (MTL) is traditionally considered to be a system that is specialized for long-term memory. Recent work has challenged this notion by demonstrating that this region can contribute to many domains of cognition beyond long-term memory, including perception and attention. One potential reason why the MTL (and hippocampus specifically) contributes broadly to cognition is that it contains relational representations-representations of multidimensional features of experience and their unique relationship to one another-that are useful in many different cognitive domains. Here, we explore the hypothesis that the hippocampus/MTL plays a critical role in attention and perception via relational representations. We compared human participants with MTL damage to healthy age- and education-matched individuals on attention tasks that varied in relational processing demands. On each trial, participants viewed two images (rooms with paintings). On "similar room" trials, they judged whether the rooms had the same spatial layout from a different perspective. On "similar art" trials, they judged whether the paintings could have been painted by the same artist. On "identical" trials, participants simply had to detect identical paintings or rooms. MTL lesion patients were significantly and selectively impaired on the similar room task. This work provides further evidence that the hippocampus/MTL plays a ubiquitous role in cognition by virtue of its relational and spatial representations and highlights its important contributions to rapid perceptual processes that benefit from attention.

Alcohol and pharmacologically similar sedatives impair encoding and facilitate consolidation of both recollection and familiarity in episodic memory.

Alcohol and other pharmacologically similar sedatives (i.e., GABAA positive allosteric modulators or PAMs) impair the encoding of new episodic memories but retroactively facilitate the consolidation of recently encoded memories. These effects are consistent for recollection (i.e., the retrieval of details) but some mixed results have been reported for familiarity (i.e., a feeling of knowing a stimulus was presented). Here, with dual-process models, we reanalyzed prior work testing the effects of GABAA PAMs at encoding or consolidation. Contrary to previous conclusions, we show that GABAA PAMs at encoding consistently impair both recollection and familiarity when an independence correction is applied to familiarity-based responses. These findings were further confirmed and extended in a dual-process signal detection analysis of a recent study on the effects of alcohol during encoding or consolidation: Alcohol at encoding impaired both recollection and familiarity, whereas alcohol at consolidation enhanced both recollection and familiarity. These findings speak to the ability of alcohol and other GABAA PAMs to induce 'blackouts,' highlighting the importance of dual-process approaches when analyzing drug manipulations at different phases of episodic memory.

Effects of Buprenorphine on Responses to Emotional Stimuli in Individuals with a Range of Mood Symptomatology.

Background: The opioid drug buprenorphine has been shown to modify responses to emotional stimuli and may have antidepressant properties. In preclinical studies, it shows antidepressant-like and anxiolytic-like effects, and a handful of clinical studies suggest it may reduce symptoms of depression in patients. We have shown that low doses of buprenorphine reduce responses to negative emotional stimuli in healthy adults. Here we extended these findings to individuals with symptoms of depression and anxiety. Methods: We examined the effects of buprenorphine on attention to emotional facial expressions and ratings of and psychophysiological responses to emotional images in adults with a range of mood symptomatology. Volunteers (n=38) were recruited with low, mild, moderate, and severe scores on the Depression-Anxiety-Stress Scale. They attended 2 laboratory sessions during which they received either placebo or 0.2 mg sublingual buprenorphine in randomized order under double-blind conditions. During peak drug effect, participants completed a visual attention task assessing responses to emotional faces and a picture-rating task assessing responses to emotional images with and without social content. Results: Buprenorphine reduced attention to fearful facial expressions as it did in our previous study, and the emotion-specific effect was especially pronounced in individuals with high Depression-Anxiety-Stress Scale scores. The drug also increased ratings of positivity of images with social content, but this effect was less strong in individuals with higher Depression-Anxiety-Stress Scale scores. Conclusions: These results suggest low doses of buprenorphine may reduce some dimensions of responses to negative emotional stimuli in individuals high on depression or anxiety, while leaving other dimensions unaffected.

Extinction of Conditioned Responses to Methamphetamine-Associated Stimuli in Healthy Humans.

RATIONALE: Contextual stimuli present during drug experiences become associated with the drug through Pavlovian conditioning and are thought to sustain drug-seeking behavior. Thus, extinction of conditioned responses is an important target for treatment. To date, acquisition and extinction to drug-paired cues have been studied in animal models or drug-dependent individuals, but rarely in non-drug users. OBJECTIVE: We have recently developed a procedure to study acquisition of conditioned responses after single doses of methamphetamine (MA) in healthy volunteers. Here, we examined extinction of these responses and their persistence after conditioning. METHODS: Healthy adults (18-35 years; N = 20) received two pairings of audio-visual stimuli with MA (20 mg oral) or placebo. Responses to stimuli were assessed before and after conditioning, using three tasks: behavioral preference, attentional bias, and subjective "liking." RESULTS: Subjects exhibited behavioral preference for the drug-paired stimuli at the first post-conditioning test, but this declined rapidly on subsequent extinction tests. They also exhibited a bias to initially look towards the drug-paired stimuli at the first post-test session, but not thereafter. Subjects who experienced more positive subjective drug effects during conditioning exhibited a smaller decline in preference during the extinction phase. Further, longer inter-session intervals during the extinction phase were associated with less extinction of the behavioral preference measure. CONCLUSIONS: Conditioned responses after two pairings with MA extinguish quickly, and are influenced by both subjective drug effects and the extinction interval. Characterizing and refining this conditioning procedure will aid in understanding the acquisition and extinction processes of drug-related conditioned responses in humans.