Integrating and fragmenting memories under stress and alcohol

Stress can powerfully influence the way we form memories, particularly the extent to which they are integrated or situated within an underlying spatiotemporal and broader knowledge architecture. These different representations in turn have significant consequences for the way we use these memories to guide later behavior. Puzzlingly, although stress has historically been argued to promote fragmentation, leading to disjoint memory representations, more recent work suggests that stress can also facilitate memory binding and integration. Understanding the circumstances under which stress fosters integration will be key to resolving this discrepancy and unpacking the mechanisms by which stress can shape later behavior. Here, we examine memory integration at multiple levels: linking together the content of an individual experience, threading associations between related but distinct events, and binding an experience into a pre-existing schema or sense of causal structure. We discuss neural and cognitive mechanisms underlying each form of integration as well as findings regarding how stress, aversive learning, and negative affect can modulate each. In this analysis, we uncover that stress can indeed promote each level of integration. We also show how memory integration may apply to understanding effects of alcohol, highlighting extant clinical and preclinical findings and opportunities for further investigation. Finally, we consider the implications of integration and fragmentation for later memory-guided behavior, and the importance of understanding which type of memory representation is potentiated in order to design appropriate interventions

Low lifetime stress exposure is associated with reduced stimulus–response memory

Exposure to stress throughout life can cumulatively influence later health, even among young adults. The negative effects of high cumulative stress exposure are well-known, and a shift from episodic to stimulus–response memory has been proposed to underlie forms of psychopathology that are related to high lifetime stress. At the other extreme, effects of very low stress exposure are mixed, with some studies reporting that low stress leads to better outcomes, while others demonstrate that low stress is associated with diminished resilience and negative outcomes. However, the influence of very low lifetime stress exposure on episodic and stimulus–response memory is unknown. Here we use a lifetime stress assessment system (STRAIN) to assess cumulative lifetime stress exposure and measure memory performance in young adults reporting very low and moderate levels of lifetime stress exposure. Relative to moderate levels of stress, very low levels of lifetime stress were associated with reduced use and retention (24 h later) of stimulus–response (SR) associations, and a higher likelihood of using context memory. Further, computational modeling revealed that participants with low levels of stress exhibited worse expression of memory for SR associations than those with moderate stress. These results demonstrate that very low levels of stress exposure can have negative effects on cognition

Low lifetime stress exposure is associated with reduced stimulus-response memory

Exposure to stress throughout life can cumulatively influence later health, even among young adults. The negative effects of high cumulative stress exposure are well-known, and a shift from episodic to stimulus-response memory has been proposed to underlie forms of psychopathology that are related to high lifetime stress. At the other extreme, effects of very low stress exposure are mixed, with some studies reporting that low stress leads to better outcomes, while others demonstrate that low stress is associated with diminished resilience and negative outcomes. However, the influence of very low lifetime stress exposure on episodic and stimulus-response memory is unknown. Here we use a lifetime stress assessment system (STRAIN) to assess cumulative lifetime stress exposure and measure memory performance in young adults reporting very low and moderate levels of lifetime stress exposure. Relative to moderate levels of stress, very low levels of lifetime stress were associated with reduced use and retention (24 h later) of stimulus-response (SR) associations, and a higher likelihood of using context memory. Further, computational modeling revealed that participants with low levels of stress exhibited worse expression of memory for SR associations than those with moderate stress. These results demonstrate that very low levels of stress exposure can have negative effects on cognition

Binge drinking is associated with higher cortisol and lower hippocampal and prefrontal gray matter volume: Prospective association with future alcohol intake

Background: Cortisol is a significant driver of the biological stress response that is potently activated by acute alcohol intake and increased with binge drinking. Binge drinking is associated with negative social and health consequences and risk of developing alcohol use disorder (AUD). Both cortisol levels and AUD are also associated with changes in hippocampal and prefrontal regions. However, no previous research has assessed structural gray matter volume (GMV) and cortisol concurrently to examine BD effects on hippocampal and prefrontal GMV and cortisol, and their prospective relationship to future alcohol intake. Methods: Individuals who reported binge drinking (BD: N = 55) and demographically matched non-binge moderate drinkers (MD: N = 58) were enrolled and scanned using high-resolution structural MRI. Whole brain voxel-based morphometry was used to quantify regional GMV. In a second phase, 65% of the sample volunteered to participate in prospective daily assessment of alcohol intake for 30 days post-scanning. Results: Relative to MD, BD showed significantly higher cortisol and smaller GMV in regions including hippocampus, dorsal lateral prefrontal cortex (dlPFC), prefrontal and supplementary motor, primary sensory and posterior parietal cortex (FWE, p < 0.05). GMV in bilateral dlPFC and motor cortices were negatively associated with cortisol levels, and smaller GMV in multiple PFC regions was associated with more subsequent drinking days in BD. Conclusion: These findings indicate neuroendocrine and structural dysregulation associated with BD relative to MD. Notably, BD-associated lower GMV regions were those involved in stress, memory and cognitive control, with lower GMV in cognitive control and motor regions also predicting higher levels of future alcohol intake in BD

Acute Stress Enhances Memory and Preference for Smoking-Related Associations in Smokers

Introduction: Nicotine dependence follows a chronic course that is characterized by repeated relapse, often driven by acute stress and rewarding memories of smoking retrieved from related contexts. These two triggers can also interact, with stress influencing retrieval of contextual memories. However, the roles of these processes in nicotine dependence remain unknown. Methods: We investigated how acute stress biases memory for smoking-associated contexts among smokers (N=65) using a novel laboratory paradigm. On Day 1, participants formed associations between visual stimuli of items (either neutral or related to smoking) and places (background scenes). On Day 2 (24 hours later), participants were exposed to an acute laboratory-based stressor (socially evaluated cold pressor test; N=32) or a matched control condition (N=33) prior to being tested on their memory recognition and preferences for each item and place. We distinguished the accuracy of memory into specific (i.e., precisely correct) or gist (i.e., lure items with similar content) categories. Results: Results demonstrated that the stressor significantly induced physiological and subjective perceived stress responses, and that stressed smokers exhibited a memory bias in favor of smoking-related items. In addition, the stressed group displayed greater preference for both smoking-related items and places that had been paired with the smoking-related items. We also found suggestive evidence that stronger smoking-related memory biases were associated with more severe nicotine dependence (i.e., years of smoking). Conclusions: These results highlight the role of stress in biasing smokers toward remembering contexts associated with smoking, and in amplifying their preference for these contexts. Implications: The current study elucidates the role of acute stress in promoting memory biases favoring smoking-related associations among smokers. The results suggest that the retrieval of smoking-biased associative memory could be a crucial factor in stress-related nicotine seeking. This may lead to a potential intervention targeting the extinction of smoking-related context memories as a preventive strategy for stress-induced relapse

The association between nephroblastoma-specific outcomes and high versus low volume treatment centers.

BACKGROUND: Though the volume-outcome relationship has been well-established in adults, low mortality rates and small sample sizes have precluded definitive demonstration in children. This study compares treatment-specific factors for children with nephroblastoma at high (HVC) versus low volume centers (LVC). METHODS: We performed a retrospective cohort study comparing patients ≤18years with unilateral nephroblastoma treated at HVCs and LVCs using the National Cancer Data Base (1998-2012). Definitions of HVCs included performing above the median, the upper two quartiles, and the highest decile of nephroblastoma resections. Outcomes included nodal sampling, margin status, time to chemotherapy and radiation, and survival. Statistical analyses included χ RESULTS: Of 2911 patients from 210 centers, 1443 (49.6%) were treated at HVCs. There was no difference in frequency of preoperative biopsy or days to radiation (p\u3e0.05). High volume centers were more likely to perform nodal sampling (RR 1.04, 95%CI 1.01-1.08) and had fewer days to chemotherapy (RR 0.80, 95%CI 0.69-0.93). Five-year survival was similar (HVC: 0.93, 95%CI 0.92-0.94; LVC: 0.93, 95%CI 0.91-0.94). CONCLUSIONS: HVCs were more likely to perform nodal sampling and had fewer days to chemotherapy. There was no difference in days to radiation or survival between centers. LEVEL OF EVIDENCE: Level II (retrospective prognosis study)