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Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a wholebrain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory–related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory.

Episodic memory, the ability to consciously recollect information and its context, varies substantially among individuals. While prior fMRI studies have identified certain brain regions linked to successful memory encoding at a group level, their role in explaining individual memory differences remains largely unexplored. Here, we analyze fMRI data of 1,498 adults participating in a picture encoding task in a single MRI scanner. We find that individual differences in responsivity of the hippocampus, orbitofrontal cortex, and posterior cingulate cortex account for individual variability in episodic memory performance. While these regions also emerge in our group-level analysis, other regions, predominantly within the lateral occipital cortex, are related to successful memory encoding but not to individual memory variation. Furthermore, our network-based approach reveals a link between the responsivity of nine functional connectivity networks and individual memory variability. Our work provides insights into the neurofunctional correlates of individual differences in visual episodic memory performance. The neural basis of individual differences in episodic memory performance is not well understood. Here, the authors show in a large fMRI dataset that activity of the hippocampus, orbitofrontal cortex and posterior cingulate cortex accounts for individual variability in memory performance.

Background Cigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study is to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation. Methods This is a placebo-controlled, double-blind, parallel group, superiority, single-centre randomized study including 255 patients. The intervention consists of a 12-week dulaglutide treatment phase with 1.5 mg once weekly or placebo subcutaneously, in addition to standard of care (behavioural counselling and pharmacotherapy with varenicline). A 40-week non-treatment phase follows. The primary outcome is the point prevalence abstinence rate at week 12. Smoking status is self-reported and biochemically confirmed by end-expiratory exhaled carbon monoxide measurement. Further endpoints include post-cessational weight gain, nicotine craving analysis, glucose homeostasis and long-term nicotine abstinence. Two separate substudies assess behavioural, functional and structural changes by functional magnetic resonance imaging and measures of energy metabolism (i.e. resting energy expenditure, body composition). Discussion Combining behavioural counselling and medical therapy, e.g. with varenicline, improves abstinence rates and is considered the standard of care. We expect a further increase in quit rates by adding a second component of medical therapy and assume a dual effect of dulaglutide treatment (blunting nicotine withdrawal symptoms and reducing post-cessational weight gain). This project is of high relevance as it explores novel treatment options aimed at preventing the disastrous consequences of nicotine consumption and obesity. Trial registration ClinicalTrials.gov NCT03204396 . Registered on June 26, 2017.

Motor skill learning is associated with profound changes in brain activation patterns over time. Associative and rostral premotor cortical and subcortical regions are mostly recruited during the early phase of explicit motor learning, while sensorimotor regions may increase their activity during the late learning phases. Distinct brain networks are therefore engaged during the early and late phases of motor skill learning. How these regions interact with one another and how information is transferred from one circuit to the other has been less extensively studied. In this study, we used functional MRI (fMRI) at 3T to follow the changes in functional connectivity in the associative/premotor and the sensorimotor networks, during extended practice (4 weeks) of an explicitly known sequence of finger movements. Evolution of functional connectivity was assessed using integration, a measure that quantifies the total amount of interaction within a network. When comparing the integration associated with a complex finger movement sequence to that associated with a simple sequence, we observed two patterns of decrease during the 4 weeks of practice. One was not specific as it was observed for all sequences, whereas a specific decrease was observed only for the execution of the learned sequence. This second decrease was a consequence of a relative decrease in associative/premotor network integration, together with a relative increase in between-network integration. These findings are in line with the hypothesis that information is transferred from the associative/premotor circuit to the sensorimotor circuit during the course of motor learning.

Increasing age is tightly linked to decreased thickness of the human neocortex. The biological mechanisms that mediate this effect are hitherto unknown. The DNA methylome, as part of the epigenome, contributes significantly to age-related phenotypic changes. Here, we identify an epigenetic signature that is associated with cortical thickness ( P =3.86 × 10 −8 ) and memory performance in 533 healthy young adults. The epigenetic effect on cortical thickness was replicated in a sample comprising 596 participants with major depressive disorder and healthy controls. The epigenetic signature mediates partially the effect of age on cortical thickness ( P <0.001). A multilocus genetic score reflecting genetic variability of this signature is associated with memory performance ( P =0.0003) in 3,346 young and elderly healthy adults. The genomic location of the contributing methylation sites points to the involvement of specific immune system genes. The decomposition of blood methylome-wide patterns bears considerable potential for the study of brain-related traits. Cortical thickness has high heritability estimates and is known to be influenced by genetic factors. Here, Freytag and colleagues show that DNA methylation patterns of peripheral blood monocytes are also correlated with cortical thickness and memory performance in human.

Psychosis progresses along a continuum. While heterogeneity is evident across the continuum, it remains unknown whether this is also reflected in white matter (WM) heterogeneity and whether parsing WM heterogeneity may reveal subgroups with more pronounced clinical features. This analysis included 212 participants consisting of healthy controls (HC, n = 59), individuals with high schizotypy (SPT, n = 27), at-risk mental state (ARMS, n = 35), and patients with first episode psychosis (FEP, n = 50) and schizophrenia (SZ, n = 41). Fractional anisotropy (FA) and mean diffusivity (MD) were derived from diffusion tensor imaging (DTI), and fibre density (FD), a non-tensor-derived diffusion marker, was computed. The Person-Based-Similarity Index (PBSI) and Coefficient of Variation Ratio (CVR) were computed to assess global and local heterogeneity. ANOVAs were performed to determine whether people with deviating PBSIs exhibit more pronounced clinical features. Global heterogeneity for all diffusion parameters significantly differed across groups, with greatest difference in heterogeneity between SZ and HC. Results further indicate that FA deviators exhibit lower global functioning and higher negative symptoms. Local FA heterogeneity was greater in FEP relative to ARMS and HC in almost all WM tracts, while SZ patients specifically showed greater heterogeneity in the right thalamic radiation and the left uncinate compared to HCs. Group differences in WM heterogeneity might be indicative of symptom specificity and duration. While these findings offer valuable insights into the neurobiological variability of psychosis, they are primarily hypothesis-generating. Future large-scale studies are warranted to test the robustness of diffusion markers and their clinical relevance.

To assess the psychological consequences of changes during the coronavirus 2019 (COVID-19) pandemic in the Iranian population.BackgroundTo assess the psychological consequences of changes during the coronavirus 2019 (COVID-19) pandemic in the Iranian population.We performed an anonymous online survey in the first 3 weeks of March 2020. Individuals older than 14 who could read Persian, and lived in Iran, were eligible for the study. The participants had to rate their stress levels and depressive symptoms (using a nine-item Patient Health Questionnaire PHQ-9) during the last 2 weeks and before the pandemic retrospectively. The changes in the psychological measurements and their association with the sociodemographic factors and burdens due to confinement were assessed.MethodsWe performed an anonymous online survey in the first 3 weeks of March 2020. Individuals older than 14 who could read Persian, and lived in Iran, were eligible for the study. The participants had to rate their stress levels and depressive symptoms (using a nine-item Patient Health Questionnaire PHQ-9) during the last 2 weeks and before the pandemic retrospectively. The changes in the psychological measurements and their association with the sociodemographic factors and burdens due to confinement were assessed.Overall, among the 3,210 subjects who participated in our study, both the stress levels and average depression scores increased. However, about 23% of the subjects reported a decrease in their stress levels. The burden of childcare, restrictions in private life, and thoughts about the future were positively correlated with the changes in the stress levels and depression scores (|r| > 0.15). However, feeling relieved in the pandemic condition, and enjoying more family time were associated with less change in the stress and depression scores. Being religious (odds ratio [OR] [CI]: 1.5 [1.3-1-8]) and older age (OR [CI]: 2.9 [1.8-4.6] for >55 years old) were identified as the resilience factors, whereas being a student (OR [CI]: 2.1 [1.6;2.7]), seeking a job (OR [CI]: 2.6 [1.8;3.9]), and history of a psychiatric disorder (OR [CI]: 3.2 [2.6;4]) were identified as the risk factors for depression.ResultsOverall, among the 3,210 subjects who participated in our study, both the stress levels and average depression scores increased. However, about 23% of the subjects reported a decrease in their stress levels. The burden of childcare, restrictions in private life, and thoughts about the future were positively correlated with the changes in the stress levels and depression scores (|r| > 0.15). However, feeling relieved in the pandemic condition, and enjoying more family time were associated with less change in the stress and depression scores. Being religious (odds ratio [OR] [CI]: 1.5 [1.3-1-8]) and older age (OR [CI]: 2.9 [1.8-4.6] for >55 years old) were identified as the resilience factors, whereas being a student (OR [CI]: 2.1 [1.6;2.7]), seeking a job (OR [CI]: 2.6 [1.8;3.9]), and history of a psychiatric disorder (OR [CI]: 3.2 [2.6;4]) were identified as the risk factors for depression.The stress levels and depressive symptoms have increased during the COVID-19 pandemic and this increase is related to different social and personal burdens due to the confinement conditions.ConclusionsThe stress levels and depressive symptoms have increased during the COVID-19 pandemic and this increase is related to different social and personal burdens due to the confinement conditions.

Background Primary polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide-1 (GLP-1) reduces appetite and food intake. In experimental models, they also play a role in thirst and drinking behavior in. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia. Methods: In this randomized, double-blind, placebo-controlled, 3-week crossover-trial, 34 patients with primary polydipsia received weekly dulaglutide (Trulicity®) 1.5mg and placebo (0.9% sodium chloride). During the last treatment week, patients attended an 8-hour evaluation visit with free water access. The primary endpoint was total fluid intake during the evaluation visits. The treatment effect was estimated using a linear mixed-effects model. In a subset of 15 patients and matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI. Results Median [IQR] total fluid intake was 2250ml [1600-2600] on dulaglutide versus 2400ml [1850-3400] on placebo. Patients on dulaglutide reduced fluid intake by 490ml [95%-CI -780, -199], p=0.002, corresponding to a relative reduction of 17%. 24-hour urinary output was reduced by -943ml [95%-CI -1473, -413]. Thirst perception in response to beverage pictures was higher in patients with primary polydipsia versus controls and lower on dulaglutide versus placebo, but functional neuronal activity was similar between groups and treatments. Conclusion: GLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a novel treatment option for these patients.

Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.

Memory performance is the result of many distinct mental processes, such as memory encoding, forgetting, and modulation of memory strength by emotional arousal. These processes, which are subserved by partly distinct molecular profiles, are not always amenable to direct observation. Therefore, computational models can be used to make inferences about specific mental processes and to study their genetic underpinnings. Here we combined a computational model-based analysis of memory-related processes with high density genetic information derived from a genome-wide study in healthy young adults. After identifying the best-fitting model for a verbal memory task and estimating the best-fitting individual cognitive parameters, we found a common variant in the gene encoding the brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) that was related to the model parameter reflecting modulation of verbal memory strength by negative valence. We also observed an association between the same genetic variant and a similar emotional modulation phenotype in a different population performing a picture memory task. Furthermore, using functional neuroimaging we found robust genotype-dependent differences in activity of the parahippocampal cortex that were specifically related to successful memory encoding of negative versus neutral information. Finally, we analyzed cortical gene expression data of 193 deceased subjects and detected significant BAIAP2 genotype-dependent differences in BAIAP2 mRNA levels. Our findings suggest that model-based dissociation of specific cognitive parameters can improve the understanding of genetic underpinnings of human learning and memory.