Assessing Stress Induced by Fluid Shifts and Reduced Cerebral Clearance during Robotic-Assisted Laparoscopic Radical Prostatectomy under Trendelenburg Positioning (UroTreND Study).

In addition to general anesthesia and mechanical ventilation, robotic-assisted laparoscopic radical prostatectomy (RALP) necessitates maintaining a capnoperitoneum and placing the patient in a pronounced downward tilt (Trendelenburg position). While the effects of the resulting fluid shift on the cardiovascular system seem to be modest and well tolerated, the effects on the brain and the blood-brain barrier have not been thoroughly investigated. Previous studies indicated that select patients showed an increase in the optic nerve sheath diameter (ONSD), detected by ultrasound during RALP, which suggests an elevation in intracranial pressure. We hypothesize that the intraoperative fluid shift results in endothelial dysfunction and reduced cerebral clearance, potentially leading to transient neuronal damage. This prospective, monocentric, non-randomized, controlled clinical trial will compare RALP to conventional open radical prostatectomy (control group) in a total of 50 subjects. The primary endpoint will be the perioperative concentration of neurofilament light chain (NfL) in blood using single-molecule array (SiMoA) as a measure for neuronal damage. As secondary endpoints, various other markers for endothelial function, inflammation, and neuronal damage as well as the ONSD will be assessed. Perioperative stress will be evaluated by questionnaires and stress hormone levels in saliva samples. Furthermore, the subjects will participate in functional tests to evaluate neurocognitive function. Each subject will be followed up until discharge. Conclusion: This trial aims to expand current knowledge as well as to develop strategies for improved monitoring and higher safety of patients undergoing RALP. The trial was registered with the German Clinical Trials Register DRKS00031041 on 11 January 2023.

Impact of the COVID-19 pandemic on obsessive-compulsive symptoms in the Swiss general population.

Background: In the early stages of the COVID-19 pandemic, mental-health experts called attention to a possible deterioration of obsessive-compulsive symptoms (OCSs). In particular, people suffering from a fear of contamination were considered a vulnerable population. Aim: The aim of this study was to investigate the change in OCSs from before to during the pandemic within the Swiss general population, and to examine a possible relationship of OCSs to stress and anxiety. Methods: This cross-sectional study was implemented as an anonymized online survey (N = 3,486). The Obsessive-Compulsive Inventory-Revised (OCI-R) was used to assess global OCS severity (range: 0-72, clinical cut-off > 18) and specific OCS dimensions (range: 0-12) during the second wave of the pandemic and retrospectively for before the pandemic. Participants were asked to report stress and anxiety in the previous 2 weeks before the survey. Results: Participants reported significantly higher OCI-R total scores during (12.73) compared to before the pandemic (9.04, mean delta increase: 3.69). Significantly more individuals reported an OCI-R total score exceeding the clinical cut-off during (24%) than before the pandemic (13%). OCS severity increased on all symptom dimensions, but was most pronounced on the washing dimension (all with p < 0.001). Self-reported stress and anxiety were weakly associated with differences in severity in total score and symptom dimensions (with R2 < 0.1 and p < 0.001). Conclusion: Our results indicate that the full spectrum of people with OCS should be considered as risk groups for symptom deterioration during a pandemic and when assessing its possible long-term effects of such.

The Iranian Corona Stress Study: Psychological Impacts of COVID-19 Pandemic in an Iranian Population.

Background: To assess the psychological consequences of changes during the coronavirus 2019 (COVID-19) pandemic in the Iranian population. Methods: 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. Results: 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. Conclusions: 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.

Human cerebellum and corticocerebellar connections involved in emotional memory enhancement.

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 whole-brain 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.

Guilt is effectively induced by a written auto-biographical essay but not reduced by experimental pain.

Introduction: The aim of the present study was (1) to validate the method of guilt-induction by means of a written auto-biographical essay and (2) to test whether experimental pain is apt to alleviate the mental burden of guilt, a concept receiving support from both empirical research and clinical observation. Methods: Three independent groups of healthy male participants were recruited. Group allocation was not randomized but within group pain/sham administration was counterbalanced over the two test-days. Groups were tested in the following consecutive order: Group A: guilt induction, heat-pain/sham, N = 59; Group B: guilt induction, cold-pressure-pain/sham, N = 43; Group C: emotionally neutral induction, heat-pain/sham, N = 39. Guilt was induced on both test-days in group A and B before pain/sham administration. Visual analog scale (VAS) guilt ratings immediately after pain/sham stimulation served as the primary outcome. In a control group C the identical heat-pain experiment was performed like in group A but a neutral emotional state was induced. Results: A consistently strong overall effect of guilt-induction (heat-pain: p < 0.001, effect size r = 0.71; CPT-pain p < 0.001, r = 0.67) was found when compared to the control-condition (p = 0.25, r = 0.08). As expected, heat- and cold-pressure-stimuli were highly painful in all groups (p < 0.0001, r = 0.89). However, previous research supporting the hypothesis that pain is apt to reduce guilt was not replicated. Conclusion: Although guilt-induction was highly effective on both test-days no impact of pain on behavioral guilt-ratings in healthy individuals could be identified. Guilt induction per se did not depend on the order of testing. The result questions previous experimental work on the impact of pain on moral emotions.

Cannabidiol enhances verbal episodic memory in healthy young participants: A randomized clinical trial.

Cannabis contains a multitude of different compounds. One of them, cannabidiol - a non-psychoactive substance - might counteract negative effects of Δ-9-Tetrahydrocannabinol on hippocampus-dependent memory impairment. The aim of the present study was to investigate the effect of vaping cannabidiol on verbal episodic memory in healthy young subjects. We used a double-blind, placebo-controlled, randomized crossover trial in 39 healthy young subjects. Participants received once a single dose of cannabidiol e-liquid (0.25 ml, 5% cannabidiol, 12.5 mg cannabidiol) and once placebo for vaping after learning 15 unrelated nouns. The primary outcome measure was the short delay verbal memory performance (number of correctly free recalled nouns) 20 min after learning. 34 participants (mean age: 22.26 [3.04]) completed all visits and entered analyses (17 received cannabidiol and 17 received placebo first). Cannabidiol enhanced verbal episodic memory performance (placebo: 7.03 [2.34]; cannabidiol 7.71 [2.48]; adjusted group difference 0.68, 95% CI 0.01 to 1.35; R2ß = .028, p = .048). Importantly, we did not detect medication effects on secondary outcome measures attention or working memory performance, suggesting that CBD has no negative impact on these basic cognitive functions. The results are in line with the idea that vaping cannabidiol interacts with the central endocannabinoid system and is capable to modulate memory processes, a phenomenon with possible therapeutic potential. Further studies are needed to investigate optimal dose-response and time-response relationships.

Effectiveness of a smartphone-based, augmented reality exposure app to reduce fear of spiders in real-life: A randomized controlled trial.

Although in vivo exposure therapy is highly effective in the treatment of specific phobias, only a minority of patients seeks therapy. Exposure to virtual objects has been shown to be better tolerated, equally efficacious, but the technology has not been made widely accessible yet. We developed an augmented reality (AR) application (app) to reduce fear of spiders and performed a randomized controlled trial comparing the effects of our app (six 30-min sessions at home over a two-week period) with no intervention. Primary outcome was subjective fear, measured by a Subjective Units of Distress Scale (SUDS) in a Behavioural Approach Test (BAT) in a real-life spider situation at six weeks follow-up. Between Oct 7, 2019, and Dec 6, 2019, 66 individuals were enrolled and randomized. The intervention led to significantly lower subjective fear in the BAT compared to the control group (intervention group, baseline: 7.12 [SD 2.03] follow-up: 5.03 [SD 2.19] vs. control group, baseline: 7.06 [SD 2.34], follow-up 6.24 [SD 2.21]; adjusted group difference -1.24, 95 % CI -2.17 to -0.31; Cohen's d = 0.57, p = 0.010). The repeated use of the AR app reduces subjective fear in a real-life spider situation, providing a low-threshold and low-cost treatment for fear of spiders.

Effectiveness of a stand-alone, smartphone-based virtual reality exposure app to reduce fear of heights in real-life: a randomized trial.

Smartphone-based virtual reality (VR) applications (apps) might help to counter low utilization rates of available treatments for fear of heights. Demonstration of effectiveness in real-life situations of such apps is crucial, but lacking so far. Objective of this study was to develop a stand-alone, smartphone-based VR exposure app-Easy Heights-and to test its effectiveness in a real-life situation. We performed a single-blind, parallel group, randomized controlled trial. We recruited 70 participants with fear of heights, aged 18-60 years. Primary outcome was performance in a real-life Behavioral Avoidance Test (BAT) on a lookout tower after a single 1-h app use (phase 1) and after additional repeated (6 × 30 min) app use at home (phase 2). After phase 2, but not phase 1, participants in the Easy Heights condition showed significantly higher BAT scores compared to participants in the control condition (Cohen's d = 1.3, p = 0.0001). Repeated use of our stand-alone, smartphone-based VR exposure app reduces avoidance behavior and fear, providing a low-threshold treatment for fear of heights.

Reducing Amygdala Activity and Phobic Fear through Cognitive Top-Down Regulation.

The amygdala is critically involved in emotional processing, including fear responses, and shows hyperactivity in anxiety disorders. Previous research in healthy participants has indicated that amygdala activity is down-regulated by cognitively demanding tasks that engage the PFC. It is unknown, however, if such an acute down-regulation of amygdala activity might correlate with reduced fear in anxious participants. In an fMRI study of 43 participants (11 men) with fear of snakes, we found reduced amygdala activity when visual stimuli were processed under high cognitive load, irrespective of whether the stimuli were of neutral or phobic content. Furthermore, dynamic causal modeling revealed that this general reduction in amygdala activity was partially mediated by a load-dependent increase in dorsolateral PFC activity. Importantly, high cognitive load also resulted in an acute decrease in perceived phobic fear while viewing the fearful stimuli. In conclusion, our data indicate that a cognitively demanding task results in a top-down regulation of amygdala activity and an acute reduction of fear in phobic participants. These findings may inspire the development of novel psychological intervention approaches aimed at reducing fear in anxiety disorders.

Visual Exploration at Higher Fixation Frequency Increases Subsequent Memory Recall.

Only a small proportion of what we see can later be recalled. Up to date it is unknown how far differences in visual exploration during encoding affect the strength of episodic memories. Here, we identified individual gaze characteristics by analyzing eye tracking data in a picture encoding task performed by 967 healthy subjects during fMRI. We found a positive correlation between fixation frequency during visual exploration and subsequent free recall performance. Brain imaging results showed a positive correlation of fixation frequency with activations in regions related to vision and memory, including the medial temporal lobe. To investigate if higher fixation frequency is causally linked to better memory, we experimentally manipulated visual exploration patterns in an independent population of 64 subjects. Doubling the number of fixations within a given exploration time increased subsequent free recall performance by 19%. Our findings provide evidence for a causal relationship between fixation frequency and episodic memory for visual information.

Women using hormonal contraceptives show increased valence ratings and memory performance for emotional information.

Perception of emotional valence and emotional memory performance vary across the menstrual cycle. However, the consequences of altered ovarian hormone levels due to the intake of hormonal contraceptives on these emotional and cognitive processes remain to be established. In the present study, which included 2169 healthy young females, we show that hormonal contraceptives (HC) users rated emotional pictures as more emotional than HC-non-users and outperformed non-users in terms of better memory recall of emotional pictures. The observed association between HC-status and memory performance was partially mediated by the perception of emotional picture valence, indicating that increased valence ratings of emotional pictures in HC-users led to their better emotional memory performance. These findings extend the knowledge about the relation of HC-intake with emotional valence perception and emotional memory performance. Further, the findings might stimulate further research investigating the interrelation of enhanced memory for emotional events and the increased risk for anxiety-related psychiatric disorders in women.

Resting-state functional connectivity remains unaffected by preceding exposure to aversive visual stimuli.

While much is known about immediate brain activity changes induced by the confrontation with emotional stimuli, the subsequent temporal unfolding of emotions has yet to be explored. To investigate whether exposure to emotionally aversive pictures affects subsequent resting-state networks differently from exposure to neutral pictures, a resting-state fMRI study implementing a two-group repeated-measures design in healthy young adults (N = 34) was conducted. We focused on investigating (i) patterns of amygdala whole-brain and hippocampus connectivity in both a seed-to-voxel and seed-to-seed approach, (ii) whole-brain resting-state networks with an independent component analysis coupled with dual regression, and (iii) the amygdala's fractional amplitude of low frequency fluctuations, all while EEG recording potential fluctuations in vigilance. In spite of the successful emotion induction, as demonstrated by stimuli rating and a memory-facilitating effect of negative emotionality, none of the resting-state measures was differentially affected by picture valence. In conclusion, resting-state networks connectivity as well as the amygdala's low frequency oscillations appear to be unaffected by preceding exposure to widely used emotionally aversive visual stimuli in healthy young adults.

Continuous theta burst stimulation over the left dorsolateral prefrontal cortex decreases medium load working memory performance in healthy humans.

The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load.

Motor threshold predicts working memory performance in healthy humans.

Cognitive functions, such as working memory, depend on neuronal excitability in a distributed network of cortical regions. It is not known, however, if interindividual differences in cortical excitability are related to differences in working memory performance. In the present transcranial magnetic stimulation study, which included 188 healthy young subjects, we show that participants with lower resting motor threshold, which is related to higher corticospinal excitability, had increased 2-back working memory performance. The findings may help to better understand the link between cortical excitability and cognitive functions and may also have important clinical implications with regard to conditions of altered cortical excitability.

Human genome-guided identification of memory-modulating drugs.

In the last decade there has been an exponential increase in knowledge about the genetic basis of complex human traits, including neuropsychiatric disorders. It is not clear, however, to what extent this knowledge can be used as a starting point for drug identification, one of the central hopes of the human genome project. The aim of the present study was to identify memory-modulating compounds through the use of human genetic information. We performed a multinational collaborative study, which included assessment of aversive memory--a trait central to posttraumatic stress disorder--and a gene-set analysis in healthy individuals. We identified 20 potential drug target genes in two genomewide-corrected gene sets: the neuroactive ligand-receptor interaction and the long-term depression gene set. In a subsequent double-blind, placebo-controlled study in healthy volunteers, we aimed at providing a proof of concept for the genome-guided identification of memory modulating compounds. Pharmacological intervention at the neuroactive ligand-receptor interaction gene set led to significant reduction of aversive memory. The findings demonstrate that genome information, along with appropriate data mining methodology, can be used as a starting point for the identification of memory-modulating compounds.