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; R; 2β; = .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

Ultrafast assessment of left ventricular dyssynchrony from nuclear myocardial perfusion imaging on a new high-speed gamma camera

Purpose: To validate the ultrafast assessment of left ventricular (LV) dyssynchrony by phase analysis using high-speed nuclear myocardial perfusion imaging (MPI) on a new gamma camera with cadmium-zinc-telluride (CZT) solid-state detector technology. Methods: In 46 patients rest MPI with 960MBq 99mTc-tetrofosmin was acquired on a dual-head detector SPECT camera (Ventri, GE Healthcare) and an ultrafast CZT camera (Discovery NM 530c, GE Healthcare) with acquisition times of 15 and 5min, respectively. LV dyssynchrony was assessed using the Emory Cardiac Toolbox with established values for histogram bandwidth (male <62.4°; female <49.7°) and standard deviations (male <24.4°; female <22.1°) as the gold standard. Evaluating CZT scan times of 0.5, 1, 2, 3 and 5min (list mode) in 16 patients revealed the preferred scan time to be 5min, which was then applied in all 46 patients. Intraclass correlation and the level of agreement in dyssynchrony detection between the CZT and Ventri cameras were assessed. Results: In LV dyssynchrony the mean histogram bandwidths with the CZT camera (n = 8) and the Ventri camera (n = 9) were 123.3 ± 50.6° and 130.2 ± 43.2° (p not significant) and 42.4 ± 13.6° vs. 43.2 ± 12.7° (p not significant). Normal bandwidths and SD obtained with the CZT camera (35.9 ± 7.7°, 12.6 ± 3.5°) and the Ventri camera (34.8 ± 6.6°, 11.1 ± 2.1°, both p not significant) excluded dyssynchrony in 38 and 37 patients, respectively. Intraclass correlation and the level of agreement between the CZT camera with a 5-min scan time and the Ventri camera were 0.94 (p < 0.001, SEE 14.4) and 96% for histogram bandwidth and 0.96 (p < 0.001, SEE 3.9) and 98% for SD. Conclusion: This ultrafast CZT camera allows accurate assessment of LV dyssynchrony with a scan time of only 5min, facilitating repeat measurements which would potentially be helpful for parameter optimization for cardiac resynchronization therap

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

Guided Viewing: An Eye Tracking Approach to Increase Memory and Reduce Anxiety

Visual exploration, the way we strategically guide our gaze through the environment, is greatly affected by cognitive states like the current focus of attention, goals and knowledge. The causal link between cognition and viewing has first been described and demonstrated in humans in the 1960s, and researchers have tried to further characterize it ever since. The advent of functional magnetic resonance imaging (fMRI) has – in combination with eye tracking – considerably benefitted the understanding of this link, as it allowed to study its neuronal under-pinnings. A key role has thereby been attributed to regions centered around the hippocampus as part of the medial temporal lobe (MTL), orchestrating visual exploration based on previous experience. However, while it is well-established that visual exploration depends on cognitive states, it is unclear if cognitive states equally depend on visual exploration. To close this gap, the aim of this thesis was to investigate if viewing can be guided to affect aspects of cognition, and more specifically, if this can be used to (1) increase memory and (2) decrease anxiety. In a first study, Fehlmann, Coynel et al. (2020), we analyzed data of a picture encoding task performed by 967 healthy subjects during fMRI and simultaneous eye tracking. We repli-cated and generalized the finding of a triadic correlation between individual visual exploration patterns (i.e. eye fixation frequency and location), brain activation in the MTL and subsequent memory performance. In a second experiment, we experimentally altered visual exploration patterns in an independent population of 64 subjects. We thereby showed that both the fixation frequency and location can be causally manipulated by guided viewing conditions to affect memory performance. In a second study, Fehlmann, Müller, et al. (2020), we investigated the intervention po-tential of guided viewing to reduce fear in 89 participants suffering from public speaking anx-iety (PSA). We thereby targeted gaze avoidance, a potential key factor in the etiology and maintenance of the condition. The repeated use of a stand-alone, smartphone- and virtual reality (VR)-based mutual gaze training was effective in reducing gaze avoidance as well as the fear of public speaking in real-life speech situations. In conclusion, the thesis showcases two studies that used guided viewing as a tool to affect cognitive states. The gained insights add to the knowledge about the interplay between viewing and cognition in general, and the causal effect of viewing on cognition in particular. The described phenomenon has great relevance for neuroscientific research and great potential for the clinical practice

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

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=0·01). 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

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

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

The Swiss Corona Stress Study

The mental consequences of the COVID-19 pandemic and the strict lockdown measures implemented by governments world-wide to fight it are currently unknown. We performed an online survey study in Switzerland and analyzed data acquired during confinement (wave 1) and during partial lifting of measures (partial deconfinement) (wave 2). Wave 1: Data from over 10’000 individuals living in Switzerland were collected between April 6 and 8, 2020, starting 3 weeks after the beginning of confinement. While 24.4% of the participants reported no change in stress levels, 49.6% of the participants reported an increase in stress levels during confinement as compared to the time before the COVID-19 pandemic. We identified several potential sources for people feeling more stressed during confinement, such as the burden related to changes at work or school, problems with childcare or not being able to spend more time with others. The changes in stress levels were highly correlated with changes in depressive symptoms. 57% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) increased from 3.4% before the COVID-19 pandemic to 9.1% during confinement. Interestingly, 26% of participants showed a decrease in stress level during confinement, suggesting that for those individuals the confinement involved a reduction of stressors and/or resulted in more time for recovery. Finally, we identified several behaviors amenable to change that were related to a reduced increase in stress level and depressive symptoms during confinement. Wave 2: Data from over 10’000 individuals living in Switzerland were collected between May 11 and June 1, 2020 during partial deconfinement. As for wave 1, we observed diverse reactions with regard to stress levels: While 28% of the participants reported no change in stress levels, 40% of the participants reported an increase in stress levels during partial deconfinement as compared to the time before the COVID-19 pandemic. We identified similar sources for people feeling more stressed as during confinement and the changes in stress levels were highly correlated with changes in depressive symptoms. 49.5% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) remained elevated with a prevalence rate of 11.7%. With regard to changeable behaviors during the pandemic, we found (as in wave 1) that spending more time pursuing new projects, spending more time pursuing hobbies at home, and light physical exercise were related to less stress increase. A comparison between the two waves indicated that while the waves did not substantially differ in the distributions of changes in stress levels or depressive symptoms, they did differ with regard to the distribution of anxiety ratings. Specifically, anxiety levels decreased from wave 1 to wave 2. Finally, we identified risk and resilience factors with regard to the development of depressive symptoms (present in both waves): A history of a prior psychiatric disorder was a risk factor for developing moderately severe or severe depressive symptoms during the pandemic. In a resilient group of people who had none or only minimal depressive symptoms before and during the pandemic, older people (≥ 55 years), men and individuals with no history of prior psychiatric disorder were overrepresented. Thus, advanced age, male gender and the absence of prior psychiatric disorder were identified as resilience factors