Attentional Biases and Their Association with Substance-Use-Related Problems and Addictive Behaviors: The Utility of a Gamified Value-Modulated Attentional Capture Task

BackgroundAttentional biases towards reward stimuli have been implicated in substance use-related problems. The value-modulated attentional capture (VMAC) task assesses such reward-related biases. The VMAC task widely used in lab studies tends to be monotonous and susceptible to low effort. We therefore tested a gamified online version of the VMAC that aimed to increase participant engagement. Our goal was to examine how VMAC is associated with substance use-related problems and addictive behaviors, and whether this association is moderated by cognitive control.MethodsWe recruited 285 participants from an online community, including heavy alcohol users. All participants completed a novel gamified version of the VMAC task, measures of substance use and addictive behaviors (addictive-like eating behavior, problematic smartphone use), the WebExec measure of problems with executive functions, and the Stroop Adaptive Deadline Task (SDL) as a measure of cognitive control.ResultsThe gamified VMAC task successfully identified value-modulated attentional capture effects towards high-reward stimuli. We found no significant associations between VMAC scores, problematic alcohol or cannabis use, addictive behaviors, or any moderation by a behavioral measure of cognitive control. Exploratory analyses revealed that self-reported cognitive problems were associated with more alcohol-, and cannabis-related problems, and addictive behaviors. Greater attentional capture (VMAC) was associated with more cannabis use-related problems among individuals with higher levels of self-reported cognitive problems.ConclusionsOur study is one of the first to demonstrate the utility of the gamified version of the VMAC task in capturing attentional reward biases. Self-reported problems with cognitive functions represent a key dimension associated with substance use-related problems and addictive behaviors

Cynomolgus monkey's choroid reference database derived from hybrid deep learning optical coherence tomography segmentation.

Cynomolgus monkeys exhibit human-like features, such as a fovea, so they are often used in non-clinical research. Nevertheless, little is known about the natural variation of the choroidal thickness in relation to origin and sex. A combination of deep learning and a deterministic computer vision algorithm was applied for automatic segmentation of foveolar optical coherence tomography images in cynomolgus monkeys. The main evaluation parameters were choroidal thickness and surface area directed from the deepest point on OCT images within the fovea, marked as the nulla with regard to sex and origin. Reference choroid landmarks were set underneath the nulla and at 500 µm intervals laterally up to a distance of 2000 µm nasally and temporally, complemented by a sub-analysis of the central bouquet of cones. 203 animals contributed 374 eyes for a reference choroid database. The overall average central choroidal thickness was 193 µm with a coefficient of variation of 7.8%, and the overall mean surface area of the central bouquet temporally was 19,335 µm2 and nasally was 19,283 µm2. The choroidal thickness of the fovea appears relatively homogeneous between the sexes and the studied origins. However, considerable natural variation has been observed, which needs to be appreciated

Value-modulated attentional capture in reward and punishment contexts, attentional control, and their relationship with psychopathology

Attentional bias towards rewards has been extensively studied in both healthy and clinical populations. Several studies have shown an association between reward value-modulated attentional capture (VMAC) and greater substance use. However, less is known about the association between these VMAC effects and internalizing symptoms. Moreover, while VMAC effects have also been found in punishment contexts, the association between punishment VMAC and psychopathology has not been studied so far. In the present two-part preregistered study, we adapted a novel VMAC task to also include a punishment context and examined associations with internalizing symptoms and substance use. Our results showed consistent VMAC effects in reward contexts across two separate studies. Attentional capture was stronger for distractors associated with high rewards than for low rewards. We replicated and extended previous findings by showing such VMAC effects in a substantially shorter task that also included alternating punishment blocks. Contrary to our expectations, we found no VMAC effects in punishment contexts and no direct associations between VMAC and symptom measures. Our results speak to the feasibility of assessing VMAC effects using a scalable and short behavioral online task, but the relationship with the development of internalizing and externalizing psychopathology remains uncertain.</p

Value-modulated attentional capture in reward and punishment contexts, attentional control, and their relationship with psychopathology

Attentional bias towards rewards has been extensively studied in both healthy and clinical populations. Several studies have shown an association between reward value-modulated attentional capture (VMAC) and greater substance use. However, less is known about the association between these VMAC effects and internalizing symptoms. Moreover, while VMAC effects have also been found in punishment contexts, the association between punishment VMAC and psychopathology has not been studied so far. In the present two-part preregistered study, we adapted a novel VMAC task to also include a punishment context and examined associations with internalizing symptoms and substance use. Our results showed consistent VMAC effects in reward contexts across two separate studies. Attentional capture was stronger for distractors associated with high rewards than for low rewards. We replicated and extended previous findings by showing such VMAC effects in a substantially shorter task that also included alternating punishment blocks. Contrary to our expectations, we found no VMAC effects in punishment contexts and no direct associations between VMAC and symptom measures. Our results speak to the feasibility of assessing VMAC effects using a scalable and short behavioral online task, but the relationship with the development of internalizing and externalizing psychopathology remains uncertain.</p

Emergent temporal signaling in human trabecular meshwork cells: role of TRPV4-TRPM4 interactions

Trabecular meshwork (TM) cells are phagocytic cells that employ mechanotransduction to actively regulate intraocular pressure. Similar to macrophages, they express scavenger receptors and participate in antigen presentation within the immunosuppressive milieu of the anterior eye. Changes in pressure deform and compress the TM, altering their control of aqueous humor outflow but it is not known whether transducer activation shapes temporal signaling. The present study combines electrophysiology, histochemistry and functional imaging with gene silencing and heterologous expression to gain insight into Ca2+ signaling downstream from TRPV4 (Transient Receptor Potential Vanilloid 4), a stretch-activated polymodal cation channel. Human TM cells respond to the TRPV4 agonist GSK1016790A with fluctuations in intracellular Ca2+ concentration ([Ca2+]i) and an increase in [Na+]i. [Ca2+]i oscillations coincided with monovalent cation current that was suppressed by BAPTA, Ruthenium Red and the TRPM4 (Transient Receptor Potential Melastatin 4) channel inhibitor 9-phenanthrol. TM cells expressed TRPM4 mRNA, protein at the expected 130-150 kDa and showed punctate TRPM4 immunoreactivity at the membrane surface. Genetic silencing of TRPM4 antagonized TRPV4-evoked oscillatory signaling whereas TRPV4 and TRPM4 co-expression in HEK-293 cells reconstituted the oscillations. Membrane potential recordings suggested that TRPM4-dependent oscillations require release of Ca2+ from internal stores. 9-phenanthrol did not affect the outflow facility in mouse eyes and eyes from animals lacking TRPM4 had normal intraocular pressure. Collectively, our results show that TRPV4 activity initiates dynamic calcium signaling in TM cells by stimulating TRPM4 channels and intracellular Ca2+ release. It is possible that TRPV4-TRPM4 interactions downstream from the tensile and compressive impact of intraocular pressure contribute to homeostatic regulation and pathological remodeling within the conventional outflow pathway

TRPC4/TRPC5 channels mediate adverse reaction to the cancer cell cytotoxic agent (-)-Englerin A

(-)-Englerin A (EA) is a natural product which has potent cytotoxic effects on renal cell carcinoma cells and other types of cancer cell but not non-cancer cells. Although selectively cytotoxic to cancer cells, adverse reaction in mice and rats has been suggested. EA is a remarkably potent activator of ion channels formed by Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) and TRPC4 is essential for EA-mediated cancer cell cytotoxicity. Here we specifically investigated the relevance of TRPC4 and TRPC5 to the adverse reaction. Injection of EA (2 mg.kg⁻¹ i.p.) adversely affected mice for about 1 hour, manifesting as a marked reduction in locomotor activity, after which they fully recovered. TRPC4 and TRPC5 single knockout mice were partially protected and double knockout mice fully protected. TRPC4/TRPC5 double knockout mice were also protected against intravenous injection of EA. Importance of TRPC4/TRPC5 channels was further suggested by pre-administration of Compound 31 (Pico145), a potent and selective small-molecule inhibitor of TRPC4/TRPC5 channels which did not cause adverse reaction itself but prevented adverse reaction to EA. EA was detected in the plasma but not the brain and so peripheral mechanisms were implicated but not identified. The data confirm the existence of adverse reaction to EA in mice and suggest that it depends on a combination of TRPC4 and TRPC5 which therefore overlaps partially with TRPC4-dependent cancer cell cytotoxicity. The underlying nature of the observed adverse reaction to EA, as a consequence of TRPC4/TRPC5 channel activation, remains unclear and warrants further investigation

Drinking Motives, Personality Traits, Life Stressors - Identifying Pathways to Harmful Alcohol Use in Adolescence Using a Panel Network Approach

BACKGROUND AND AIMS: Models of alcohol use risk suggest that drinking motives represent the most proximal risk factors on which more distal factors converge. However, little is known about how distinct risk factors influence each other and alcohol use on different temporal scales (within a given moment vs. over time). We aimed to estimate the dynamic associations of distal (personality and life stressors) and proximal (drinking motives) risk factors, and their relationship to alcohol use in adolescence and early adulthood using a novel graphical vector autoregressive (GVAR) panel network approach.DESIGN, SETTING, AND CASES: We estimated panel networks on data from the IMAGEN study, a longitudinal European cohort study following adolescents across three waves (ages 16, 19, 22). Our sample consisted of 1829 adolescents (51% females) who reported alcohol use on at least one assessment wave.MEASUREMENTS: Risk factors included personality traits (NEO-FFI: neuroticism, extraversion, openness, agreeableness, and conscientiousness; SURPS: impulsivity and sensation seeking), stressful life events (LEQ: sum scores of stressful life events), and drinking motives (DMQ: social, enhancement, conformity, coping anxiety, coping depression). We assessed alcohol use (AUDIT: quantity and frequency) and alcohol-related problems (AUDIT: related problems).FINDINGS: Within a given moment, social (partial correlation (pcor) =0.17) and enhancement motives (pcor=0.15) co-occurred most strongly with drinking quantity and frequency, while coping depression motives (pcor=0.13), openness (pcor=0.05), and impulsivity (pcor=0.09) were related to alcohol-related problems. The temporal network showed no predictive associations between distal risk factors and drinking motives. Social motives (beta=0.21), previous alcohol use (beta=0.11), and openness (beta=0.10) predicted alcohol-related problems over time (all p&lt;0.01).CONCLUSIONS: Heavy and frequent alcohol use, along with social drinking motives, appear to be key targets for preventing the development of alcohol-related problems throughout late adolescence. We found no evidence for personality traits and life stressors predisposing towards distinct drinking motives over time.</p