Sufficient reliability of the behavioral and computational readouts of a probabilistic reversal learning task

Task-based measures that capture neurocognitive processes can help bridge the gap between brain and behavior. To transfer tasks to clinical application, reliability is a crucial benchmark because it imposes an upper bound to potential correlations with other variables (e.g., symptom or brain data). However, the reliability of many task readouts is low. In this study, we scrutinized the retest reliability of a probabilistic reversal learning task (PRLT) that is frequently used to characterize cognitive flexibility in psychiatric populations. We analyzed data from N = 40 healthy subjects, who completed the PRLT twice. We focused on how individual metrics are derived, i.e., whether data were partially pooled across participants and whether priors were used to inform estimates. We compared the reliability of the resulting indices across sessions, as well as the internal consistency of a selection of indices. We found good to excellent reliability for behavioral indices as derived from mixed-effects models that included data from both sessions. The internal consistency was good to excellent. For indices derived from computational modeling, we found excellent reliability when using hierarchical estimation with empirical priors and including data from both sessions. Our results indicate that the PRLT is well equipped to measure individual differences in cognitive flexibility in reinforcement learning. However, this depends heavily on hierarchical modeling of the longitudinal data (whether sessions are modeled separately or jointly), on estimation methods, and on the combination of parameters included in computational models. We discuss implications for the applicability of PRLT indices in psychiatric research and as diagnostic tools

Reliance on model-based and model-free control in obesity

Consuming more energy than is expended may reflect a failure of control over eating behaviour in obesity. Behavioural control arises from a balance between two dissociable strategies of reinforcement learning: model-free and model-based. We hypothesized that weight status relates to an imbalance in reliance on model-based and model-free control, and that it may do so in a linear or quadratic manner. To test this, 90 healthy participants in a wide BMI range (normal-weight (n=31), overweight (n=29), obese (n=30)) performed a sequential decision-making task. The primary analysis indicated that obese participants relied less on model-based control than overweight and normal-weight participants, with no difference between overweight and normal-weight participants. In line, secondary continuous analyses revealed a negative linear, but not quadratic, relationship between BMI and model-based control. Computational modelling of choice behaviour suggested that a mixture of both strategies was shifted towards less model-based control in obese participants. Furthermore, exploratory analyses of separate weights for model-free and model-based control showed stronger reliance on model-free control with increased BMI. Our findings suggest that obesity may indeed be related to an imbalance in behavioural control as expressed in a phenotype of less model-based control potentially resulting from enhanced reliance on model-free computations

Anodal tDCS over the medial prefrontal cortex enhances behavioral adaptation after punishments during reversal learning through increased updating of unchosen choice options

The medial prefrontal cortex (mPFC) is thought to be central for flexible behavioral adaptation. However, the causal relationship between mPFC activity and this behavior is incompletely understood. We investigated whether transcranial direct current stimulation (tDCS) over the mPFC alters flexible behavioral adaptation during reward-based decision-making, targeting Montreal Neurological Institute (MNI) coordinates X = -8, Y = 62, Z = 12, which has previously been associated with impaired behavioral adaptation in alcohol-dependent patients. Healthy human participants (n = 61) received either anodal (n = 30) or cathodal (n = 31) tDCS versus sham tDCS while performing a reversal learning task. To assess the mechanisms of reinforcement learning (RL) underlying our behavioral observations, we applied computational models that varied with respect to the updating of the unchosen choice option. We observed that anodal stimulation over the mPFC induced increased choice switching after punishments compared with sham stimulation, whereas cathodal stimulation showed no effect on participants' behavior compared with sham stimulation. RL revealed increased updating of the unchosen choice option under anodal as compared with sham stimulation, which accounted well for the increased tendency to switch after punishments. Our findings provide a potential model for tDCS interventions in conditions related to flexible behavioral adaptation, such as addiction

Modeling subjective relevance in schizophrenia and its relation to aberrant salience

In schizophrenia, increased aberrant salience to irrelevant events and reduced learning of relevant information may relate to an underlying deficit in relevance detection. So far, subjective estimates of relevance have not been probed in schizophrenia patients. The mechanisms underlying belief formation about relevance and their translation into decisions are unclear. Using novel computational methods, we investigated relevance detection during implicit learning in 42 schizophrenia patients and 42 healthy individuals. Participants underwent functional magnetic resonance imaging while detecting the outcomes in a learning task. These were preceded by cues differing in color and shape, which were either relevant or irrelevant for outcome prediction. We provided a novel definition of relevance based on Bayesian precision and modeled reaction times as a function of relevance weighted unsigned prediction errors (UPE). For aberrant salience, we assessed responses to subjectively irrelevant cue manifestations. Participants learned the contingencies and slowed down their responses following unexpected events. Model selection revealed that individuals inferred the relevance of cue features and used it for behavioral adaption to the relevant cue feature. Relevance weighted UPEs correlated with dorsal anterior cingulate cortex activation and hippocampus deactivation. In patients, the aberrant salience bias to subjectively task-irrelevant information was increased and correlated with decreased striatal UPE activation and increased negative symptoms. This study shows that relevance estimates based on Bayesian precision can be inferred from observed behavior. This underscores the importance of relevance detection as an underlying mechanism for behavioral adaptation in complex environments and enhances the understanding of aberrant salience in schizophrenia

Discontinuing atovaquone/proguanil prophylaxis ad-hoc post-exposure and during-travel dose-sparing prophylactic regimens against P. falciparum malaria: an update with pointers for future research

© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Background: Atovaquone/proguanil (AP) is a highly effective malaria chemoprophylaxis combination. According to current guidelines, AP is taken once daily during, and continued for seven days post exposure. A systematic review by Savelkoel et al. summarised data up to 2017 on abbreviated AP regimens, and concluded that discontinuing AP upon return may be effective, although the available data was insufficient to modify current recommendations. The same applies to other studies evaluating during-travel dose-sparing regimens. Methods: A literature search in Pubmed and Embase was performed including search terms related to AP prophylaxis and pharmacokinetics to search for recent studies on abbreviated AP regimens published since 2017. Results: Since the 2017 review, no new studies assessing discontinuing AP ad-hoc post-exposure prophylaxis have been published. Two new studies were identified assessing other abbreviated AP regimens; one investigated a twice-weekly AP regimen in 32 travellers, and one a three-day AP course in therapeutic dose (1000/400 mg) prior to exposure in 215 travellers. No malaria cases were detected in the study participants adhering to these regimens. Conclusions: Further research would be needed if the research question is considered of sufficient importance to facilitate evidence-based decision-making to modify current guidelines, as efficacy studies in travellers are fraught with confounders. We recommend human challenge trials to study abbreviated AP regimens pertaining to malaria chemoprophylaxis as they allow for rational, subject number, time- and cost-saving trial designs.info:eu-repo/semantics/publishedVersio

Lateral prefrontal model-based signatures are reduced in healthy individuals with high trait impulsivity

High impulsivity is an important risk factor for addiction with evidence from endophenotype studies. In addiction, behavioral control is shifted toward the habitual end. Habitual control can be described by retrospective updating of reward expectations in ‘model-free’ temporal-difference algorithms. Goal- directed control relies on the prospective consideration of actions and their outcomes, which can be captured by forward-planning ‘model-based’ algorithms. So far, no studies have examined behavioral and neural signatures of model- free and model-based control in healthy high-impulsive individuals. Fifty healthy participants were drawn from the upper and lower ends of 452 individuals, completing the Barratt Impulsiveness Scale. All participants performed a sequential decision-making task during functional magnetic resonance imaging (fMRI) and underwent structural MRI. Behavioral and fMRI data were analyzed by means of computational algorithms reflecting model-free and model-based control. Both groups did not differ regarding the balance of model-free and model-based control, but high-impulsive individuals showed a subtle but significant accentuation of model-free control alone. Right lateral prefrontal model-based signatures were reduced in high-impulsive individuals. Effects of smoking, drinking, general cognition or gray matter density did not account for the findings. Irrespectively of impulsivity, gray matter density in the left dorsolateral prefrontal cortex was positively associated with model-based control. The present study supports the idea that high levels of impulsivity are accompanied by behavioral and neural signatures in favor of model-free behavioral control. Behavioral results in healthy high-impulsive individuals were qualitatively different to findings in patients with the same task. The predictive relevance of these results remains an important target for future longitudinal studies

The 2009 L’Aquila (Central Italy) Seismic Sequence.

On April 6 (01:32 UTC) 2009 a MW 6.1 normal faulting earthquake struck the axial area of the Abruzzo region in Central Italy. The earthquake heavily damaged the city of L’Aquila and its surroundings, causing 308 casualties, 70,000 evacuees and incalculable losses to the cultural heritage. We present the geometry of the fault system composed by two main normal fault planes, reconstructed by means of seismicity distribution: almost 3000 events with ML≥1.9 occurred in the area during the 2009. The events have been located with a 1D velocity model we computed for the area by using data of the seismic sequence. The mainshock, located at around 9.3 km of depth beneath the town of L’Aquila, activated a 50° (+/- 3) SW-dipping and ~135° NW-trending normal fault with a length of about 16 km. The aftershocks activated the whole 10 km of the upper crust up to the surface. The geometry of the fault is coherent with the mapped San Demetrio-Paganica and Mt. Stabiata normal faults. The whole normal fault system that reached about 50 km of length by the end of December in the NW-trending direction, was activated within the first few days of the sequence when most of the energetic events occurred. The main shock fault plane was activated by a foreshock sequence culminated with a MW 4.0 on the 30th of March (13:38 UTC), showing extensional kinematic with a minor left lateral component. The second major structure, located to the north close to Campotosto village, is controlled by a MW 5.0 which occurred on the same day of the main shock (the 6th of April at 23:15 UTC) and by a MW 5.2 event (9th of April - 00:53 UTC). The fault plane shows a shallower dip angle with respect to the main fault plane, of about 35° with a tendency to flattening towards the deepest portion. Due to the lack of seismicity above 5 km depth, the connection between this structure and the mapped Monti della Laga fault is not straightforward. This northern segment is recognisable for about 12-14 km of length, always NW-trending and forming a right lateral step with the main fault plane. The result is a en-echelon system overlapping for about 6 km. Seismicity pattern also highlights the activation of numerous minor normal fault segments within the whole fault system. The deepest is located at around 13-15 km of depth, south of the L’Aquila mainshock, and it seems to be antithetic to the main fault plane

The 2009 L'Aquila (central Italy) seismic sequence

On April 6 (01:32 UTC) 2009 a MW 6.1 normal faulting earthquake struck the axial area of the Abruzzo region in central Italy. The earthquake heavily damaged the city of L’Aquila and its surroundings, causing 308 casualties, 70,000 evacuees and incalculable losses to the cultural heritage. We present the geometry of the fault system composed of two main normal fault planes, reconstructed by means of seismicity distribution: almost 3000 events with ML≥1.9 occurred in the area during 2009. The events have been located with a 1D velocity model we computed for the area by using data of the seismic sequence. The mainshock, located at around a 9.3 km depth beneath the town of L’Aquila, activated a 50° (+/- 3) SW-dipping and ~135° NW-trending normal fault with a length of about 16 km. The aftershocks activated the whole 10 km of the upper crust up to the surface. The geometry of the fault is coherent with the mapped San Demetrio-Paganica and Mt. Stabiata normal faults. The whole normal fault system that reached about 40 km of length by the end of December in the NW-trending direction, was activated within the first few days of the sequence when most of the energetic events occurred. The main shock fault plane was activated by a foreshock sequence that culminated with a MW 4.0 on March 30 (13:38 UTC), showing extensional kinematics with a minor left lateral component. The second major structure, located to the north close to Campotosto village, is controlled by an MW 5.0 event, which occurred on the same day of the main shock (April 6 at 23:15 UTC), and by an MW 5.2 event (April 9 at 00:53 UTC). The fault plane shows a shallower dip angle with respect to the main fault plane, of about 35° with a tendency to flattening towards the deepest portion. Due to the lack of seismicity above a 5 km depth, the connection between this structure and the mapped Monti della Laga fault is not straightforward. This northern segment is recognisable for about 12-14 km of length, always NW-trending and forming a right lateral step with the main fault plane. The result is a en-echelon system overlapping for about 6 km. The seismicity pattern also highlights the activation of numerous minor normal fault segments within the whole fault system. The deepest is located at around a 13-15 km depth, south of the L’Aquila mainshock, and it seems to be antithetic to the main fault plane

Release of copper-amended particles from micronized copper-pressure-treated wood during mechanical abrasion

Background: We investigated the particles released due to abrasion of wood surfaces pressure-treated with micronized copper azole (MCA) wood preservative and we gathered preliminary data on its in vitro cytotoxicity for lung cells. The data were compared with particles released after abrasion of untreated, water (0% MCA)-pressure-treated, chromated copper (CC)-pressure-treated wood, and varnished wood. Size, morphology, and composition of the released particles were analyzed. Results: Our results indicate that the abrasion of MCA-pressure-treated wood does not cause an additional release of nanoparticles from the unreacted copper (Cu) carbonate nanoparticles from of the MCA formulation. However, a small amount of released Cu was detected in the nanosized fraction of wood dust, which could penetrate the deep lungs. The acute cytotoxicity studies were performed on a human lung epithelial cell line and human macrophages derived from a monocytic cell line. These cell types are likely to encounter the released wood particles after inhalation. Conclusions: Our findings indicate that under the experimental conditions chosen, MCA does not pose a specific additional nano-risk, i.e. there is no additional release of nanoparticles and no specific nano-toxicity for lung epithelial cells and macrophages