Persisting inhibition biases efficient rule inference under uncertainty.

Introduction: Task set inhibition supports optimal switching among tasks by actively suppressing the interference from recently executed competing task sets. It is typically studied in cued task-switching paradigms where there is no uncertainty about the task set or rule to prepare for on each trial. While inhibition has been shown to influence the speed and the accuracy of task execution, affecting task set retrieval, preparation, or implementation in conditions of task set switching, it remains uninvestigated whether it also affects rule selection under uncertainty. Methods: We implemented an ad-hoc four-rule card sorting task and categorized the rules selected by participants after a rule shift according to the recency of their last usage. We included a measure of working memory capacity (WMC) to control for its involvement in the rule selection process. Results: Participants exhibited a reduced preference for recently abandoned rules than less recently abandoned ones. Furthermore, we found that such a preference was not associated with WMC. Discussion: The results suggest that decision-making processes underlying rule inference and selection may be influenced by task-set inhibition, configuring as a conflict adjustment mechanism to the sequential history of rules application.

Decision-Making and Risk-Propensity Changes during and after the COVID-19 Pandemic Lockdown.

The imposition of lockdowns during the COVID-19 pandemic placed individuals under conditions of environmental stress, threatening individual and collective wellbeing. This study aimed to investigate the temporal effects of isolation and confinement during and after the Italian lockdown on decision-making, risk propensity, and cognitive control processes. The present study covered almost the entire Italian lockdown period (each week from the end of March to mid-May 2020), plus a follow-up measure (September 2020). At each time-point, respondents completed online behavioral tasks, which involved measuring risk-propensity (Balloon Analogue Risk Task), decision-making (Iowa Gambling Task), and cognitive flexibility (Category Switch Task). They also filled in questionnaires regarding subjective stress and anxiety. The main findings showed that the decision-making abilities of the respondents were affected as the confinement progressed. Furthermore, individuals who were more subjectively impacted by the lockdown/isolation experience exhibited impaired decision-making, especially during the lockdown. The results of the study highlight that prolonged confinement may affect human decision making, and help understand individuals' misbehaviors during emergencies and develop effective countermeasures aimed at reducing the burden of the healthcare system.

Decision-Making and Abuse, What Relationship in Victims of Violence?

Gender-Based violence is a worldwide persisting phenomenon: during their lifetime, 30% of women have experienced sexual and/or physical violence. The literature has investigated for several years the association between abuse and possible psychiatric and psychological consequences which may occur even after many years. The most common consequences involve mood and stress disorders (e.g., depression and PTSD). These disorders seem to have secondary long-term effects, such as decision-making and cognitive function impairments. Therefore, the present literature synthesis aimed to investigate whether and how the decision-making capacities of individuals experiencing violence can change because of abuse. We conducted a thematic synthesis using PRISMA guidelines: through a double-blind procedure, 4599 studies were screened; a total of 46 studies were selected for full-text reading, which was reduced to 13 by excluding papers with a wrong focus. To better understand the results of the thematic synthesis, two main focuses have been identified: "leave or stay decision making" and "multifactorial dimensions of decision making". Results showed that decision-making is an important process in avoiding secondary victimization.

The long-lasting effects of early life adversities are sex dependent: The signature of miR-34a.

BACKGROUND: Exposure to early life adversities (ELA) can influence a plethora of biological mechanisms leading to stress-related disorders later in life through epigenetic mechanisms, such as microRNAs (miRs). MiR-34 is a critical modulator of stress response and stress-induced pathologies and a link between ELA and miR-34a has been reported. METHODS: Here using our well-established model of ELA (Repeated Cross Fostering) we investigate the behavioral long-term effects of ELA in male and female mice. We also assess basal and ELA-induced miR-34a expression in adult mice and investigate whether ELA affects the later miR-34a response to adult acute stress exposure across brain areas (medial preFrontal Cortex, Dorsal Raphe Nuclei) and peripheral organs (heart, plasma) in animals from both sexes. Finally, based on our previous data demonstrating the critical role of Dorsal Raphe Nuclei miR-34a expression in serotonin (5-HT) transmission, we also investigated prefrontal-accumbal 5-HT outflow induced by acute stress exposure in ELA and Control females by in vivo intracerebral microdialysis. RESULTS: ELA not just induces a depressive-like state as well as enduring changes in miR-34a expression, but also alters miR-34a expression in response to adult acute stress exclusively in females. Finally, altered DRN miR-34a expression is associated with prefrontal-accumbal 5-HT release under acute stress exposure in females. LIMITATIONS: Translational study on humans is necessary to verify the results obtained in our animal models of ELA-induced depression. CONCLUSIONS: This is the first evidence showing long-lasting sex related effects of ELA on brain and peripheral miR-34a expression levels in an animal model of depression-like phenotype.

Perception of the temporal order of digits during rapid serial visual presentation is influenced by their ordinality.

Psychological research has extensively shown that individuals are limited in their ability to process environmental information temporally. In a rapid serial visual presentation, the ability to identify the second of two targets presented in close succession among distractors is usually impaired, a phenomenon known as attentional blink (AB). Paradoxically, when the second target immediately succeeds the first one (lag 1), such an ability is relatively spared, but individuals are more prone to misreport their correct temporal succession. Competitive mechanisms based on prior entry and perceptual integration processes have been suggested to account for the apparent loss of temporal information. We report findings from four experiments, showing that, once identified, categorical dimensions of the stimuli used as targets (here, the ordinality of numbers) may guide the perception and the resulting report of their temporal order. Specifically, at lag 1 individuals more frequently encode the two digits in ascending order. Such a biased regularization may represent another possible outcome of the failure in temporal segregation observed at lag 1, indicating that a mechanism based on prior entry is not generalizable in explaining order reversals. The kind of stimuli chosen as targets in AB paradigms can activate high-level categorical dimensions capable of influencing the performance on this task.

The impact of stimulus format on task inhibition during task switching.

Switching between competing tasks is supported by active inhibition of the preceding task. The level of task stimulus processing at which interference between competing tasks must occur for inhibition to be recruited is still unclear. Here, we investigated whether inhibition is recruited by task conflict occurring at an early or late (semantic) stage of task stimulus processing by dissociating the task stimulus format from its meaning. In two experiments, participants performed three different numerical judgment tasks on numerical stimuli that could be presented as digits or number words (e.g., "6" or "six") in a cued task-switching procedure. The effects of the change of stimulus format for the inhibition of the previous task were investigated and assessed by the N-2 task repetition cost, an index of the extent to which task representations are inhibited. The N-2 task repetition cost observed in the same stimulus format condition disappeared when target stimuli on task N-1 were presented in a different format from stimuli of task N-2 and N. This occurred both when the format changed from digits to number words stimuli (Experiment 1) as well as when it changed from number words to digits stimuli (Experiment 2). Results indicated that task set inhibition is recruited very early during the stimulus processing stage. They also provided evidence that task inhibition is not tied to task preparation processes but operates as a reactive, rather than proactive mechanism of conflict resolution.

Changes in sleep pattern and dream activity across and after the COVID-19 lockdown in Italy: A longitudinal observational study.

A large body of evidence has documented the impact of the global COVID-19 outbreak - and especially the lockdown period - on sleep quality and quantity. Here, we present the first Italian longitudinal study on sleep and COVID-19 considering four different time points collected during lockdown (from 29 March 2020 to 3 May 2020) and a subsequent follow-up period (October 2020). We used an online survey to collect socio-demographic and COVID-19 related information. Subjects were also asked to complete a sleep diary at each time point of the study. Our longitudinal sample included 147 participants. Statistical comparison across time intervals showed remarkable changes in sleep patterns during and after the lockdown. In particular, during lockdown we observed longer sleep latency, less ease of falling asleep, a higher total bedtime, and a lower dream frequency. The week-by-week evaluation described relatively stable patterns in the observed measures during the lockdown period, except for dream frequency, affected by a rapid increase in the early phase of lockdown. Our findings are in line with the current literature. Furthermore, the prospective longitudinal investigation comprising several time points offered the possibility of (a) observing the temporal dynamics and the different entities of such changes over time, and (b) reducing the typical memory bias for these studies.

Early life adversity affecting the attachment bond alters ventral tegmental area transcriptomic patterning and behavior almost exclusively in female mice.

Early life experiences that affect the attachment bond formation can alter developmental trajectories and result in pathological outcomes in a sex-related manner. However, the molecular basis of sex differences is quite unknown. The dopaminergic system originating from the ventral tegmental area has been proposed to be a key mediator of this process. Here we exploited a murine model of early adversity (Repeated Cross Fostering, RCF) to test how interfering with the attachment bond formation affects the VTA-related functions in a sex-specific manner. Through a comprehensive behavioral screening, within the NiH RDoC framework, and by next-generation RNA-Seq experiments, we analyzed the long-lasting effect of RCF on behavioral and transcriptional profiles related to the VTA, across two different inbred strains of mouse in both sexes. We found that RCF impacted to an extremely greater extent VTA-related behaviors in females than in males and this result mirrored the transcriptional alterations in the VTA that were almost exclusively observed in females. The sexual dimorphism was conserved across two different inbred strains in spite of their divergent long lasting consequences of RCF exposure. Our data suggest that to be female primes a sub-set of genes to respond to early environmental perturbations. This is, to the best of our knowledge, the first evidence of an almost exclusive effect of early life experiences on females, thus mirroring the extremely stronger impact of precocious aversive events reported in clinical studies in women.

"Stay at Home" in Italy during the COVID-19 Outbreak: A Longitudinal Study on Individual Well-Being among Different Age Groups.

The restrictions imposed by the Italian government because of the coronavirus outbreak have been shown to be demanding on the Italian population. Data were collected at four different time points from 29 March 2020 to 3 May 2020 and during the final follow-up survey on 12 October 2020. In the present study, we provided longitudinal evidence on the relationship between the lockdown and mental health dimensions, such as emotional state, perceived stress, and time perspective, for three age groups. The results allowed us to observe their psychological status from different perspectives at five different time points. Notably, a negative effect of the lockdown individual well-beings emerged as a trend, and differences in individual adaptation strategies to a prolonged stressful situation were observed at the follow-up. Indeed, pairwise comparisons between age groups showed that the young adult group (18-23 years old) seemed to be the most psychologically affected by the lockdown. The findings are discussed according to the most recent literature on the topic. To the best of our knowledge, this is one of the first longitudinal studies carried out in Italy concerning the general psychological effects of the coronavirus lockdown.

COVID-19 lockdown and poor sleep quality: Not the whole story.

A growing body of evidence consistently describes the side-effects of coronavirus disease 2019 lockdown on mental health and sleep quality. We conducted a longitudinal web-based survey of 217 Italian participants at two time points: lockdown and subsequent follow-up. To thoroughly investigate lockdown-related changes in sleep quality, we first evaluated variations in overall sleep quality assessed by the Pittsburgh Sleep Quality Index. We then examined sleep changes in specific components of sleep quality. Results revealed a clear dissociation of sleep effects, as a function of the specific domain considered, with longer sleep latency, worse sleep efficiency, and massive sleep medication use during forced confinement. On the other hand, we simultaneously observed an increased sleep duration and better daytime functioning. Our present findings highlight the importance of an accurate examination of sleep quality during lockdown, as the effects were not uniform across populations and different sleep domains.

Different semantic and affective meaning of the words associated to physical and social pain in cancer patients on early palliative/supportive care and in healthy, pain-free individuals.

Early palliative/supportive care (ePSC) is a medical intervention focused on patient's needs, that integrates standard oncological treatment, shortly after a diagnosis of advanced/metastatic cancer. ePSC improves the appropriate management of cancer pain. Understanding the semantic and emotional impact of the words used by patients to describe their pain may further improve its assessment in the ePSC setting. Psycholinguistics assumes that the semantic and affective properties of words affect the ease by which they are processed and comprehended. Therefore, in this cross-sectional survey study we collected normative data about the semantic and affective properties of words associated to physical and social pain, in order to investigate how patients with cancer pain on ePSC process them compared to healthy, pain-free individuals. One hundred ninety patients and 124 matched controls rated the Familiarity, Valence, Arousal, Pain-relatedness, Intensity, and Unpleasantness of 94 words expressing physical and social pain. Descriptive and inferential statistics were performed on ratings in order to unveil patients' semantic and affective representation of pain and compare it with those from controls. Possible effects of variables associated to the illness experience were also tested. Both groups perceived the words conveying social pain as more negative and pain-related than those expressing physical pain, confirming previous evidence of social pain described as worse than physical pain. Patients rated pain words as less negative, less pain-related, and conveying a lower intense and unpleasant pain than controls, suggesting either an adaptation to the pain experience or the role played by ePSC in improving patients' ability to cope with it. This exploratory study suggests that a chronic pain experience as the one experienced by cancer patients on ePSC affects the semantic and affective representation of pain words.

Sleep in Isolated, Confined, and Extreme (ICE): A Review on the Different Factors Affecting Human Sleep in ICE.

The recently renewed focus on the human exploration of outer space has boosted the interest toward a variety of questions regarding health of astronauts and cosmonauts. Among the others, sleep has traditionally been considered a central issue. To extend the research chances, human sleep alterations have been investigated in several analog environments, called ICEs (Isolated, Confined, and Extreme). ICEs share different features with the spaceflight itself and have been implemented in natural facilities and artificial simulations. The current paper presents a systematic review of research findings on sleep disturbances in ICEs. We looked for evidence from studies run in polar settings (mostly Antarctica) during space missions, Head-Down Bed-Rest protocols, simulations, and in a few ICE-resembling settings such as caves and submarines. Even though research has shown that sleep can be widely affected in ICEs, mostly evidencing general and non-specific changes in REM and SWS sleep, results show a very blurred picture, often with contradictory findings. The variable coexistence of the many factors characterizing the ICE environments (such as isolation and confinement, microgravity, circadian disentrainment, hypoxia, noise levels, and radiations) does not provide a clear indication of what role is played by each factor per se or in association one with each other in determining the pattern observed, and how. Most importantly, a number of methodological limitations contribute immensely to the unclear pattern of results reported in the literature. Among them, small sample sizes, small effect sizes, and large variability among experimental conditions, protocols, and measurements make it difficult to draw hints about whether sleep alterations in ICEs do exist due to the specific environmental characteristics, and which of them plays a major role. More systematic and cross-settings research is needed to address the mechanisms underlying the sleep alterations in ICE environments and possibly develop appropriate countermeasures to be used during long-term space missions.

Decreased inhibitory control after partial sleep deprivation in individuals reporting binge eating: preliminary findings.

BACKGROUND: Poor executive functions are associated with dysregulated eating and greater caloric intake in healthy samples. In parallel, findings suggested that sleep deprivation impairs executive functions. METHODS: We investigated whether partial sleep deprivation impairs executive functions in individuals reporting binge eating (BE, N = 14) and healthy controls (C, N = 13). Switch cost and backward inhibition were measured using the Task Switching Paradigm after a habitual night of sleep and after a night of partial sleep deprivation. RESULTS: Results showed a Night by Group interaction on the backward inhibition. The two groups differed in the habitual night, evidencing higher inhibitory control in BE compared to C. Additionally, after partial sleep deprivation, compared to the habitual night, backward inhibition decreased in BE group. This preliminary study was the first to explore the impact of sleep deprivation on executive functions in participants reporting binge eating and healthy controls, thus highlighting their potential role in influencing eating behavior.

RISC RNA sequencing in the Dorsal Raphè reveals microRNAs regulatory activities associated with behavioral and functional adaptations to chronic stress.

The Dorsal Raphe (DR) is the primary source of serotonergic input in the brain and a center for the homeostatic maintenance of the serotonergic tone. Under repeated stimulation, it can undergo adaptive modifications that alter serotonergic neurotransmission, which can lead to behavioral dysfunction. Post-transcriptional regulation by microRNAs is implicated in these adaptations. However, a global microRNA/target network effect on the DR neuroplasticity has yet to be elucidated. Here we investigate the microRNAs/mRNAs regulatory activity in the mouse DR after a chronic stress experience. First, we assessed the behavioral consequences of repeated restraint stress exposure and the functional adaptations of the DR by measuring the change in acute stress-induced serotonin release. Then, through next generation RNA-Seq of Argonaute2-bound RNA (RISC-Seq) we identified microRNAs and their targets that are associated to the RISC complex of the DR in unstressed and stressed mice. We mapped the potential microRNA/mRNA network within the stress-altered transcripts, uncovering new interactions that contribute to the chronic stress-induced DR modifications.

Out with the Old and in with the New: the Contribution of Prefrontal and Cerebellar Areas to Backward Inhibition.

The inhibitory mechanism named backward inhibition (BI) counteracts interference of previous tasks supporting task switching. For instance, if task set A is inhibited when switching to task B, then it should take longer to immediately return to task set A (as occurring in an ABA sequence), as compared to a task set that has not been just inhibited (as occurring in a CBA sequence), because extra time will be needed to overcome the inhibition of task set A.The evidenced prefrontal and cerebellar role in inhibitory control suggests their involvement even in BI. Here, for the first time, we modulated the excitability of multiple brain sites (right presupplementary motor area (pre-SMA), left and right cerebellar hemispheres) through continuous theta burst stimulation (cTBS) in a valuable sham-controlled order-balanced within-subject experimental design in healthy individuals performing two domain-selective (verbal and spatial) task-switching paradigms. Verbal BI was abolished by prefrontal or cerebellar stimulations through opposite alterations of the basal pattern: cTBS on pre-SMA increased CBA reaction times, disclosing the current prefrontal inhibition of any interfering old task. Conversely, cerebellar cTBS decreased ABA reaction times, disclosing the current cerebellar recognition of sequences in which it is necessary to overcome previously inhibited events.

Anodal tDCS over the right parietal but not frontal cortex enhances the ability to overcome task set inhibition during task switching.

Switching between tasks requires individuals to inhibit mental representations of the previous task demands and to activate representations of the new task demands. The inhibition of the executed task remains active for a while so that when the inhibited task set must be re-activated shortly after, the need to overcome residual task set inhibition leads to behavioral costs. In a sham-controlled balanced-order within-subjects experimental design we investigated whether applying right anodal/left cathodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal or parietal cortex modulated the ability to overcome persistent task inhibition during task switching. Results showed that right anodal/left cathodal tDCS over the parietal cortex improves performance selectively when switching back to a recently inhibited task that requires previous inhibition to be overcome. Right Anodal/left cathodal tDCS over the prefrontal cortex improves performance during task switching in general, either when re-engaging in a inhibited task or when engaging in a non-inhibited task. Results suggest a different contribution of prefrontal and parietal regions to task switching, with parietal cortex being selectively involved in overcoming persistent task inhibition and prefrontal cortex being more generally involved in the control of task set during task switching.

MicroRNA-34a Regulates the Depression-like Behavior in Mice by Modulating the Expression of Target Genes in the Dorsal Raphè.

Chronic stress exposure is known to increase vulnerability to the expression of psychiatric disorders, such as depression. Clinical and preclinical evidences support the involvement of the microRNA-34 family in stress-related psychiatric conditions and in the regulation of stress responses. However, the mechanism and the multiple targets by which the microRNA-34 family can affect the stress response and stress-related behavioral alteration are not fully known. Here, with the aid of constitutive and conditional genetic strategy, we examined the role of microRNA-34 family in the expression of depression-like phenotype in mice induced by chronic stress exposure, and we identified their "in vivo" targets during the stressful challenge. We found that microRNA-34a, under chronic stress, is significantly up-regulated in the mouse raphe nuclei, where its recruitment is necessary to induce depression-like behavioral alterations and impact the function of the serotonergic system. Moreover, by next-generation RNA-seq of Ago-2-bound mRNAs, we identified genes that are targeted by microRNA-34a in response to chronic stress and that are likely to mediate its effects.

Bilateral Theta Transcranial Alternating Current Stimulation (tACS) Modulates EEG Activity: When tACS Works Awake It Also Works Asleep.

PURPOSE: Recent studies demonstrate that 5-Hz bilateral transcranial alternating current stimulation (θ-tACS) on fronto-temporal areas affects resting EEG enhancing cortical synchronization, but it does not affect subjective sleepiness. This dissociation raises questions on the resemblance of this effect to the physiological falling asleep process. The current study aimed to evaluate the ability of fronto-temporal θ-tACS to promote sleep. SUBJECTS AND METHODS: Twenty subjects (10 F/10 M; mean age: 24.60 ± 2.9 y) participated in a single-blind study consisting of two within-subject sessions (active/sham), one week apart in counterbalanced order. Stimulation effects on EEG were assessed during wake and post-stimulation nap. The final sample included participants who fell asleep in both sessions (n=17). RESULTS: Group analyses on the whole sample reported no θ-tACS effects on subjective sleepiness and sleep measures, while a different scenario came to light by analysing data of responders to the stimulation (ie, subjects actually showing the expected increase of theta activity in the wake EEG after the θ-tACS, n=7). Responders reported a significant increase in subjective sleepiness during wakefulness after the active stimulation as compared to the sham. Moreover, the sleep after the θ-tACS compared to sham in this sub-group showed: (1) greater slow-wave activity (SWA); (2) SWA time-course revealing increases much larger as closer to the sleep onset; (3) stimulation-induced changes in SWA during sleep topographically associated to those in theta activity during wake. CONCLUSION: Subjects who show the expected changes during wake after the stimulation also had a consistent pattern of changes during sleep. The enhancement of cortical synchronization by θ-tACS during wakefulness actually corresponds to increased sleep pressure, but it occurs only in some individuals. Thus, θ-tACS can enhance sleep, although individual factors to be further investigated affect the actual responsiveness to this treatment.

Access to consciousness of briefly presented visual events is modulated by transcranial direct current stimulation of left dorsolateral prefrontal cortex.

Adaptive behaviour requires the ability to process goal-relevant events at the expense of irrelevant ones. However, perception of a relevant visual event can transiently preclude access to consciousness of subsequent events - a phenomenon called attentional blink (AB). Here we investigated involvement of the left dorsolateral prefrontal cortex (DLPFC) in conscious access, by using transcranial direct current stimulation (tDCS) to potentiate or reduce neural excitability in the context of an AB task. In a sham-controlled experimental design, we applied between groups anodal or cathodal tDCS over the left DLPFC, and examined whether this stimulation modulated the proportion of stimuli that were consciously reported during the AB period. We found that tDCS over the left DLPFC affected the proportion of consciously perceived target stimuli. Moreover, anodal and cathodal tDCS had opposing effects, and exhibited different temporal patterns. Anodal stimulation attenuated the AB, enhancing conscious report earlier in the AB period. Cathodal stimulation accentuated the AB, reducing conscious report later in the AB period. These findings support the notion that the DLPFC plays a role in facilitating information transition from the unconscious to the conscious stage of processing.

Memory for positional movements as a component of the visuospatial working memory.

Though the Corsi block-tapping task (CBT) is widely used for assessing visuospatial memory, information about what exactly it measures is still debated. We investigated such issue by observing how motor, visual, and spatial secondary tasks affect the performance on three versions of the CBT. Results showed a double dissociation pattern, wherein two motor secondary tasks had larger effects when the CBT was administered by the examiner tapping on the blocks. A spatial secondary task had larger effects when the CBT was administered by automatically illuminating the blocks. Finally, a visual secondary task had larger effects on a two-dimensional, computerized version of the CBT. These findings suggest that memory for movements plays a relevant role in the CBT, and are especially relevant due to their implications for assessment of brain-damaged patients, besides providing further evidence of a fractionation of visuospatial memory into multiple subcomponents.