Pathological Behavior Research Articles

A Novel Compound Ligusticum Cycloprolactam Alleviates Neuroinflammation After Ischemic Stroke via the FPR1/NLRP3 Signaling Axis.

Microglia/macrophages, as pivotal immune cells in the central nervous system (CNS), play a critical role in neuroinflammation associated with ischemic brain injury. Targeting their activation through pharmacological interventions represents a promising strategy to alleviate neurological deficits, thereby harboring significant implications for the prevention and treatment of ischemic stroke. Ligusticum cycloprolactam (LIGc), a novel monomeric derivative of traditional Chinese medicine, has shown potential as a therapeutic agent; however, its specific role in cerebral ischemic injury remains unclear. In vitro experiments utilized lipopolysaccharide (LPS)-induced inflammation models of RAW264.7 cells and primary mouse microglia. Invivo studies employed LPS-induced neuroinflammation models in mice and a transient middle cerebral artery occlusion (tMCAO) mouse model to evaluate the impact of LIGc on neuroinflammation and microglia/macrophage phenotypic alterations. Further elucidation of the molecular mechanisms underlying these effects was achieved through RNA-Seq analyses. LIGc exhibited the capacity to attenuate LPS-induced production of pro-inflammatory markers in macrophages and microglia, facilitating their transition to an anti-inflammatory phenotype. In models of LPS-induced neuroinflammation and tMCAO, LIGc ameliorated pathological behaviors and neurological deficits while mitigating brain inflammation. RNA-seq analyses revealed formyl peptide receptor 1 (FPR1) as a critical mediator of LIGc's effects. Specifically, FPR1 enhances the pro-inflammatory phenotype of microglia/macrophages and inhibits their anti-inflammatory response by upregulating NLR family pyrin domain protein 3 (NLRP3) inflammasomes, thus aggravating inflammatory processes. Conversely, LIGc exerts anti-inflammatory effects by downregulating the FPR1/NLRP3 signaling axis. Furthermore, FPR1 overexpression or NLRP3 agonists reversed the effects of LIGc observed in this study. Our findings suggest that LIGc holds promise in improving ischemic brain injury and neuroinflammation through modulation of microglia/macrophage polarization. Mechanistically, LIGc attenuates the pro-inflammatory phenotype and promotes the anti-inflammatory phenotype by targeting the FPR1/NLRP3 signaling pathway, ultimately reducing inflammatory responses and mitigating neurological damage.

The MRL Model: A Valuable Tool in Studies of Autoimmunity-Brain Interactions.

The link between systemic autoimmunity, brain pathology, and aberrant behavior is still largely unexplored field of biomedical science. Accumulating evidence points to causal relationships between immune factors, neurodegeneration, and neuropsychiatric manifestations. By documenting autoimmunity-associated neuronal degeneration and cytotoxicity of the cerebrospinal fluid from disease-affected subjects, the murine MRL model has shown high validity in revealing principal pathogenic circuits. In addition, unlike any other autoimmune strain, MRL mice produce antibodies commonly found in patients suffering from lupus and other autoimmune disorders. This review highlights the importance of the MRL model as a useful preparation for understanding the links between the immune system and brain function.

EPID-20. PRIMARY INTRAMEDULLARY PILOMYXOID ASTROCYTOMA OF SPINAL CORD (PIPASC): A SYSTEMATIC REVIEW OF CASE REPORTS AND CASE SERIES OF TWO DECADES

Abstract BACKGROUND Pilomyxoid Astrocytoma (PMA), new variant of pilocytic astrocytoma, is more aggressive and relatively rare, mostly seen in children and commonly found in brain. Primary intramedullary pilomyxoid astrocytoma of spinal cord (PIPASC) is extremely rare. The distinct aggressive and pathological behavior, poor prognosis and the diversity in response to various treatment modalities makes the PIPASC an oncologic enigma. We aim to evaluate the clinical manifestations, histopathologic spectrum and onco-surgical management of this neoplasm. MATERIALS AND METHODS After an extensive literature search using PubMed Central and Google Scholar, eight case reports and one case series of patients with spinal PA were retrieved and included using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines without applying any filter of time, study type or place. Case presentations of 12 patients were analyzed in this review. RESULTS Pediatric preponderance of the neoplasm (75%) with the mean age of 7.90 ± 4.51 years was noted. Sensory deficits and scoliotic deformity were the most common presenting symptom and sign in 83.33% and 33.33% of patients, respectively. Thoracic spine (50%) was most commonly affected region. MRI showed the most consistent findings of cord compression in 100% cases and the lesion appeared hypointense on T1- weighted images (T1WI) and hyperintense on T2-weighted images (33.33%). The average post treatment survival duration was found to be more than 2 years. CONCLUSIONS Occurrence of PIPASC among pediatric population is rare. They have possibility of extraneural metastasis, can differentiate into more malignant glioma and get recurrent due to which they require a long-term follow-up of the patients. Further studies are required to investigate the utility of chemotherapy and radiotherapy in its management.

TRANCE STEREOTYPIES IN HUMAN AND PRIMATE PANTOMIMICRY

The authors reviewed and analysed Russian and foreign experimental studies on pantomimic stereotypes. Initially, stereotypical behaviuor was negatively evaluated. Modern research considers adaptive functions and possibilities of self-stimulation as a way to harmonise emotional and mental state. A comparative analysis of circular, pendulum and diagonal movements in children and Old World monkeys was conducted using an ethological approach to the study of behavioural patterns. Human observations were conducted in the psychoneurological department of Silischeva Astrakhan Regional Children’s Clinical Hospital, 40 preschool children with mental dysontogenesis participated. Five laboratory macaques and a family of hamadryas baboons kept in an aviary with homologous kinesics were observed in Sukhumi nursery. According to the authors’ team, walking (running) in a circle and diagonally, swinging the body “right-to-leftˮ in the pantomimic production of children and monkeys are associated with self-stimulation of an altered state of consciousness. Trance stereotypes divert attention from external stressors and stimuli and harmonise mental homeostasis. The study may be of interest to anthropologists, primatologists, specialists in the study of the psyche and pathological behaviour of animals and Homo sapiens.

A promising drug repurposing approach for Alzheimer's treatment: Givinostat improves cognitive behavior and pathological features in APP/PS1 mice

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by memory loss, speech and motor defects, personality changes, and psychological disorders. The exact cause of AD remains unclear. Current treatments focus on maintaining neurotransmitter levels or targeting β-amyloid (Aβ) protein, but these only alleviate symptoms and do not reverse the disease. Developing new drugs is time-consuming, costly, and has a high failure rate. Utilizing multi-omics for drug repositioning has emerged as a new strategy. Based on transcriptomic perturbation data of over 40,000 drugs in human cells from the LINCS-L1000 database, our study employed the Jaccard index and hypergeometric distribution test for reverse transcriptional feature matching analysis, identifying Givinostat as a potential treatment for AD. Our research found that Givinostat improved cognitive behavior and brain pathology in models and enhanced hippocampal synaptic plasticity. Transcriptome sequencing revealed increased expression of mitochondrial respiratory chain complex proteins in the brains of APP/PS1 mice after Givinostat treatment. Functionally, Givinostat restored mitochondrial membrane potential, reduced reactive oxygen species, and increased ATP content in Aβ-induced HT22 cells. Additionally, it improved mitochondrial morphology and quantity in the hippocampus of APP/PS1 mice and enhanced brain glucose metabolic activity. These effects are linked to Givinostat promoting mitochondrial biogenesis and improving mitochondrial function. In summary, Givinostat offers a promising new strategy for AD treatment by targeting mitochondrial dysfunction.

Implementations of sign- and goal-tracking behavior in humans: A scoping review.

Animal research has identified two major phenotypes in the tendency to attribute incentive salience to a reward-associated cue. Individuals called "sign-trackers" (STs) preferentially approach the cue, assigning both predictive and incentive values to it. In contrast, individuals called "goal-trackers" (GTs) preferentially approach the location of the upcoming reward, assigning only a predictive value to the cue. The ST/GT model has been shown to be relevant to understanding addiction vulnerability and other pathological behaviors in animals. Therefore, recent studies tried to implement this animal model in the human population. This scoping review aimed to identify and map evidence of human sign- and goal-tracking. Studies that explicitly measured human sign- and goal-tracking or related phenomena (e.g., attentional bias induced by reward-related cues), using paradigms in line with the animal model, were eligible for this review. We searched for published, unpublished, and gray literature (PhD theses, posters, conference papers) through the following databases: MEDLINE, Scopus, PsycINFO, Embase, OSF, and Google Scholar. The JBI scoping review methodology was adopted. Screening and extraction were carried out by three reviewers, in pairs. A total of 48 studies were identified. These studies used various experimental paradigms and used the term "sign-tracking" inconsistently, sometimes implicitly or not at all. We conclude that the literature on human sign-tracking is very heterogeneous on many levels. Overall, evidence supports the existence of sign- and goal-tracking behaviors in humans, although further validated research is crucially needed.

Maternal exploitation: impact of maternal food snatching behaviour on the growth of their offspring in Japanese macaques.

There is little information on maternal behaviour that deprives offspring of food, but some Japanese macaque, Macaca fuscata, mothers have been observed to snatch food from their offspring and eat it. This study investigated maternal food snatching behaviour (MFSB) and its impact on the growth of their offspring in provisioned, free-ranging Japanese macaques. The amount of food a mother snatched from her offspring was estimated to be 51.2% by dry weight compared to the amount of solid food an infant of the same age took in. Body mass growth of affected infants indicated a below-average mass gain. The study suggests that MFSB might be a pathological behaviour and provides the first detailed account of parental exploitation in animals.

Body, image, and digital technology in adolescence and contemporary youth culture.

The physical, psychological and social changes that occur during adolescence constitute a physiological crisis that is necessary for development and growth. The establishment of a suitable "self-image" is important for facilitating harmonious psychophysical development during this time. In the current era, digital technology (DT) serves as an extraordinary means of communication for young people, who make significant use of images as a mode of expression. Accordingly, there is growing interest in the relationship between physical development, self-image and use of DT. A review of the published literature on the topic was carried out in April 2024. Fourteen studies (n = 14) were inclused from search of electronic databases such as PubMed, CINAHL, PsycInfo, MedLine, and Cochrane Library. The aim of this study is to explore the influence of (DT) on cultural models of adolescent body image, and how this "social" culture can affect wellbeing and development. It was considered that the rise of DT and social media (SM) emphasized in young people the culture of appearance, adherence to ideal models (thinness ideal) and social comparison at an unprecedented level. It was estimated that the digital mechanism works on the adolescent's vulnerability and stimulates the desire for experimentation and amplifies cultural beliefs that expose the young to deviant or pathological behaviors on the body. The use of digital images emphasizes the perception of self by making it more real and alive but empty of content. Our framework highlights that the adolescent can defend himself if he leaves the homologation that the SM condition, regains his own experiences, fill with emotional content and real life the images and the representation of the body.

Severity levels of anorexia nervosa and atypical anorexia nervosa in a Korean cohort.

Despite its potential for informing tailored treatments, the severity of eating disorders (EDs) lacks clear conceptualisation. The present retrospective cohort study examined the clinical validity and utility of severity specifiers for anorexia nervosa (AN) and atypical AN in a Korean population. Data from 696 Korean outpatients with AN or atypical AN were analysed. Severity criteria for AN from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the Medical Emergencies in Eating Disorders (MEED) guidance were used. Severity criteria applied for atypical AN were the frequency of intermittent fasting (ED Diagnostic Scale item 17), Eating Disorder Examination Questionnaire global scores, and the degree of weight suppression. Prevalence of extreme cases of AN in our cohort was higher than in Western populations in previous studies. MEED guidance further subclassified extreme AN, revealing distinct psychopathological profiles across severity levels. The proposed severity classification for atypical AN based on the weight loss behaviour of intermittent fasting showed merit. These findings suggest a potential need for a more nuanced AN severity classification that better represents severe medical aspects and encompasses cultural and ethnic diversities. In atypical AN, there is a need to examine severity indices measuring pathological behaviours.

Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming.

Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 12, and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety, and other behavioral features. Mice treated with vehicle (n = 18) manifested a 118.71 ± 95.96% increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60 ± 17.90% in mice treated with psilocybin (n = 16) and by 19.20 ± 20.05% in mice treated with psychedelic mushroom extract (n = 16) (p = 0.001 for effect of time; p = 0.0001 for time × treatment interaction). Five mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n = 12) and psychedelic mushroom extract (n = 13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study. Prepared with BioRender ( https://www.biorender.com/ ).

Early Adversity Affects Cerebellar Structure and Function-A Systematic Review of Human and Animal Studies.

Recent research has highlighted cerebellar involvement in cognition and several psychiatric conditions such as mood and anxiety disorders and schizophrenia. Attention-deficit/hyperactivity disorder and autism spectrum disorder have been linked to reduced cerebellar volume as well. Cerebellar alterations are frequently present after early adversity in humans and animals, but a systematic integration of results is lacking. To this end, a systematic literature search was conducted in PubMed, Web of Science, and EBSCO databases using the keywords "early adversity OR early life stress" AND "cerebellum OR cerebellar." A total of 45 publications met the inclusion criteria: 25 studies investigated human subjects and 20 reported results from animal models. Findings in healthy subjects show bilateral volume reduction and decreased functional connectivity within the cerebellum and between the cerebellum and frontal regions after adversity throughout life, especially when adversity was assessed with the Childhood Trauma Questionnaire. In clinical populations, adults demonstrate increased cerebellar volume and functional connectivity after adversity, whereas pediatric patients show reduced cerebellar volume. Animal findings reveal cerebellar alterations without necessarily co-occurring pathological behavior, highlighting alterations in stress hormone receptor levels, cell density, and neuroinflammation markers. Cerebellar alterations after early adversity are robust findings across human and animal studies and occur independent of clinical symptoms.

Adaptive control of cardiac rhythms

Cardiac rhythms are related to heart electrical activity, being the essential aspect of the cardiovascular physiology. Usually, these rhythms are represented by electrocardiograms (ECGs) that are useful to detect cardiac pathologies. Essentially, the heart activity starts in the sinoatrial node (SA) node, the natural pacemaker, propagating to the atrioventricular node (AV), and finally reaching the His-Purkinje complex (HP). This paper investigates the control of cardiac rhythms in order to induce normal rhythms from pathological responses. A mathematical model that presents close agreement with experimental measurements is employed to represent the heart functioning. The adopted model comprises a network of three nonlinear oscillators that represent each one of the cardiac nodes, connected by delayed couplings. The pathological behavior is induced by an external stimulus in the SA node. An adaptive controller is proposed acting in the SA node considering an strategy based on the signal obtained by the natural pacemaker and its regularization. The incorporation of adaptive compensation in a Lyapunov-based control scheme allows the compensation for the unknown dynamics. The controller ability to deal with interpatient variability is evaluated by assuming that the heart model is not available to the controller design, being used only in the simulator to assess the control performance. Results show that the adaptive term can reduce the control effort by around 3% while reducing the tracking error by 20%, when compared to the conventional feedback approach. Additionally, the controller can avoid abnormal rhythms, turning the ECG closer to the expected normal behavior and preventing critical cardiac responses. Therefore, this work demonstrates that an adaptive controller can be used to regulate the ECG signal without prior information about the system and disregarding inter- and intrapatient variability.

12210 Prognostic Determinants of Aggressive Histology Papillary Thyroid Carcinoma: A Pathway to Personalized Treatment

Abstract Disclosure: M. Almaghrabi: None. G. Sindi: None. H. Sasseville: None. S. Radi: None. M. Tamilia: None. Background: Papillary thyroid carcinoma (PTC), the most common form of thyroid malignancy, generally presents with a favorable prognosis. However, aggressive variants of Papillary Thyroid Carcinoma (AV-PTC), such as tall cell, hobnail, columnar, and solid forms, pose significant challenges in prognosis and treatment, due to their unique pathological behaviors and increased risks of recurrence and mortality. The management debate for AV-PTC without invasive characteristics is ongoing. It's argued that aggressive histology alone should not dictate the clinical management of PTC patients lacking aggressive features. Objectives: This study aims to investigate the prognostic impact of invasive features in AV-PTC and their implications on clinical outcomes. Methods: We conducted a retrospective cohort study of AV-PTC patients treated from 2008 to 2022, analyzing medical records to identify prognostic factors related to disease recurrence, persistence, and overall survival. This involved distinguishing between groups with invasive characteristics—identified as one of the following: extrathyroidal extension, lymphovascular invasion, the presence of positive lymph nodes, or the detection of distant metastases upon diagnosis, and non-invasive AV-PTC groups. Results: Key findings from our comparison between invasive and non-invasive groups of AV-PTC highlighted significant factors associated with poorer outcomes in the invasive group. These included multifocality (P=0.001), larger tumor size (P=0.047), extra thyroid extension (P=0.002), lymph vascular invasion (P<0.001), the presence of contralateral nodules (P=0.018), and positive surgical margins (P=0.003). Moreover, advanced tumor stage and increased lymph node involvement were more common in invasive cases (P=0.012, P=0.040). Despite no significant differences in genetic mutations between groups (P=0.396), the Ki-67 index was numerically higher in the invasive group. Hemithyroidectomy followed by completion thyroidectomy, performed in 12 patients (22.2%). Survival analysis further highlighted the significance of these invasive features, with Kaplan-Meier curves indicating a 5-year freedom from recurrence rate of 77.18% and a 10-year rate of 68.61%. Univariable Cox regression revealed that the tumor size, positive margins, and tumor stage predicted recurrence. Seven patients had distant metastasis, and all were in the invasion group (18.92%) p= 0.088. Conclusion: Our study emphasizes the critical role of certain invasive features in determining the prognosis of AV-PTC. The adoption of more extensive treatments for patients without invasive features highlights the complexity of treating AV-PTC and the importance of personalized treatment plans. This research advances our understanding of AV-PTC, advocating for individualized approaches to enhance patient outcomes. Presentation: 6/3/2024

Exploring waveforms with non-GR deviations for extreme mass-ratio inspirals

The fundamental process of detecting and examining the polarization modes of gravitational waves plays a pivotal role in enhancing our grasp on the precise mechanisms behind their generation. A thorough investigation is essential for delving deeper into the essence of gravitational waves and rigorously evaluating and validating the range of modified gravity theories. In this line of interest, a general description of black holes in theories beyond general relativity can serve a meaningful purpose where distinct deviation parameters can be mapped to solutions representing distinct theories. Employing a refined version of the deformed Kerr geometry, which is free from pathological behaviours such as unphysical divergences in the metric, we explore an extreme mass-ratio inspiral system, wherein a stellar-mass object perturbs a supermassive black hole. We compute the effects of deformation parameters on the rate of change of orbital energy and angular momentum, orbital evolution and phase dynamics with leading order post-Newtonian corrections. With the waveform analysis, we assess the plausibility of detecting deviations from general relativity through observations facilitated by the Laser Interferometer Space Antenna (LISA), simultaneously constraining the extent of these deviations. Therefore, this analysis provides an understanding while highlighting the essential role of observations in advancing gravitational phenomena beyond general relativity.

Group Social Dynamics in a Seminatural Setup Reflect the Adaptive Value of Aggression in Male Mice

BackgroundMaladaptive aggression in humans is associated with several psychiatric conditions and lacks effective treatment. Nevertheless, tightly regulated aggression is essential for survival throughout the animal kingdom. Studying how social dominance hierarchies regulate aggression and access to resources in an enriched environment (EE) can narrow the translational gap between aggression in animal models and normal and pathological human behavior. MethodsThe social box is a seminatural setup for automatic and prolonged monitoring of mouse group dynamics. We utilized the social box to decipher tradeoffs between aggression, social avoidance, resource allocation, and dominance in 2 mouse models of increased aggression: 1) a model of early exposure to an EE and 2) a model of oxytocin receptor deficiency (OxtR−/−). While an EE increases aggression as an adaptive response to external stimuli, hyperaggression in OxtR−/− mice is accompanied by marked abnormalities in social behavior. ResultsEE groups exhibited significant social avoidance, and an increased proportion of their encounters developed into aggressive interactions, resulting in lower levels of exploratory activity and overall aggression. The hierarchy in EE groups was more stable than in control groups, and dominance was correlated with access to resources. In OxtR−/− groups, mice engaged in excessive social encounters and aggressive chasing, accompanied by increased overall activity. In OxtR−/− groups, dominance hierarchies existed but were not correlated with access to resources. ConclusionsMeasuring aggression and social dominance hierarchies in a seminatural setup reveals the adaptive value of aggression in EE and OxtR−/− mice, respectively. This approach can enhance translational research on pathological aggression.

Scrutinizing black hole stability in cubic vector Galileon theories

In a subclass of generalized Proca theories where a cubic vector Galileon term breaks the U(1) gauge invariance, it is known that there are static and spherically symmetric black hole (BH) solutions endowed with nonvanishing temporal and longitudinal vector components. Such hairy BHs are present for a vanishing vector-field mass (m=0) with a non-zero cubic Galileon coupling β 3. We study the linear stability of those hairy BHs by considering even-parity perturbations in the eikonal limit. In the angular direction, we show that one of the three dynamical perturbations has a nontrivial squared propagation speed c Ω,1 2, while the other two dynamical modes are luminal.We could detect two different unstable behaviors of perturbations in all the parameter spaces of hairy asymptotically flat BH solutions we searched for. In the first case, an angular Laplacian instability on the horizon is induced by negative c Ω,1 2. For the second case, it is possible to avoid this horizon instability, but in such cases, the positivity of c Ω,1 2 is violated at large distances. Hence these hairy BHs are generally prone to Laplacian instabilities along the angular direction in some regions outside the horizon. Moreover, we also encounter a pathological behavior of the radial propagation speeds c r possessing two different values of c r 2 for one of the dynamical perturbations. Introducing the vector-field mass m to cubic vector Galileons, however, we show that the resulting no-hair Schwarzschild BH solution satisfies all the linear stability conditions in the small-scale limit, with luminal propagation speeds of three dynamical even-parity perturbations.

Normalizing flow sampling with Langevin dynamics in the latent space

AbstractNormalizing flows (NF) use a continuous generator to map a simple latent (e.g. Gaussian) distribution, towards an empirical target distribution associated with a training data set. Once trained by minimizing a variational objective, the learnt map provides an approximate generative model of the target distribution. Since standard NF implement differentiable maps, they may suffer from pathological behaviors when targeting complex distributions. For instance, such problems may appear for distributions on multi-component topologies or characterized by multiple modes with high probability regions separated by very unlikely areas. A typical symptom is the explosion of the Jacobian norm of the transformation in very low probability areas. This paper proposes to overcome this issue thanks to a new Markov chain Monte Carlo algorithm to sample from the target distribution in the latent domain before transporting it back to the target domain. The approach relies on a Metropolis adjusted Langevin algorithm whose dynamics explicitly exploits the Jacobian of the transformation. Contrary to alternative approaches, the proposed strategy preserves the tractability of the likelihood and it does not require a specific training. Notably, it can be straightforwardly used with any pre-trained NF network, regardless of the architecture. Experiments conducted on synthetic and high-dimensional real data sets illustrate the efficiency of the method.

Dynamic brain entropy predicts risky decision-making across transdiagnostic dimensions of psychopathology

ObjectivesMaladaptive risky decision-making is a common pathological behavior among patients with various psychiatric disorders. Brain entropy, which measures the complexity of brain time series signals, provides a novel approach to assessing brain health. Despite its potential, the dynamics of brain entropy have seldom been explored. This study aimed to construct a dynamic model of brain entropy and examine its predictive value for risky decision-making in patients with mental disorders, utilizing resting-state functional magnetic resonance imaging (rs-fMRI). MethodsThis study analyzed the rs-fMRI data from a total of 198 subjects, including 48 patients with bipolar disorder (BD), 47 patients with schizophrenia (SZ), 40 patients with adult attention deficit hyperactivity disorder (ADHD), as well as 63 healthy controls (HC). Time series signals were extracted from 264 brain regions based on rs-fMRI. The traditional static entropy and dynamic entropy (coefficient of variation, CV; rate of change, Rate) were constructed, respectively. Support vector regression was employed to predict risky decision-making utilizing leave-one-out cross-validation within each group. ResultsOur findings showed that CV achieved the best performances in HC and BD groups (r = −0.58, MAE = 6.43, R2 = 0.32; r = −0.78, MAE = 12.10, R2 = 0.61), while the Rate achieved the best in SZ and ADHD groups (r = −0.69, MAE = 10.20, R2 = 0.47; r = −0.78, MAE = 7.63, R2 = 0.60). For the dynamic entropy, the feature selection threshold rather than the time window length and overlapping ratio influenced predictive performance. ConclusionsThese results suggest that dynamic brain entropy could be a more effective predictor of risky decision-making than traditional static brain entropy. Our findings offer a novel perspective on exploring brain signal complexity and can serve as a reference for interventions targeting risky decision-making behaviors, particularly in individuals with psychiatric diagnoses.

Continuum versus micromechanical modeling of corneal biomechanics

Two alternative numerical models of the human cornea are used to simulate the mechanical response under the action of a physiological intraocular pressure (IOP). The first model is continuum or macromechanical, considering the stromal tissue as a bulk material with stochastic distribution of the spatial variability of reinforcing collagen fibers. The second model is discrete or micromechanical, considering the sole collagen-crosslink stiffening micro-structure. The geometry of the two models is reconstructed from corneal topographer images. Simulations consider the behavior of a healthy cornea and of a keratoconus cornea. For the keratoconus the material properties of a portion of the cornea are reduced to 1/8 of the values used for the healthy tissue. It is found that, for suitable choice of the material parameters for the discrete model, in the healthy case the mechanical responses of the two models are fully comparable. In the keratoconus case, both models capture with comparable accuracy the anterior shape of the conus; in addition, the discrete model is able to describe the tissue thinning typical of the pathology. Despite the inclusion of stochastic material properties, starting from a healthy condition, continuum models of the cornea are not able to predict the thinning of a keratoconus cornea, while the inclusion of the underlying collagen microstructure allows for a proper description of pathologic mechanical behaviors.

Behavioral economic analysis of the comorbidity of alcohol problems and posttraumatic stress: Findings from high-risk young adults and general community adults.

A behavioral economic reinforcer pathology model theorizes that alcohol problems are influenced by steep delay discounting, overvaluation of alcohol reinforcement, and low reinforcement from alcohol-free activities. Extending this account to the comorbidity of alcohol problems and posttraumatic stress disorder (PTSD), the present study tested the hypothesis that alcohol problems and PTSD symptom severity would interact and be positively associated with indicators from these three domains. High-risk emerging adults from North America (Study 1, n = 1,311, Mage = 22.13) and general community adults from Canada (Study 2, n = 1,506, Mage = 36.80) completed measures of alcohol problems, PTSD symptoms, delay discounting, alcohol demand, and proportionate alcohol-related reinforcement. Across studies, regression analyses revealed significant main effects of alcohol problems and PTSD symptoms in relation to selected reinforcer pathology indicators, but no significant interactions were present for delay discounting or proportionate alcohol-related reinforcement. Interactions were observed for alcohol consumption at $0 (intensity) and the rate of change in consumption across the demand curve (elasticity; Study 1) and for elasticity and maximum alcohol expenditure (Omax; Study 2), but not in the predicted directions. Higher synergistic severity was associated with lower alcohol reinforcing value in each case. These findings reveal expected relations between reinforcer pathology indicators and both alcohol problems and PTSD symptomatology in general but did not support the hypothesized synergistic relationship. The relation between alcohol problems and PTSD is more complex than predicted by existing extensions of the reinforcer pathology model, warranting further investigation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).