Hasil untuk "Neurosciences. Biological psychiatry. Neuropsychiatry"

Jessica Schlünzen, Patricia Kulla, Joachim Kruse

Some studies suggest Imagery Rescripting (ImRs) may be more effective than Imaginal Exposure (IE) for processing trauma when non-fear emotions are predominant. ImRs has been proposed to work through positive memory revaluation and increasing mastery, while IE focuses on fear toleration through inhibitory learning. We present standardized ImRs and IE analogues to explore their impact on non-fear emotions and underlying mechanisms. Forty-one participants selected an autobiographic event and were randomly assigned to ImRs, IE, or a control condition. Core elements of ImRs and IE were delivered via audio. We repeatedly assessed event-related emotions, distress, mastery, and tolerance for negative emotions. Participants in ImRs showed greater reductions in distress, fear, and anger, but not in self-conscious emotions, compared to IE. Unexpectedly, IE participants experienced increased negative emotions, including fear, with no specific advantage for increasing tolerance. Reductions in negative emotions were also observed in the control group. We found tentative indications for positive revaluation following ImRs. In conclusion, the ImRs analogue largely facilitated expected changes, while IE led to adverse effects. We discuss potential reasons for these findings and suggest improvements for the analogues and overall procedure.

Neha Kamboj, Sanya Sharma, Rahul Kumar

Neurodegenerative disorders, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are among the most significant health concerns worldwide, characterized by neuronal dysfunction, oxidative stress, neuroinflammation, and protein misfolding. Epigallocatechin gallate, a green tea polyphenol, has been reported to possess multifaceted neuroprotective properties. It reduces oxidative stress through free radical scavenging, activation of antioxidant enzymes, and stabilization of mitochondrial function. It also inhibits neuroinflammation through modulation of key signaling pathways. It suppresses amyloid-beta aggregation in Alzheimer’s and alpha-synuclein fibrillation in Parkinson’s, thus attenuating toxic protein accumulation. Its activity in the induction of autophagy and promotion of synaptic plasticity supports neuronal survival and function. However, low bioavailability and metabolic instability hinder its translation into the clinic. Strategies including nanoparticle encapsulation, structural modifications, and combination therapies are being explored to overcome these challenges. Future research could establish epigallocatechin gallate as a viable candidate for managing neurodegenerative disorders.

Ifrah Tariq, Ernest Fraenkel

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet patient responses remain highly variable, and the biological mechanisms underlying resistance are poorly understood. While machine learning models hold promise for predicting responses to ICIs, most existing methods lack interpretability and do not effectively leverage the biological structure inherent to multi-omics data. Here, we introduce the Biologically Disentangled Variational Autoencoder (BDVAE), a deep generative model that integrates transcriptomic and genomic data through modality- and pathway-specific encoders. Unlike existing rigid, pathway-informed models, BDVAE employs a modular encoder architecture combined with variational inference to learn biologically meaningful latent features associated with immune, genomic, and metabolic processes. Applied to a pan-cancer cohort of 366 patients across four cancer types treated with ICIs, BDVAE accurately predicts treatment response (AUC-ROC = 0.94 on unseen test data) and uncovers critical resistance mechanisms, including immune suppression, metabolic shifts, and neuronal signaling. Importantly, BDVAE reveals that resistance spans a continuous biological spectrum rather than strictly binary states, reflecting gradations of tumor dysfunction. Several latent features correlate with survival outcomes and known clinical subtypes, demonstrating BDVAE's capability to generate interpretable, clinically relevant insights. These findings underscore the value of biologically structured machine learning in elucidating complex resistance patterns and guiding precision immunotherapy strategies.

Parsa Omidi, Xingshuai Huang, Axel Laborieux et al.

Memory is fundamental to intelligence, enabling learning, reasoning, and adaptability across biological and artificial systems. While Transformer architectures excel at sequence modeling, they face critical limitations in long-range context retention, continual learning, and knowledge integration. This review presents a unified framework bridging neuroscience principles, including dynamic multi-timescale memory, selective attention, and consolidation, with engineering advances in Memory-Augmented Transformers. We organize recent progress through three taxonomic dimensions: functional objectives (context extension, reasoning, knowledge integration, adaptation), memory representations (parameter-encoded, state-based, explicit, hybrid), and integration mechanisms (attention fusion, gated control, associative retrieval). Our analysis of core memory operations (reading, writing, forgetting, and capacity management) reveals a shift from static caches toward adaptive, test-time learning systems. We identify persistent challenges in scalability and interference, alongside emerging solutions including hierarchical buffering and surprise-gated updates. This synthesis provides a roadmap toward cognitively-inspired, lifelong-learning Transformer architectures.

Richard Fechner, Jens Dörpinghaus, Robert Rockenfeller et al.

<b>Background:</b> Biomedical data are usually collections of longitudinal data assessed at certain points in time. Clinical observations assess the presences and severity of symptoms, which are the basis for the description and modeling of disease progression. Deciphering potential underlying unknowns from the distinct observation would substantially improve the understanding of pathological cascades. Hidden Markov Models (HMMs) have been successfully applied to the processing of possibly noisy continuous signals. We apply ensembles of HMMs to categorically distributed multivariate time series data, leaving space for expert domain knowledge in the prediction process. <b>Methods:</b> We use an ensemble of HMMs to predict the loss of free walking ability as one major clinical deterioration in the most common autosomal dominantly inherited ataxia disorder worldwide. <b>Results:</b> We present a prediction pipeline that processes data paired with a configuration file, enabling us to train, validate and query an ensemble of HMMs. In particular, we provide a theoretical and practical framework for multivariate time-series inference based on HMMs that includes constructing multiple HMMs, each to predict a particular observable variable. Our analysis is conducted on pseudo-data, but also on biomedical data based on Spinocerebellar ataxia type 3 disease. <b>Conclusions:</b> We find that the model shows promising results for the data we tested. The strength of this approach is that HMMs are well understood, probabilistic and interpretable models, setting it apart from most Deep Learning approaches. We publish all code and evaluation pseudo-data in an open-source repository.

Moonkwang Jeong, Xiangzhou Tan, Felix Fischer et al.

Small-scale robots hold great potential for targeted cargo delivery in minimally-inv asive medicine. However, current robots often face challenges to locomote efficiently on slip pery biological tissue surfaces, especially when loaded with heavy cargos. Here, we report a magnetic millirobot that can walk on rough and slippery biological tissues by anchoring itself on the soft tissue surface alternatingly with two feet and reciprocally rotating the body to mov e forward. We experimentally studied the locomotion, validated it with numerical simulations and optimized the actuation parameters to fit various terrains and loading conditions. Further more, we developed a permanent magnet set-up to enable wireless actuation within a huma n-scale volume which allows precise control of the millirobot to follow complex trajectories, cl imb vertical walls, and carry cargo up to four times of its own weight. Upon reaching the targ et location, it performs a deployment sequence to release the liquid drug into tissues. The ro bust gait of our millirobot on rough biological terrains, combined with its heavy load capacity, make it a versatile and effective miniaturized vehicle for targeted cargo delivery.

Francesca Pischiutta, Helena Cavaleiro, Helena Cavaleiro et al.

Traumatic brain injury (TBI) is a major worldwide neurological disorder with no neuroprotective treatment available. Three-dimensional (3D) in vitro models of brain contusion serving as a screening platform for drug testing are lacking. Here we developed a new in vitro model of brain contusion on organotypic cortical brain slices and tested its responsiveness to mesenchymal stromal cell (MSC) derived secretome. A focal TBI was induced on organotypic slices by an electromagnetic impactor. Compared to control condition, a temporal increase in cell death was observed after TBI by propidium iodide incorporation and lactate dehydrogenase release assays up to 48 h post-injury. TBI induced gross neuronal loss in the lesion core, with disruption of neuronal arborizations measured by microtubule-associated protein-2 (MAP-2) immunostaining and associated with MAP-2 gene down-regulation. Neuronal damage was confirmed by increased levels of neurofilament light chain (NfL), microtubule associated protein (Tau) and ubiquitin C-terminal hydrolase L1 (UCH-L1) released into the culture medium 48 h after TBI. We detected glial activation with microglia cells acquiring an amoeboid shape with less ramified morphology in the contusion core. MSC-secretome treatment, delivered 1 h post-injury, reduced cell death in the contusion core, decreased NfL release in the culture media, promoted neuronal reorganization and improved microglia survival/activation. Our 3D in vitro model of brain contusion recapitulates key features of TBI pathology. We showed protective effects of MSC-secretome, suggesting the model stands as a tractable medium/high throughput, ethically viable, and pathomimetic biological asset for testing new cell-based therapies.

F. Ghrissi, F. Fekih-romdhane, M. Stambouli et al.

Introduction Violence is a common behavioral and health concern among adolescents, aged 12 to 18 years old. In fact, aggressiveness may result in severe outcome in a critical age characterised by biological, psychological, and social changes. Schizophrenia is a severe and chronic condition, with elevated level of aggressiveness. Since unaffected biological relatives of schizophrenia patients share similar though less severe neurocognitive and behavioral abnormalities seen in their affected relatives, they are at increased risk of violence mainly during adolescence. However, studies including adolescents with schizophrenia first degree history are scarce. Objectives The aim of this survey was to evaluate the aggressiveness among unaffected adolescents with fist degree family history of schizophrenia and in a control group of adolescents with no family psychiatric history. Methods In this purpose wo conducted a case-control cross sectional study in Razi hospital during three months: from July to September 2022. Unaffected adolescents aged 12 to 18 whom first-degree relatives were diagnosed with schizophrenia according to DSM-5 criteria were included. Adolescents with psychiatric conditions or medical affections associated with psychiatric presentation were not included. Control group was selected amongst the population. Sociodemographic data were collected on a preestablished questionnaire and the following scales were used: The Life History of Aggression LHA, an 11 items self-reported tool, in the Arabic version, The Aggression Questionnaire AQ which is a 29 items self-reported scale in Arabic version. Written informed consent was obtained from the legal tutor of each adolescent. Results Results of this survey are ongoing. Conclusions Results of this survey are ongoing. Disclosure of Interest None Declared

Dalibor Sila, Francisco Luis Casnati, Mária Vojtková et al.

Background: Endovascular treatment of patients with chronic subdural hematoma using middle meningeal artery (MMA) embolization could become an alternative to surgical hematoma evacuation. The aim of the study was to compare methods and identify parameters to help determine the correct treatment modality. Methods: We retrospectively reviewed 142 cases conducted internally; 78 were treated surgically and 64 were treated using MMA embolization. We analyzed the treatment failure rate and complications, and using a binary logistic regression model, we identified treatment failure risk factors. Results: We found a comparable treatment failure rate of 23.1% for the surgery group and 21.9% for the MMA embolization group. However, in the MMA embolization group, 11 cases showed treatment failure due to early neurological worsening with a need for concomitant surgery. We also found a recurrence of hematoma in 15.4% of cases in the surgery group and 6.3% of cases in the MMA embolization group. Conclusion: Both modalities have their advantages; however, correct identification is crucial for treatment success. According to our findings, hematomas with a maximal width of <18 mm, a midline shift of <5 mm, and no acute or subacute (hyperdense) hematoma could be treated with MMA embolization. Hematomas with a maximal width of >18 mm, a midline shift of >5 mm, and no membranous segmentation could have better outcomes after surgical treatment.

Silvia Stahl Merlin, Sonia Maria Dozzi Brucki

Background Some psychological and personality characteristics of individuals seem to determine behavioral patterns that are associated with better health throughout life and, consequently, prevent the progression of early cognitive changes to dementia.

Johannes Schmidt-Hieber

Recently, significant progress has been made regarding the statistical understanding of artificial neural networks (ANNs). ANNs are motivated by the functioning of the brain, but differ in several crucial aspects. In particular, the locality in the updating rule of the connection parameters in biological neural networks (BNNs) makes it biologically implausible that the learning of the brain is based on gradient descent. In this work, we look at the brain as a statistical method for supervised learning. The main contribution is to relate the local updating rule of the connection parameters in BNNs to a zero-order optimization method. It is shown that the expected values of the iterates implement a modification of gradient descent.

Richard Moulange, Max Langenkamp, Tessa Alexanian et al.

Recent advancements in generative machine learning have enabled rapid progress in biological design tools (BDTs) such as protein structure and sequence prediction models. The unprecedented predictive accuracy and novel design capabilities of BDTs present new and significant dual-use risks. For example, their predictive accuracy allows biological agents, whether vaccines or pathogens, to be developed more quickly, while the design capabilities could be used to discover drugs or evade DNA screening techniques. Similar to other dual-use AI systems, BDTs present a wicked problem: how can regulators uphold public safety without stifling innovation? We highlight how current regulatory proposals that are primarily tailored toward large language models may be less effective for BDTs, which require fewer computational resources to train and are often developed in an open-source manner. We propose a range of measures to mitigate the risk that BDTs are misused, across the areas of responsible development, risk assessment, transparency, access management, cybersecurity, and investing in resilience. Implementing such measures will require close coordination between developers and governments.

Hyukje Lee, Sang-Won Yoo, Joong-Seok Kim

Kelly Y. C. Lai, Se-Fong Hung, Hannah W. S. Lee et al.

School-based mental health support services allow children and adolescents easy access to services without requirement of traveling to clinics and hospitals. We describe a School Mental Health Support Scheme (SMHSS) piloted in Hong Kong and discuss the challenges and learnings from the experience. This conceptual paper argues that accessibility is not the only advantage of such services. Teachers are significant others in child development, alongside with families. They play a central role in impacting the children's/adolescents' needs for competence and adult attachment, while schools provide an expanded social network of peers for one's social relationship. The fulfillment of these needs has powerful implications in the mental health of the children/adolescents. Teachers can help students to develop a sense of competence with self-worth and self-identity via providing guidance and feedback, whether they be on one's strengths or weaknesses, with acceptance, tolerance and unconditional positive regard. Particularly, the latter define a form of teacher-student relationship or adult attachment that offers the children/adolescents emotional security and nourishment, protecting them from failings and adversities. Teachers can also supervise and guide their students' social development with peers at schools. A recent meta-analysis has found preliminary evidence that those school-based mental health services integrated into the teachers' routine teaching activities are more effective. Teachers, who are overworked and stressed by the schools' overemphasis on academics and grades, have yet to fully grasp their unique roles in supporting students with mental health needs. This paper ends by advocating a paradigm shift in which both the healthcare professionals and educators should forge a mutually beneficial collaboration in jointly enhancing the mental health of children/adolescents at schools.

Nitin Joseph, Sooraj Suresh, Satwiki Prasad et al.

Abstract Background Restless leg syndrome (RLS) is a common neurological morbidity. It is, however, a frequently underdiagnosed medical condition. This study was hence done to assess the occurrence and severity of RLS among participants and to study its determinants and its association with quality of sleep. This was a cross-sectional study conducted among the general population of Mangalore in July 2021. Data were collected using a Google Form. The International Restless Legs Syndrome Study Group Rating Scale was used to diagnose RLS and its severity. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Results The prevalence of RLS among the 202 participants was 24(11.9%). Among them, 5 were already diagnosed with RLS. Their mean age at onset was 40.4 ± 25.3 years. Among the rest 197 participants, 19(9.6%) were newly diagnosed with RLS. The severity of RLS was mild, moderate and severe among 7(36.8%), 9(47.4%) and 3(15.8%) participants, respectively. Five (26.3%) of the 19 newly diagnosed participants were identified as RLS sufferers. In multivariable analysis, the presence of diabetes mellitus and family history of RLS were  associated with the presence of RLS among the participants. The mean Global PSQI value was 5.0 ± 3.1. Sleep latency was prolonged (p = 0.001), and sleep disturbances (p = 0.01) were higher among participants newly diagnosed with RLS (n = 19) compared to those without RLS (n = 178). Subjective sleep quality was poor (p = 0.038), and sleep disturbances (p = 0.016) were more among participants with severe degree RLS. Conclusions The prevalence of RLS in the present study was higher than that reported in previous Indian studies. Unpleasant sensations in RLS affected sleep initiation and maintenance among the affected. A multi-disciplinary approach is required to control its determinants and address other sleep-related problems among the RLS affected population.

Lingran Xiao, Yanfei Wang, Shiying Li et al.

The pathway is a biological term that refers to a series of interactions between molecules in a cell that causes a certain product or a change in the cell. Pathway analysis is a powerful method for gene expression analysis. Through pathway maps, the lists of genes that are differentially expressed across the given phenotypes are translated into various biological phenomena. Visualizing a pathway map manually is a common practice nowadays because of the limitations of existing solutions to draw complicated graphs (i.e. directed graphs, graphs with edge crossings, etc). This project provides a solution to draw pathway maps automatically based on spectral graph theory and topological sort. Various methods are taken to enhance pathway maps' readability. Significant reductions in the number of edge crossings and the sum of adjacent nodes are achieved.

Grazia Ceschi, Garance Selosse, Reginald D.V. Nixon et al.

Background: Research has shown that posttraumatic anger is common after a traumatic experience, represents a risk factor for post-trauma psychopathology, and can be screened for using the Dimensions of Anger Reactions Scale-5 (DAR-5), a concise five-item measure. However, a French version of the DAR-5 is not yet available. Objective: We aimed to provide a French adaptation (DAR-5-F) and to replicate, in a French community sample, the psychometric properties of the original DAR-5. Method: After translation using transcultural psychometric principles, the DAR-5-F was presented to 822 fluent French speakers alongside validated scales of anger (State-Trait Anger Expression Inventory-2), anxiety and depression (Hospital Anxiety and Depression Scale), alcohol misuse (Alcohol Use Disorders Identification Test-Consumption), and trauma exposure (Life Events Checklist-5). Results: Confirmatory factor analyses confirmed that DAR-5-F scores fit a single-factor model as described with the English version of the scale. The scale showed noteworthy internal consistency and robust convergent validity with trait anger. The screening DAR-5-F cut-off of ≥12 successfully differentiated high from low scores of STAXI-2, anxiety, depression, and traumatic exposure. Conclusions: The DAR-5 is a robust, psychometrically strong brief scale of anger useful for post-trauma screening, with the DAR-5-F now available for use in French-speaking populations. Future research that examines relationships between the DAR-5-F and variables such as trauma severity and posttraumatic stress symptoms will further improve our understanding of these phenomena.

Franziska Labrenz, Sopiko Knuf-Rtveliashvili, Sigrid Elsenbruch

Although the broad role of fear and hypervigilance in conditions of the gut-brain axis like irritable bowel syndrome is supported by converging evidence, the underlying mechanisms remain incompletely understood. Even in healthy individuals, it remains unclear how pain-related fear may contribute to pain-related attentional biases for acute visceral pain. Building on our classical fear conditioning work in a clinically relevant model of visceral pain, we herein elucidated pain-related attentional biases shaped by associative learning in healthy women and men, aiming to elucidate possible sex differences and the role of psychological traits. To this end, we compared the impact of differentially conditioned pain-predictive cues on attentional biases in healthy women and men. Sixty-four volunteers accomplished a visual dot-probe task and subsequently underwent pain-related fear conditioning where one visual cue (CS+) was contingently paired with a painful rectal distention (US) while another cue remained unpaired (CS−). During the following test phase, the dot-probe task was repeated to investigate changes in attentional biases in response to differentially valenced cues. While pain-related learning was comparable between groups, men revealed more pronounced attentional engagement with the CS+ and CS− whereas women demonstrated stronger difficulties to disengage from the CS+ when presented with a neutral cue. However, when both CS+ and CS− were presented together, women revealed stronger difficulties to disengage from the CS−. Regression analyses revealed an interaction of sex, with negative affect predicting stronger avoidance of the CS+ and stronger difficulties to disengage attention from the CS− in men. These results provide first evidence that pain-related fear conditioning may induce attentional biases differentially in healthy women and men. Hence, sex differences may play a role in attentional mechanisms underlying hypervigilance, and may be modulated by psychological vulnerability factors relevant to chronic visceral pain.

E.G. Pedachenko, V.V. Moroz, V.A. Yatsyk et al.

Stroke is a global medical and socio-economic problem and a great demand for alternative therapies, the leading one being stem cell (SC) therapy. Pathogenetic processes in ischemic stroke (II) trigger the mechanisms of necrotic and apoptotic death of neurons with the formation of the central infarct zone («core of ischemia») and the ischemic «penumbra» zone; the severity and reversibility of the injury directly depends on the duration of ischemia. In parallel with pathogenetic processes, endogenous neurogenesis occurs – the proliferation of neurogenic stem and progenitor cells (NSC/NPC) and their migration into the ischemic focus; however, most NSCs and newly formed neurons undergo apoptosis and recovery of lost functions does not occur. Significant efforts are being made to find ways to control neurogenesis, in particular through the transplantation of exogenous SCs. The main factors preventing the use of SCs in humans are moral, ethical, religious and legal aspects related to the source and method of obtaining cells, as well as possible immunocompromised complications due to incompatibility of donor cells with the recipient of the main histocompatibility complex antigens. The safest is the use of autologous SCs (the patient’s own cells), as it does not require the use of immunosuppressive protocols. Due to the relative safety and ease of production, the most common are multipotent mesenchymal stem cells (MSCs), namely MSCs of the bone marrow (BM). Numerous preclinical studies in experimental animals with modeled II, as well as clinical trials conducted over the past 15 years, have shown the safety and feasibility of transplantation of autologous MSCs in patients with severe neurological deficits after II. Two different approaches to the use of MSCs are discussed: neuroprotection in the acute phase and neurorestoration in the chronic phase II. Proposals are currently being developed for phase II/III clinical trials in acute and chronic stroke using BM MSCs, the results of which will form the basis for certified standardized II treatment protocols.

Alexander Levit, Sonny Cheng, Olivia Hough et al.

Hypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheimer disease. In this study, male transgenic Fischer 344 rats (TgAPP21) overexpressing a pathogenic human amyloid precursor protein received 8 weeks of Angiotensin II infusion to increase blood pressure, and the rats were evaluated for astrocytosis, microgliosis, and cognitive function. A linear relationship between astrocytosis and blood pressure was observed in the corpus callosum and cingulum of wildtype rats, with hypertensive wildtype rats matching the elevated baseline astrocytosis seen in normotensive transgenic rats. In contrast, hypertensive transgenic rats did not demonstrate a further increase of astrocytosis, suggesting a deficient response. Angiotensin II infusion did not affect activation of microglia, which were elevated in the white matter and hippocampus of transgenic rats. Angiotensin II infusion did impair both wildtype and transgenic rats’ executive functions in the Morris Water Maze. These results present important implications for the interaction between hypertension and pathogenic human amyloid precursor protein expression, as Angiotensin II infusion produced cognitive impairments in both genotypes, but transgenic rats were additionally impaired in developing a normal astrocytic response to elevated blood pressure.