Pub Date : 2026-02-10DOI: 10.3390/brainsci16020207
Lukas Rau, Oliver Granert, Nils G Margraf, Stephan Schneider, Ulf Jensen-Kondering
Background/Objectives: In medical diagnostics, (semi-)automatic detection of pathological structures in images is becoming increasingly important. In particular, detecting cerebral microbleeds (CMBs) poses a challenge in clinical practice because the process is time-consuming and prone to error. Methods: Compared to previous methods of (semi-) automatic CMB detection that rely on large training datasets, we propose a method that can be adapted with a small dataset while still performing well. We propose a workflow that uses a two-stage approach to detect cerebral microbleeds that can be trained with a small dataset. The first stage is a 3D U-Net that retrieves potential CMB locations in the SWI image volume. Then, a 3D convolutional neural network (CNN) is used for discrimination to distinguish between real CMB and CMB mimics. Results: Using a dataset of 15 MRI scans with 40 marked CMBs, we are able to achieve a sensitivity of 97.5%. Conclusions: We showed that it is possible to create a workflow with high sensitivity using only a few training samples, enabling smaller radiological facilities to train networks using their own datasets. Even though the workflow performs well on a small dataset, it still requires further testing with other larger datasets.
{"title":"A Two-Stage Localization and Refinement Neural Network Structure for Data-Efficient Microbleed Detection.","authors":"Lukas Rau, Oliver Granert, Nils G Margraf, Stephan Schneider, Ulf Jensen-Kondering","doi":"10.3390/brainsci16020207","DOIUrl":"10.3390/brainsci16020207","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In medical diagnostics, (semi-)automatic detection of pathological structures in images is becoming increasingly important. In particular, detecting cerebral microbleeds (CMBs) poses a challenge in clinical practice because the process is time-consuming and prone to error. <b>Methods</b>: Compared to previous methods of (semi-) automatic CMB detection that rely on large training datasets, we propose a method that can be adapted with a small dataset while still performing well. We propose a workflow that uses a two-stage approach to detect cerebral microbleeds that can be trained with a small dataset. The first stage is a 3D U-Net that retrieves potential CMB locations in the SWI image volume. Then, a 3D convolutional neural network (CNN) is used for discrimination to distinguish between real CMB and CMB mimics. <b>Results</b>: Using a dataset of 15 MRI scans with 40 marked CMBs, we are able to achieve a sensitivity of 97.5%. <b>Conclusions</b>: We showed that it is possible to create a workflow with high sensitivity using only a few training samples, enabling smaller radiological facilities to train networks using their own datasets. Even though the workflow performs well on a small dataset, it still requires further testing with other larger datasets.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Yasunaga et al. Associations Among Developmental Coordination Disorder Traits, Neurodevelopmental Difficulties and University Personality Inventory Scores in Undergraduate Students at a Japanese National University: A Cross-Sectional Correlational Study. <i>Brain Sci.</i> 2025, <i>15</i>, 895.","authors":"Masanori Yasunaga, Ryutaro Higuchi, Keita Kusunoki, Naoto Mochizuki","doi":"10.3390/brainsci16020206","DOIUrl":"10.3390/brainsci16020206","url":null,"abstract":"<p><p><b>Error in Table</b> [...].</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10DOI: 10.3390/brainsci16020209
Michel B Janho, Maria N Papaliaga, Athina A Samara, Stamatia Papoutsopoulou, Matthaios Speletas, Nikolaos Christodoulou, Eftihia Asprodini
Introduction: Caffeine is the most consumed psychostimulant worldwide. Schizophrenia is an uncommon mental disorder affecting 0.34% of the global population. The aim of the current study was to investigate a possible association between caffeine consumption and symptom profile, dangerous behavior, and cognitive functions in patients with schizophrenia.
Methods: This prospective cohort study included consecutive patients diagnosed with schizophrenia who were admitted to the psychiatry ward or visited the psychiatry outpatient clinics at a tertiary University Hospital in Greece for a period of 12 months. All patients underwent an extensive psychiatric and cognitive function assessment using the standardized Greek version of the Positive and Negative Symptom Scale (PANSS), the generalized anxiety disorder scale (GAD-7), and the Addenbrooke cognitive test (ACE-R).
Results: In total, 53 patients were included in the present study. Mean age of the participants was 45 ± 11 years. The mean age at onset was 23 ± 7 years, while mean duration of illness from age of onset was 21.58 years. Caffeine serum levels exhibited a positive correlation with the poor attention component of the general psychopathology PANSS subscale, as well as with the attention and orientation component in the ACE-R. Moreover, another positive correlation was observed between the perilous behavior PANSS subscale and caffeine serum levels. Conversely as caffeine serum levels increased, fewer negative symptoms were reported, specifically, the poor rapport and passive/apathetic social withdrawal of the negative PANSS subscale.
Conclusions: In summary, this study highlights the significant associations between caffeine serum levels, symptom severity, and cognition among patients with schizophrenia. While the findings provide valuable insights, they should be interpreted with caution due to the study's several limitations. More larger scale cohort studies are needed in order to elucidate the impact of caffeine consumption in patients with schizophrenia.
{"title":"Association Between Caffeine Levels and Symptom Profile in Schizophrenia: Results from a Cohort Study in Central Greece.","authors":"Michel B Janho, Maria N Papaliaga, Athina A Samara, Stamatia Papoutsopoulou, Matthaios Speletas, Nikolaos Christodoulou, Eftihia Asprodini","doi":"10.3390/brainsci16020209","DOIUrl":"10.3390/brainsci16020209","url":null,"abstract":"<p><strong>Introduction: </strong>Caffeine is the most consumed psychostimulant worldwide. Schizophrenia is an uncommon mental disorder affecting 0.34% of the global population. The aim of the current study was to investigate a possible association between caffeine consumption and symptom profile, dangerous behavior, and cognitive functions in patients with schizophrenia.</p><p><strong>Methods: </strong>This prospective cohort study included consecutive patients diagnosed with schizophrenia who were admitted to the psychiatry ward or visited the psychiatry outpatient clinics at a tertiary University Hospital in Greece for a period of 12 months. All patients underwent an extensive psychiatric and cognitive function assessment using the standardized Greek version of the Positive and Negative Symptom Scale (PANSS), the generalized anxiety disorder scale (GAD-7), and the Addenbrooke cognitive test (ACE-R).</p><p><strong>Results: </strong>In total, 53 patients were included in the present study. Mean age of the participants was 45 ± 11 years. The mean age at onset was 23 ± 7 years, while mean duration of illness from age of onset was 21.58 years. Caffeine serum levels exhibited a positive correlation with the poor attention component of the general psychopathology PANSS subscale, as well as with the attention and orientation component in the ACE-R. Moreover, another positive correlation was observed between the perilous behavior PANSS subscale and caffeine serum levels. Conversely as caffeine serum levels increased, fewer negative symptoms were reported, specifically, the poor rapport and passive/apathetic social withdrawal of the negative PANSS subscale.</p><p><strong>Conclusions: </strong>In summary, this study highlights the significant associations between caffeine serum levels, symptom severity, and cognition among patients with schizophrenia. While the findings provide valuable insights, they should be interpreted with caution due to the study's several limitations. More larger scale cohort studies are needed in order to elucidate the impact of caffeine consumption in patients with schizophrenia.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12939408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10DOI: 10.3390/brainsci16020208
Nan Zhang, Weichao An, Shengnan Li, Jinglong Wu
Background: Resting-state functional MRI (rs-fMRI) studies typically rely on linear Pearson correlation to characterize brain connectivity, potentially overlooking the distributional characteristics of functional networks. This study introduces a kernel-transformed functional connectivity (FC) entropy framework to quantify network dedifferentiation in bipolar disorder (BD). Methods: We utilized a Gaussian kernel function to execute a nonlinear similarity transformation (referred to as reweighting) on standard linear correlation matrices. This approach acts as a functional filter to amplify the contrast between strong and weak connections. Multiscale entropy (global, modular, and nodal) was subsequently calculated to characterize the uniformity of connectivity weight distributions. Results: Compared to Normal Controls (NCs), patients with BD exhibited significantly higher entropy at the global level and within the Default Mode, Salience, and Somatosensory-Motor networks, indicating widespread network dedifferentiation (distributional flattening). These alterations were robust across different kernel widths and remained significant after rigorously controlling for head motion (Mean FD). Furthermore, manic symptom severity (YMRS) was negatively correlated with global entropy, suggesting a pathological "locking-in" or rigidity of specific neural circuits during manic states. Conclusions: The kernel-transformed FC entropy serves as a distribution-sensitive complement to conventional linear metrics. Our findings highlight network dedifferentiation as a key pathophysiological feature of BD and suggest this framework as a promising candidate metric for characterizing network dysregulation.
{"title":"Kernel-Transformed Functional Connectivity Entropy Reveals Network Dedifferentiation in Bipolar Disorder.","authors":"Nan Zhang, Weichao An, Shengnan Li, Jinglong Wu","doi":"10.3390/brainsci16020208","DOIUrl":"10.3390/brainsci16020208","url":null,"abstract":"<p><p><b>Background</b>: Resting-state functional MRI (rs-fMRI) studies typically rely on linear Pearson correlation to characterize brain connectivity, potentially overlooking the distributional characteristics of functional networks. This study introduces a kernel-transformed functional connectivity (FC) entropy framework to quantify network dedifferentiation in bipolar disorder (BD). <b>Methods</b>: We utilized a Gaussian kernel function to execute a nonlinear similarity transformation (referred to as reweighting) on standard linear correlation matrices. This approach acts as a functional filter to amplify the contrast between strong and weak connections. Multiscale entropy (global, modular, and nodal) was subsequently calculated to characterize the uniformity of connectivity weight distributions. <b>Results</b>: Compared to Normal Controls (NCs), patients with BD exhibited significantly higher entropy at the global level and within the Default Mode, Salience, and Somatosensory-Motor networks, indicating widespread network dedifferentiation (distributional flattening). These alterations were robust across different kernel widths and remained significant after rigorously controlling for head motion (Mean FD). Furthermore, manic symptom severity (YMRS) was negatively correlated with global entropy, suggesting a pathological \"locking-in\" or rigidity of specific neural circuits during manic states. <b>Conclusions</b>: The kernel-transformed FC entropy serves as a distribution-sensitive complement to conventional linear metrics. Our findings highlight network dedifferentiation as a key pathophysiological feature of BD and suggest this framework as a promising candidate metric for characterizing network dysregulation.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.3390/brainsci16020202
Xu Duan, Songyun Xie, Yujie Cui, Ting Ji, Hao Yan
Background: Motor imagery-based brain-computer interfaces (MI-BCIs) enable individuals who are unable to perform physical movements to interact with the external world by imagining movements. Users are typically classified as good performers or BCI-illiterate based on the classification accuracy of distinct EEG patterns (e.g., 60% or 70%). Yet, studies show that approximately 70% of users fall within intermediate accuracies between 60% and 80%, and although exceed the chance level, they often fail to achieve reliable MI-BCI control. Intermediate users often exhibit asymmetric motor imagery abilities between left and right hands, highlighting the need for refined early assessment and stratified training approaches. Methods: We employed ICA to decompose each participant's EEG data and extract independent ERD/ERS components as indicators using a rule-based automated framework. This framework integrated dipole localization, ERD/ERS characteristics, and frequency-band power features of ICs. Importantly, we applied a power spectral parameterization approach to remove the 1/f-like background activity in power estimation and used statistical methods to precisely estimate the latency and duration of ERD. The extracted indicators were subsequently subjected to clustering analysis to categorize participants into four groups. Results: In addition to good performers (24.8%) and poor performers (35.8%), two groups were identified: LgoodRpoor (27.5%), who performed well in left-hand MI but poorly in right-hand MI, and LpoorRgood (11.9%), who showed the opposite pattern. Notably, these unilateral performers did not show significant differences in contralateral ERD but exhibited substantial differences in ipsilateral ERS. Conclusions: The proposed independent event-related brain dynamics model enables more refined stratification of MI-BCI users. Findings from this characterization study may inform the design of graded training protocols, especially for users demonstrating unilateral motor imagery proficiency.
{"title":"A Neurophysiological Stratification Framework for Intermediate Motor Imagery-BCI Users Based on Independent Event-Related Brain Dynamics.","authors":"Xu Duan, Songyun Xie, Yujie Cui, Ting Ji, Hao Yan","doi":"10.3390/brainsci16020202","DOIUrl":"10.3390/brainsci16020202","url":null,"abstract":"<p><p><b>Background:</b> Motor imagery-based brain-computer interfaces (MI-BCIs) enable individuals who are unable to perform physical movements to interact with the external world by imagining movements. Users are typically classified as good performers or BCI-illiterate based on the classification accuracy of distinct EEG patterns (e.g., 60% or 70%). Yet, studies show that approximately 70% of users fall within intermediate accuracies between 60% and 80%, and although exceed the chance level, they often fail to achieve reliable MI-BCI control. Intermediate users often exhibit asymmetric motor imagery abilities between left and right hands, highlighting the need for refined early assessment and stratified training approaches. <b>Methods:</b> We employed ICA to decompose each participant's EEG data and extract independent ERD/ERS components as indicators using a rule-based automated framework. This framework integrated dipole localization, ERD/ERS characteristics, and frequency-band power features of ICs. Importantly, we applied a power spectral parameterization approach to remove the 1/f-like background activity in power estimation and used statistical methods to precisely estimate the latency and duration of ERD. The extracted indicators were subsequently subjected to clustering analysis to categorize participants into four groups. <b>Results:</b> In addition to good performers (24.8%) and poor performers (35.8%), two groups were identified: LgoodRpoor (27.5%), who performed well in left-hand MI but poorly in right-hand MI, and LpoorRgood (11.9%), who showed the opposite pattern. Notably, these unilateral performers did not show significant differences in contralateral ERD but exhibited substantial differences in ipsilateral ERS. <b>Conclusions:</b> The proposed independent event-related brain dynamics model enables more refined stratification of MI-BCI users. Findings from this characterization study may inform the design of graded training protocols, especially for users demonstrating unilateral motor imagery proficiency.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.3390/brainsci16020204
Lysiane Le Tirant, Maxim Likhanov, Marie Mazerolle, Alexandrine Morand, Francis Eustache, Pascal Huguet, Aging Consortium, Isabelle Régner
Background: Cognitive aging is highly heterogeneous, not only in performance but also in how individuals perceive their own aging. Such self-perceptions may shape emotional reactions and adaptation to memory difficulties, yet little is known about their organization in patients referred to a memory clinic for a first diagnostic consultation. The primary aim of this study was to identify the internal configuration of self-perceptions of aging in such patients. A secondary aim was to compare these patterns with those observed in older adults recruited in a research unit of experimental psychology, who reported subjective complaints but had no medical referral. Methods: In total, 130 memory clinic patients and 84 laboratory participants completed, prior to the same neuropsychological testing, a psychosocial questionnaire assessing four domains: self-perceptions of memory deficits, attitudes toward aging, aging stereotypes, and multiple facets of subjective age. Network analysis was applied to examine how these variables were interrelated and to determine their relative importance in each group. Results: Across both samples, network analyses revealed distinct organizational patterns. Patients showed a unified representational system characterized by more positive associations and centered on subjective age variables. By contrast, the laboratory group showed a two-cluster network with more negative connections, organized around negative aging stereotypes. Conclusions: These findings provide novel insights into the psychosocial profile of memory clinic patients, highlighting the added value of network approaches for capturing the interrelations among key self-representations of aging and memory, and for informing and contextualizing clinical evaluation.
{"title":"Self-Perceptions of Aging in Older Adults: A Network Analysis of Clinical and Non-Clinical Samples.","authors":"Lysiane Le Tirant, Maxim Likhanov, Marie Mazerolle, Alexandrine Morand, Francis Eustache, Pascal Huguet, Aging Consortium, Isabelle Régner","doi":"10.3390/brainsci16020204","DOIUrl":"10.3390/brainsci16020204","url":null,"abstract":"<p><p><b>Background:</b> Cognitive aging is highly heterogeneous, not only in performance but also in how individuals perceive their own aging. Such self-perceptions may shape emotional reactions and adaptation to memory difficulties, yet little is known about their organization in patients referred to a memory clinic for a first diagnostic consultation. The primary aim of this study was to identify the internal configuration of self-perceptions of aging in such patients. A secondary aim was to compare these patterns with those observed in older adults recruited in a research unit of experimental psychology, who reported subjective complaints but had no medical referral. <b>Methods</b>: In total, 130 memory clinic patients and 84 laboratory participants completed, prior to the same neuropsychological testing, a psychosocial questionnaire assessing four domains: self-perceptions of memory deficits, attitudes toward aging, aging stereotypes, and multiple facets of subjective age. Network analysis was applied to examine how these variables were interrelated and to determine their relative importance in each group. <b>Results</b>: Across both samples, network analyses revealed distinct organizational patterns. Patients showed a unified representational system characterized by more positive associations and centered on subjective age variables. By contrast, the laboratory group showed a two-cluster network with more negative connections, organized around negative aging stereotypes. <b>Conclusions</b>: These findings provide novel insights into the psychosocial profile of memory clinic patients, highlighting the added value of network approaches for capturing the interrelations among key self-representations of aging and memory, and for informing and contextualizing clinical evaluation.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.3390/brainsci16020205
Xueqi Lai, Peng Zhong
Cold-inducible RNA-binding protein (CIRP) is a critical molecule in the central nervous system (CNS) with functions that depend on its subcellular localization, exhibiting biphasic regulatory roles in both physiological and pathological processes. Under physiological conditions, intracellular cold-inducible RNA-binding protein (iCIRP) contributes to the maintenance of circadian rhythms by regulating the stability of core clock gene mRNAs and exerts neuroprotective effects during mild hypothermia by preserving the blood-brain barrier and inhibiting apoptosis. Pathologically, extracellular cold-inducible RNA-binding protein (eCIRP) functions as a damage-associated molecular pattern (DAMP) that drives neuroinflammation and brain injury. In ischemic stroke (IS), eCIRP promotes neutrophil extracellular trap (NET) formation and increases microglial activity via the Toll-like receptor 4 (TLR4) pathway. In cerebral ischemia-reperfusion (I/R) injury, eCIRP activates oxidative stress and the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome through the TLR4 axis, exacerbating mitochondrial damage. In intracerebral hemorrhage (ICH), eCIRP further amplifies inflammation via the interleukin-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In traumatic brain injury (TBI), eCIRP activates the endoplasmic reticulum stress pathway, intensifying apoptosis. In Alzheimer's disease (AD), eCIRP regulates tau phosphorylation and β-amyloid (Aβ) metabolism and may mediate the link between alcohol exposure and AD pathology. Preclinical studies indicate that serum eCIRP levels correlate with IS and ICH severity, highlighting its potential as a biomarker. This systematic review elucidates the mechanisms of CIRP in CNS diseases, providing insights for understanding and preventing conditions such as IS, cerebral I/R injury, ICH, TBI, and AD.
{"title":"The Role of Cold-Inducible RNA-Binding Protein (CIRP) in Neurological Disorders.","authors":"Xueqi Lai, Peng Zhong","doi":"10.3390/brainsci16020205","DOIUrl":"10.3390/brainsci16020205","url":null,"abstract":"<p><p>Cold-inducible RNA-binding protein (CIRP) is a critical molecule in the central nervous system (CNS) with functions that depend on its subcellular localization, exhibiting biphasic regulatory roles in both physiological and pathological processes. Under physiological conditions, intracellular cold-inducible RNA-binding protein (iCIRP) contributes to the maintenance of circadian rhythms by regulating the stability of core clock gene mRNAs and exerts neuroprotective effects during mild hypothermia by preserving the blood-brain barrier and inhibiting apoptosis. Pathologically, extracellular cold-inducible RNA-binding protein (eCIRP) functions as a damage-associated molecular pattern (DAMP) that drives neuroinflammation and brain injury. In ischemic stroke (IS), eCIRP promotes neutrophil extracellular trap (NET) formation and increases microglial activity via the Toll-like receptor 4 (TLR4) pathway. In cerebral ischemia-reperfusion (I/R) injury, eCIRP activates oxidative stress and the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome through the TLR4 axis, exacerbating mitochondrial damage. In intracerebral hemorrhage (ICH), eCIRP further amplifies inflammation via the interleukin-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In traumatic brain injury (TBI), eCIRP activates the endoplasmic reticulum stress pathway, intensifying apoptosis. In Alzheimer's disease (AD), eCIRP regulates tau phosphorylation and β-amyloid (Aβ) metabolism and may mediate the link between alcohol exposure and AD pathology. Preclinical studies indicate that serum eCIRP levels correlate with IS and ICH severity, highlighting its potential as a biomarker. This systematic review elucidates the mechanisms of CIRP in CNS diseases, providing insights for understanding and preventing conditions such as IS, cerebral I/R injury, ICH, TBI, and AD.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.3390/brainsci16020201
Klara Ferenc, Piotr Semik, Justyna Paprocka
Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system (CNS) that predominantly affects children and young adults. ADEM typically follows an infectious or, less commonly, immunization-related trigger, and despite decades of clinical observation, its etiopathogenesis remains only partially understood. Clinically, the diagnosis of ADEM continues to pose significant challenges due to the absence of disease-specific biomarkers and its clinical and radiological overlap with other acquired demyelinating syndromes. This narrative review aims to summarize and critically discuss current knowledge on ADEM, with particular emphasis on its etiopathogenesis and clinical characteristics, highlighting the potential implications of recent research for clinical practice and management of this disease. Particular emphasis is placed on post-infectious immune mechanisms, including molecular mimicry, blood-brain barrier (BBB) disruption, loss of immune tolerance, and neuroinflammatory cascades. A wide spectrum of infectious triggers-viral, bacterial, parasitic-as well as post-vaccination, post-transplantation, paraneoplastic, metabolic, and host-related genetic factors are discussed in the context of immune dysregulation leading to CNS demyelination. We also highlight characteristic clinical and neuroimaging features that may aid in differentiating ADEM from other demyelinating syndromes, while acknowledging current diagnostic limitations. The integration of recent advances in ADEM immunopathogenesis with established clinical and radiological insights underscores the complexity of this disorder and highlights the evolving nature of current concepts regarding its diagnosis and clinical heterogeneity.
{"title":"Acute Disseminated Encephalomyelitis (ADEM): Current View into Etiopathogenesis and Clinical Features.","authors":"Klara Ferenc, Piotr Semik, Justyna Paprocka","doi":"10.3390/brainsci16020201","DOIUrl":"10.3390/brainsci16020201","url":null,"abstract":"<p><p>Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system (CNS) that predominantly affects children and young adults. ADEM typically follows an infectious or, less commonly, immunization-related trigger, and despite decades of clinical observation, its etiopathogenesis remains only partially understood. Clinically, the diagnosis of ADEM continues to pose significant challenges due to the absence of disease-specific biomarkers and its clinical and radiological overlap with other acquired demyelinating syndromes. This narrative review aims to summarize and critically discuss current knowledge on ADEM, with particular emphasis on its etiopathogenesis and clinical characteristics, highlighting the potential implications of recent research for clinical practice and management of this disease. Particular emphasis is placed on post-infectious immune mechanisms, including molecular mimicry, blood-brain barrier (BBB) disruption, loss of immune tolerance, and neuroinflammatory cascades. A wide spectrum of infectious triggers-viral, bacterial, parasitic-as well as post-vaccination, post-transplantation, paraneoplastic, metabolic, and host-related genetic factors are discussed in the context of immune dysregulation leading to CNS demyelination. We also highlight characteristic clinical and neuroimaging features that may aid in differentiating ADEM from other demyelinating syndromes, while acknowledging current diagnostic limitations. The integration of recent advances in ADEM immunopathogenesis with established clinical and radiological insights underscores the complexity of this disorder and highlights the evolving nature of current concepts regarding its diagnosis and clinical heterogeneity.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.3390/brainsci16020203
Wolfgang Taube, Naima Mory, Franziska Peier, Michael Mouthon, Joelle N Chabwine, Benedikt Lauber
Background/Objectives: It is widely recognized that malfunctions in the GABAergic system can be one of the underlying mechanisms in chronic pain. However, the use of GABAergic drugs to improve pain perception has strong and unwanted side effects, particularly in terms of sedation. Therefore, the present exploratory single-case study tested an alternative treatment using balance training to upregulate the GABAergic system in a 62-year-old patient with widespread chronic pain. Previously, balance training was shown to increase short-interval intracortical inhibition (SICI), a neurophysiological marker commonly associated with GABA-mediated intracortical inhibition, as assessed using paired-pulse transcranial magnetic stimulation (TMS), in healthy young and older adults. Therefore, we hypothesized that the balance-training-induced increase in GABAA-related intracortical inhibition would alleviate pain and increase quality of life. Methods: After two baseline measures, the patient participated in two balance training periods of 4 weeks each, followed by two detraining phases of 2 months each. At baseline and after each intervention and each detraining, intracortical inhibition (i.e., SICI) as well as pain and 'well-being' (questionnaires) was assessed. Results: Our results demonstrated enhanced and better modulated intracortical inhibition after 4 weeks of balance training, which was in line with analgesia and improved sleep and mood scores. However, after the first detraining, all parameters went back to baseline. In a subsequent second period of 4 weeks of balance training, intracortical inhibition was again increased, even above the values of the first training period. Pain, sleep, and mood scores were also further improved. After the second detraining period, all values dropped back close to their baseline values. Conclusions: The findings support the assumption that the GABAergic system is highly relevant in the processing and perception of pain. More importantly, our results suggest the possibility that balance training may be an effective way not only to upregulate intracortical inhibition but also to alleviate pain and improve well-being in patients with unspecific chronic pain.
{"title":"Balance Training-Related Changes in Intracortical Inhibition and Symptom Severity in a Patient with Chronic Neuropathic Pain: A Single-Case Study.","authors":"Wolfgang Taube, Naima Mory, Franziska Peier, Michael Mouthon, Joelle N Chabwine, Benedikt Lauber","doi":"10.3390/brainsci16020203","DOIUrl":"10.3390/brainsci16020203","url":null,"abstract":"<p><p><b>Background/Objectives</b>: It is widely recognized that malfunctions in the GABAergic system can be one of the underlying mechanisms in chronic pain. However, the use of GABAergic drugs to improve pain perception has strong and unwanted side effects, particularly in terms of sedation. Therefore, the present exploratory single-case study tested an alternative treatment using balance training to upregulate the GABAergic system in a 62-year-old patient with widespread chronic pain. Previously, balance training was shown to increase short-interval intracortical inhibition (SICI), a neurophysiological marker commonly associated with GABA-mediated intracortical inhibition, as assessed using paired-pulse transcranial magnetic stimulation (TMS), in healthy young and older adults. Therefore, we hypothesized that the balance-training-induced increase in GABA<sub>A</sub>-related intracortical inhibition would alleviate pain and increase quality of life. <b>Methods</b>: After two baseline measures, the patient participated in two balance training periods of 4 weeks each, followed by two detraining phases of 2 months each. At baseline and after each intervention and each detraining, intracortical inhibition (i.e., SICI) as well as pain and 'well-being' (questionnaires) was assessed. <b>Results</b>: Our results demonstrated enhanced and better modulated intracortical inhibition after 4 weeks of balance training, which was in line with analgesia and improved sleep and mood scores. However, after the first detraining, all parameters went back to baseline. In a subsequent second period of 4 weeks of balance training, intracortical inhibition was again increased, even above the values of the first training period. Pain, sleep, and mood scores were also further improved. After the second detraining period, all values dropped back close to their baseline values. <b>Conclusions</b>: The findings support the assumption that the GABAergic system is highly relevant in the processing and perception of pain. More importantly, our results suggest the possibility that balance training may be an effective way not only to upregulate intracortical inhibition but also to alleviate pain and improve well-being in patients with unspecific chronic pain.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: This study compared spectral profile analysis thresholds, speech-in-noise perception, and cerebral asymmetry among Carnatic musicians, Bharatanatyam dancers, and non-trained individuals and examined the influence of training duration on these measures.
Method: A total of 105 right-handed adults (18-30 years) with normal hearing were divided into Carnatic musicians (n = 35), Bharatanatyam dancers (n = 35), and non-trained controls (n = 35). Spectral stream segregation was measured using the spectral profile analysis task, and speech-in-noise perception was evaluated using the Kannada QuickSIN under right, left, and binaural conditions. Cerebral asymmetry was derived from the Laterality Index. As data were non-normally distributed, non-parametric tests were used.
Results: Significant group differences emerged for spectral profile thresholds, with dancers outperforming musicians and controls. Both trained groups showed superior speech-in-noise performance compared to non-trained individuals across all listening conditions, though no differences were observed between musicians and dancers. Non-trained listeners displayed a clear right-ear advantage, whereas trained groups showed minimal or no hemispheric asymmetry. Training duration negatively correlated with selected spectral profile thresholds in both trained groups and with binaural SNR-50 in dancers, indicating training-related auditory enhancement.
Conclusions: Musicians and dancers demonstrate better spectral discrimination, improved speech-in-noise perception, and reduced cerebral asymmetry compared to non-trained peers. These findings underscore training-induced auditory neuroplasticity and suggest that long-term engagement in music or dance promotes efficient auditory processing and greater bilateral hemispheric involvement.
{"title":"Comparison of Auditory Stream Segregation Abilities and Cerebral Asymmetry in Processing Speech in Noise in Carnatic Musicians, Bharatanatyam Dancers, and Non-Trained Individuals.","authors":"Sreeraj Konadath, Aysha Nida, Praveen Prakash, Vijaya Kumar Narne, Sunil Kumar Ravi, Reesha Oovattil Hussain","doi":"10.3390/brainsci16020200","DOIUrl":"10.3390/brainsci16020200","url":null,"abstract":"<p><strong>Aim: </strong>This study compared spectral profile analysis thresholds, speech-in-noise perception, and cerebral asymmetry among Carnatic musicians, Bharatanatyam dancers, and non-trained individuals and examined the influence of training duration on these measures.</p><p><strong>Method: </strong>A total of 105 right-handed adults (18-30 years) with normal hearing were divided into Carnatic musicians (n = 35), Bharatanatyam dancers (n = 35), and non-trained controls (n = 35). Spectral stream segregation was measured using the spectral profile analysis task, and speech-in-noise perception was evaluated using the Kannada QuickSIN under right, left, and binaural conditions. Cerebral asymmetry was derived from the Laterality Index. As data were non-normally distributed, non-parametric tests were used.</p><p><strong>Results: </strong>Significant group differences emerged for spectral profile thresholds, with dancers outperforming musicians and controls. Both trained groups showed superior speech-in-noise performance compared to non-trained individuals across all listening conditions, though no differences were observed between musicians and dancers. Non-trained listeners displayed a clear right-ear advantage, whereas trained groups showed minimal or no hemispheric asymmetry. Training duration negatively correlated with selected spectral profile thresholds in both trained groups and with binaural SNR-50 in dancers, indicating training-related auditory enhancement.</p><p><strong>Conclusions: </strong>Musicians and dancers demonstrate better spectral discrimination, improved speech-in-noise perception, and reduced cerebral asymmetry compared to non-trained peers. These findings underscore training-induced auditory neuroplasticity and suggest that long-term engagement in music or dance promotes efficient auditory processing and greater bilateral hemispheric involvement.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}