Brain Sciences

21 pages, 1260 KiB

Open AccessArticle

Understanding Pediatric Bipolar Disorder Through the Investigation of Clinical, Neuroanatomic, Neurophysiological and Neurocognitive Dimensions: A Pilot Study

by Alessio Simonetti, Evelina Bernardi, Sherin Kurian, Antonio Restaino, Claudia Calderoni, Emanuela De Chiara, Francesca Bardi, Gabriele Sani, Jair C. Soares and Kirti Saxena

Brain Sci. 2025, 15(2), 152; https://doi.org/10.3390/brainsci15020152 (registering DOI) - 3 Feb 2025

Abstract

Background: Pathophysiological models of pediatric bipolar disorder (PBD) are lacking. Multimodal approaches may provide a comprehensive description of the complex relationship between the brain and behavior. Aim: To assess behavioral, neuropsychological, neurophysiological, and neuroanatomical alterations in youth with PBD. Methods: [...] Read more.

Background: Pathophysiological models of pediatric bipolar disorder (PBD) are lacking. Multimodal approaches may provide a comprehensive description of the complex relationship between the brain and behavior. Aim: To assess behavioral, neuropsychological, neurophysiological, and neuroanatomical alterations in youth with PBD. Methods: Subjects with PBD (n = 23) and healthy controls (HCs, n = 23) underwent (a) clinical assessments encompassing the severity of psychiatric symptoms, (b) neuropsychological evaluation, (c) analyses of event-related potentials (related to the passive viewing of fearful, neutral, and happy faces during electroencephalography recording, and (d) cortical thickness and deep gray matter volume measurement using magnetic resonance imaging. Canonical correlation analyses were used to assess the relationships between these dimensions. Results: Youth with PBD had higher levels of anxiety (p < 0.001) and borderline personality features (p < 0.001), greater commission errors for negative stimuli (p = 0.003), delayed deliberation time (p < 0.001), and smaller risk adjustment scores (p = 0.002) than HCs. Furthermore, they showed cortical thinning in the frontal, parietal, and occipital areas (all p < 0.001) and greater P300 for happy faces (p = 0.29). In youth with PBD, cortical thickening and P300 amplitude positively correlated with more commission errors for negative stimuli, longer deliberation times, reduced risk adjustment, higher levels of panic and separation anxiety, and greater levels of negative relationships, whereas they negatively correlated with levels of depression (overall loadings > or <0.3). Limitations: Small sample size, cross-sectional design, and limited variables investigated. Conclusions: This preliminary work showed that multimodal assessment might be a viable tool for providing a pathophysiological model that unifies brain and behavioral alterations in youth with PBD. Full article

(This article belongs to the Section Neuropsychiatry)

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23 pages, 757 KiB

Open AccessSystematic Review

Tetrahydrobiopterin and Autism Spectrum Disorder: A Systematic Review of a Promising Therapeutic Pathway

by Clóvis Colpani Filho, Lucas Melfior, Sthephanie Luiz Ramos, Mateus Santos Oliveira Pizi, Lilian Freitas Taruhn, Margrit Ellis Muller, Thiago Kucera Nunes, Luísa de Oliveira Schmitt, Joana Margarida Gaspar, Miguel de Abreu de Oliveira, Giovanna Tassinari, Luisa Cruz and Alexandra Latini

Brain Sci. 2025, 15(2), 151; https://doi.org/10.3390/brainsci15020151 - 3 Feb 2025

Viewed by 114

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, along with restricted and repetitive patterns of behavior, interests, or activities. ASD encompasses a wide spectrum of clinical presentations and functional impairments, ranging from mild to [...] Read more.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, along with restricted and repetitive patterns of behavior, interests, or activities. ASD encompasses a wide spectrum of clinical presentations and functional impairments, ranging from mild to severe. Despite its prevalence, the underlying physiopathological mechanisms of ASD remain largely unknown, resulting in a lack of effective targeted therapeutic interventions, contributing to significant financial and emotional burdens on affected families and the healthcare system. Emerging evidence suggests that dysfunction in the tetrahydrobiopterin (BH4) pathway may impair the activity of monoaminergic and nitric oxide (NO)-dependent neurons in individuals with ASD. To explore this potential mechanism, we conducted a systematic review to analyze such impairments to gather information on whether the off-label use of BH4 could represent a novel pharmacological approach for managing ASD. Following the PRISMA 2020 guidelines, we systematically reviewed the literature from four databases: PubMed, Virtual Health Library, Cochrane Library, and SciELO, from January 1967 to December 2021. The quality of the included studies was assessed using the Newcastle–Ottawa scale. The inclusion criteria for this systematic review focused on identifying articles published in English that contained the following keywords, used in various combinations: autism, ASD, autism spectrum disorder, BH4, tetrahydrobiopterin, neopterin, NO, nitric oxide. The analysis was performed between December 2020 and December 2021. The collected data demonstrated that BH4 metabolism was altered in individuals with ASD. Lower levels of BH4 were reported in biological samples from ASD-affected individuals compared to age- and sex-matched controls. Additionally, neopterin levels were elevated in plasma and urine, but decreased in cerebrospinal fluid, while nitric oxide levels were consistently reported to be higher across studies. Treatment with BH4 has shown potential in improving ASD-related symptoms. The reported increase in neopterin in biological fluids indicates inflammation, while the reduction in BH4 levels suggests a potential shift in its metabolic role. Specifically, BH4 may be diverted from its primary role in neurotransmitter synthesis to function as an antioxidant or to perpetuate inflammation through NO production. Given that BH4 is a critical cofactor in monoaminergic neurotransmission, its dysfunction highlights the molecule's therapeutic potential. BH4, already FDA-approved for other conditions, emerges as a promising off-label candidate to alleviate ASD symptomatology. Full article

(This article belongs to the Special Issue Unraveling Autism: Neurobiological Mechanisms and Emerging Therapeutic Advances)

14 pages, 1094 KiB

Open AccessArticle

Vinpocetine, a Phosphodiesterase Type 1 Inhibitor, Mitigates Locomotor Hyperactivity in Female Mice Exposed to Lead During Development

by Ulisses C. Araujo, Fernanda Nunes, Bruno S. Gonçalves, Regina A. A. Gomes, Maria de Fátima R. Moreira, Andre Nunes-Freitas, Thomas E. Krahe, Yael de Abreu-Villaça, Alex C. Manhães and Cláudio C. Filgueiras

Brain Sci. 2025, 15(2), 150; https://doi.org/10.3390/brainsci15020150 - 2 Feb 2025

Viewed by 460

Abstract

Background/Objectives Studies in rodents indicate that disruptions in both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are involved in the development of hyperactive behavior. We examined whether vinpocetine, a phosphodiesterase type 1 inhibitor that enhances brain cAMP and cGMP [...] Read more.

Background/Objectives Studies in rodents indicate that disruptions in both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are involved in the development of hyperactive behavior. We examined whether vinpocetine, a phosphodiesterase type 1 inhibitor that enhances brain cAMP and cGMP levels, could mitigate locomotor hyperactivity in mice exposed to lead during early development. Methods Swiss mice were exposed to 90 ppm of lead in their drinking water throughout gestation and the first ten postnatal days. At postnatal day 10 (PN10), blood lead levels (BLLs) were about 30 µg/dL. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or a vehicle 4 h before the evaluation of locomotor activity in the open field. Results Lead-exposed males did not display differences in locomotor activity compared to controls, while lead-exposed females showed a significant increase in locomotion. Vinpocetine treatment significantly reversed the lead-induced hyperactivity in females. Conclusions These findings suggest that the cAMP and cGMP signaling pathways play a role in the hyperactivity induced by lead exposure. Full article

(This article belongs to the Special Issue Role of Inflammation, Oxidative Stress, and Metabolic Dysfunction in Neurodevelopmental and Neurodegenerative Diseases: Pharmacological Targets and Therapeutic Interventions)

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17 pages, 853 KiB

Open AccessReview

Eye-Tracking Metrics as a Digital Biomarker for Neurocognitive Disorders in Multiple Sclerosis: A Scoping Review

by Sonja Cecchetti, Andrew T. Duchowski and Marco Cavallo

Brain Sci. 2025, 15(2), 149; https://doi.org/10.3390/brainsci15020149 - 31 Jan 2025

Viewed by 378

Abstract

Multiple sclerosis (MS) is an autoimmune disease classified as neurodegenerative because it can be associated with the more or less progressive development of neurological symptoms and cognitive deficits. In recent years, various studies have started to investigate eye movements in relation to cognitive [...] Read more.

Multiple sclerosis (MS) is an autoimmune disease classified as neurodegenerative because it can be associated with the more or less progressive development of neurological symptoms and cognitive deficits. In recent years, various studies have started to investigate eye movements in relation to cognitive impairment in persons with MS by means of eye-tracking equipment. However, the high heterogeneity of the paradigms used in different studies, as well as the different methodologies included, makes it difficult to provide a complete and precise picture of this important research and clinical issue. The purpose of the present in-depth scoping review was to map the existing literature in this field to determine which metrics may be relevant when dealing with the neurocognitive profile of people with MS. From the analyses of the included studies, the anti-saccade latency and errors were the most frequently proposed metrics. Correlation analyses between these metrics and cognitive measures showed significant associations between them, calling for a deeper investigation of this promising research and clinical field. The results of the present scoping review strongly suggest that eye tracking may play a crucial role in clinical practice during the early detection of neurocognitive disorders. There is a great need for primary research that addresses the full complexity of MS in its different phenotypes and the disease-related variables from a multidisciplinary perspective. Future research should clarify whether oculomotor dysfunction in MS follows or precedes cognitive deficits. Full article

(This article belongs to the Special Issue Eye-Tracking Monitoring of Neurological and Psychiatric Conditions Across Life Span)

20 pages, 676 KiB

Open AccessSystematic Review

Systematic Review of Self-Assessment Scales for Negative Symptoms in Schizophrenia

by Lucie Métivier and Sonia Dollfus

Brain Sci. 2025, 15(2), 148; https://doi.org/10.3390/brainsci15020148 - 31 Jan 2025

Viewed by 309

Abstract

Background/Objectives: Negative symptoms (NSs) significantly impair the outcome of schizophrenia, primarily due to their effect on quality of life and their resistance to pharmacological treatments. Several scales have been developed to assess the various dimensions of NSs, including avolition, anhedonia, alogia, social [...] Read more.

Background/Objectives: Negative symptoms (NSs) significantly impair the outcome of schizophrenia, primarily due to their effect on quality of life and their resistance to pharmacological treatments. Several scales have been developed to assess the various dimensions of NSs, including avolition, anhedonia, alogia, social withdrawal, and blunted affect. While observer-rated scales are the most commonly used, self-assessment tools remain underutilized. However, self-assessments offer a promising approach for gaining insights into the personal experiences of individuals. The objective of this review was to identify and report the psychometric properties of self-assessment scales for NSs that are relevant for both research and clinical practice, with a focus on tools that assess multiple domains of NSs in order to support comprehensive evaluations and tailored therapeutic strategies. Methods: We conducted an exhaustive literature review following PRISMA guidelines to identify self-evaluation scales that evaluate several domains of NSs in the MEDLINE and Web of Science databases. The COSMIN checklist was used to assess the methodological quality of each tool. Results: Our review identified five self-assessment scales. Among these, two scales received a Grade A recommendation for use in clinical or research practice: the Self-evaluation Negative Symptom (SNS), which assesses the five domains of NSs, and the Motivation And Pleasure Scale Self-report (MAP-SR), which evaluates anhedonia, avolition, and social withdrawal. Conclusions: The SNS and the MAP-SR are the only tools with sufficient psychometric properties, making them reliable for use in both research and clinical practice. Despite the development of self-assessment tools for NSs, their integration into research and clinical settings remains limited, highlighting the need for increased utilization to enhance the understanding and management of these symptoms. Full article

(This article belongs to the Section Neuropsychiatry)

15 pages, 571 KiB

Open AccessArticle

Binaural Pulse Modulation (BPM) as an Adjunctive Treatment for Anxiety: A Pilot Study

by Gerry Leisman, Joseph Wallach, Yanin Machado-Ferrer, Mauricio-Chinchilla Acosta, Abraham-Gérard Meyer, Robert Lebovits and Scott Donkin

Brain Sci. 2025, 15(2), 147; https://doi.org/10.3390/brainsci15020147 - 31 Jan 2025

Viewed by 353

Abstract

Background: Treating psychiatric illnesses or influencing mental states with neurofeedback is challenging, likely due to the limited spatial specificity of EEG and the complications arising from the inadequate signal-to-noise ratio reduction of single-trial EEG. Objective: This pilot study aimed to investigate the feasibility [...] Read more.

Background: Treating psychiatric illnesses or influencing mental states with neurofeedback is challenging, likely due to the limited spatial specificity of EEG and the complications arising from the inadequate signal-to-noise ratio reduction of single-trial EEG. Objective: This pilot study aimed to investigate the feasibility of employing a binaural pulse mode-modulation (BPM) device to reduce anxiety by self-regulation. We desired to determine whether anxiety could be significantly reduced or regulated using BPM-type systems. Methods: Sixty adult participants were examined with self-reported anxiety tests (COVID Stress Scale, Generalized Anxiety Disorder 7, Beck Depression Inventory-II), which were completed before treatment, after four weeks, and after 12 weeks post-treatment. This BPM device produced two frequencies which combined to create a binaural pulse through differential auditory tone presentations. The participant calibrated the suitable target tone for optimal treatment efficacy. Each participant adjusted the binaural pulse to enhance the emotional intensity felt when envisioning an experience with comparable emotional significance or while performing a cognitive task while concurrently listening to music. The “treatment” relied on the individual’s regulation of binaural pulses to obtain the desired state. The training concentrated on particular facets of their psychological challenges while listening to an auditory tone, adjusting a knob until the sound amplified the intended emotional state. Another knob was turned to intensify the emotional state associated with distress reduction. Results: On the self-reported measures, the BPM treatment group was significantly better than the sham treatment (control) groups (p < 0.01). These findings indicate that over the four-week intervention period, BPM was similarly effective. On the GAD-7, the significant difference over time was noted before treatment and at the end of treatment for the experimental group, with the average GAD-7 score at the end of treatment being significantly lower (p < 0.01). Conclusions: BPM seems to induce a short-term alteration in self-reported distress levels during therapy. This study’s limitations are examined, and recommendations for future research are provided. Full article

(This article belongs to the Special Issue Neuromodulation and Neurostimulation in Psychiatric Disorders)

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17 pages, 3841 KiB

Open AccessArticle

Response Assessment in Long-Term Glioblastoma Survivors Using a Multiparametric MRI-Based Prediction Model

by Laiz Laura de Godoy, Archith Rajan, Amir Banihashemi, Thara Patel, Arati Desai, Stephen Bagley, Steven Brem, Sanjeev Chawla and Suyash Mohan

Brain Sci. 2025, 15(2), 146; https://doi.org/10.3390/brainsci15020146 - 31 Jan 2025

Viewed by 374

Abstract

Purpose: Early treatment response assessments are crucial, and the results are known to better correlate with prognosis and survival outcomes. The present study was conducted to differentiate true progression (TP) from pseudoprogression (PsP) in long-term-surviving glioblastoma patients using our previously established multiparametric MRI-based [...] Read more.

Purpose: Early treatment response assessments are crucial, and the results are known to better correlate with prognosis and survival outcomes. The present study was conducted to differentiate true progression (TP) from pseudoprogression (PsP) in long-term-surviving glioblastoma patients using our previously established multiparametric MRI-based predictive model, as well as to identify clinical factors impacting survival outcomes in these patients. Methods: We report six patients with glioblastoma that had an overall survival longer than 5 years. When tumor specimens were available from second-stage surgery, histopathological analyses were used to classify between TP (>25% characteristics of malignant neoplasms; n = 2) and PsP (<25% characteristics of malignant neoplasms; n = 2). In the absence of histopathology, modified RANO criteria were assessed to determine the presence of TP (n = 1) or PsP (n = 1). The predictive probabilities (PPs) of tumor progression were measured from contrast-enhancing regions of neoplasms using a multiparametric MRI-based prediction model. Subsequently, these PP values were used to define each lesion as TP (PP ≥ 50%) or PsP (PP < 50%). Additionally, detailed clinical information was collected. Results: Our predictive model correctly identified all patients with TP (n = 3) and PsP (n = 3) cases, reflecting a significant concordance between histopathology/modified RANO criteria and PP values. The overall survival varied from 5.1 to 12.3 years. Five of the six glioblastoma patients were MGMT promoter methylated. All patients were female, with a median age of 56 years. Moreover, all six patients had a good functional status (KPS ≥ 70), underwent near-total/complete resection, and received alternative therapies. Conclusions: Multiparametric MRI can aid in assessing treatment response in long-term-surviving glioblastoma patients. Full article

(This article belongs to the Special Issue Advanced Approaches to the Diagnosis and Treatment of Central Nervous System Tumors)

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14 pages, 506 KiB

Open AccessArticle

Multidomain Cognitive Tele-Neurorehabilitation Training in Long-Term Post-Stroke Patients: An RCT Study

by Marianna Contrada, Gennarina Arabia, Martina Vatrano, Caterina Pucci, Isabel Mantia, Federica Scarfone, Giusi Torchia, Maria Quintieri, Antonio Cerasa and Loris Pignolo

Brain Sci. 2025, 15(2), 145; https://doi.org/10.3390/brainsci15020145 - 31 Jan 2025

Viewed by 357

Abstract

Purpose: Over the past decade, tele-neurorehabilitation (TNR) has emerged as a vital and effective tool for delivering continuous care to stroke patients, playing a key role in enhancing functional recovery and ensuring consistent access to rehabilitation services. In the field of TNR, various [...] Read more.

Purpose: Over the past decade, tele-neurorehabilitation (TNR) has emerged as a vital and effective tool for delivering continuous care to stroke patients, playing a key role in enhancing functional recovery and ensuring consistent access to rehabilitation services. In the field of TNR, various protocols are utilized to ensure effective cognitive stimulation at home. Recent preliminary studies highlight the employment of multidomain cognitive interventions, which would seem to induce more stable and relevant cognitive recovery in stroke patients. A randomized controlled trial (RCT) study was conducted to compare the effectiveness of a TNR multidomain cognitive approach to conventional face-to-face cognitive treatment. Methods: A total of 30 patients with stroke were equally enrolled and randomly assigned to the experimental and control groups. In the experimental group, patients received sessions of home-based cognitive virtual reality rehabilitation system (VRRS) training. The control group underwent traditional face-to-face cognitive multidomain treatment at the hospital. The therapy was given for one hour every day for four weeks in both groups. Specific cognitive domains, including memory, praxis skills, executive functions, and speech therapy, were stimulated in the procedure. Neuropsychological evaluations were performed at three timepoints: at baseline (T0), at the end of TNR (T1), and six months later (T2). Results: The TNR group demonstrated significant improvements in working memory and language abilities, as well as in depressive symptoms and caregiver burden, with an average decrease of 2.07. Most of this improvement persisted 6 months after treatment. The group that received face-to-face cognitive treatment showed improvements (not persisting at T2) after treatment in a task measuring constructive apraxia and alternating attention with the cognitive skill of set-shifting. Conclusions: According to our findings, multidomain cognitive TNR may be useful in enhancing cognitive outcomes in stroke populations (even six months after treatment concludes). TNR may also be a viable way to deliver these interventions since it boosts people’s motivation to train and, consequently, their adherence to treatment while also having a positive effect on caregivers’ distress management. Full article

(This article belongs to the Special Issue Recent Advances in Neurorehabilitation: Emerging Techniques and Technologies)

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34 pages, 2413 KiB

Open AccessReview

Epigallocatechin-3-Gallate, Quercetin, and Kaempferol for Treatment of Parkinson’s Disease Through Prevention of Gut Dysbiosis and Attenuation of Multiple Molecular Mechanisms of Pathogenesis

by Alexis Kalu and Swapan K. Ray

Brain Sci. 2025, 15(2), 144; https://doi.org/10.3390/brainsci15020144 - 31 Jan 2025

Viewed by 302

Abstract

Parkinson’s disease (PD) is a neurodegenerative condition in which degeneration mostly occurs in the dopamine (DA)-producing neurons within the substantia nigra in the midbrain. As a result, individuals with this condition suffer from progressively worsening motor impairment because of the resulting DA deficiency, [...] Read more.

Parkinson’s disease (PD) is a neurodegenerative condition in which degeneration mostly occurs in the dopamine (DA)-producing neurons within the substantia nigra in the midbrain. As a result, individuals with this condition suffer from progressively worsening motor impairment because of the resulting DA deficiency, along with an array of other symptoms that, over time, force them into a completely debilitating state. As an age-related disease, PD has only risen in prevalence over the years; thus, an emphasis has recently been placed on discovering a new treatment for this condition that is capable of attenuating its progression. The gut microbiota has become an area of intrigue among PD studies, as research into this topic has shown that imbalances in the gut microbiota (colloquially known as gut dysbiosis) seemingly promote the primary etiologic factors that have been found to be associated with PD and its pathologic progression. With this knowledge, research into PD treatment has begun to expand beyond synthetic pharmaceutical compounds, as a growing emphasis has been placed on studying plant-derived polyphenolic compounds, namely flavonoids, as a new potential therapeutic approach. Due to their capacity to promote a state of homeostasis in the gut microbiota and their long-standing history as powerful medicinal agents, flavonoids have begun to be looked at as promising therapeutic agents capable of attenuating several of the pathologic states seen amidst PD through indirect and direct means. This review article focuses on three flavonoids, specifically epigallocatechin-3-gallate, quercetin, and kaempferol, discussing the mechanisms through which these powerful flavonoids can potentially prevent gut dysbiosis, neuroinflammation, and other molecular mechanisms involved in the pathogenesis and progression of PD, while also exploring their real-world application and how issues of bioavailability and potential drug interactions can be circumvented or exploited. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

16 pages, 454 KiB

Open AccessArticle

Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry

by Jaime Raymond, Ileana M. Howard, Jasmine Berry, Theodore Larson, D. Kevin Horton and Paul Mehta

Brain Sci. 2025, 15(2), 143; https://doi.org/10.3390/brainsci15020143 - 31 Jan 2025

Viewed by 456

Abstract

Background/Objectives: To examine if head injury (HI) is associated with age at ALS diagnosis in the United States. Methods: In this cross-sectional populationf-based analysis, we identified patients with ALS who were registered from 2015 to 2023 who completed the Registry’s head trauma survey [...] Read more.

Background/Objectives: To examine if head injury (HI) is associated with age at ALS diagnosis in the United States. Methods: In this cross-sectional populationf-based analysis, we identified patients with ALS who were registered from 2015 to 2023 who completed the Registry’s head trauma survey module. The association between HI and age at ALS diagnosis was assessed using multivariate analysis. Results: Of the 3424 respondents, 56.6% had experienced a HI. The adjusted odds ratio (aOR) for an ALS diagnosis before age 60 years for patients with a HI was 1.24 (95% CI, 1.07–1.45). One or two HIs had an aOR of 1.15 (95% CI, 0.97–1.36), and five or more HIs had an aOR of 1.58 (95% CI, 1.19–2.09). HI before age 18 years yielded an aOR of 2.03 (95% CI, 1.53–2.70) as well as HI between the ages of 18 and 30 years (aOR = 1.48, 95% CI: 1.06–2.06)). When narrowing the analysis to patients with HI before age 18 compared with patients with no HI, we found an association with HI that led to an emergency department or hospital visit (aOR = 1.50 (95% CI: 1.21–1.86)). Conclusions: In this cross-sectional analysis of ALS patients, HIs occurring in childhood and early adulthood and the number of HIs increased the odds of being diagnosed before age 60 years. These results suggest that HI continues to be a risk factor for ALS and could be associated with a younger age of diagnosis. Full article

(This article belongs to the Section Neuromuscular and Movement Disorders)

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4 pages, 143 KiB

Open AccessEditorial

Brain Mechanisms of Hypnosis

by Giuseppe De Benedittis

Brain Sci. 2025, 15(2), 142; https://doi.org/10.3390/brainsci15020142 - 31 Jan 2025

Viewed by 287

Abstract

Hypnosis is the longest-lasting of all psychotherapies and one of the oldest practiced methods for the control of pain and other stress-related chronic disorders [...] Full article

(This article belongs to the Special Issue Brain Mechanism of Hypnosis)

23 pages, 1149 KiB

Open AccessArticle

Psychological Determinants of Conflict with the Law and Susceptibility to Rehabilitation in Relation to the Presence of Symptoms of Attention Deficit Hyperactivity Disorder

by Agnieszka Nowogrodzka, Mirosław Andrusiewicz and Ewa Mojs

Brain Sci. 2025, 15(2), 141; https://doi.org/10.3390/brainsci15020141 - 31 Jan 2025

Viewed by 400

Abstract

Background/Objectives: Many prison-sentenced individuals exhibit symptoms of mental dysfunctions, including attention deficit hyperactivity disorder (ADHD). The presence of co-occurring mental disorders further complicates their rehabilitation and social reintegration efforts. Given these challenges, understanding the role of specific disorders, such as ADHD, is critical [...] Read more.

Background/Objectives: Many prison-sentenced individuals exhibit symptoms of mental dysfunctions, including attention deficit hyperactivity disorder (ADHD). The presence of co-occurring mental disorders further complicates their rehabilitation and social reintegration efforts. Given these challenges, understanding the role of specific disorders, such as ADHD, is critical for developing targeted interventions tailored to the needs of incarcerated individuals and improving their outcomes. This research aimed to clarify the relationships among hyperactivity, criminal behavior, and psychological functioning to inform preventative and therapeutic strategies. Methods: This study investigated the complex interplay among attention deficit hyperactivity disorder (ADHD) symptoms, criminal behavior, and various psychological factors in a sample of 391 male inmates from low-security Polish prisons and a control group of non-offending men. Principal component analysis (PCA) and Spearman’s rank correlation were used to analyze the relationships among ADHD severity, type of crime (no crime, property crime, crime involving aggression), family functioning, childhood trauma, early maladaptive schemas, and mental health disorders. Results: The results revealed that while traumatic experiences were present across all groups, stronger family cohesion and support were associated with the absence of ADHD symptoms and criminal behavior. As ADHD severity and criminal behavior escalated, particularly in cases involving aggression, family support diminished, and maladaptive schemas, including “disconnection and rejection” and “excessive vigilance and inhibition”, became more prominent, alongside increased correlations with mental health issues (anxiety and depression). Conclusions: The findings underscore the crucial role of family environment and early intervention in mitigating the risks associated with ADHD and criminal behavior, highlighting the need for comprehensive interventions targeting maladaptive schemas and providing support for both internalizing and externalizing symptoms. Limitations include the retrospective nature of data collection and the exclusive focus on male inmates in low-security facilities. Full article

(This article belongs to the Topic Personality, Health and Well-Being among Different Age Groups)

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14 pages, 339 KiB

Open AccessArticle

Efficacy of Body Representation Rehabilitation Training for Adults with Unilateral Brain Damage: A Preliminary Study

by Maria Cropano, Mariachiara Gaita, Erica Dolce, Silvia Canino, Valentina Gerarda Angelillo, Antonella Di Vita, Maddalena Boccia, Simona Raimo and Liana Palermo

Brain Sci. 2025, 15(2), 140; https://doi.org/10.3390/brainsci15020140 - 30 Jan 2025

Viewed by 353

Abstract

Background/Objectives: Body representations (BRs) are essential for guiding movements, maintaining spatial awareness, and achieving effective interactions with the environment. Several studies suggest that BRs are frequently impaired following unilateral brain damage, emphasising the need for tailored rehabilitation interventions; however, there is a lack [...] Read more.

Background/Objectives: Body representations (BRs) are essential for guiding movements, maintaining spatial awareness, and achieving effective interactions with the environment. Several studies suggest that BRs are frequently impaired following unilateral brain damage, emphasising the need for tailored rehabilitation interventions; however, there is a lack of studies evaluating the effectiveness of training specifically designed to improve different kinds of functional BRs after stroke. Therefore, the present study aimed to present and implement a specific rehabilitation training program for BR alterations and evaluate its effectiveness in a sample of adults with unilateral brain damage. Methods: Nine adults with unilateral brain damage and seven age- and education-matched healthy controls were recruited. Both groups underwent a neuropsychological assessment to evaluate BR (action- and nonaction-oriented). Additionally, functional autonomy and motor functioning were assessed in the patient group. Following an initial assessment (T0), the patients participated in a BR-specific rehabilitation intervention. At the end of the rehabilitation program (T1), both groups were re-evaluated with the same tasks used at T0. Results: At T0, the patient group performed worse on BR tasks than the controls. At T1, a significant improvement in the nonaction-oriented BR and functional autonomy was observed in the patient group. Conclusions: This preliminary study suggests the effectiveness of a targeted rehabilitation intervention for BR in promoting enhanced body boundary awareness and greater accuracy in the perception of body part positions, possibly leading to increased functional autonomy. These findings highlight the importance of incorporating BR training in rehabilitation programs for adults with acquired brain damage, alongside motor rehabilitation. Full article

(This article belongs to the Section Neurorehabilitation)

24 pages, 1422 KiB

Open AccessArticle

Processing of Scene-Grammar Inconsistencies in Children with Developmental Language Disorder—Insights from Implicit and Explicit Measures

by Daniela Bahn, Dilara Deniz Türk, Nikol Tsenkova, Gudrun Schwarzer, Melissa Le-Hoa Võ and Christina Kauschke

Brain Sci. 2025, 15(2), 139; https://doi.org/10.3390/brainsci15020139 - 30 Jan 2025

Viewed by 333

Abstract

Background/Objectives: Developmental language disorders (DLD) are often associated with co-occurring neurodevelopmental difficulties, including attentional or social–emotional problems. Another nonverbal domain, i.e., visual cognition and its relationship to DLD, is virtually unexplored. However, learning visuospatial regularities – a scene-grammar - is crucial for navigating [...] Read more.

Background/Objectives: Developmental language disorders (DLD) are often associated with co-occurring neurodevelopmental difficulties, including attentional or social–emotional problems. Another nonverbal domain, i.e., visual cognition and its relationship to DLD, is virtually unexplored. However, learning visuospatial regularities – a scene-grammar - is crucial for navigating our daily environment. These regularities show certain similarities to the structure of language and there is preliminary evidence for a relationship between scene processing and language competence in preschoolers with and without DLD. This study compared implicit and explicit visuospatial knowledge of everyday indoor scenes in older children, aged 6 to 10 years, of both groups. Methods: We measured ‘dwell times’ on semantic and syntactic object – scene inconsistencies via eye-tracking and performance in an object-placement task, and their associations with children’s language, visual, and cognitive skills. Results: Visual attention towards object-scene inconsistencies was highly comparable between groups, but children with DLD scored lower in a visual perception test and higher language skills were associated with higher visuo-cognitive performance in both tasks. In the explicit scene-grammar measurement, this relationship only existed for children with DLD and disappeared when nonverbal cognitive performance was controlled. Conclusions: Our study suggests the existence of mild problems in visuospatial processing co-occurring with DLD, which is partly influenced by age and nonverbal cognitive ability. The acquisition of visual cognition and linguistic knowledge is an interactive, multimodal process where the perception of objects in scenes might affect how the words for these objects are learned and vice versa. A better understanding of this interplay could eventually have impact on the diagnosis and treatment of DLD. Full article

(This article belongs to the Special Issue Neurodevelopmental Disorders and Early Language Acquisition)

18 pages, 2885 KiB

Open AccessArticle

Effect of Vibro-Tactile Stimulation Sequence and Support Surface Inclination on Gait and Balance Measures

by Christopher P. Engsberg, Nathaniel H. Hunt, Steven Barlow and Mukul Mukherjee

Brain Sci. 2025, 15(2), 138; https://doi.org/10.3390/brainsci15020138 - 30 Jan 2025

Viewed by 384

Abstract

The plantar surfaces of the feet are important for balance control during walking, specifically by allowing for the perception of pressure movements during stance. Background/Objectives: The current study aimed to perturb CoP movement perception in healthy individuals by applying vibrations to the [...] Read more.

The plantar surfaces of the feet are important for balance control during walking, specifically by allowing for the perception of pressure movements during stance. Background/Objectives: The current study aimed to perturb CoP movement perception in healthy individuals by applying vibrations to the soles of the feet in different stimulation sequences: a natural pattern that followed CoP movement (gait-like) and a perturbing pattern that did not follow the CoP (random) during walking. We hypothesized that the gait-like stimulation sequence would be similar to walking without any stimulation and therefore have no effect on balance measures and that the random sequence would negatively affect balance measures such as the anteroposterior (AP) and mediolateral (ML) margins of stability (MoSs) and foot placement area. Methods: Subjects walked at a level angle and 5.0 and 8.0 degrees of incline and with low visual conditions to increase reliance on tactile sensations from the feet. Results: No significant effect of the stimulation sequence was found at any incline, while there was a significant effect of incline. As the incline increased from level to 5 deg, subjects reduced their AP MoS measured at heel strikes from 4.36 ± 0.56 cm to 1.95 ± 1.07 cm and increased their foot placement area from 24.04 ± 11.13 cm² to 38.98 ± 17.47 cm². However, the AP MoS measured at midstance did not significantly change as the incline increased. Conclusions: The stimulation sequence had no effect on the dependent measures, but the subjects could still feel the vibrations on the plantar surfaces during walking; this implies that similar stimulation techniques could be a useful method for applying directive biofeedback without negatively impacting gait. Overall, this study demonstrates the detailed control of our tactile system and the adaptability of healthy individuals while walking with a perturbing stimulation. Full article

(This article belongs to the Special Issue Multisensory Perception of the Body and Its Movement)

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25 pages, 653 KiB

Open AccessReview

The Role of Immune Cells in Moyamoya Disease

by Sheng Wang, Qian Jiang, Yuan Liu, Xincheng Zhang, Yimin Huang and Huaqiu Zhang

Brain Sci. 2025, 15(2), 137; https://doi.org/10.3390/brainsci15020137 - 30 Jan 2025

Viewed by 267

Abstract

Moyamoya disease (MMD) is a rare progressive cerebrovascular disorder characterized by the stenosis or occlusion of the terminal segments of the internal carotid arteries, leading to the development of abnormal collateral vascular networks. These networks are a compensatory mechanism for reduced blood flow [...] Read more.

Moyamoya disease (MMD) is a rare progressive cerebrovascular disorder characterized by the stenosis or occlusion of the terminal segments of the internal carotid arteries, leading to the development of abnormal collateral vascular networks. These networks are a compensatory mechanism for reduced blood flow to the brain. Despite extensive research, the exact etiology of MMD remains unknown, although recent studies suggest that immune system dysfunction plays a critical role in its pathogenesis. In particular, the involvement of immune cells such as T cells, macrophages, and dendritic cells has been increasingly recognized. These immune cells contribute to the inflammatory process and vascular remodeling observed in MMD patients, further complicating the disease’s progression. Inflammation and immune-mediated damage to the vessel walls may accelerate the narrowing and occlusion of arteries, exacerbating ischemic events in the brain. Additionally, studies have revealed that certain genetic and environmental factors can influence immune system activation in MMD, linking these pathways to disease development. This review aims to provide a comprehensive overview of the immune mechanisms at play in MMD, focusing on how immune cells participate in vascular injury and remodeling. Understanding these immunological processes may offer new therapeutic targets to halt or reverse disease progression, potentially leading to more effective treatment strategies for MMD. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

32 pages, 5318 KiB

Open AccessReview

Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours

by Smita Khilar, Antonina Dembinska-Kenner, Helen Hall, Nikolaos Syrmos, Gianfranco K. I. Ligarotti, Puneet Plaha, Vasileios Apostolopoulos, Salvatore Chibbaro, Giuseppe Maria Vincenzo Barbagallo and Mario Ganau

Brain Sci. 2025, 15(2), 136; https://doi.org/10.3390/brainsci15020136 - 30 Jan 2025

Viewed by 725

Abstract

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the [...] Read more.

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood–brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following the PRISMA-ScR guidelines and checklist was conducted using key terms input into PubMed to find articles that reflect emerging trends in the utilisation of nanomedicine in drug delivery for primary and secondary brain tumours. (3) Results: The review highlights various strategies by which different nanoparticles can be exploited to bypass the BBB; we provide a synthesis of the literature on the ongoing contributions to therapeutic protocols based on chemotherapy, immunotherapy, focused ultrasound, radiotherapy/radiosurgery, and radio-immunotherapy. (4) Conclusions: The emerging trends summarised in this scoping review indicate encouraging advantageous properties of nanoparticles as potential effective drug delivery mechanisms; however, there are still nanotoxicity issues that largely remain to be addressed before the translation of these innovations from laboratory to clinical practice. Full article

(This article belongs to the Special Issue Advanced Clinical Technologies in Treating Neurosurgical Diseases)

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14 pages, 2079 KiB

Open AccessArticle

The Problem with Time: Application of Partial Least Squares Analysis on Time-Frequency Plots to Account for Varying Time Intervals with Applied EEG Data

by Jessie M. H. Szostakiwskyj, Filomeno Cortese, Raneen Abdul-Rhaman, Sarah J. Anderson, Amy L. Warren, Rebecca Archer, Emma Read and Kent G. Hecker

Brain Sci. 2025, 15(2), 135; https://doi.org/10.3390/brainsci15020135 - 30 Jan 2025

Viewed by 368

Abstract

Background/Objectives: When attempting to study neurocognitive mechanisms with electroencephalography (EEG) in applied ecologically valid settings, responses to stimuli may differ in time, which presents challenges to traditional EEG averaging methods. In this proof-of-concept paper, we present a method to normalize time over unequal [...] Read more.

Background/Objectives: When attempting to study neurocognitive mechanisms with electroencephalography (EEG) in applied ecologically valid settings, responses to stimuli may differ in time, which presents challenges to traditional EEG averaging methods. In this proof-of-concept paper, we present a method to normalize time over unequal trial lengths while preserving frequency content. Methods: Epochs are converted to time-frequency space where they are resampled to contain an equal number of timepoints representing the proportion of trial complete rather than true time. To validate this method, we used EEG data recorded from 8 novices and 4 experts in veterinary medicine while completing decision-making tasks using two question types: multiple-choice and script concordance questions used in veterinary school exams. Results: The resulting resampled time-frequency data were analyzed with partial least squares (PLS), a multivariate technique that extracts patterns of data that support a contrast between conditions and groups while controlling for Type I error. We found a significant latent variable representing a difference between question types for experts only. Conclusions: Despite within and between subject differences in timing, we found consistent differences between question types in experts in gamma and beta bands that are consistent with changes resulting from increased information load and decision-making. This novel analysis method may be a viable path forward to preserve ecological validity in EEG studies. Full article

(This article belongs to the Special Issue Advances in Educational Neuroscience: Current Status and Future Directions)

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23 pages, 2560 KiB

Open AccessReview

Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials

by Ladan Dawoody Nejad and Erik P. Pioro

Brain Sci. 2025, 15(2), 134; https://doi.org/10.3390/brainsci15020134 - 30 Jan 2025

Viewed by 360

Abstract

Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10–15% of cases being familial and the majority being sporadic with no known cause. There are no animal models for the 85–90% of sporadic ALS cases. More creative, sophisticated models of ALS [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10–15% of cases being familial and the majority being sporadic with no known cause. There are no animal models for the 85–90% of sporadic ALS cases. More creative, sophisticated models of ALS disease are required to unravel the mysteries of this complicated disease. While ALS patients urgently require new medications and treatments, suitable preclinical in vitro models for drug screening are lacking. Therefore, human-derived induced pluripotent stem cell (hiPSC) technology offers the opportunity to model diverse and unreachable cell types in a culture dish. In this review, we focus on recent hiPSC-derived ALS neuronal and non-neuronal models to examine the research progress of current ALS 2D monocultures, co-cultures, and more complex 3D-model organoids. Despite the challenges inherent to hiPSC-based models, their application to preclinical drug studies is enormous. Full article

(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis: Recent Considerations for Diagnosis, Pathogenesis and Therapy)

15 pages, 796 KiB

Open AccessArticle

Emotional Availability in Autism Intervention: A Mother–Father Comparative Analysis

by Silvia Perzolli, Giulio Bertamini, Paola Venuti and Arianna Bentenuto

Brain Sci. 2025, 15(2), 133; https://doi.org/10.3390/brainsci15020133 - 29 Jan 2025

Viewed by 464

Abstract

Background/Objectives: The literature highlights the importance of parental involvement in autism treatment. However, much research has predominantly focused on child outcomes and cognitive dimensions. This study explores the impact of an early intensive intervention with parental involvement, focusing on changes in parents’ affective [...] Read more.

Background/Objectives: The literature highlights the importance of parental involvement in autism treatment. However, much research has predominantly focused on child outcomes and cognitive dimensions. This study explores the impact of an early intensive intervention with parental involvement, focusing on changes in parents’ affective exchanges. Notably, given the paucity of studies on fathers in the intervention context, this study examines the comparative trajectory of change considering both caregivers. Methods: Twenty autistic preschoolers were monitored for one year during a parental-based intervention. Child–mother and child–father play interactions were coded with the Emotional Availability Scales at baseline and at 12 months. Repeated measures linear mixed-effect models were employed to investigate time and caregiver effects and their interaction. Results: Results highlighted both similarities and differences in change trajectories between caregivers. Parental sensitivity, structuring, and non-intrusiveness significantly increased for both parents with fathers showing more prominent gains in structuring the interaction while being non-intrusive. Child responsiveness and involvement significantly increased, showing similar trajectories with both caregivers. Children were generally more involved while interacting with their fathers. Conclusion: Parent–child interactions with caregivers evolved toward more adaptive exchanges regarding emotional availability for children’s and parents’ dimensions. Fathers appeared to be particularly receptive regarding acquiring structuring abilities and non-intrusive behaviors. Our results underscore the importance of investigating parental features as well as the importance of actively involving caregivers to support distal outcomes and generalization. Full article

(This article belongs to the Section Developmental Neuroscience)

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14 pages, 380 KiB

Open AccessReview

Natural Source of Drugs Targeting Central Nervous System Tumors—Focus on NAD(P)H Oxidoreductase 1 (NQO1) Activity

by Nikola M. Stojanovic, Milica Mitić, Jovan Ilić, Milica Radić, Miša Radisavljević, Marko Baralić and Miljan Krstić

Brain Sci. 2025, 15(2), 132; https://doi.org/10.3390/brainsci15020132 - 29 Jan 2025

Viewed by 338

Abstract

Central nervous system (CNS) tumors involve a large and diverse group of malignancies that arise from various cell types within the brain tissue. Although there are advances in treatments, CNS tumors still remain challenging, due to their complex biology and the delicate nature [...] Read more.

Central nervous system (CNS) tumors involve a large and diverse group of malignancies that arise from various cell types within the brain tissue. Although there are advances in treatments, CNS tumors still remain challenging, due to their complex biology and the delicate nature of the surrounding tissue. NAD(P)H O=oxidoreductase 1 (NQO1) is an enzyme that plays a critical role in the detoxification of quinones, protecting cells from oxidative stress. In CNS tumors this enzyme is often overexpressed, which contributes to the resistance of tumor cells to chemotherapy by enhancing their antioxidant defenses. NQO1 influences the progression of CNS tumors by affecting downstream signaling pathways, such as those involving the transcription factor SNAIL, as well as others that are associated with tumor behavior. Plants represent a valuable source of numerous constituents with different chemical structures known to affect different molecular signaling pathways associated with different pathologies. Full article

(This article belongs to the Special Issue Brain Tumors: From Molecular Basis to Therapy)

22 pages, 4307 KiB

Open AccessArticle

A Computational Analysis of the Effect of Hard Choices on the Individuation of Values

by Norberto M. Grzywacz

Brain Sci. 2025, 15(2), 131; https://doi.org/10.3390/brainsci15020131 - 29 Jan 2025

Viewed by 395

Abstract

Background/Objectives: Experimental studies show that when an individual makes choices, they affect future decisions. Future choices tend to be consistent with past ones. This tendency matters in the context of ambivalent situations because they may not lead to clear choices, often leading people [...] Read more.

Background/Objectives: Experimental studies show that when an individual makes choices, they affect future decisions. Future choices tend to be consistent with past ones. This tendency matters in the context of ambivalent situations because they may not lead to clear choices, often leading people to make “arbitrary” decisions. Thus, because of choice consistency with the past, people’s decision-making values diverge. Thus, hard choices may contribute to the individuation of values. Methods: Here, we develop a Bayesian framework for the effects of cognitive choice consistency on decision-making. This framework thus extends earlier cognitive-science Bayesian theories, which focus on other tasks, such as inference. The minimization of total surprisals considering the history of stimuli and chosen actions implements choice consistency in our framework. We then use a computational model based on this framework to study the effect of hard choices on decision-making values. Results: The results for action selection based on sensory stimuli show that hard choices can cause the spontaneous symmetry breaking of the decision-making space. This spontaneous symmetry breaking is different across individuals, leading to individuation. If in addition, rewards are given to certain choices, then the direction of the symmetry breaking can be guided by these incentives. Finally, we explore the effects of the parametric complexity of the model, the number of choices, and the length of choice memory. Conclusions: Considering the brain’s mechanism of choice consistency and the number of hard choices made in life, we hypothesize that they contribute to individuality. We assess this hypothesis by placing our study in the context of the cognition-of-individuality literature and proposing experimental tests of our computational results. Full article

(This article belongs to the Section Cognitive, Social and Affective Neuroscience)

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17 pages, 1316 KiB

Open AccessArticle

Mitochondrial Dysfunction Correlates with Brain Amyloid Binding, Memory, and Executive Function in Down Syndrome: Implications for Alzheimer’s Disease in Down Syndrome

by Jessica A. Beresford-Webb, Catherine J. McAllister, Alison Sleigh, Madeleine J. Walpert, Anthony J. Holland and Shahid H. Zaman

Brain Sci. 2025, 15(2), 130; https://doi.org/10.3390/brainsci15020130 - 28 Jan 2025

Viewed by 416

Abstract

Background/Objectives: Mitochondrial dysfunction is increasingly recognized as a central contributor to neurodegenerative diseases and age-related cognitive decline. Individuals with Down syndrome (DS) are at high risk of neurodegeneration due to Alzheimer’s disease (AD). This study aims to explore the relationship between mitochondrial dysfunction, [...] Read more.

Background/Objectives: Mitochondrial dysfunction is increasingly recognized as a central contributor to neurodegenerative diseases and age-related cognitive decline. Individuals with Down syndrome (DS) are at high risk of neurodegeneration due to Alzheimer’s disease (AD). This study aims to explore the relationship between mitochondrial dysfunction, brain amyloid-beta (Aβ) deposition, and cognitive decline in this population. Methods: We investigated mitochondrial function, brain amyloid-beta burden, and cognitive performance in a pilot study of a cohort of 10 eligible adults with DS selected from a sample of 28 individuals with DS. Phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) was used to assess mitochondrial function in skeletal muscle using a post-exercise paradigm, while positron emission tomography using ¹¹C-Pittsburgh compound B (PiB-PET) measured brain Aβ deposition. Cognitive performance was evaluated using the Cambridge Cognitive Examination adapted for individuals with Down syndrome (CAMCOG-DS) and executive function batteries. Results: Significant correlations were observed between slowed phosphocreatine (PCr) recovery in muscle and increased Aβ deposition in key brain regions, particularly the striatum. Cognitive performance inversely correlated with mitochondrial function, with pronounced deficits in memory and executive function tasks. Notably, an individual carrying the APOE-ε4 allele exhibited the poorest mitochondrial function, highest Aβ burden, and most severe cognitive impairment, suggesting a potential interaction between genetic risk and mitochondrial health. Conclusions: These findings highlight the role of mitochondrial dysfunction in DS-associated AD (DSAD) and its impact on cognition in adults. The results support targeting mitochondrial pathways as a potential therapeutic strategy to mitigate AD progression in DS populations. Further research with larger cohorts and longitudinal designs is needed to clarify causative mechanisms and develop effective interventions. Full article

(This article belongs to the Special Issue Down Syndrome: Pathophysiology, Cognitive Assessments and Potential Therapies)

19 pages, 752 KiB

Open AccessArticle

MSEI-ENet: A Multi-scale EEG-Inception Integrated Encoder Network for Motor Imagery EEG Decoding

by Pengcheng Wu, Keling Fei, Baohong Chen and Lizheng Pan

Brain Sci. 2025, 15(2), 129; https://doi.org/10.3390/brainsci15020129 - 28 Jan 2025

Viewed by 407

Abstract

Background: Due to complex signal characteristics and distinct individual differences, the decoding of a motor imagery electroencephalogram (MI-EEG) is limited by the unsatisfactory performance of suboptimal traditional models. Methods: A subject-independent model named MSEI-ENet is proposed for multiple-task MI-EEG decoding. It employs a [...] Read more.

Background: Due to complex signal characteristics and distinct individual differences, the decoding of a motor imagery electroencephalogram (MI-EEG) is limited by the unsatisfactory performance of suboptimal traditional models. Methods: A subject-independent model named MSEI-ENet is proposed for multiple-task MI-EEG decoding. It employs a specially designed multi-scale structure EEG-inception module (MSEI) for comprehensive feature learning. The encoder module further helps to detect discriminative information by its multi-head self-attention layer with a larger receptive field, which enhances feature representation and improves recognition efficacy. Results: The experimental results on Competition IV dataset 2a showed that our proposed model yielded an overall accuracy of 94.30%, MF1 score of 94.31%, and Kappa of 0.92. Conclusions: A performance comparison with state-of-the-art methods demonstrated the effectiveness and generalizability of the proposed model on challenging multi-task MI-EEG decoding. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

16 pages, 3117 KiB

Open AccessArticle

Minocycline Ameliorates Staphylococcus aureus-Induced Neuroinflammation and Anxiety-like Behaviors by Regulating the TLR2 and STAT3 Pathways in Microglia

by Jiao Zou, Junwei Gao, Weilong Shang and Xiaotang Fan

Brain Sci. 2025, 15(2), 128; https://doi.org/10.3390/brainsci15020128 - 28 Jan 2025

Viewed by 428

Abstract

Background: Anxiety disorders are the most common mental illnesses. S. aureus is a Gram-positive opportunistic pathogen most commonly associated with anxiety-like behaviors. Minocycline ameliorates Gram-negative bacterial LPS-induced anxiety-like behaviors by suppressing microglia activation. However, the effects of minocycline on anxiety-like behaviors caused by [...] Read more.

Background: Anxiety disorders are the most common mental illnesses. S. aureus is a Gram-positive opportunistic pathogen most commonly associated with anxiety-like behaviors. Minocycline ameliorates Gram-negative bacterial LPS-induced anxiety-like behaviors by suppressing microglia activation. However, the effects of minocycline on anxiety-like behaviors caused by S. aureus infections have received little attention. In this study, we aimed to investigate the molecular mechanism and effect of minocycline on anxiety-like behaviors caused by S. aureus infection. Methods: BV2 and N9 microglial cells were treated in vitro. The effects of minocycline on lipoteichoic acid (LTA)-stimulated inflammatory responses, STAT3 activation, and GLS1 expression were assessed using Western blotting, and cytokine secretion was determined using an ELISA. A mouse model was used to evaluate the capacity of minocycline to ameliorate anxiety-like behaviors caused by S. aureus infection. Results: We found that ≥100 μmol/L of minocycline remarkably attenuated LTA-induced TLR2 signaling pathway activation and proinflammatory cytokine expression in microglial cells. Minocycline prevented LTA-stimulated STAT3 activation and GLS1 expression in vitro. LTA-induced TLR2, TNF-α, IL-6, and GLS1 expression was markedly reduced by the inhibition of STAT3 phosphorylation. Mice were pretreated with 50 mg/kg of minocycline, significantly attenuating microglial activation and neuroinflammation. Minocycline also effectively alleviated the anxiety-like behaviors induced by S. aureus infection. Conclusions: Our findings indicate that minocycline alleviates S. aureus infection-induced anxiety-like behaviors by suppressing microglia activation. Full article

(This article belongs to the Section Behavioral Neuroscience)

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28 pages, 1230 KiB

Open AccessArticle

Effects of Competition on Left Prefrontal and Temporal Cortex During Conceptual Comparison of Brand-Name Product Pictures: Analysis of fNIRS Using Tensor Decomposition

by Terrence M. Barnhardt, Jasmine Y. Chan, Behnaz Ghoraani and Teresa Wilcox

Brain Sci. 2025, 15(2), 127; https://doi.org/10.3390/brainsci15020127 - 28 Jan 2025

Viewed by 393

Abstract

Abstract: Background/Objectives: Recent theories of the neurocognitive architecture of semantic memory have included a distinction between semantic control in the left inferior frontal gyrus (LIFG) and semantic representation in the left anterior temporal lobe (LATL). Support for this distinction has been found [...] Read more.

Abstract: Background/Objectives: Recent theories of the neurocognitive architecture of semantic memory have included a distinction between semantic control in the left inferior frontal gyrus (LIFG) and semantic representation in the left anterior temporal lobe (LATL). Support for this distinction has been found both in tasks in which high semantic selection demands have been instantiated and in tasks in which previous presentations of semantic information that compete with target information have been instantiated. Methods: In the current study, these manipulations were combined in a novel manner into a single task in which brand-name product pictures were used. Functional near-infrared spectroscopy (fNIRS) was used to measure hemodynamic activity and tensor decomposition, in addition to grand averaging, was used to analyze the fNIRS output. Results: Both analytic methods converged on the same set of findings. That is, in line with past studies, greater activity in the LIFG was observed in the competitive condition than in a repeated condition. However, unlike past studies, greater activity in the competitive condition was also observed in both the left and right anterior temporal lobes (ATLs). Conclusions: While it was possible that the novel combination of high selection and competition into a single task unlocked a semantic selection mechanism in the bilateral ATL, a number of other post-hoc explanations were offered for this unusual finding, including a re-interpretation of the high-selection task as an ad hoc categorization task. Finally, the convergence of the tensor decomposition and grand averaging approaches on the same set of findings supported tensor decomposition as a viable approach to the analysis of fNIRS data. Full article

(This article belongs to the Section Cognitive, Social and Affective Neuroscience)

13 pages, 810 KiB

Open AccessArticle

Differential Effects of Electroconvulsive Therapy on Patients with Schizophrenia Versus Depressive Disorder: Clinical Distinction Between Antipsychotic and Antidepressant Effects of Electroconvulsive Therapy

by Naho Nakayama, Tatsuo Nakahara, Hideyuki Iwanaga, Manabu Hashimoto, Takako Mitsudo, Yoshiomi Imamura, Hiroko Kunitake, Yoshito Mizoguchi and Takefumi Ueno

Brain Sci. 2025, 15(2), 126; https://doi.org/10.3390/brainsci15020126 - 27 Jan 2025

Viewed by 437

Abstract

Objective: Electroconvulsive therapy (ECT) is utilized for treating psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). We aimed to compare pre- and post-ECT treatment outcomes between patients with SCZ and a combined group of patients with MDD [...] Read more.

Objective: Electroconvulsive therapy (ECT) is utilized for treating psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). We aimed to compare pre- and post-ECT treatment outcomes between patients with SCZ and a combined group of patients with MDD and BD (MDD+BD) to assess the distinction between the antipsychotic and antidepressant effects of ECT. Methods: ECT was administered to patients with SCZ (n = 17) and those with MDD+BD (n = 7). Symptoms were evaluated using the brief psychiatric rating scale (BPRS), clinical global impression scale (CGI), and global assessment of functioning (GAF). Plasma brain-derived neurotrophic factor (BDNF) levels were also measured. Results: The BPRS, CGI, and GAF scores significantly differed after ECT compared with those before ECT in each patient group. However, no significant differences were observed between the groups for each disorder. No significant differences were observed in plasma BDNF levels between the groups at baseline and during ECT. At baseline, only depression scores were more favorable in the SCZ group, whereas positive symptoms and disorganization scores were higher in the MDD+BD group. During treatment, positive symptoms, activation, and disorganization items were significantly more favorable in the MDD+BD group compared with the SCZ group. Total BPRS scores were not associated with plasma BDNF levels; however, rating scores of the several items related to activation, resistance, and disorganization were positively correlated with BDNF levels. Conclusion: ECT effects on several clinical outcomes in the MDD+BD group were associated with plasma BDNF levels. These findings suggest that ECT may be more effective for treating MDD than SCZ. Full article

(This article belongs to the Section Cognitive, Social and Affective Neuroscience)

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14 pages, 1988 KiB

Open AccessArticle

Effectiveness of Adding a Pain Neuroscience Education Program to a Multimodal Physiotherapy Intervention in Patients with Chronic Shoulder Pain: A Randomized Clinical Trial

by Jose Angel Delgado-Gil, Eva Prado-Robles, María Nieves Muñoz-Alcaraz and Jesús Seco-Calvo

Brain Sci. 2025, 15(2), 125; https://doi.org/10.3390/brainsci15020125 - 27 Jan 2025

Viewed by 691

Abstract

Objectives: The purpose of this study was to assess the efficacy of a pain neuroscience education program completed by patients with shoulder pain. Methods: A randomized, controlled trial was performed. Fifty-five patients satisfied the eligibility criteria, agreed to participate, and were [...] Read more.

Objectives: The purpose of this study was to assess the efficacy of a pain neuroscience education program completed by patients with shoulder pain. Methods: A randomized, controlled trial was performed. Fifty-five patients satisfied the eligibility criteria, agreed to participate, and were randomized into an experimental group (n = 27) or control group (n = 28). A manual therapy and exercises program was administered for both groups. The experimental group also received a 4-week pain neuroscience education protocol (1 session/week, 75 min per session). The measurements taken included the active range of motion, pain, disability, catastrophizing, kinesiophobia, and therapeutic alliance. The outcomes were assessed at baseline and 5 weeks after completion of treatment. The primary outcome analyzed was the group × time interaction. Results: The 2 × 2 analysis of variance revealed a significant group × time interaction for the active range of motion (F = 15.27; p = 0.011), disability (F = 6.14; p = 0.01), catastrophizing (F = 8.79; p = 0.01), kinesiophobia (F = 7.62; p = 0.008), and therapeutic alliance (p = 0.03) in favor of the experimental group. Conclusions: This study showed that the patients with shoulder pain who completed the pain neuroscience program achieved significantly better results in terms of their active range of motion, disability, catastrophizing, kinesiophobia, and therapeutic alliance compared to those achieved by the control group. Therefore, pain neuroscience education may be beneficial in the treatment of patients with shoulder pain. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

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20 pages, 2463 KiB

Open AccessArticle

CLTNet: A Hybrid Deep Learning Model for Motor Imagery Classification

by He Gu, Tingwei Chen, Xiao Ma, Mengyuan Zhang, Yan Sun and Jian Zhao

Brain Sci. 2025, 15(2), 124; https://doi.org/10.3390/brainsci15020124 - 27 Jan 2025

Viewed by 551

Abstract

Background: Brain–computer interface (BCI) technology opens up new avenues for human–machine interaction and rehabilitation by connecting the brain to machines. Electroencephalography (EEG)-based motor imagery (MI) classification is a key component of BCI technology, which is capable of translating neural activity in the brain [...] Read more.

Background: Brain–computer interface (BCI) technology opens up new avenues for human–machine interaction and rehabilitation by connecting the brain to machines. Electroencephalography (EEG)-based motor imagery (MI) classification is a key component of BCI technology, which is capable of translating neural activity in the brain into commands for controlling external devices. Despite the great potential of BCI technology, the challenges of extracting and decoding brain signals limit its wide application. Methods: To address this challenge, this study proposes a novel hybrid deep learning model, CLTNet, which focuses on solving the feature extraction problem to improve the classification of MI-EEG signals. In the preliminary feature extraction stage, CLTNet uses a convolutional neural network (CNN) to extract time series, channel, and spatial features of EEG signals to obtain important local information. In the deep feature extraction stage, the model combines the long short-term memory (LSTM) network and the Transformer module to capture time-series data and global dependencies in the EEG. The LSTM explains the dynamics of the brain activity, while the Transformer’s self-attention mechanism reveals the global features of the time series. Ultimately, the CLTNet model classifies motor imagery EEG signals through a fully connected layer. Results: The model achieved an average accuracy of 83.02% and a Kappa value of 0.77 on the BCI IV 2a dataset, and 87.11% and a Kappa value of 0.74 on the BCI IV 2b dataset, both of which outperformed the traditional methods. Conclusions: The innovation of the CLTNet model is that it integrates multiple network architectures, which offers a more comprehensive understanding of the characteristics of the EEG signals during motor imagery, providing a more comprehensive perspective and establishing a new benchmark for future research in this area. Full article

(This article belongs to the Section Computational Neuroscience and Neuroinformatics)

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14 pages, 4556 KiB

Open AccessArticle

Ouabain Counteracts Retinal Ganglion Cell Death Through Modulation of BDNF and IL-1 Signaling Pathways

by Amanda Candida da Rocha Oliveira, Camila Saggioro Figueiredo, Ícaro Raony, Juliana Salles Von-Held-Ventura, Marcelo Gomes Granja, Thalita Mázala-de-Oliveira, Vinícius Henrique Pedrosa-Soares, Aline Araujo dos Santos and Elizabeth Giestal-de-Araujo

Brain Sci. 2025, 15(2), 123; https://doi.org/10.3390/brainsci15020123 - 26 Jan 2025

Viewed by 441

Abstract

Background: Ouabain is a steroid hormone that binds to the sodium pump (Na⁺, K⁺-ATPase) at physiological (nanomolar) concentrations, activating different signaling pathways. This interaction has been shown to prevent the axotomy-induced death of retinal ganglion cells (RGCs), although the [...] Read more.

Background: Ouabain is a steroid hormone that binds to the sodium pump (Na⁺, K⁺-ATPase) at physiological (nanomolar) concentrations, activating different signaling pathways. This interaction has been shown to prevent the axotomy-induced death of retinal ganglion cells (RGCs), although the underlying mechanisms remain unclear. Objective: In this study, we investigated potential mechanisms by which ouabain promotes RGC survival using primary cultures of rat neural retina. Results: Our findings indicate that ouabain regulates brain-derived neurotrophic factor (BDNF) signaling in retinal cells via matrix metalloproteinase-9-mediated processing of proBDNF to mature BDNF (mBDNF) and by increasing the phosphorylation of the mBDNF receptor, tropomyosin-related receptor kinase B. Ouabain also enhances the maturation of interleukin (IL)-1β through the increased activation of caspase-1, which mediates the processing of proIL-1β into IL-1β, and transiently upregulates both IL-1 receptor and IL-1 receptor antagonist (IL-1Ra). Treatment using either IL-1β or IL-1Ra alone is sufficient to enhance RGC survival similarly to that achieved with ouabain. Finally, we further show that ouabain prevents RGC death through a complex signaling mechanism shared by BDNF and IL-1β, which includes the activation of the Src and protein kinase C pathways. Conclusions: Collectively, these results suggest that ouabain stimulates the maturation and signaling of both BDNF and IL-1β, which act as key mediators of RGC survival. Full article

(This article belongs to the Special Issue Retinal Neurochemistry and Development)

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Brain Sci., Volume 15, Issue 2 (February 2025) – 56 articles

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