Brain Sciences

26 pages, 3893 KiB

Open AccessArticle

The Neural Mechanisms of Private Speech in Second Language Learners’ Oral Production: An fNIRS Study

by Rong Jiang, Zhe Xiao, Yihan Jiang and Xueqing Jiang

Brain Sci. 2025, 15(5), 451; https://doi.org/10.3390/brainsci15050451 (registering DOI) - 25 Apr 2025

Background: According to Vygotsky’s sociocultural theory, private speech functions both as a tool for thought regulation and as a transitional form between outer and inner speech. However, its role in adult second language (L2) learning—and the neural mechanisms supporting it—remains insufficiently understood. [...] Read more.

Background: According to Vygotsky’s sociocultural theory, private speech functions both as a tool for thought regulation and as a transitional form between outer and inner speech. However, its role in adult second language (L2) learning—and the neural mechanisms supporting it—remains insufficiently understood. This study thus examined whether private speech facilitates L2 oral production and investigated its underlying neural mechanisms, including the extent to which private speech resembles inner speech in its regulatory function and the transitional nature of private speech. Methods: In Experiment 1, to identify natural users of private speech, 64 Chinese-speaking L2 English learners with varying proficiency levels were invited to complete a picture-description task. In Experiment 2, functional near-infrared spectroscopy (fNIRS) was used to examine the neural mechanisms of private speech in 32 private speech users identified in Experiment 1. Results: Experiment 1 showed that private speech facilitates L2 oral production. Experiment 2 revealed that private and inner speech elicited highly similar patterns of functional connectivity. Among high-proficiency learners, private speech exhibited enhanced connectivity between the language network and the thought-regulation network, indicating involvement of higher-order cognitive processes. In contrast, among low-proficiency learners, connectivity was primarily restricted to language-related regions, suggesting that private speech supports basic linguistic processing at early stages. Furthermore, both private and outer speech showed stronger connectivity in speech-related brain regions. Conclusions: This is the first study to examine the neural mechanisms of private speech in L2 learners by using fNIRS. The findings provide novel neural evidence that private speech serves as both a regulatory scaffold and a transitional form bridging outer and inner speech. Its cognitive function appears to evolve with increasing L2 proficiency. Full article

(This article belongs to the Section Behavioral Neuroscience)

15 pages, 4420 KiB

Open AccessArticle

Bayesian-Optimized Convolutional Neural Networks for Classifying Primary Tumor Origin of Brain Metastases from MRI

by Jawed Nawabi, Semil Eminovic, Alexander Hartenstein, Georg Lukas Baumgaertner, Nils Schnurbusch, Madhuri Rudolph, David Wasilewski, Julia Onken, Eberhard Siebert, Edzard Wiener, Georg Bohner, Andrea Dell'Orco, Mike P. Wattjes, Bernd Hamm, Uli Fehrenbach and Tobias Penzkofer

Brain Sci. 2025, 15(5), 450; https://doi.org/10.3390/brainsci15050450 - 25 Apr 2025

Abstract

Background/Objectives: This study evaluates whether convolutional neural networks (CNNs) can be trained to determine the primary tumor origin from MRI images alone in patients with metastatic brain lesions. Methods: This retrospective, monocentric study involved the segmentation of 1175 brain lesions from [...] Read more.

Background/Objectives: This study evaluates whether convolutional neural networks (CNNs) can be trained to determine the primary tumor origin from MRI images alone in patients with metastatic brain lesions. Methods: This retrospective, monocentric study involved the segmentation of 1175 brain lesions from MRI scans of 436 patients with histologically confirmed primary tumor origins. The four most common tumor types—lung adenocarcinoma, small cell lung cancer, breast cancer, and melanoma—were selected, and a class-balanced dataset was created through under-sampling. This resulted in 276 training datasets and 88 hold-out test datasets. Bayesian optimization was employed to determine the optimal CNN architecture, the most relevant imaging sequences, and whether the masking of images was necessary. We compared the performance of the CNN with that of two expert radiologists specializing in neuro-oncological imaging. Results: The best-performing CNN from the Bayesian optimization process used masked images across all available MRI sequences. It achieved Area-Under-the-Curve (AUC) values of 0.75 for melanoma, 0.65 for small cell lung cancer, 0.64 for breast cancer, and 0.57 for lung adenocarcinoma. Masked images likely improved performance by focusing the CNN on relevant regions and reducing noise from surrounding tissues. In comparison, Radiologist 1 achieved AUCs of 0.55, 0.52, 0.45, and 0.51, and Radiologist 2 achieved AUCs of 0.68, 0.55, 0.64, and 0.43 for the same tumor types, respectively. The CNN consistently showed higher accuracy, particularly for melanoma and breast cancer. Conclusions: Bayesian optimization enabled the creation of a CNN that outperformed expert radiologists in classifying the primary tumor origin of brain metastases from MRI. Full article

(This article belongs to the Section Neuro-oncology)

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22 pages, 1055 KiB

Open AccessPerspective

Non-Invasive Brain Stimulation and Artificial Intelligence in Communication Neuroprosthetics: A Bidirectional Approach for Speech and Hearing Impairments

by Thorsten Rudroff

Brain Sci. 2025, 15(5), 449; https://doi.org/10.3390/brainsci15050449 - 25 Apr 2025

Abstract

This perspective paper introduces a novel bidirectional framework for communication neuroprosthetics that integrates non-invasive brain stimulation (NIBS) with artificial intelligence (AI) to address both speech production and auditory processing impairments. Traditional approaches typically target only one aspect of communication, while this framework supports [...] Read more.

This perspective paper introduces a novel bidirectional framework for communication neuroprosthetics that integrates non-invasive brain stimulation (NIBS) with artificial intelligence (AI) to address both speech production and auditory processing impairments. Traditional approaches typically target only one aspect of communication, while this framework supports the complete communication cycle. The integration of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) with advanced AI algorithms enables the personalized, adaptive enhancement of neural signals for both speaking and listening functions. This paper examines current evidence for NIBS efficacy in communication disorders, explores AI innovations in neural signal processing, and discusses implementation considerations for closed-loop systems. This bidirectional approach has the potential to provide more natural, effective communication support while promoting neuroplasticity for long-term recovery. The framework presented offers a roadmap for developing accessible communication interventions that could significantly improve the quality of life for individuals with speech and hearing impairments resulting from neurological conditions. Full article

(This article belongs to the Special Issue The Future of Human–Machine Collaboration: AI in Neural Rehabilitation and Assistive Technologies)

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12 pages, 952 KiB

Open AccessArticle

Theta Burst TMS over the Pre-SMA Improves Inhibitory Control in Gambling Disorder Subjects as Assessed with Stop Signal Task

by Gioele Gavazzi, Carlo Cavaliere, Marco Salvatore, Nikolaos Makris and Stefano Pallanti

Brain Sci. 2025, 15(5), 448; https://doi.org/10.3390/brainsci15050448 - 25 Apr 2025

Abstract

Background. Inhibitory control failure represents a central trait in substance and behavioral addictions, which includes patients affected with gambling disorder (GD). In GD patients, research on this trait of the addiction cycle has primarily focused on the use of pharmacological treatments for its [...] Read more.

Background. Inhibitory control failure represents a central trait in substance and behavioral addictions, which includes patients affected with gambling disorder (GD). In GD patients, research on this trait of the addiction cycle has primarily focused on the use of pharmacological treatments for its assessment. More recently, modification of neural activity using transcranial magnetic stimulation (TMS) has been used to explore the dimensions of GD using patient questionnaires. Methods. Herein, we evaluated the use of continuous Theta burst stimulation (cTBS) over the pre-supplementary motor area (pre-SMA) to determine if it modified inhibitory control in the stop signal task of patients affected by GD when compared with a group of healthy controls without cTBS treatment. Results. To the best of our knowledge, our study is the first to report that TMS treatment of GD patients is associated with a behavioral improvement of stop signal reaction time. Conclusion. Our results suggest that this TMS-mediated improvement in the efficiency of inhibitory control in GD patients warrants further mechanistic studies in a larger cohort to determine if can be used as a treatment modality. Full article

(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)

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10 pages, 265 KiB

Open AccessArticle

Quantity and Quality Matter: Different Neuroanatomical Substrates of Apathy in Alzheimer’s Disease and Behavioural Variant Frontotemporal Dementia

by Luciano Inácio Mariano, Thiago de Oliveira Maciel, Henrique Cerqueira Guimarães, Leandro Boson Gambogi, Antônio Lúcio Teixeira Júnior, Paulo Caramelli and Leonardo Cruz de Souza

Brain Sci. 2025, 15(5), 447; https://doi.org/10.3390/brainsci15050447 - 25 Apr 2025

Abstract

Background: Apathy is almost ubiquitous across neurodegenerative diseases and can be a general model for understanding neuropsychiatric symptoms in dementia. Methods: We assessed apathy via Starkstein’s Apathy Scale—caregiver version (SAS-C) in patients with Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). Neuropsychological [...] Read more.

Background: Apathy is almost ubiquitous across neurodegenerative diseases and can be a general model for understanding neuropsychiatric symptoms in dementia. Methods: We assessed apathy via Starkstein’s Apathy Scale—caregiver version (SAS-C) in patients with Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). Neuropsychological and structural neuroimaging data were also collected. Images were processed using the FreeSurfer program, and cortical thickness data were acquired for 68 brain regions. Results: Patients with bvFTD had statistically higher levels of apathy than those with AD. The multivariate linear regression model found that the left entorhinal cortex (lEC) was the only region statistically associated with apathy in the AD group (F(1,31) = 5.17; p = 0.030; R2 = 0.527), whereas, for bvFTD, the right lateral orbitofrontal cortex achieved significant association with apathy (F(1,30) = 5.69; p = 0.009; R2 = 0.804). Conclusions: These results demonstrate that apathy is associated with multiple brain regions, reinforcing its multidimensionality and specific profiles. Full article

(This article belongs to the Special Issue Frontotemporal Dementia: Behavioural and Neuroimaging Studies)

18 pages, 1065 KiB

Open AccessReview

Multimodal Neuroimaging of Obesity: From Structural-Functional Mechanisms to Precision Interventions

by Wenhua Liu, Na Li, Dongsheng Tang, Lang Qin and Zhiqiang Zhu

Brain Sci. 2025, 15(5), 446; https://doi.org/10.3390/brainsci15050446 - 25 Apr 2025

Abstract

Purpose: Obesity’s metabolic consequences are well documented; however, its neurobiological underpinnings remain elusive. This systematic review addresses a critical gap by synthesizing evidence on obesity-induced neuroplasticity across structural, functional, and molecular domains through advanced neuroimaging. Methods: According to PRISMA guidelines, we systematically searched [...] Read more.

Purpose: Obesity’s metabolic consequences are well documented; however, its neurobiological underpinnings remain elusive. This systematic review addresses a critical gap by synthesizing evidence on obesity-induced neuroplasticity across structural, functional, and molecular domains through advanced neuroimaging. Methods: According to PRISMA guidelines, we systematically searched (2015–2024) across PubMed/Web of Science, employing MeSH terms: (“Obesity” [Majr]) AND (“Neuroimaging” [Mesh] OR “Magnetic Resonance Imaging” [Mesh]). A total of 104 studies met the inclusion criteria. The inclusion criteria required the following: (1) multimodal imaging protocols (structural MRI/diffusion tensor imaging/resting-state functional magnetic resonance imaging (fMRI)/positron emission tomography (PET)); (2) pre-/post-intervention longitudinal design. Risk of bias was assessed via the Newcastle-Ottawa Scale. Key Findings: 1. Structural alterations: 7.2% mean gray matter reduction in prefrontal cortex (Cohen’s d = 0.81). White matter integrity decline (FA reduction β = −0.33, p < 0.001) across 12 major tracts. 2. Functional connectivity: Resting-state hyperactivity in mesolimbic pathways (fALFF + 23%, p-FDR < 0.05). Impaired fronto–striatal connectivity (r = −0.58 with BMI, 95% CI [−0.67, −0.49]). 3. Interventional reversibility: Bariatric surgery restored prefrontal activation (Δ = +18% vs. controls, p = 0.002). Neurostimulation (transcranial direct current stimulation (tDCS) enhanced cognitive control (post-treatment β = 0.42, p = 0.009). Conclusion: 1. Obesity induces multidomain neural reorganization beyond traditional reward circuits. 2. Neuroimaging biomarkers (e.g., striatal PET-dopamine binding potential) predict intervention outcomes (AUC = 0.79). 3. Precision neuromodulation requires tripartite integration of structural guidance, functional monitoring, and molecular profiling. Findings highlight neuroimaging’s pivotal role in developing stage-specific therapeutic strategies. Full article

(This article belongs to the Special Issue Application of MRI in Brain Diseases)

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13 pages, 4131 KiB

Open AccessArticle

Differential Effects of Light Spectra on Sleep Architecture and Melatonin in Rats

by Yuan-Chun Chiu, Pei-Lu Yi and Fang-Chia Chang

Brain Sci. 2025, 15(5), 445; https://doi.org/10.3390/brainsci15050445 - 25 Apr 2025

Abstract

Artificial light exposure, particularly from blue-rich sources, has raised concerns about its impact on sleep and circadian rhythms. While blue light’s effects are well-documented, the comparative impact of longer wavelengths, such as orange light (590–635 nm), remains underexplored. This study investigated the effects [...] Read more.

Artificial light exposure, particularly from blue-rich sources, has raised concerns about its impact on sleep and circadian rhythms. While blue light’s effects are well-documented, the comparative impact of longer wavelengths, such as orange light (590–635 nm), remains underexplored. This study investigated the effects of 8 h blue (470–490 nm) and orange light exposures (500 lux) on sleep architecture in the next consecutive three days in Sprague-Dawley rats during the light or dark phase of a 12:12 h light–dark cycle. Sleep–wake states were assessed via electroencephalography (EEG) over 72 h. Blue light during the light period suppressed rapid eye movement (REM) sleep acutely and enhanced non-NREM sleep on Days 2 and 3. Orange light during the light period induced no immediate changes but increased NREM sleep on Day 2 with a biphasic REM response—suppression followed by rebound—persisting into Day 3. Blue light during the dark period increased NREM sleep during exposure, followed by suppression in the subsequent light period, with effects normalizing by Day 2. Blue light exposure suppressed melatonin levels compared to controls. These findings highlight spectral and temporal influences on sleep, with blue light exerting stronger acute effects and orange light eliciting delayed, biphasic responses. The results suggest implications for managing light exposure to mitigate sleep disruptions in modern environments. Full article

(This article belongs to the Special Issue The Relationship Between Sleep and the Brain: New Insights into Sleep Disorders and Their Effects on Mental Health, Cognition, and Quality of Life)

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18 pages, 2263 KiB

Open AccessArticle

Delayed Effects of tDCS Combined with Cognitive Behavioral Therapy in Major Depression: A Randomized, Double-Blind Pilot Trial

by Sandra Carvalho, Catarina Gomes Coelho and Jorge Leite

Brain Sci. 2025, 15(5), 444; https://doi.org/10.3390/brainsci15050444 - 25 Apr 2025

Abstract

Aims: This pilot study assessed the potential psychosocial and therapeutic impacts of augmenting transcranial direct current stimulation (tDCS) with cognitive behavioral therapy (CBT) in treatment-naïve patients diagnosed with major depressive disorder (MDD). Methods: In this double-blind randomized controlled trial, 10 subjects were randomized [...] Read more.

Aims: This pilot study assessed the potential psychosocial and therapeutic impacts of augmenting transcranial direct current stimulation (tDCS) with cognitive behavioral therapy (CBT) in treatment-naïve patients diagnosed with major depressive disorder (MDD). Methods: In this double-blind randomized controlled trial, 10 subjects were randomized into two groups—CBT with active tDCS (active tDCS; n = 6; M = 33.3 years; 4 females) or CBT with sham tDCS (Sham; n = 4; M = 31.2 years; 2 females). Severity of depression was measured with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI). Participants’ secondary outcomes included life satisfaction, sleep quality, and anxiety symptoms. They were assessed at baseline, following treatment (week 6), and at 2, 4, 8, and 12-week follow-ups. Results: By week 12, the active tDCS group’s BDI scores showed greater improvement relative to the sham group. There were also significant differences between groups over time in MADRS scores. Sleep quality also improved in the active tDCS group, with many participants achieving symptom-free status—defined as BDI scores of 9 or less and supported by consistently low MADRS scores—by the end of the follow-up period. Conclusions: These preliminary data indicate that the combination of tDCS with CBT may optimize the treatment of MDD through depressive symptom relief and improved sleep, while also prolonging the benefits of treatment. Full article

(This article belongs to the Section Neuropsychiatry)

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21 pages, 1337 KiB

Open AccessArticle

Ankle Somatosensation and Lower-Limb Neuromuscular Function on a Lunar Gravity Analogue

by Ashleigh Marchant, Nick Ball, Jeremy Witchalls, Sarah B. Wallwork and Gordon Waddington

Brain Sci. 2025, 15(5), 443; https://doi.org/10.3390/brainsci15050443 - 24 Apr 2025

Abstract

Background/Objectives: The adverse effects of low gravity on human physiology are well documented; however, much of the literature is directed at changes which occur in microgravity (µg: weightlessness) with relatively less documented on changes in hypogravity (<1 g; >µg: gravity less than [...] Read more.

Background/Objectives: The adverse effects of low gravity on human physiology are well documented; however, much of the literature is directed at changes which occur in microgravity (µg: weightlessness) with relatively less documented on changes in hypogravity (<1 g; >µg: gravity less than Earth’s but more than microgravity). Somatosensation and neuromuscular control may be of particular importance for astronauts as they prepare for future missions to walk on the Moon. This study aimed to explore the effect of reduced weight bearing (to simulate conditions of hypogravity) on ankle somatosensation, lower-limb muscle activity, tone, and stiffness, compared to full weight bearing. Methods: Participants completed an ankle somatosensory acuity task (active movement extent discrimination assessment [AMEDA]) in two body positions: (1) upright standing (1 g), and (2) in a head-elevated supine, semi-weight bearing (0.16 g) position using a custom-built inclined “wedge bed”. The second position induced ~16% body weight on to the plantar aspect of the feet, simulating that of lunar gravity. We compared the AMEDA scores between the two positions. Lower-limb muscle activity was recorded via surface EMG throughout the AMEDA task for both positions. The ankle AMEDA has five depths of ankle inversion. We compared muscle activity between the body positions, and muscle activity between inversion depths “1” and “5” (within each position). Lower-limb muscle tone and muscle stiffness were assessed at rest in both body positions using the MyotonPRO. Results: Fifty-five participants between the ages of 18 and 65 (28 females, 27 males; mean age of 40 years) completed the study. The AMEDA scores, muscle tone and stiffness were reduced when the participants were on the lunar wedge bed, compared to upright standing (p = 0.002; p < 0.001; p < 0.001). Some lower-limb muscles exhibited less activity in the lunar wedge-bed position compared to upright standing (tibialis anterior, peroneus longus, vastus lateralis, rectus femoris; p < 0.05) but others were unchanged (gastrocnemius, vastus medialis; p > 0.05). Muscle activity was unchanged between the AMEDA depths (p = 0.188). Conclusions: The results provide insight into how the somatosensory and neuromuscular systems respond to reduced weight bearing and potentially lunar gravity conditions, thereby informing how to target interventions for future missions. Full article

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

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18 pages, 6710 KiB

Open AccessArticle

Papain Affects the Percentage and Morphology of Microglia in Hippocampal Neuron–Glial Cultures

by Ivan A. Tumozov, Valentina N. Mal’tseva, Sergei A. Maiorov, Artem M. Kosenkov and Sergei G. Gaidin

Brain Sci. 2025, 15(5), 442; https://doi.org/10.3390/brainsci15050442 - 24 Apr 2025

Abstract

Background. Microglia, accounting for 5–15% of total brain cells, represent an essential population of glial cells in the cultures used for modeling neuroinflammation in vitro. However, microglia proliferation is poor in neuron–glial cultures. Here, we studied the population composition of rat hippocampal neuron–glial [...] Read more.

Background. Microglia, accounting for 5–15% of total brain cells, represent an essential population of glial cells in the cultures used for modeling neuroinflammation in vitro. However, microglia proliferation is poor in neuron–glial cultures. Here, we studied the population composition of rat hippocampal neuron–glial cell cultures prepared utilizing papain (PAP cultures) and trypsin (TRY cultures) as proteolytic enzymes for cell isolation. Methods. To evaluate the percentage and morphology of microglia in TRY and PAP cultures and cultures incubated in the presence of TGFβ+MCSF+cholesterol, which should enhance microglia proliferation, we used an immunostaining and calcium imaging approach in combination with staining using the recently developed vital microglia fluorescent probe CDr20. Results. We have shown that the microglia percentage in PAP cultures was higher than in TRY cultures. Microglia in PAP cultures are predominantly polarized, while bushy morphology was more characteristic of TRY cultures. We have also demonstrated that the TGFβ+MCSF+cholesterol combination increases the microglia number both in PAP and TRY cultures (up to 25–30%) and promotes the appearance of ameboid microglia characterized by high mobility. However, the significant appearance of ameboid microglia was observed already at the early stages of cultivation (2 DIV) in TRY cultures, while in PAP cultures, the described transformation was observed at 7 DIV. Based on the absence of the ATP-induced Ca²⁺ response, round shape, significant proliferation, and high mobility, we have suggested that ameboid microglia are reactive. Conclusions. Thus, our results demonstrate that papain is a more suitable proteolytic enzyme for preparing mixed hippocampal neuron–glial cultures with a higher percentage of heterogeneous microglia and functional neurons and astrocytes (tricultures). Full article

(This article belongs to the Special Issue New Advances in Neuroimmunology and Neuroinflammation)

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23 pages, 4829 KiB

Open AccessArticle

The Size and Localization of Ribeye and GluR2 in the Auditory Inner Hair Cell Synapse of C57BL/6 Mice Are Affected by Short-Pulse Corticosterone in a Sex-Dependent Manner

by Ewa Domarecka, Heidi Olze and Agnieszka J. Szczepek

Brain Sci. 2025, 15(5), 441; https://doi.org/10.3390/brainsci15050441 - 24 Apr 2025

Abstract

Background: Inner hair cell (IHC) ribbon synapses are the initial synapses in the auditory pathway, comprising presynaptic ribbons and postsynaptic glutamate receptors on the peripheral afferent fibers. The excitatory neurotransmitter glutamate primarily signals through AMPA-type heterotetrameric receptors (AMPARs), composed of GluR1, GluR2, GluR3, [...] Read more.

Background: Inner hair cell (IHC) ribbon synapses are the initial synapses in the auditory pathway, comprising presynaptic ribbons and postsynaptic glutamate receptors on the peripheral afferent fibers. The excitatory neurotransmitter glutamate primarily signals through AMPA-type heterotetrameric receptors (AMPARs), composed of GluR1, GluR2, GluR3, and GluR4 subunits. Research shows that corticosterone affects AMPA receptor subunits in the central nervous system. The present study investigates the effects of corticosterone on AMPA receptor subunits in the murine cochlea. Methods: Cochlear explants were isolated from male and female C57BL/6 pups (postnatal days 4–5), treated for 20 min with 100 nM corticosterone, and cultured for an additional 24 h. The concentration of AMPAR protein subunits was quantified using an ELISA assay, while gene expression was analyzed using RT-PCR. The synaptic localization patterns of GluR2 and Ribeye were examined using immunofluorescence and confocal microscopy. Results: Male C57BL/6 mice have a significantly greater basal concentration of the GluR2 subunit than females and more GluR2 puncta per IHC than females. Corticosterone increases the size of Ribeye in males and increases twofold GluR2/Ribeye colocalization in the apical region of females. Conclusions: Exposure of membranous cochleae to corticosterone induces changes consistent with neuroplasticity in the auditory periphery. The observed effect is sex-dependent. Full article

(This article belongs to the Special Issue Recent Advances in Hearing Impairment)

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13 pages, 2329 KiB

Open AccessArticle

Surface EEG Evidence for Cerebellar Control of Distal Upper Limbs in Humans

by Anna Latorre, Kais Humaidan, Mauro Sanna, Maria Lucrezia Lavena, Sara Pittalis, Clio Raimondi, Elias Paolo Casula and Lorenzo Rocchi

Brain Sci. 2025, 15(5), 440; https://doi.org/10.3390/brainsci15050440 - 24 Apr 2025

Abstract

Background/Objectives: The cerebellum plays a crucial role in motor control, but its direct electrophysiological investigation in humans is challenging. Electrocerebellograms (ECeGs), recorded via surface electrodes below the inion, have been proposed as a non-invasive method to assess cerebellar activity. However, its interpretation [...] Read more.

Background/Objectives: The cerebellum plays a crucial role in motor control, but its direct electrophysiological investigation in humans is challenging. Electrocerebellograms (ECeGs), recorded via surface electrodes below the inion, have been proposed as a non-invasive method to assess cerebellar activity. However, its interpretation is complicated by potential interference from occipital alpha rhythms and neck muscle signals. This study aimed to investigate whether ECeG signals genuinely reflect cerebellar involvement during upper limb movement and to explore possible confounding influences. Methods: We recorded electroencephalograms (EEGs) from occipital (Oz) and cerebellar electrodes (Cb1 and Cb2), alongside EMGs from forearm muscles in healthy individuals performing sinusoidal (~1 Hz) and tremor-like (~4 Hz) wrist movements. To assess occipital contamination, recordings were obtained under both eyes-open and eyes-closed conditions. Results: Occipital alpha power was present in Cb1 and Cb2 but was less affected by eye-opening than at Oz, suggesting a partially distinct neural source. During the tremor condition, movement-frequency power increased at Cb2 and C3 (corresponding to the ipsilateral cerebellar hemisphere and contralateral motor cortex), indicating authentic cerebellar activity. No significant movement-related EEG changes were observed during sinusoidal movements, likely due to weaker neuronal synchronization. Conclusions: These findings suggest that ECeGs can detect cerebellar signals linked to movement, especially during faster and rhythmic motions, and are only moderately affected by occipital contamination. This supports the feasibility of non-invasive cerebellar electrophysiology and underscores the need for further methodological refinement to enhance signal specificity. Full article

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

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21 pages, 4993 KiB

Open AccessArticle

The Impact of Distance and Altitude on Railway Environmental Noise Based on Cerebral Oxygenated Hemoglobin Saturation

by Min-kyeong Kim and Duckshin Park

Brain Sci. 2025, 15(5), 439; https://doi.org/10.3390/brainsci15050439 - 24 Apr 2025

Abstract

Railways are considered an environmentally sustainable mode of transportation but can pose significant environmental challenges due to their operation and associated activities. Among these, noise generation is a persistent source of public complaints. In Korea, a maximum distance of 100 m from buildings [...] Read more.

Railways are considered an environmentally sustainable mode of transportation but can pose significant environmental challenges due to their operation and associated activities. Among these, noise generation is a persistent source of public complaints. In Korea, a maximum distance of 100 m from buildings has been proposed for new railway developments in residential areas, although this guideline lacks a solid foundation based on experimental evidence. Noise barriers are often installed as a mitigation measure; however, there is no standardized guideline for their height in relation to their effectiveness at varying distances. The distances and altitudes set in this study took into account accessibility and the height of noise barriers on actual railway sites. In particular, we examined the effects of altitude above and distance from a railway site under the assumption that the prefrontal cortex would be physiologically affected by noise exposure. In this study, we conducted the first analysis in Korea of cerebral blood flow changes in response to noise, to assess quantitatively the stress effects caused by railway environmental noise at varying distances from, and altitudes above, a railway. Using functional near-infrared spectroscopy (fNIRS), we measured prefrontal cortex activation in 10 adult males (average age: 33.2 years). Brain activation was evaluated under different distances from (40 and 100 m) and altitudes above (1st and 4th floors of a building) a railway through a paired-sample t-test analysis. Discomfort was felt at relatively close distances to the railway, and there were no differences in perceived discomfort between the examined floors. Brain activation due to environmental noise was highest in channel 43 (left DLPFC) for altitude (floor) and in channel 37 (left FPC) for distance. Significant differences in activation were observed in the corresponding Brodmann areas, varying based on altitude and distance (p < 0.05). These results provide valuable scientific data for the preliminary design phase of new railway developments, particularly with regard to determining appropriate residential distance and noise barrier specifications, to enhance comfort of nearby residents. Furthermore, they may contribute to the improvement of quality of life by reducing stress caused by railway environmental noise. Full article

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16 pages, 6019 KiB

Open AccessArticle

Prefrontal Blood Flow Activity During Drawing Intervention in School-Age Children with Autism: An fNIRS Hyperscanning Study

by Guanghui Li, Daren Wei, Ze Lyu, Yalong Xing, Yan Li and Wu Song

Brain Sci. 2025, 15(5), 438; https://doi.org/10.3390/brainsci15050438 - 24 Apr 2025

Abstract

Background/Objectives: Art-based interventions have been shown to enhance communication skills in children with autism spectrum disorder (ASD), yet their impact on prefrontal hemodynamics remains unclear. Methods: This study employed functional near-infrared spectroscopy (fNIRS) to examine hemoglobin oxygenation (HbO) changes in the prefrontal cortex [...] Read more.

Background/Objectives: Art-based interventions have been shown to enhance communication skills in children with autism spectrum disorder (ASD), yet their impact on prefrontal hemodynamics remains unclear. Methods: This study employed functional near-infrared spectroscopy (fNIRS) to examine hemoglobin oxygenation (HbO) changes in the prefrontal cortex of school-age children with ASD, providing empirical support for its therapeutic efficacy. Sixty age-matched children participated in a 9-week art therapy program, including twenty ASD children and forty typically developing peers. Assessments included self-portrait drawing (SPD), the Diagnostic Drawing Series (DDS), and the General Quality of Life Inventory (GQOL-74). In addition, we performed fNIRS measurements in the ASD participants and observed changes in prefrontal HbO at rest and while drawing. Results: The drawing intervention significantly enhanced drawing ability, emotional expression, and cognitive skills, with the intervention group outperforming the controls. ASD participants exhibited distinct prefrontal connectivity patterns with visual, motor, and language-related regions, including the dorsolateral prefrontal cortex, frontal eye field, and Broca’s area. Task-based painting interventions indirectly influenced the frontal lobe’s hemodynamic characteristics, indicating drawing intervention as an effective intervention for ASD. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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17 pages, 1876 KiB

Open AccessArticle

Exploring the Impact of Backward and Forward Locomotor Treadmill Training in Chronic Stroke Survivors with Severe Post-Stroke Walking Impairment: A Single-Center Pilot Randomized Controlled Trial

by Saiprasad Naidu, Khwahish Singh, Tamiel Murray, Colin Drury, Erin Palermo, Heidi J. Sucharew, Changchun Xie, Pierce Boyne, Kari Dunning and Oluwole O. Awosika

Brain Sci. 2025, 15(5), 437; https://doi.org/10.3390/brainsci15050437 - 24 Apr 2025

Abstract

Background: Defined as a self-selected speed of <0.4 m/s, chronic stroke survivors falling in this category are classified as “severe”, usually homebound and sedentary, and they experience worse outcomes. Limited rehabilitation strategies are available to improve walking speed and related outcomes in this [...] Read more.

Background: Defined as a self-selected speed of <0.4 m/s, chronic stroke survivors falling in this category are classified as “severe”, usually homebound and sedentary, and they experience worse outcomes. Limited rehabilitation strategies are available to improve walking speed and related outcomes in this subgroup, and questions regarding effective rehabilitation options remain. The objective of this study was to determine the effects of backward (BLTT) and forward (FLTT) locomotor treadmill training on overground walking speed, spatiotemporal symmetry, and dynamic postural stability. Methods: In this single-center, assessor-blinded, randomized controlled pilot trial, 14 stroke survivors with severe waking impairment underwent 12 sessions of BLTT (n = 7) or FLTT (n = 7). The primary outcome was the proportion of participants reaching clinically meaningful important difference (MCID) on the 10-meter walk test following training completion. Secondary outcomes were between-group differences in walking speed, spatiotemporal symmetry, and completion time on the 3-meter timed up and go (3M TUG) at 24 h, 30 days, and 90 days POST. Results: Two subjects in the BLTT group (28.6%) and one (14.3%) in FLTT achieved MCID following training; however, most subjects did not, with significant variability in response. At 24 h POST, the median (IQR) percent change in walking speed was 28.9 (9.01–36.7) and 17.4 (12.6–39.7) with BLTT and FLTT, respectively; however, no between-group differences were seen (p = 0.80) at this time point or at 30 (p > 0.99) and 90 (p > 0.99) days follow up. Likewise, there were no significant between-group differences in spatiotemporal symmetry and the 3M TUG across time points. Conclusions: While preliminary, this study found that 12 training sessions did not lead to group-level achievement of MCID for walking speed in our cohort and found no significant between-group differences in walking capacity or dynamic postural stability. Future well-powered dosing trials and mechanistically driven studies are needed to optimize and identify predictors of training response. Full article

(This article belongs to the Special Issue The Rehabilitation of Neurologic Disorders)

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16 pages, 3092 KiB

Open AccessReview

Sphingosine-1-Phosphate Modulation in Neurological Disorders: Insights from MS and Stroke

by Briana Maktabi, Faheem Shehjar, Zachary Senger, Logan Kountz, Syed Hasan, Kenan Maaieh, Kylee Hoersten, Jovana Duric and Zahoor A. Shah

Brain Sci. 2025, 15(5), 436; https://doi.org/10.3390/brainsci15050436 - 24 Apr 2025

Abstract

Multiple sclerosis is a chronic autoimmune disease in which the immune system attacks the protective sheath or myelin that covers nerve fibers, impacting the brain’s ability to communicate with other areas of the body. This abnormal immune response recruits inflammatory substances, which appear [...] Read more.

Multiple sclerosis is a chronic autoimmune disease in which the immune system attacks the protective sheath or myelin that covers nerve fibers, impacting the brain’s ability to communicate with other areas of the body. This abnormal immune response recruits inflammatory substances, which appear as lesions on the brain and spinal cord. A stroke is characterized by a sudden impairment of neurological function resulting from the loss or restriction of blood flow due to acute damage to a localized area of the central nervous system, including the brain, retina, or spinal cord. While strokes, both ischemic and hemorrhagic, are different in terms of their pathogenesis to MS, mechanisms such as neuroinflammation and neurodegeneration are common denominators among these conditions. Recent studies highlight the involvement of the sphingosine-1-phosphate receptor in the treatment of strokes and how fingolimod, an S1P receptor modulator employed in MS treatment, may play a role in the treatment of stroke-like symptoms. This review aims to explore the potential link between stroke and MS, providing a comprehensive analysis of the existing evidence. It will also shed light on the role of S1P receptors in the pathophysiology of stroke, offering insights into their mechanistic contributions. Furthermore, the review will examine recent studies investigating the therapeutic potential of the S1P modulator, fingolimod, in acute stroke patients, highlighting its efficacy and potential clinical applications. Through this multifaceted approach, we hope to contribute to the development of a deeper understanding of these interconnected neurological conditions and their treatment strategies. Full article

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12 pages, 567 KiB

Open AccessArticle

Neurodevelopmental Tics with Co-Morbid Functional Tic-like Behaviors: Diagnostic Challenges of a Complex Tourette Syndrome Phenotype

by Andrea Eugenio Cavanna, Virginia Caimi, Elisa Capriolo, Matteo Marinoni, Gabriele Arienti, Anna Riva, Renata Nacinovich and Stefano Seri

Brain Sci. 2025, 15(5), 435; https://doi.org/10.3390/brainsci15050435 - 23 Apr 2025

Abstract

Background/Objectives: The co-morbidity between neurodevelopmental tics and functional tic-like behaviors (FTBs) in patients with Tourette syndrome (TS) is relatively under-investigated. The demographic and clinical characteristics of a large sample of patients with TS who presented with co-morbid FTBs (functional overlay) were assessed [...] Read more.

Background/Objectives: The co-morbidity between neurodevelopmental tics and functional tic-like behaviors (FTBs) in patients with Tourette syndrome (TS) is relatively under-investigated. The demographic and clinical characteristics of a large sample of patients with TS who presented with co-morbid FTBs (functional overlay) were assessed to raise awareness of this complex clinical presentation and to shed light on the differential diagnosis between the two conditions. Methods: We analyzed the clinical data of 63 patients (44 females, mean age 24 years, range 13–40) with pre-existing TS who (sub)acutely developed co-morbid FTBs (TS + FTBs) after the onset of the COVID-19 pandemic and compared them with 63 age- and gender-matched controls with TS (neurodevelopmental tics only). The diagnosis of co-morbid FTBs was validated by the European Society for the Study of Tourette Syndrome (ESSTS) criteria. Results: Complex vocal tics (p < 0.001), including coprolalia (p = 0.002), and self-injurious behaviors (p < 0.001), often as part of tic attacks (p < 0.001), were confirmed to be more commonly reported by the group of patients with TS + FTBs, who were also more likely to present with anxiety (p < 0.001) and other functional neurological symptoms (p < 0.001) compared to patients with TS. Conclusions: Patients with TS and co-morbid FTBs can pose significant diagnostic and treatment challenges. By systematically applying ESSTS criteria, we confirmed specific red flags for the diagnosis of functional overlay in patients with TS. The correct identification of this composite clinical phenotype plays a key role in preventing the misdiagnosis of treatment-resistant TS and implementing tailored treatment interventions. Full article

(This article belongs to the Special Issue Clinical Research on Tourette Syndrome: Advances and Challenges)

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14 pages, 1171 KiB

Open AccessArticle

Hypertension a Predictive Risk Factor on Progression to Alzheimer’s Disease Using APOEε4 as a Benchmark

by Mingfei Li, Ying Wang, Lewis Kazis and Weiming Xia

Brain Sci. 2025, 15(5), 434; https://doi.org/10.3390/brainsci15050434 - 23 Apr 2025

Abstract

Background: Comorbidities such as hypertension and hypercholesterolemia are risk factors associated with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). The most significant genetic risk factor is the ε4 allele of the apolipoprotein E gene (APOE). The aim of this paper is to [...] Read more.

Background: Comorbidities such as hypertension and hypercholesterolemia are risk factors associated with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). The most significant genetic risk factor is the ε4 allele of the apolipoprotein E gene (APOE). The aim of this paper is to determine whether hypertension is the most significant but modifiable risk factor to delay AD onset. Method: A cohort of patients with MCI (N = 3052) is developed from the documented database (N = 43,999) within the National Alzheimer’s Coordinating Center (NACC) during the time period from June 2005 to May 2021. Cox proportional hazard models with propensity score weights on demographic information and comorbidities at baseline are applied to examine association of hypertension and hypercholesterolemia with AD onset among MCI patients. Associations are compared to APOE genotypes and AD onset. In addition, the association of hypertension with decline rates in Mini-Mental State Examination (MMSE) scores are reported. Results: After controlling for age, sex, race, APOEε4, and reported comorbidities, the results show that MCI patients who subsequently develop hypertension within 18 months after their first diagnosis of MCI have a significantly higher risk of AD onset (HR = 2.77, 95%CI (1.66, 4.65), p value < 0.0001), compared to MCI patients with no hypertension or a late occurrence of hypertension after 18 months. This significant association is validated through a Random Forest method, a machine learning approach with bootstrap simulations. In addition, patients with early hypertension have significantly higher MMSE score declining rates compared to those without hypertension (coefficient = 0.988, p = 0.0054.). Conclusions: Hypertension is the most significant risk factor comparable to the genetic risk factor APOEε4 allele. Our finding is unique, as we did not observe a similar outcome in those with early hypercholesterolemia. Thus, among all comorbidities, hypertension is the most significant risk factor similar to the genetic risk factor APOEε4 allele. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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21 pages, 5345 KiB

Open AccessArticle

Intranasal Transplantation of Microbiota Derived from Parkinson’s Disease Mice Induced Astrocyte Activation and Neurodegenerative Pathology from Nose to Brain

by Yi-Meng Xia, Mei-Xuan Zhang, Xiao-Yu Ma, Lu-Lu Tan, Ting Li, Jian Wu, Ming-An Li, Wei-Jiang Zhao, Chen-Meng Qiao, Xue-Bing Jia, Yan-Qin Shen and Chun Cui

Brain Sci. 2025, 15(5), 433; https://doi.org/10.3390/brainsci15050433 - 23 Apr 2025

Abstract

Background: Parkinson’s disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota–nose–brain axis might be involved in the pathogenesis of PD. However relative studies are rare. Methods: By [...] Read more.

Background: Parkinson’s disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota–nose–brain axis might be involved in the pathogenesis of PD. However relative studies are rare. Methods: By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP. Results: 16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology. Conclusions: We present evidence supporting the microbiota–nose–brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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30 pages, 12912 KiB

Open AccessArticle

Neurophysiological Markers of Design-Induced Cognitive Changes: A Feasibility Study with Consumer-Grade Mobile EEG

by Nathalie Gerner, David Pickerle, Yvonne Höller and Arnulf Hartl

Brain Sci. 2025, 15(5), 432; https://doi.org/10.3390/brainsci15050432 - 23 Apr 2025

Abstract

Background: Evidence-based design aims to create healthy environments grounded in scientific data, yet the influence of spatial qualities on cognitive processes remains underexplored. Advances in neuroscience offer promising tools to address this gap while meeting both scientific and practical demands. Consumer-grade mobile EEG [...] Read more.

Background: Evidence-based design aims to create healthy environments grounded in scientific data, yet the influence of spatial qualities on cognitive processes remains underexplored. Advances in neuroscience offer promising tools to address this gap while meeting both scientific and practical demands. Consumer-grade mobile EEG devices are increasingly used; however, their lack of transparency complicates output interpretation. Well-established EEG indicators from cognitive neuroscience may offer a more accessible and interpretable alternative. Methods: This feasibility study explored the sensitivity of five established EEG power band ratios to cognitive shifts in response to subtle environmental design experiences. Twenty participants completed two crossover sessions in an office-like setting with nature-inspired versus urban-inspired design elements. Each session included controlled phases of focused on-screen cognitive task and off-screen breaks. Results: Factorial analyses revealed no significant interaction effects of cognitive state and environmental exposure on EEG outcomes. Nonetheless, frontal (θ/β) and frontocentral (β/[α + θ]) ratios showed distinct patterns across cognitive states, with more pronounced contrasts in the nature-inspired compared to the urban-inspired design conditions. Conversely, occipital ([θ + α]/β), (θ/α), and (β/α) ratios remained consistent across exposures. Data triangulation with autonomic nervous system responses and performance metrics supported these observations. Conclusions: The findings suggest that EEG power band ratios can capture brain–environment interactions. However, limitations of consumer-grade EEG devices challenge both scientific rigour and practical application. Refining methodological reliability could improve interpretability, supporting more transparent and robust data-driven design decisions. Full article

(This article belongs to the Special Issue Neuroarchitecture: Humans in the Built Environment)

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18 pages, 1770 KiB

Open AccessFeature PaperArticle

The Role of Physical Activity on Spatial and Temporal Cognitive Processing in Young Women

by Joaquín Castillo-Escamilla, María del Mar Salvador-Viñas and José Manuel Cimadevilla

Brain Sci. 2025, 15(5), 431; https://doi.org/10.3390/brainsci15050431 - 23 Apr 2025

Abstract

Background/Objectives: Physical activity (PA) has many benefits for both physical and cognitive health. It has also been related to improvements in memory and executive functions. However, its impact on time estimation remains less explored. Time is a key component of episodic memory, which [...] Read more.

Background/Objectives: Physical activity (PA) has many benefits for both physical and cognitive health. It has also been related to improvements in memory and executive functions. However, its impact on time estimation remains less explored. Time is a key component of episodic memory, which also involves spatial components to give a full context to events. Given the clear evidence of the benefits of PA in spatial navigation and the anatomical overlap with temporal estimation through the hippocampus, the latter could be affected in a similar way. Therefore, this study aimed to check how PA can influence time processing and spatial memory. We wanted to check if PA influenced time and space with the same directionality. Methods: Forty-two (n = 42) female university students participated in this study, divided into a Sport (n = 25) or Sedentary (n = 17) Group depending on their participation in PA for a minimum of 3 h a week. They were addressed in two different cognitive capabilities. The first was time processing, measured by the Time Comparison Task, which controlled for several key aspects of time literature in its design. Moreover, we measured spatial navigation skills, using a well-proven virtual spatial navigation task, The Boxes Room. Accuracy and mean response times were registered per task. Results: Significant correlations were observed between spatial and temporal task performance. In addition, PA influenced spatial and time processing in a similar way, with the Sport Group outperforming the Sedentary Group in accuracy and response times for both tasks. Conclusions: These findings provide evidence that PA influences time processing similarly to its established effects on spatial memory, which could help developing sports programs that further enhance this skill. Full article

(This article belongs to the Special Issue Neuropsychological Exploration of Spatial Cognition and Navigation)

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11 pages, 242 KiB

Open AccessReview

Perspectives on Precision Psychiatry Using Antipsychotics in the Management of Bipolar Disorder

by Michele Fornaro, Alessandro Miola, Domenico De Berardis, Alessio Squassina, Mirko Manchia and Marco Solmi

Brain Sci. 2025, 15(5), 430; https://doi.org/10.3390/brainsci15050430 - 23 Apr 2025

Abstract

Background/Objectives: Precision medicine is not just hype. Instead, it represents a high bar for developing more effective, safer, and better-tolerated therapies in medicine, without exception in psychiatry, including bipolar disorder (BD). A burgeoning body of narrative reviews and perspective papers has already appraised [...] Read more.

Background/Objectives: Precision medicine is not just hype. Instead, it represents a high bar for developing more effective, safer, and better-tolerated therapies in medicine, without exception in psychiatry, including bipolar disorder (BD). A burgeoning body of narrative reviews and perspective papers has already appraised the boundaries of precision medicine in BD. Methods: This brief perspective follows a narrative, critical approach focusing explicitly on the antipsychotic management of BD using precision approaches. Results: While most controversies align with those previously appraised in BD’s overall precision medicine approach, specific insights are provided herein. Conclusions: Beyond other implications and the strengthened call for valid diagnostic coding systems, the implementation of shared decision-making tools and pharmacogenomics studies focusing on persons with BD are particularly warranted. Full article

(This article belongs to the Special Issue Personalized Approach to the Diagnosis and Treatment of Bipolar Disorder)

19 pages, 1823 KiB

Open AccessArticle

The Perception of Trustworthiness and Emotional Identification in Women Experiencing Intimate Partner Violence: A Behavioral Pilot Study

by Valentina Silvestri, Silvia Gobbo, Erica Pugliese, Francesco Mancini and Federica Visco-Comandini

Brain Sci. 2025, 15(5), 429; https://doi.org/10.3390/brainsci15050429 - 23 Apr 2025

Abstract

Background: Research indicates that traumatic events, such as interpersonal violence, can significantly affect how individuals perceive facial characteristics and assess trust. This study aims to explore trustworthiness and emotional perception in women experiencing intimate partner violence (IPV). Methods: Twenty-four women who have experienced [...] Read more.

Background: Research indicates that traumatic events, such as interpersonal violence, can significantly affect how individuals perceive facial characteristics and assess trust. This study aims to explore trustworthiness and emotional perception in women experiencing intimate partner violence (IPV). Methods: Twenty-four women who have experienced IPV and twenty-four control participants completed an online task. They rated the trustworthiness of male and female faces, chose the more trustworthy face in a pairwise task, and identified emotions displayed by faces. Results: The results revealed that survivors of IPV showed lower accuracy in trustworthiness judgments, particularly for male faces, and in recognizing fear in male faces, compared to the control group. Conclusions: These preliminary findings, constrained by the limited sample size, are discussed in the context of the Pathological Affective Dependence theory and a perceptual model of social face perception, shedding light on the complex interplay between trauma, social perception, and emotional processing. Full article

(This article belongs to the Special Issue Understanding Human Social Cognition: Integration of Neural, Cognitive, Behavioral, Affective, and Social Determinants)

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10 pages, 1500 KiB

Open AccessArticle

Efficacy and Safety of Prolonged Adjuvant Temozolomide Treatment in Glioblastoma: Prospective Study of 81 Patients Undergoing up to 101 Cycles of Treatment

by Giulio Bonomo, Francesco Certo, Erica Grasso, Giuseppa Fiumanò, Davide Barbagallo, Rosario Caltabiano, Giuseppe Broggi, Gaetano Magro, Andrea Maugeri, Antonella Agodi, Fiorenza Latteri, Hector Sotoparra, Giovanni Buscema, Corrado Spatola, Alessandro Pluchino and Giuseppe M. V. Barbagallo

Brain Sci. 2025, 15(5), 428; https://doi.org/10.3390/brainsci15050428 - 23 Apr 2025

Abstract

Background: Although several studies investigated the efficacy of long-term adjuvant temozolomide (TMZ) therapy in glioblastomas (GBs), no univocal data are currently available, and this topic remains controversial. The present study on our ongoing experience aims to assess whether the extended STUPP protocol confers [...] Read more.

Background: Although several studies investigated the efficacy of long-term adjuvant temozolomide (TMZ) therapy in glioblastomas (GBs), no univocal data are currently available, and this topic remains controversial. The present study on our ongoing experience aims to assess whether the extended STUPP protocol confers prognostic benefits with acceptable safety. Methods: From 2004 to 2018, 81 patients with a new diagnosis of GB according to the World Health Organization (WHO) 2021 classification, treated with gross total resection (GTR) or subtotal resection (STR), were enrolled. Patients were divided into Group A (long-term TMZ; N = 40) and Group B (standard STUPP protocol; N = 41). Results: In the extended STUPP group, compared with the standard STUPP group, progression-free survival (PFS) and overall survival (OS) were significantly improved (PFS: 27.8 vs. 7.5 months, p = 0.00001; OS: 35.9 vs. 11.3 months, p = 0.0001). To mitigate a potential survival bias, we focused on those in Group B who completed the recommended six cycles. Patients in Group A demonstrated a prolonged OS compared to Group B (27 vs. 10 months, p < 0.001). Similar findings were observed in a focused analysis of patients who had achieved a minimum survival of 12 months (27 vs. 15 months, p < 0.001) or 18 months (34 vs. 24 months, p = 0.044). Conclusions: Our analysis demonstrates a PFS and OS advantage with extended STUPP and suggests that young patients without corpus callosum invasion, with methylguanine-DNA methyltransferase (MGMT) promoter methylation, and treated with GTR are the best candidates. No significant safety difference emerged between extended and standard TMZ treatment. Full article

(This article belongs to the Special Issue Editorial Board Collection Series: Advances in Neuro-Oncology)

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4 pages, 172 KiB

Open AccessEditorial

Re-Evaluating the Role of Robotic Gait Training in Post-Stroke Balance Rehabilitation

by Rocco Salvatore Calabrò

Brain Sci. 2025, 15(5), 427; https://doi.org/10.3390/brainsci15050427 - 22 Apr 2025

Abstract

The latest meta-analysis conducted by Loro et al [...] Full article

(This article belongs to the Section Neurorehabilitation)

17 pages, 850 KiB

Open AccessReview

Epidemiology of Tourette Syndrome

by Abdullah Yasir Yilmaz and Joseph Jankovic

Brain Sci. 2025, 15(5), 426; https://doi.org/10.3390/brainsci15050426 - 22 Apr 2025

Abstract

Background/Objectives: Tourette syndrome (TS) is a neurodevelopmental disorder, manifested by tics and a variety of behavioral comorbidities that cluster strongly within families, suggesting a combination of genetic and environmental risk factors. The underlying pathophysiology of TS remains to be elucidated. Understanding the incidence [...] Read more.

Background/Objectives: Tourette syndrome (TS) is a neurodevelopmental disorder, manifested by tics and a variety of behavioral comorbidities that cluster strongly within families, suggesting a combination of genetic and environmental risk factors. The underlying pathophysiology of TS remains to be elucidated. Understanding the incidence and prevalence across different populations provides valuable insights into the etiology and pathogenesis of the condition and aids in the development of effective treatment strategies. Methods: A comprehensive literature search was conducted on PubMed covering the period from 1 January 2000 to 1 January 2025. The search used the terms “Tourette syndrome”, “tics”, “tic disorders”, “epidemiology”, “prevalence”, and “incidence”. Results: The prevalence of TS is estimated to be about 1% in children and adolescents and approximately 0.01% in adults, with a male-to-female (M:F) ratio of about 4:1. The prevalence of tic disorders is higher in all studies performed in special education populations. Conclusions: Despite substantial methodological variability, our review of the literature indicates that TS is a relatively common neurobehavioral disorder, affecting nearly 1% of children, especially boys. Raising global awareness and expanding training in TS should lead to better identification of undiagnosed patients. Full article

(This article belongs to the Special Issue Clinical Research on Tourette Syndrome: Advances and Challenges)

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4 pages, 163 KiB

Open AccessCorrection

Correction: Moreno Escobar et al. Employing Siamese Networks as Quantitative Biomarker for Assessing the Effect of Dolphin-Assisted Therapy on Pediatric Cerebral Palsy. Brain Sci. 2024, 14, 778

by Jesús Jaime Moreno Escobar, Oswaldo Morales Matamoros, Erika Yolanda Aguilar del Villar, Hugo Quintana Espinosa and Liliana Chanona Hernández

Brain Sci. 2025, 15(5), 425; https://doi.org/10.3390/brainsci15050425 - 22 Apr 2025

Abstract

An error was identified and corrected in the telephone extension originally listed in the original publication [...] Full article

18 pages, 343 KiB

Open AccessReview

Drugs Used in “Chemsex”/Sexualized Drug Behaviour—Overview of the Related Clinical Psychopharmacological Issues

by Fabrizio Schifano, Stefania Bonaccorso, Davide Arillotta, Amira Guirguis, John Martin Corkery, Giuseppe Floresta, Gabriele Duccio Papanti Pelletier, Norbert Scherbaum and Nicolò Schifano

Brain Sci. 2025, 15(5), 424; https://doi.org/10.3390/brainsci15050424 - 22 Apr 2025

Abstract

Background: “Chemsex” involves the intake of a range of drugs (e.g., synthetic cathinones, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, methamphetamine, “poppers”, type V phosphodiesterase (PDE) inhibitors, MDMA/ecstasy, cocaine, cannabis, and occasionally a few other molecules as well, to enhance and prolong sexual experiences. This [...] Read more.

Background: “Chemsex” involves the intake of a range of drugs (e.g., synthetic cathinones, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, methamphetamine, “poppers”, type V phosphodiesterase (PDE) inhibitors, MDMA/ecstasy, cocaine, cannabis, and occasionally a few other molecules as well, to enhance and prolong sexual experiences. This paper aims to provide an overview of the clinical pharmacology of the vast range of drugs that are being used for chemsex with a focus on both the medical and psychopathological disturbances that they can produce. Methods: A narrative literature review was conducted using Pubmed, Scopus, and Web of Science databases. A total of 273 papers published up to January 2025 were screened; articles were selected based on relevance to chemsex/sexualized used behaviour and related substances. Both human and preclinical studies were considered. Results: The use of stimulants is likely related to the need to increase as much as possible both sexual arousal and performance but also to increase social interactions. Furthermore, the empathogenic/entactogenic activities of some MDMA-like “love drugs” facilitate the occurrence of “feeling closer/more intimate” emotional sensations, and GHB/GBL may provide the user with a subjective sensation of disinhibition, hence facilitating condomless meetings with a higher number of random partners. Conversely, ketamine may be used to both enjoy its psychotropic dissociative characteristics and facilitate the potentially painful receptive anal intercourse and/or fisting experiences. Most typically, these drugs are consumed in combination, with polydrug exposure possibly facilitating the occurrence of serotonergic syndrome, seizures, drug–drug pharmacokinetics’ interaction, and sympathomimetic overstimulation. Following these polydrug exposures, a range of psychopathological conditions have at times been reported. These issues may lead to misuse of opiates/opioids, gabapentinoids, and/or antipsychotics. Conclusions: Further actions should aim at reducing the stigma that prevents individuals from accessing necessary healthcare and support services. A multidisciplinary approach that combines medical, psychological, and social support remains key to managing the complex challenges posed by chemsex-related drug use. Full article

(This article belongs to the Special Issue From Satiety to Psychiatry: Exploring the Role of GLP-1 Receptor Agonists in Mental Health, Substance Use and Neuropsychiatric Disorders)

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Brain Sci., Volume 15, Issue 5 (May 2025) – 28 articles

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