Previous Issue
Volume 15, August
 
 

Brain Sci., Volume 15, Issue 9 (September 2025) – 15 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
11 pages, 610 KiB  
Article
Comparison of Simoa and Lumipulse Neurofilament Light Chain Measurements in Alzheimer’s Cerebrospinal Fluid: Preliminary Findings
by Silvia Boschi, Alberto Mario Chiarandon, Aurora Cermelli, Chiara Lombardo, Giulia Gioiello, Giulia Montesano, Elisa Rubino, Giulio Mengozzi, Innocenzo Rainero and Fausto Roveta
Brain Sci. 2025, 15(9), 911; https://doi.org/10.3390/brainsci15090911 - 24 Aug 2025
Abstract
Background: Neurofilament light chain (NfL) is a promising biomarker of neuroaxonal injury, increasingly used to monitor neurodegeneration in Alzheimer’s disease (AD). Multiple analytical platforms are available for NfL quantification in cerebrospinal fluid (CSF), but data on cross-platform consistency remain limited. Objective: This pilot [...] Read more.
Background: Neurofilament light chain (NfL) is a promising biomarker of neuroaxonal injury, increasingly used to monitor neurodegeneration in Alzheimer’s disease (AD). Multiple analytical platforms are available for NfL quantification in cerebrospinal fluid (CSF), but data on cross-platform consistency remain limited. Objective: This pilot study aimed to provide CSF NfL concentrations measured using Simoa and Lumipulse immunoassays in patients with biologically confirmed AD. Methods: Twenty-eight patients with cognitive impairment fulfilling the biological criteria for AD were enrolled. CSF NfL levels were measured using both Simoa and Lumipulse immunoassays. Statistical analyses assessed intra-individual agreement, correlation between platforms, and associations with cognitive status. Results: NfL concentrations measured with Simoa and Lumipulse showed a strong positive correlation between platforms (Spearman’s ρ = 0.965, p < 0.001), demonstrating excellent analytical concordance. Conclusions: In this pilot study, Simoa and Lumipulse yielded strongly correlated CSF NfL measurements, providing initial evidence of cross-platform consistency. However, these findings require confirmation in larger and diverse cohorts before definitive validation. Full article
Show Figures

Figure 1

22 pages, 608 KiB  
Systematic Review
Effects of Cognitive Training with Virtual Reality in Older Adults: A Systematic Review
by Christian Daniel Navarro-Ramos, Joselinn Murataya-Gutiérrez, Christian Oswaldo Acosta-Quiroz, Raquel García-Flores and Sonia Beatriz Echeverría-Castro
Brain Sci. 2025, 15(9), 910; https://doi.org/10.3390/brainsci15090910 - 23 Aug 2025
Abstract
Background/Objective: The use of immersive virtual reality (VR) for cognitive training in older adults has shown promising results in recent years. However, the number of well-designed studies remains limited, and variability in methodologies makes it difficult to draw generalizable conclusions. This systematic review [...] Read more.
Background/Objective: The use of immersive virtual reality (VR) for cognitive training in older adults has shown promising results in recent years. However, the number of well-designed studies remains limited, and variability in methodologies makes it difficult to draw generalizable conclusions. This systematic review aims to examine the effects of VR-based cognitive training in older adults, describe the technological characteristics of these interventions, identify current gaps in the literature, and suggest future research directions. Methods: Following PRISMA guidelines, a search was conducted across major databases (PubMed, PsycINFO, Scopus, ProQuest, ACM, and Web of Science) from 2018 to 2025. The database search identified 156 studies, of which 12 met the inclusion criteria after screening and eligibility assessment. Across these studies, a total of 3202 older adult participants (aged 60 years or older) were included. Interventions varied in duration from 4 to 36 sessions, targeting domains such as memory, executive function, attention, and global cognition. Most interventions were based on cognitive training, with a few employing cognitive stimulation or cognitive rehabilitation approaches. Quality was assessed using the Effective Public Health Practice Project tool. Results: Most studies reported positive effects of VR interventions on cognitive domains such as attention, executive functions, and global cognition. Fewer studies showed improvements in memory. The majority used head-mounted displays connected to computers and custom-built software, often without public access. Sample sizes were generally small, and blinding procedures were often unclear. The average methodological quality was moderate. Conclusions: Immersive VR has potential as an effective tool for cognitive training in older adults. Future research should include larger randomized controlled trials, long-term follow-up, standardized intervention protocols, and the development of accessible software to enable replication and broader application in clinical and community settings. Full article
Show Figures

Figure 1

28 pages, 371 KiB  
Review
Synthetic Emotions and the Illusion of Measurement: A Conceptual Review and Critique of Measurement Paradigms in Affective Science
by Dana Rad, Corina Costache-Colareza, Ruxandra-Victoria Paraschiv and Liviu Gavrila-Ardelean
Brain Sci. 2025, 15(9), 909; https://doi.org/10.3390/brainsci15090909 - 23 Aug 2025
Abstract
The scientific study of emotion remains fraught with conceptual ambiguity, methodological limitations, and epistemological blind spots. This theoretical paper argues that existing paradigms frequently capture synthetic rather than natural emotional states—those shaped by social expectations, cognitive scripting, and performance under observation. We propose [...] Read more.
The scientific study of emotion remains fraught with conceptual ambiguity, methodological limitations, and epistemological blind spots. This theoretical paper argues that existing paradigms frequently capture synthetic rather than natural emotional states—those shaped by social expectations, cognitive scripting, and performance under observation. We propose a conceptual framework that distinguishes natural emotion—spontaneous, embodied, and interoceptively grounded—from synthetic forms that are adaptive, context-driven, and often unconsciously rehearsed. These reactions often involve emotional scripts rather than genuine, spontaneous affective experiences. Drawing on insights from affective neuroscience, psychological measurement, artificial intelligence, and neurodiversity, we examine how widely used tools such as EEG, polygraphy, and self-report instruments may capture emotional conformity rather than authenticity. We further explore how affective AI systems trained on socially filtered datasets risk replicating emotional performance rather than emotional truth. By recognizing neurodivergent expression as a potential site of emotional transparency, we challenge dominant models of emotional normalcy and propose a five-step agenda for reorienting emotion research toward authenticity, ecological validity, and inclusivity. This post-synthetic framework invites a redefinition of emotion that is conceptually rigorous, methodologically nuanced, and ethically inclusive of human affective diversity. Full article
(This article belongs to the Special Issue Defining Emotion: A Collection of Current Models)
16 pages, 1085 KiB  
Article
Predicting Regional Cerebral Blood Flow Using Voxel-Wise Resting-State Functional MRI
by Hongjie Ke, Bhim M. Adhikari, Yezhi Pan, David B. Keator, Daniel Amen, Si Gao, Yizhou Ma, Paul M. Thompson, Neda Jahanshad, Jessica A. Turner, Theo G. M. van Erp, Mohammed R. Milad, Jair C. Soares, Vince D. Calhoun, Juergen Dukart, L. Elliot Hong, Tianzhou Ma and Peter Kochunov
Brain Sci. 2025, 15(9), 908; https://doi.org/10.3390/brainsci15090908 - 23 Aug 2025
Abstract
Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD). Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) [...] Read more.
Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD). Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) artifacts. Cortical patterns of MDD-related CBF differences decoded from rsfMRI using a PVA-corrected approach showed excellent agreement with CBF measured using single-photon emission computed tomography (SPECT) and arterial spin labeling (ASL). A support vector machine algorithm was trained to decode cortical voxel-wise CBF from temporal and power-spectral features of voxel-level rsfMRI time series while accounting for PVA. Three datasets, Amish Connectome Project (N = 300; 179 M/121 F, both rsfMRI and ASL data), UK Biobank (N = 8396; 3097 M/5319 F, rsfMRI data), and Amen Clinics Inc. datasets (N = 372: N = 183 M/189 F, SPECT data), were used. Results: PVA-corrected CBF values predicted from rsfMRI showed significant correlation with the whole-brain (r = 0.54, p = 2 × 10−5) and 31 out of 34 regional (r = 0.33 to 0.59, p < 1.1 × 10−3) rCBF measures from 3D ASL. PVA-corrected rCBF values showed significant regional deficits in the UKBB MDD group (Cohen’s d = −0.30 to −0.56, p < 10−28), with the strongest effect sizes observed in the frontal and cingulate areas. The regional deficit pattern of MDD-related hypoperfusion showed excellent agreement with CBF deficits observed in the SPECT data (r = 0.74, p = 4.9 × 10−7). Consistent with previous findings, this new method suggests that perfusion signals can be predicted using voxel-wise rsfMRI signals. Conclusions: CBF values computed from widely available rsfMRI can be used to study the impact of neuropsychiatric disorders such as MDD on cerebral neurophysiology. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
Show Figures

Figure 1

17 pages, 529 KiB  
Systematic Review
Risk, Precipitating, and Perpetuating Factors in Functional Neurological Disorder: A Systematic Review Across Clinical Subtypes
by Ioannis Mavroudis, Katerina Franekova, Foivos Petridis, Alin Ciobîca, Gabriel Dăscălescu, Emil Anton, Ciprian Ilea, Sotirios Papagiannopoulos and Dimitrios Kazis
Brain Sci. 2025, 15(9), 907; https://doi.org/10.3390/brainsci15090907 - 23 Aug 2025
Abstract
Background: Functional Neurological Disorder (FND) encompasses conditions with neurological symptoms inconsistent with structural pathology, arising instead from complex interactions between psychological, biological, and social factors. Despite growing research, the etiological and risk factor landscape remains only partially understood, complicating diagnosis and treatment. Objective: [...] Read more.
Background: Functional Neurological Disorder (FND) encompasses conditions with neurological symptoms inconsistent with structural pathology, arising instead from complex interactions between psychological, biological, and social factors. Despite growing research, the etiological and risk factor landscape remains only partially understood, complicating diagnosis and treatment. Objective: This systematic review maps risk factors for major FND subtypes such as functional seizures (psychogenic non-epileptic seizures or PNES), functional cognitive disorder (FCD), functional movement disorders (FMD), functional weakness and sensory disturbances, functional visual symptoms, and functional gait abnormalities by categorizing predisposing, precipitating, and perpetuating influences. Methods: A systematic search of PubMed, PsycINFO, Scopus, and Web of Science initially identified 245 records. After removal of 64 duplicates, 181 studies were screened by title and abstract. Of these, 96 full texts were examined in detail, and finally 23 studies met the predefined inclusion criteria. Data were extracted and analyzed thematically within a biopsychosocial framework, with results summarized in subtype-specific profiles. Results: Childhood adversity, especially emotional, physical, or sexual abuse, emerged as a robust and consistent predisposing factor across PNES cohorts. Psychiatric history (notably anxiety, depression, and PTSD), neurodevelopmental traits (more frequent in FCD), and personality patterns such as alexithymia and somatization also contributed to vulnerability. Precipitating influences included acute psychological stress, intrapersonal conflict, or concurrent medical illness. Perpetuating factors comprise maladaptive illness beliefs, avoidance behaviors, insufficient explanation or validation by healthcare providers, and secondary gains related to disability. While several risk factors were shared across subtypes, others appeared subtype-specific (trauma was especially associated with PNES, whereas neurodevelopmental traits were more characteristic of FCD). Conclusions: FND arises from a dynamic interplay of predisposing, precipitating, and perpetuating factors, with both shared and subtype-specific influences. Recognizing this heterogeneity can enhance diagnostic precision, guide tailored intervention, and inform future research into the neurobiological and psychosocial mechanisms underlying FND. Full article
(This article belongs to the Section Neuropsychology)
11 pages, 393 KiB  
Systematic Review
Systematic Review of the Treatment of Anosognosia for Hemiplegia in Stroke
by Dong Chan Kim, Junghyeon Park and Min Wook Kim
Brain Sci. 2025, 15(9), 906; https://doi.org/10.3390/brainsci15090906 - 23 Aug 2025
Abstract
Background/Objectives: Anosognosia for hemiplegia (AHP) is a multifaceted syndrome in which stroke survivors fail to recognize motor impairments. Although AHP has significant clinical implications, rehabilitation strategies have remained fragmented and underexplored. This systematic review aimed to critically evaluate rehabilitation interventions for AHP [...] Read more.
Background/Objectives: Anosognosia for hemiplegia (AHP) is a multifaceted syndrome in which stroke survivors fail to recognize motor impairments. Although AHP has significant clinical implications, rehabilitation strategies have remained fragmented and underexplored. This systematic review aimed to critically evaluate rehabilitation interventions for AHP published between 2006 and 2025, categorize intervention types, and assess clinical outcomes to inform future research and practice. Methods: A structured search was conducted in the PubMed and PsycINFO databases on 31 March 2025, using predefined keywords related to stroke, anosognosia, and rehabilitation. The eligible studies included randomized controlled trials, case–control studies, and case studies. Following title, abstract, and full-text screening, nine studies focusing on rehabilitation interventions for AHP were selected and analyzed. Results: The interventions reviewed included sensorimotor recalibration techniques, neuromodulatory approaches, error-based cognitive training, and self-observation in video replay strategies. Interventions emphasizing motor intention monitoring, error correction, and self-observation were more consistently associated with durable improvements in motor awareness than neglect-based spatial interventions were. However, many studies were limited by small sample sizes and a lack of standardized outcome measures. Assessment methodologies vary widely, highlighting the need for multidimensional theory-driven evaluation tools. Conclusions: Effective rehabilitation for AHP requires strategies targeting disrupted self-monitoring and agency mechanisms, rather than spatial realignment alone. The video self-observation and error-based learning paradigms show particular promise. Future research should focus on controlled trials, longitudinal tracking, and the integration of individualized, mechanism-specific rehabilitation models to optimize outcomes for stroke survivors with AHP. Full article
(This article belongs to the Special Issue Anosognosia and the Determinants of Self-Awareness)
Show Figures

Figure 1

25 pages, 1403 KiB  
Protocol
Discrimination and Integration of Phonological Features in Children with Autism Spectrum Disorder: An Exploratory Multi-Feature Oddball Protocol
by Mingyue Zuo, Yang Zhang, Rui Wang, Dan Huang, Luodi Yu and Suiping Wang
Brain Sci. 2025, 15(9), 905; https://doi.org/10.3390/brainsci15090905 - 23 Aug 2025
Abstract
Background/Objectives: Children with Autism Spectrum Disorder (ASD) often display heightened sensitivity to simple auditory stimuli, but have difficulty discriminating and integrating multiple phonological features (segmental: consonants and vowels; suprasegmental: lexical tones) at the syllable level, which negatively impacts their communication. This study aims [...] Read more.
Background/Objectives: Children with Autism Spectrum Disorder (ASD) often display heightened sensitivity to simple auditory stimuli, but have difficulty discriminating and integrating multiple phonological features (segmental: consonants and vowels; suprasegmental: lexical tones) at the syllable level, which negatively impacts their communication. This study aims to investigate the neural basis of segmental, suprasegmental and combinatorial speech processing challenges in Mandarin-speaking children with ASD compared with typically developing (TD) peers. Methods: Thirty children with ASD and thirty TD peers will complete a multi-feature oddball paradigm to elicit auditory ERP during passive listening. Stimuli include syllables with single (e.g., vowel only), dual (e.g., vowel + tone), and triple (consonant + vowel + tone) phonological deviations. Neural responses will be analyzed using temporal principal component analysis (t-PCA) to isolate overlapping ERP components (early/late MMN), and representational similarity analysis (RSA) to assess group differences in neural representational structure across feature conditions. Expected Outcomes: We adopt a dual-framework approach to hypothesis generation. First, from a theory-driven perspective, we integrate three complementary models, Enhanced Perceptual Functioning (EPF), Weak Central Coherence (WCC), and the Neural Complexity Hypothesis (NCH), to account for auditory processing in ASD. Specifically, we hypothesize that ASD children will show enhanced or intact neural discriminatory responses to isolated segmental deviations (e.g., vowel), but attenuated or delayed responses to suprasegmental (e.g., tone) and multi-feature deviants, with the most severe disruptions occurring in complex, multi-feature conditions. Second, from an empirically grounded, data-driven perspective, we derive our central hypothesis directly from the mismatch negativity (MMN) literature, which suggests reduced MMN amplitudes (with the exception of vowel deviants) and prolonged latencies accompanied by a diminished left-hemisphere advantage across all speech feature types in ASD, with the most pronounced effects in complex, multi-feature conditions. Significance: By testing alternative hypotheses and predictions, this exploratory study will clarify the extent to which speech processing differences in ASD reflect cognitive biases (local vs. global, per EPF/WCC/NCH) versus speech-specific neurophysiological disruptions. Findings will advance our understanding of the sensory and integrative mechanisms underlying communication difficulties in ASD, particularly in tonal language contexts, and may inform the development of linguistically tailored interventions. Full article
(This article belongs to the Special Issue Language Perception and Processing)
Show Figures

Figure 1

26 pages, 1350 KiB  
Article
ADL-Focused Occupation-Based Neurobehavioral Evaluation Software: Addition of a Rasch-Based Stroke Subscale to Measure Outcomes
by Guðrún Árnadóttir, Laufey Halla Atladóttir, Garðar Ingvarsson, Helgi Sigtryggsson and Bjarni Ármann Atlason
Brain Sci. 2025, 15(9), 904; https://doi.org/10.3390/brainsci15090904 - 23 Aug 2025
Abstract
Background: Measurements are necessary in rehabilitation for evaluating service effectiveness. The ADL-focused Occupation-based Neurobehavioral Evaluation (A-ONE) is used for evaluating ADL performance and the impact of neurobehavioral impairments on the performance. Recently, Rasch-based software was constructed for the A-ONE ADL and neurobehavioral scales. [...] Read more.
Background: Measurements are necessary in rehabilitation for evaluating service effectiveness. The ADL-focused Occupation-based Neurobehavioral Evaluation (A-ONE) is used for evaluating ADL performance and the impact of neurobehavioral impairments on the performance. Recently, Rasch-based software was constructed for the A-ONE ADL and neurobehavioral scales. It converts ordinal rating scale scores into measures, estimates missing data values and calculates the statistical significance of changes. Objectives: To expand the A-ONE software by developing a cerebrovascular accident (CVA) neurobehavioral subscale. Additionally, to pilot-test whether the ADL and CVA scales of the software can detect statistically significant improvements. Method: Rasch analysis was used for evaluating the item fit, PCA, person separation and reliability to establish the internal validity of the CVA subscale (n = 222). The external validity (n = 22) was obtained by comparing A-ONE software measures to Winsteps measures. Subsequently 21 pre–post-intervention comparisons were made of stroke patients using both the ADL and CVA scales. Results: All set criteria for internal and external validity were met. By using the software clinically after incorporating the CVA subscale, statistically significant changes were detected in 90.5% of comparisons using the ADL scale and 36.4% using the CVA scale. The intervention program used was determined to consist of 66.4% occupation-based activities. Conclusions: This study is the first to deliver a clinically deployable Rasch-based CVA subscale integrated into routine occupational therapy software. The A-ONE software offers considerable time saving for therapists and the potential to detect significant differences in performance and impairment impact. It contributes to the removal of clinical obstacles toward the use of the instrument as an outcome measure and encourages the use of measures in rehabilitation. Full article
14 pages, 623 KiB  
Review
AI-Driven Multimodal Brain-State Decoding for Personalized Closed-Loop TENS: A Comprehensive Review
by Jiahao Du, Shengli Luo and Ping Shi
Brain Sci. 2025, 15(9), 903; https://doi.org/10.3390/brainsci15090903 - 23 Aug 2025
Abstract
Chronic pain is a dynamic, brain-wide condition that eludes effective management by conventional, static treatment approaches. Transcutaneous Electrical Nerve Stimulation (TENS), traditionally perceived as a simple and generic modality, is on the verge of a significant transformation. Guided by advances in brain-state decoding [...] Read more.
Chronic pain is a dynamic, brain-wide condition that eludes effective management by conventional, static treatment approaches. Transcutaneous Electrical Nerve Stimulation (TENS), traditionally perceived as a simple and generic modality, is on the verge of a significant transformation. Guided by advances in brain-state decoding and adaptive algorithms, TENS can evolve into a precision neuromodulation system tailored to individual needs. By integrating multimodal neuroimaging—including the spatial resolution of functional magnetic resonance imaging (fMRI), the temporal sensitivity of an Electroencephalogram (EEG), and the ecological validity of functional near-infrared spectroscopy (fNIRS)—with real-time machine learning, we envision a paradigm shift from fixed stimulation protocols to personalized, closed-loop modulation. This comprehensive review outlines a translational framework to reengineer TENS from an open-loop device into a responsive, intelligent therapeutic platform. We examine the underlying neurophysiological mechanisms, artificial intelligence (AI)-driven infrastructures, and ethical considerations essential for implementing this vision in clinical practice—not only for chronic pain management but also for broader neuroadaptive healthcare applications. Full article
Show Figures

Figure 1

15 pages, 1081 KiB  
Article
Examination of the Psychometric Properties of the Observable Social Cognition Rating Scale (OSCARS) in Arabic-Speaking Patients with Schizophrenia
by Feten Fekih-Romdhane, Georges Kerbage, Nagham Hachem, Michelle El Murr, Georges Haddad, Rony Abou Khalil, Frederic Harb, Elissar El Hayek and Souheil Hallit
Brain Sci. 2025, 15(9), 902; https://doi.org/10.3390/brainsci15090902 - 22 Aug 2025
Abstract
Background/Objectives: No Arabic-language version of the Observable Social Cognition Rating Scale (OSCARS) is available that allows to properly and specifically assess social cognition (SC) in Arabic-speaking populations. This study aimed to examine the preliminary psychometric characteristics of the Arabic translated version of [...] Read more.
Background/Objectives: No Arabic-language version of the Observable Social Cognition Rating Scale (OSCARS) is available that allows to properly and specifically assess social cognition (SC) in Arabic-speaking populations. This study aimed to examine the preliminary psychometric characteristics of the Arabic translated version of the OSCARS, including factor structure, reliability, concurrent validity, and measurement invariance across sex. Methods: This cross-sectional study has been conducted during February and March 2024 and included 113 chronic, remitted, and clinically stable patients with schizophrenia. Results: The originally proposed two-factor model (Social Cognitive Bias and Social Cognitive Ability) showed acceptable model fit after removal of two items that yielded low factor loadings (items 2 and 3). Total and factor scores showed good internal consistency, with Cronbach’s alpha of 0.85–0.94. Measurement invariance was established across sex groups at the configural, metric, and scalar levels. No significant differences emerged between male and female patients for latent mean scores of the OSCARS. Finally, concurrent validity was supported by appropriate patterns of correlations with functioning, recovery, and emotional intelligence measures. Conclusions: The Arabic OSCARS stands out as a brief, valid, reliable, and comprehensive assessment tool to evaluate SC in Arabic-speaking patients with schizophrenia based on the perspectives of interviewers. Offering this measure to clinicians and researchers who work in Arab settings may close the existing gap in the assessment of SC in schizophrenia. Due to its easy and fast application, the Arabic OSCARS is believed to be highly valuable in clinical and research practices. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
Show Figures

Figure 1

18 pages, 1083 KiB  
Article
Optimizing Gait Outcomes in Parkinson’s Disease: The Effects of Musical Groove and Familiarity
by Emily A. Ready, Jeffrey D. Holmes, Eryn P. Lonnee and Jessica A. Grahn
Brain Sci. 2025, 15(9), 901; https://doi.org/10.3390/brainsci15090901 - 22 Aug 2025
Viewed by 29
Abstract
Background. Parkinson’s Disease (PD) is a neurological condition that can severely impair gait, often through changes to gait parameters including stride length, velocity, and variability. Therapeutic interventions such as Rhythmic Auditory Stimulation (RAS®) target gait dysfunction in PD by using the [...] Read more.
Background. Parkinson’s Disease (PD) is a neurological condition that can severely impair gait, often through changes to gait parameters including stride length, velocity, and variability. Therapeutic interventions such as Rhythmic Auditory Stimulation (RAS®) target gait dysfunction in PD by using the regular beat of music or metronome clips to cue normalized walking patterns. Previous research has suggested that auditory cue properties (e.g., familiarity and groove) and individual factors (e.g., beat perception ability and susceptibility to dual-task interference) influence auditory cueing treatment efficacy in healthy young and older adults; however, optimization of rhythmic cueing across individuals with PD remains understudied. Methods. To address this, we explored the effects of familiarity, groove, beat perception ability, and synchronization instructions on gait in patients with PD during accelerated auditory cues. Individuals with idiopathic PD were randomized to walk freely or synchronized to music and metronome cues played 10% faster than their baseline walking cadence. Musical stimuli varied in self-reported familiarity and perceived groove and beat perception ability was assessed to classify participants as good or poor beat perceivers. Results. Overall, high-groove music and synchronized walking elicited faster gait patterns compared to low-groove music and free walking, respectively, as demonstrated by increased gait velocity and cadence. Familiarity and beat perception ability did not significantly affect gait in individuals with PD. Discussion. Altogether, our results indicate that high-groove music and synchronized walking lead to the greatest gait improvements during cueing, regardless of beat perception ability. Conclusion. Future studies and clinical interventions should consider stimulus type and synchronization instructions when implementing cueing therapies for gait dysfunction in PD in order to optimize treatment responses. Full article
(This article belongs to the Special Issue Focusing on the Rhythmic Interventions in Movement Disorders)
Show Figures

Figure 1

16 pages, 653 KiB  
Study Protocol
Targeting Fear of Cancer Recurrence with Internet-Based Emotional Freedom Techniques (iEFT) and Mindfulness Meditation Intervention (iMMI) (BGOG-gyn1b/REMOTE)
by Laura Tack, Lore Mertens, Marte Vandeweyer, Fien Florin, Emma Pauwels, Thaïs Baert, Tom Boterberg, Christel Fontaine, Kurt Geldhof, Caroline Lamot, Christine Langenaeken, Jeroen Mebis, Laure-Anne Teuwen, Katherine Vandenborre, Heidi Van den Bulck, Florence Van Ryckeghem, Mohammad Najlah, Patricia Schofield and Philip R. Debruyne
Brain Sci. 2025, 15(9), 900; https://doi.org/10.3390/brainsci15090900 - 22 Aug 2025
Viewed by 40
Abstract
Approximately one-third of cancer survivors report a need for professional help to cope with Fear of Cancer Recurrence (FCR). In the REMOTE trial, we aim to investigate the efficacy of two internet-based mind-body techniques to address this currently unmet medical need. Cancer survivors, [...] Read more.
Approximately one-third of cancer survivors report a need for professional help to cope with Fear of Cancer Recurrence (FCR). In the REMOTE trial, we aim to investigate the efficacy of two internet-based mind-body techniques to address this currently unmet medical need. Cancer survivors, screened using the Cancer Worry Scale (CWS), are randomly assigned to one of the three study groups: (1) internet-based emotional freedom techniques (iEFT) (n = 113), (2) an active control condition internet-based mindfulness meditation intervention (iMMI) (n = 113), or (3) a wait-list control group (WLC) (n = 113). The interventions iEFT and iMMI are conducted remotely using Microsoft Teams (Microsoft, Redmond, WA), and participants have access to an online platform via the MyNexuzHealth application (nexuzhealth NV, Hasselt, Belgium). The primary endpoint is the level of FCR. Secondary outcomes are emotional distress and quality of life (QoL). If iEFT and/or iMMI appear to be effective in reducing FCR, they could be readily implemented in clinical practice. Full article
Show Figures

Figure 1

19 pages, 1010 KiB  
Review
Interaction Between α-Synuclein and DJ-1 in Parkinson’s Disease
by Pouya Sobhifar and David R. Brown
Brain Sci. 2025, 15(9), 899; https://doi.org/10.3390/brainsci15090899 - 22 Aug 2025
Viewed by 42
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders among the elderly. The exact etiology of sporadic PD is still unknown; however, there is general consensus that the accumulation and aggregation of α-synuclein (α-syn) are among the prominent pathological features. The [...] Read more.
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders among the elderly. The exact etiology of sporadic PD is still unknown; however, there is general consensus that the accumulation and aggregation of α-synuclein (α-syn) are among the prominent pathological features. The precise function of α-syn in the healthy human brain is not agreed upon, although it has been reported to play a role in vesicular trafficking and neurotransmitter release. Dutch Juvenile-1 (DJ-1) is a multifunctional protein involved in regulating an array of mechanisms, including oxidative stress, ferroptosis, mitochondrial and dopamine homeostasis. Loss-of-function of DJ-1 was reported to cause familial PD, and oxidative inactivation of DJ-1 has been observed in sporadic cases, suggesting that both genetic and post-translational events converge on common disease pathways. This review proposes that loss of DJ-1 function may elevate intracellular α-syn levels, leading to their aggregation and consequent neurotoxicity. Reports suggest that DJ-1 can inhibit α-syn aggregation, facilitate α-syn clearance via chaperone-mediated autophagy, and act as a deglycase or glyoxalase to neutralize glycated α-syn species. Clinical studies have also reported altered DJ-1 oxidation states in PD patient samples, supporting its potential as a biomarker. By bridging familial and sporadic PD mechanisms, DJ-1 emerges as a compelling therapeutic target with the potential to mitigate α-syn–mediated neurodegeneration across both forms. However, further research is required to fully establish its clinical relevance and translational potential. Full article
(This article belongs to the Collection Collection on Molecular and Cellular Neuroscience)
Show Figures

Figure 1

26 pages, 1915 KiB  
Article
From Cortex to Cardiac Response: tDCS of the Prefrontal Cortex Improves Autonomic Markers of Emotion Regulation
by Catarina Gomes Coelho, Jorge Leite, Raquel Pinto, Paulo P. P. Machado and Sandra Carvalho
Brain Sci. 2025, 15(9), 898; https://doi.org/10.3390/brainsci15090898 - 22 Aug 2025
Viewed by 46
Abstract
Background: Emotion regulation (ER) plays a vital role in mental health, spanning mood, anxiety, and personality disorders. Cognitive reappraisal (CR) is one of the most common ER strategies and depends on prefrontal brain areas, but its success varies, and its neural basis is [...] Read more.
Background: Emotion regulation (ER) plays a vital role in mental health, spanning mood, anxiety, and personality disorders. Cognitive reappraisal (CR) is one of the most common ER strategies and depends on prefrontal brain areas, but its success varies, and its neural basis is not fully clear. Interest is growing in using transcranial direct current stimulation (tDCS) to support ER, yet most studies have focused only on the dorsolateral prefrontal cortex (dlPFC) and used simple tasks. Objective: This study explored whether tDCS applied to either the dlPFC or the ventromedial prefrontal cortex (vmPFC) could shape autonomic responses during CR while people watched emotionally engaging film clips. Methods: Participants were randomly assigned to receive either active or sham tDCS over the dlPFC or vmPFC. While stimulated, they used CR strategies (positive reappraisal, fictional reappraisal, or distancing) to manage their reactions to negative film scenes. Heart rate (HR), skin conductance (SC), and respiratory rate (RR) were tracked throughout as physiological indicators. Results: Active dlPFC tDCS combined with CR led to significantly greater reductions in HR toward the end of emotional exposure, compared to sham or non-CR conditions. dlPFC stimulation also lowered HR even without explicit CR, pointing to possible effects on automatic regulation. vmPFC effects were inconsistent, and no reliable effects were observed for SC or RR. Conclusions: These results suggest that tDCS effects on autonomic ER depend on the brain region and timing. dlPFC stimulation may strengthen both intentional and automatic emotion regulation, especially when combined with reappraisal, highlighting the value of realistic emotional tasks in neuromodulation studies. Full article
Show Figures

Figure 1

10 pages, 4700 KiB  
Article
Nucleus Accumbens Dopamine Levels Fluctuate Across Different States of Consciousness Under Sevoflurane Anesthesia
by Weiwei Bao, Fangjiaqi Wei, Jian Huang, Zhili Huang and Changhong Miao
Brain Sci. 2025, 15(9), 897; https://doi.org/10.3390/brainsci15090897 - 22 Aug 2025
Viewed by 82
Abstract
Background: Dopamine (DA) is a critical neurotransmitter that regulates many physiological and behavioral processes. The central dopaminergic system plays a pivotal role in modulating general anesthesia (GA). DA release in the brain is mainly concentrated in the nucleus accumbens (NAc), prefrontal cortex, hypothalamus, [...] Read more.
Background: Dopamine (DA) is a critical neurotransmitter that regulates many physiological and behavioral processes. The central dopaminergic system plays a pivotal role in modulating general anesthesia (GA). DA release in the brain is mainly concentrated in the nucleus accumbens (NAc), prefrontal cortex, hypothalamus, and dorsal striatum. Several NAc neuron subtypes are essential for modulating states of consciousness during GA. However, whether NAc DA signal dynamics correlate with different states of consciousness under sevoflurane anesthesia remains to be elucidated. In this study, we measured the dynamic fluctuations of NAc DA levels throughout sevoflurane anesthesia to verify its role. Methods: An intensity-based genetically encoded DA indicator, dLight1.1, was employed to track DA release in the NAc. Fiber photometry combined with electroencephalogram/electromyogram recordings was employed to synchronously track NAc DA signal dynamics across different states of consciousness under sevoflurane anesthesia. Results: Under 2.5% sevoflurane exposure, DA release in the NAc significantly increased during the initial 100 s of sevoflurane induction, which was designated as sevo on-1 (mean ± standard error of the mean [SEM]; baseline vs. sevo on-1, p = 0.0261), and continued to decrease in the subsequent anesthesia maintenance phases (sevo on-1 vs. sevo on-4, p = 0.0070). Following the cessation of sevoflurane administration (with intervals denoted as sevooff), NAc DA gradually returned to baseline levels (sevo on-1 vs. sevo off-1, p = 0.0096; sevo on-1 vs. sevo off-3, p = 0.0490; sevo on-1 vs. sevo off-4, p = 0.0059; sevo on-4 vs. sevo off-4, p = 0.0340; sevo off-1 vs. sevo off-4, p = 0.0451). During the induction phase, NAc DA signal dynamics markedly increased during the pre-loss of consciousness (LOC) period (pre-anesthesia baseline vs. pre-LOC, p = 0.0329) and significantly declined after LOC (pre-LOC vs. post-LOC, p = 0.0094). For the emergence period, NAc DA release exhibited a noticeable increase during the initial period after recovery of consciousness (ROC) (anesthesia baseline vs. post-ROC, p = 0.0103; pre-ROC vs. post-ROC, p = 0.0086). Furthermore, the DA signals peaked rapidly upon the initiation of the burst wave and then gradually attenuated, indicating a positive correlation with the burst wave onset during burst suppression events. Conclusions: Our findings revealed that NAc DA neurotransmitter signal dynamics correlate with different states of consciousness throughout sevoflurane anesthesia. Full article
(This article belongs to the Section Systems Neuroscience)
Show Figures

Figure 1

Previous Issue
Back to TopTop