Journal Description
Brain Sciences
Brain Sciences
is an international, peer-reviewed, open access journal on neuroscience, published monthly online by MDPI. The British Neuro-Oncology Society (BNOS) and Panhellenic Federation of Alzheimer's Disease and Related Disorders (PFADRD) are affiliated with Brain Sciences and their members receive a discount on article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, PSYNDEX, PsycInfo, CAPlus / SciFinder, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.2 days after submission; acceptance to publication is undertaken in 1.9 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Journal Cluster of Neurosciences: Brain Sciences, Neurology International, NeuroSci, Clinical and Translational Neuroscience, Neuroglia, Psychiatry International, Clocks & Sleep and Journal of Dementia and Alzheimer's Disease.
Impact Factor:
2.8 (2024);
5-Year Impact Factor:
3.1 (2024)
Latest Articles
Electroencephalographic Biomarkers in Tinnitus: A Narrative Review of Current Approaches and Clinical Perspectives
Brain Sci. 2025, 15(12), 1332; https://doi.org/10.3390/brainsci15121332 (registering DOI) - 14 Dec 2025
Abstract
Background/Objectives: Tinnitus causes significant cognitive and emotional distress; however, its clinical assessment mostly relies on subjective measures without evaluation of objective indices. In this narrative review, we examined the potential of electroencephalography (EEG)-based neurophysiological markers as objective biomarkers in tinnitus assessment. Methods
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Background/Objectives: Tinnitus causes significant cognitive and emotional distress; however, its clinical assessment mostly relies on subjective measures without evaluation of objective indices. In this narrative review, we examined the potential of electroencephalography (EEG)-based neurophysiological markers as objective biomarkers in tinnitus assessment. Methods: The Web of Science, PubMed, EMBASE, and MEDLINE databases were searched to identify research articles on EEG-based analysis of individuals with tinnitus. Studies in which treatment and control groups were compared across four analytical domains (spectral power analysis, functional connectivity, microstate analysis, and entropy measures) were included. Qualitative synthesis was conducted to elucidate neurophysiological mechanisms, methodological characteristics, and clinical implications. Results: Analysis of 18 studies (n = 1188 participants) revealed that tinnitus is characterized by distributed neural dysfunction that extends beyond the auditory system. Spectral power analyses revealed sex-dependent, frequency-specific abnormalities across distributed brain regions. Connectivity analyses demonstrated elevated long-range coupling in high-frequency bands concurrent with diminished low-frequency synchronization. Microstate analyses revealed alterations in spatial configuration and transition probabilities. Entropy quantification indicated elevated complexity, particularly in the frontal and auditory cortices. Conclusions: EEG-derived neurophysiological markers demonstrate associations with tinnitus in group analyses and show potential for elucidating pathophysiological mechanisms. However, significant limitations, including low spatial resolution, small sample sizes, methodological heterogeneity, and lack of validation for individual-level diagnosis or treatment prediction, highlight the need for cautious interpretation. Standardized analytical protocols, larger validation studies, multimodal neuroimaging integration, and demonstration of clinical utility in prospective trials are required before EEG markers can be established as biomarkers for tinnitus diagnosis and management.
Full article
(This article belongs to the Special Issue Neural Correlates of Cognitive Workload and Learning: Portable Brain Monitoring During Skill Acquisition and Real-World Task Performance)
Open AccessSystematic Review
Exploring the Bidirectional Relationship Between Numerical Cognition and Motor Performance: A Systematic Review
by
Eliane Rached, Jihan Allaw, Joy Khayat, Hassan Karaki, Ahmad Diab, Antonio Pinti and Ahmad Rifai Sarraj
Brain Sci. 2025, 15(12), 1331; https://doi.org/10.3390/brainsci15121331 (registering DOI) - 14 Dec 2025
Abstract
Background: Numerical cognition and motor performance rely on overlapping brain systems, yet the extent of their reciprocal interaction remains unclear. This systematic review explores how number processing influences motor execution and how motor activity shapes numerical cognition, emphasizing the neural mechanisms underlying these
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Background: Numerical cognition and motor performance rely on overlapping brain systems, yet the extent of their reciprocal interaction remains unclear. This systematic review explores how number processing influences motor execution and how motor activity shapes numerical cognition, emphasizing the neural mechanisms underlying these associations. Methods: A comprehensive search of Scopus, PubMed, MEDLINE, SPORTDiscus, PsycINFO, and SpringerLink, as well as journal citations and conference proceedings (up to August 2025), identified experimental studies examining the interplay between numerical cognition and motor performance in healthy adults. Both randomized and non-randomized designs were included. Two reviewers independently screened, extracted data, and assessed study quality following PRISMA and Cochrane Risk of Bias guidelines. Results: Twelve studies met the inclusion criteria. Most showed that numerical stimuli facilitated motor responses, with congruent number–movement pairings yielding faster reactions and more efficient kinematics. Mental calculation often enhanced motor output (e.g., force, jump height), though interferences emerged under high cognitive load. Conversely, motor actions consistently biased numerical judgments, aligning with spatial–numerical associations. Conclusions: Evidence suggests a predominant pattern of facilitation, likely reflecting shared networks between cognitive and motor resources. These findings advance theoretical understanding and highlight promising translational applications in education, sport, and neurorehabilitation.
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(This article belongs to the Topic Advances in Motor Control and Neuromotor Interfacing in Sports)
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Open AccessReview
The Neural Contributions to Reactive Balance Control: A Scoping Review of EEG, fNIRS, MRI, and PET Studies
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Andrew S. Monaghan, Taylor Takla, Edward Ofori, Daniel S. Peterson, Wendy Wu, Nora E. Fritz and Jason K. Longhurst
Brain Sci. 2025, 15(12), 1330; https://doi.org/10.3390/brainsci15121330 (registering DOI) - 13 Dec 2025
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Background/Objectives: Rapid postural reactions are critical for preventing falls, yet the neural systems supporting these responses are not fully understood, particularly with respect to aging and neurological disorders. Understanding how the brain detects, interprets, and responds to balance disturbances is essential for
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Background/Objectives: Rapid postural reactions are critical for preventing falls, yet the neural systems supporting these responses are not fully understood, particularly with respect to aging and neurological disorders. Understanding how the brain detects, interprets, and responds to balance disturbances is essential for developing new interventions. This scoping review aimed to synthesize evidence from neuroimaging studies to identify the cortical and subcortical mechanisms underlying reactive balance and to characterize how these mechanisms are altered by aging and pathology. Methods: A structured search of EMBASE, PubMed, and CINAHL (7 November 2024) identified studies examining neural activity during experimentally induced balance perturbations. Sixty-one studies met inclusion criteria (EEG n = 45; MRI n = 9; fNIRS n = 8; PET n = 1) and were analyzed for patterns of regional activation and age- or disease-related differences. Results: Evidence converges on a distributed network supporting reactive balance. Sensorimotor, premotor, supplementary motor, and prefrontal cortices show consistent involvement, while cerebellar, brainstem, and basal ganglia structures contribute to rapid, automatic responses. Aging and neurological conditions commonly heighten cortical activation, suggesting reduced automaticity and increased reliance on compensatory control. Conclusions: Reactive balance emerges from coordinated activity across cortico-subcortical systems that are altered by aging and pathology. Further research incorporating multimodal imaging approaches and more ecologically realistic perturbation paradigms is needed to clarify mechanistic pathways and inform precision-based fall-prevention strategies.
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Open AccessArticle
Lesion-Symptom Mapping of Acute Speech Deficits After Left vs. Right Hemisphere Stroke: A Retrospective Analysis of NIHSS Best Language Scores and Clinical Neuroimaging
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Nilofar Sherzad, Roger Newman-Norlund, John Absher, Leonardo Bonilha, Christopher Rorden, Julius Fridriksson and Sigfus Kristinsson
Brain Sci. 2025, 15(12), 1329; https://doi.org/10.3390/brainsci15121329 (registering DOI) - 13 Dec 2025
Abstract
Background: Recent research suggests that damage to right hemisphere regions homotopic to the left hemisphere language network affects language abilities to a greater extent than previously thought. However, few studies have investigated acute disruption of language after lesion to the right hemisphere.
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Background: Recent research suggests that damage to right hemisphere regions homotopic to the left hemisphere language network affects language abilities to a greater extent than previously thought. However, few studies have investigated acute disruption of language after lesion to the right hemisphere. Here, we examined lesion correlates of acute speech deficits following left and right hemisphere ischemic stroke to clarify the neural architecture underlying early language dysfunction. Methods: We retrospectively analyzed 410 patients (225 left, 185 right hemisphere lesions) from the Stroke Outcome Optimization Project dataset. Presence and severity of speech deficits was measured using the National Institute of Health Stroke Scale Best Language subscore within 48 h of onset. Manual lesion masks were derived from clinical MRI scans and normalized to MNI space. Lesion-symptom mapping was conducted using voxelwise and region-of-interest analyses with permutation correction (5000 iterations; p < 0.05), controlling for total lesion volume. Results: Speech deficits were observed in 53.7% of the cohort (58.2% left, 48.1% right hemisphere lesions). In the full sample, the presence of speech deficits was associated with bilateral subcortical and perisylvian damage, including the external and internal capsules, insula, putamen, and superior fronto-occipital fasciculus. Severity of speech deficits localized predominantly to left hemisphere structures, with peak associations in the external capsule (Z = 6.39), posterior insula (Z = 5.64), and inferior fronto-occipital fasciculus (Z = 5.43). In the right hemisphere cohort, the presence and severity of speech deficits were linked to homologous regions, including the posterior insula (Z = 3.70) and external capsule (Z = 3.63), although with smaller effect sizes relative to the left hemisphere cohort. Right hemisphere lesions resulted in milder deficits despite larger lesion volumes compared with left hemisphere lesions. Conclusions: Acute speech impairment following right hemisphere stroke is associated with damage to a homotopic network encompassing perisylvian cortical and subcortical regions analogous to the dominant left hemisphere language network. These findings demonstrate that damage to the right hemisphere consistently results in acute speech deficits, challenging the traditional left-centric view of post-stroke speech impairment. These results have important implications for models of bilateral language representation and the neuroplastic mechanisms supporting language recovery.
Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Post-Stroke and Progressive Aphasias)
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Open AccessArticle
Effects of Continuous Theta Burst Stimulation to the Dorsolateral Prefrontal Cortex on Attention to Emotional Stimuli: A Randomized Controlled Trial
by
Katerina Konikkou, Aimé Isdahl-Troye, Maria Sikki and Kostas Fanti
Brain Sci. 2025, 15(12), 1328; https://doi.org/10.3390/brainsci15121328 (registering DOI) - 13 Dec 2025
Abstract
Background/Objectives: The use of theta-burst stimulation (TBS) over the dorsolateral prefrontal cortex (DLPFC) to modulate cognitive function is gaining increasing interest, since it is more time-efficient than standard repetitive transcranial magnetic stimulation. However, the impact of TBS protocols on specific cognitive processes,
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Background/Objectives: The use of theta-burst stimulation (TBS) over the dorsolateral prefrontal cortex (DLPFC) to modulate cognitive function is gaining increasing interest, since it is more time-efficient than standard repetitive transcranial magnetic stimulation. However, the impact of TBS protocols on specific cognitive processes, such as emotional attention, remains understudied. This study aimed to examine the differential effect of continuous TBS (cTBS) over the left and right DLPFC on the facilitation of attention towards emotional (i.e., pleasant and distressing) versus neutral stimuli. Methods: In this randomized controlled trial, ninety-one healthy young adults were randomly allocated to receive either real or sham stimulation over the right or left DLPFC (i.e., left/right real cTBS and left/right sham cTBS), and then completed a computerized dot-probe task that included distressing, pleasant, and neutral images. Results: Participants who received real cTBS showed slower response times to probes replacing neutral images compared to emotional images, whereas no differences were found between stimuli in the sham conditions. No hemisphere-dependent effects were observed for distressing or pleasant images, suggesting that cTBS modulated attentional performance in a comparable manner when administered over the left or right DLPFC. Conclusions: These findings contribute to the literature on emotional attention, underscoring the role of DLPFC in attentional control, which is a valuable cognitive target for advancing the design and implementation of cTBS protocols.
Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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Open AccessArticle
Recognising Emotions from the Voice: A tDCS and fNIRS Double-Blind Study on the Role of the Cerebellum in Emotional Prosody
by
Sharon Mara Luciano, Laura Sagliano, Alessia Salzillo, Luigi Trojano and Francesco Panico
Brain Sci. 2025, 15(12), 1327; https://doi.org/10.3390/brainsci15121327 (registering DOI) - 13 Dec 2025
Abstract
Background: Emotional prosody refers to the variations in pitch, pause, melody, rhythm, and stress of pronunciation conveying emotional meaning during speech. Although several studies demonstrated that the cerebellum is involved in the network subserving recognition of emotional facial expressions, there is only
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Background: Emotional prosody refers to the variations in pitch, pause, melody, rhythm, and stress of pronunciation conveying emotional meaning during speech. Although several studies demonstrated that the cerebellum is involved in the network subserving recognition of emotional facial expressions, there is only preliminary evidence suggesting its possible contribution to recognising emotional prosody by modulating the activity of cerebello-prefrontal circuits. The present study aims to further explore the role of the left and right cerebellum in the recognition of emotional prosody in a sample of healthy individuals who were required to identify emotions (happiness, anger, sadness, surprise, disgust, and neutral) from vocal stimuli selected from a validated database (EMOVO corpus). Methods: Anodal transcranial Direct Current Stimulation (tDCS) was used in offline mode to modulate cerebellar activity before the emotional prosody recognition task, and functional near-infrared spectroscopy (fNIRS) was used to monitor stimulation-related changes in oxy- and deoxy- haemoglobin (O2HB and HHB) in prefrontal areas (PFC). Results: Right cerebellar stimulation reduced reaction times in the recognition of all emotions (except neutral and disgust) as compared to both the sham and left cerebellar stimulation, while accuracy was not affected by the stimulation. Haemodynamic data revealed that right cerebellar stimulation reduced O2HB and increased HHB in the PFC bilaterally relative to the other stimulation conditions. Conclusions: These findings are consistent with the involvement of the right cerebellum in modulating emotional processing and in regulating cerebello-prefrontal circuits.
Full article
(This article belongs to the Topic The Relationship Between Bodily, Autonomic, and Communicative Behaviors and the Experiential and Cognitive Aspects of Emotion)
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Open AccessArticle
Brain Activation Features in Response to the Expectation of Receiving Rewards Through Aggression
by
Jia-Ming Wei, Xiaoyun Zhao and Ling-Xiang Xia
Brain Sci. 2025, 15(12), 1326; https://doi.org/10.3390/brainsci15121326 (registering DOI) - 12 Dec 2025
Abstract
Background: Reward expectation is an important motivation for aggression. However, despite substantial progress in behavioral studies related to reward expectation in aggression, the neural basis underlying this process remains unclear. Methods: To investigate the brain correlates of aggressive reward expectation, we
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Background: Reward expectation is an important motivation for aggression. However, despite substantial progress in behavioral studies related to reward expectation in aggression, the neural basis underlying this process remains unclear. Methods: To investigate the brain correlates of aggressive reward expectation, we developed the Harm–Gain Task (HGT). In this task, participants were informed that they could gain money by causing harm to another person and were instructed to evaluate their satisfaction with the anticipated monetary reward. Additionally, we designed a questionnaire to measure participants’ moral disengagement concerning aggressive decision-making in the HGT. Thirty-four healthy Chinese university students completed the HGT while in the scanner, and their functional images were acquired using a 3.0-T Siemens Tim Trio scanner. Data from two participants were excluded from the analysis due to excessive head motion. Finally, data from 32 participants (15 males, Mage = 19.97 years, SDage = 2.07 years) were included in the analyses. Results: Findings show that during the reward expectation phase of the HGT, (1) relative to the baseline condition, the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and middle cingulate cortex (MCC) were significantly activated. Conversely, activation in the bilateral dorsolateral prefrontal cortex (DLPFC), bilateral inferior parietal lobule (IPL), and bilateral lateral temporal cortex (LTC) was attenuated. (2) As the monetary amount raised, activation in the OFC and ACC significantly increased, while activation in the DLPFC, IPL, and LTC significantly decreased. (3) As the monetary amount raised, the heightened activation in the OFC and ACC was significantly correlated with participants’ aggressive behavior and moral disengagement scores. Conclusions: The results provide preliminary evidence regarding neural correlates in aggressive reward expectation, promoting further exploration of the cognitive neural mechanisms underlying aggression.
Full article
(This article belongs to the Special Issue Neural Mechanisms Underlying Social Cognition and Emotional Processing)
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Open AccessReview
Brain Age Acceleration on MRI Due to Poor Sleep: Associations, Mechanisms, and Clinical Implications
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Eman A. Toraih, Mohammad H. Hussein, Abdulrahman Omar A. Alali, Asseel Farhan K. Alanazi, Nasser Rakan Almjlad, Turki Helal D. Alanazi, Rawaf Awadh T. Alanazi and Manal S. Fawzy
Brain Sci. 2025, 15(12), 1325; https://doi.org/10.3390/brainsci15121325 - 12 Dec 2025
Abstract
Sleep disturbances, affecting nearly half of middle-aged adults, have emerged as modifiable determinants of brain health and dementia risk. Recent advances in machine learning applied to MRI enable the estimation of “brain age,” a biomarker that quantifies deviation from normative neural aging. This
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Sleep disturbances, affecting nearly half of middle-aged adults, have emerged as modifiable determinants of brain health and dementia risk. Recent advances in machine learning applied to MRI enable the estimation of “brain age,” a biomarker that quantifies deviation from normative neural aging. This review synthesizes and critically evaluates converging evidence that poor sleep accelerates biological brain aging, identifies mechanistic pathways, and delineates translational barriers to clinical application. Across large-scale cohorts comprising more than 25,000 participants, suboptimal sleep independently predicts 1–3 years of MRI-derived brain age acceleration, even after adjusting for vascular and metabolic confounders. Objective sleep fragmentation and altered sleep-stage architecture exhibit sleep-specific neuroanatomical signatures, independent of amyloid and tau pathology, while inflammatory, vascular, and glymphatic mechanisms mediate a small fraction of the effect. Experimental sleep deprivation studies demonstrate reversibility of accelerated brain aging, highlighting opportunities for early intervention. Translation to clinical practice is constrained by methodological heterogeneity, reliance on self-reported sleep metrics, limited population diversity, and the absence of randomized intervention trials demonstrating causal reversibility. Addressing these gaps through standardized MRI-based biomarkers, longitudinal mechanistic studies, and interventional trials could establish sleep optimization as a viable neuroprotective strategy for dementia prevention.
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(This article belongs to the Section Sleep and Circadian Neuroscience)
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Open AccessArticle
Core Body Temperature Negatively Correlates with Whole-Brain Gray Matter Volume: A Pilot Study in the Context of Global Warming
by
Keisuke Kokubun, Kiyotaka Nemoto, Yoshimitsu Yamamoto, Ayumu Mitera and Yoshinori Yamakawa
Brain Sci. 2025, 15(12), 1324; https://doi.org/10.3390/brainsci15121324 - 12 Dec 2025
Abstract
Global warming has been associated with various adverse effects on human physiology, yet its potential impact on brain structure remains largely unexplored. The present pilot study investigated the relationship between core body temperature and whole-brain gray matter volume (GMV) in healthy adults. Twenty-seven
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Global warming has been associated with various adverse effects on human physiology, yet its potential impact on brain structure remains largely unexplored. The present pilot study investigated the relationship between core body temperature and whole-brain gray matter volume (GMV) in healthy adults. Twenty-seven participants (19 males, 8 females; mean age = 38.6 ± 10.3 years) underwent MRI scanning and core temperature assessment. Correlation and partial correlation analyses were performed to examine the association between core body temperature and GMV, controlling for demographic and physiological covariates summarized by the first principal component. Core body temperature showed a significant negative correlation with whole-brain GMV (r = −0.496, p = 0.009; 95% CI = −0.737 to −0.143) and a trend-level significant partial correlation after covariate adjustment (r = −0.373, p = 0.060; 95% CI = −0.660 to 0.008). These trends remained after correction for multiple comparisons using the Benjamini–Hochberg false discovery rate. Exploratory analyses across 116 AAL regions identified the left Fusiform gyrus as showing a significant negative correlation with core body temperature (r = −0.643, p < 0.001). Given the modest sample size, these findings should be interpreted cautiously as preliminary, hypothesis-generating evidence. They suggest that even subtle variations in body temperature within the normal physiological range may relate to differences in global brain structure. Possible mechanisms include heat-induced inflammation, oxidative stress, and increased metabolic load on neural tissue. Understanding how individual differences in body temperature relate to brain morphology may provide insights into the neural health consequences of rising environmental temperatures.
Full article
(This article belongs to the Special Issue Climate-Related Neurological Problems and Diseases)
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Open AccessReview
Innovations in Meta-Analytic and Computational Methods in the Neuroscientific Investigation of Psychiatric and Neurological Disorders
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Chris H. Miller, Thomas J. Farrer, Jonathan D. Moore, Matthew J. Wright, Caitlin Baten, Ellen Woo, J. Paul Hamilton, Matthew D. Sacchet, Lance D. Erickson, Shawn D. Gale and Dawson W. Hedges
Brain Sci. 2025, 15(12), 1323; https://doi.org/10.3390/brainsci15121323 - 12 Dec 2025
Abstract
Recent advancements in neuroimaging and genetics have generated a rapid proliferation of primary studies in these fields, leading to the development and application of meta-analytic methods, which have contributed substantially to our understanding of psychiatric and neurological disorders. The current narrative review discusses
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Recent advancements in neuroimaging and genetics have generated a rapid proliferation of primary studies in these fields, leading to the development and application of meta-analytic methods, which have contributed substantially to our understanding of psychiatric and neurological disorders. The current narrative review discusses four such innovations and applications in meta-analytic techniques and how they have advanced our understanding of clinical conditions: (1) multilevel kernel density analysis (MKDA) of functional magnetic resonance imaging (fMRI) studies, (2) meta-analyses of positron emission tomography (PET) imaging of neuroinflammation, (3) Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium neuroimaging protocols, and (4) meta-genome-wide association studies (Meta-GWASs) and polygenic risk scores (PRSs). These meta-analytic methods have contributed substantially to our understanding of psychiatric and neurological disorders by refining robust neural models, identifying transdiagnostic and disease-specific biomarkers of inflammation, uncovering numerous genetic risk variants with improved prediction models, and underscoring the polygenic and pleiotropic architecture of these conditions. Future research should continue to develop techniques for harmonizing multimodal data analysis, pursue both biomarker- and mechanism-driven approaches to discovery, and leverage biological discoveries to advance development of precision treatments and diagnostic frameworks.
Full article
(This article belongs to the Section Neural Engineering, Neuroergonomics and Neurorobotics)
Open AccessArticle
The Relation of Alpha Asymmetry to Physical Activity Duration and Intensity
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Bryan Montero-Herrera, Megan M. O’Brokta, Praveen A. Pasupathi and Eric S. Drollette
Brain Sci. 2025, 15(12), 1322; https://doi.org/10.3390/brainsci15121322 - 11 Dec 2025
Abstract
Background/Objectives: Regular physical activity (PA) benefits mood and cognition, yet the neural markers associated with free-living PA remain unclear. Alpha asymmetry (AA), a neural marker of affective and motivational states, may help predict individuals’ preferred activity intensity and duration. To examine the relationship
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Background/Objectives: Regular physical activity (PA) benefits mood and cognition, yet the neural markers associated with free-living PA remain unclear. Alpha asymmetry (AA), a neural marker of affective and motivational states, may help predict individuals’ preferred activity intensity and duration. To examine the relationship between resting-state AA in frontal and parietal regions, positive affect, and accelerometer-derived PA metrics were measured. Methods: Fifty-nine participants (age = 21.8 years) wore wrist accelerometers for 7 days, completed resting-state electroencephalography (EEG; alpha power 8–13 Hz), and completed the Positive and Negative Affect Schedule (PANAS). PA metrics included sedentary time (ST), light PA (LPA), moderate-to-vigorous PA (MVPA), average acceleration (AvAcc), intensity gradient (IG), and the most active X minutes (M2–M120). Multiple regression models tested AA to PA associations while accounting for sex and positive affect. Results: Although frontal AA was included as a key neural candidate, the observed associations emerged only at parietal sites. Greater right parietal AA power was associated with the most active M60, M30, M15, M10, and M5. For IG, greater AA power was observed in the left parietal region. No significant associations emerged for LPA, MVPA, AvAcc, M120, or M2. Across models, higher positive affect consistently predicted greater PA engagement. Conclusions: While resting frontal AA is theoretically relevant to motivational processes, the findings indicate that parietal AA more strongly differentiates individuals’ tendencies toward specific PA intensities and durations. Positive affect is associated with PA engagement. These findings identify parietal AA as a promising neural correlate for tailoring PA strategies aimed at sustaining active lifestyles.
Full article
(This article belongs to the Section Behavioral Neuroscience)
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Open AccessReview
Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases
by
Kristina V. Smirnova, Liudmila P. Smirnova and Tamara G. Amstislavskaya
Brain Sci. 2025, 15(12), 1321; https://doi.org/10.3390/brainsci15121321 - 11 Dec 2025
Abstract
The brain and muscle ARNT-like 1 protein, also known as BMAL1 or ARNTL1, is one of the key transcriptional regulators of circadian rhythms that controls the diurnal dynamics of a wide range of behavioral, hormonal, and biochemical factors in most living creatures around
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The brain and muscle ARNT-like 1 protein, also known as BMAL1 or ARNTL1, is one of the key transcriptional regulators of circadian rhythms that controls the diurnal dynamics of a wide range of behavioral, hormonal, and biochemical factors in most living creatures around the Earth. This protein also regulates many physiological processes, and its disruption leads to pathological conditions in organisms, including nervous system disorders. The high evolutionary conservativity of BMAL1 allows for the construction of in vitro and in vivo models using experimental animals and the investigation of BMAL1-dependent molecular mechanisms of these diseases. In this review, we have collected data from human and animal studies concerning the roles of BMAL1 in processes such as neuroinflammation, trauma and neurodegeneration, neurodevelopment and myelinization, mood disorders, addictions, cognitive functions, and neurosignaling. Additionally, we provide information about the biochemical regulation of BMAL1 and pharmacological approaches to change its activity. Here, we conclude that BMAL1 functions in the nervous system go far beyond circadian rhythm regulation in most cell types, including neurons, glial cells, and microglial cells. Under pathological conditions, lack or overexpression of this protein can exert both protective and destructive effects. Thus, proper therapeutic modulation of BMAL1 activity is a promising approach for improving nervous system disorders.
Full article
(This article belongs to the Special Issue Translational Omics in Neurodegenerative and Neurodevelopmental Disorders)
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Open AccessArticle
Predictors of Futile Inter-Hospital Transfer for Endovascular Thrombectomy in Anterior Circulation Acute Ischemic Stroke Due to Large Vessel Occlusion
by
Tushar B. Patil, Aviraj Satish Deshmukh, Zacharie Gagné, Christine Hawkes, Aris H. Katsanos, Naif Faisal Alharbi, Mohammed Mesfer Alwadai, Rhonda McNicolle-White, Mukul Sharma and Brian van Adel
Brain Sci. 2025, 15(12), 1320; https://doi.org/10.3390/brainsci15121320 - 11 Dec 2025
Abstract
Background: Endovascular therapy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO), but inter-hospital transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) can result in delayed treatment and worse outcomes. Up to 30–40% of
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Background: Endovascular therapy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO), but inter-hospital transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) can result in delayed treatment and worse outcomes. Up to 30–40% of patients transferred may not receive EVT. This study investigates the causes of futile transfers to a CSC in Canada, aiming to identify its predictors. Methods: We conducted a retrospective analysis of consecutive patients transferred for EVT between 1 April 2017 and 31 December 2020, from PSCs and community hospitals (CH) to a CSC in an urban area of Canada. Data on demographics, clinical characteristics, and treatment outcomes were collected. Descriptive and comparative analyses were performed to identify factors contributing to non-receipt of EVT. Results: Of the transferred 326 patients, 241 (73.9%) underwent EVT, and 85 (26%) did not. The main reasons for not performing EVT were recanalization of the target vessel (44.7%), infarct growth (29.4%), clinical improvement or low NIHSS (17.6%), and hemorrhagic transformation (8.2%). Predictors of futility were lower NIHSS at presentation, intravenous thrombolysis (IVT) at the PSC, and greater ASPECTS decay during transport. Conclusions: Our study concluded that 26% of inter-hospital transfers for EVT were futile, primarily due to infarct growth, recanalization of the target vessel, and low NIHSS. These findings suggest that closer monitoring of clinical status, consideration of direct transfers to CSCs, and enhanced triage strategies may help reduce futile transfers and improve patient outcomes.
Full article
(This article belongs to the Special Issue Advancements in Diagnosis and Treatment of Stroke and Cerebral Aneurysms: A Call for Innovative Research Submissions)
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Open AccessArticle
Serum Cortisol and Interleukin-6 as Key Biomarkers for a Diagnostic Algorithm of Combat-Related PTSD
by
Yana Zorkina, Alexander Berdalin, Olga Abramova, Aleksandr Reznik, Valeriya Ushakova, Vladimir Mukhin, Daria Riabinina, Alina Khamidova, Olga Pavlova, Konstantin Pavlov, Elizaveta Golubeva, Angelina Zeltser, Georgy Kostyuk and Anna Morozova
Brain Sci. 2025, 15(12), 1319; https://doi.org/10.3390/brainsci15121319 - 10 Dec 2025
Abstract
Background: Post-traumatic stress disorder (PTSD) is a severe psychiatric condition prevalent among combat veterans. Its diagnosis is challenging due to the heterogeneity of clinical presentations and the complex interplay of pathogenic factors. Objective: This study aimed to develop and validate a diagnostic algorithm
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Background: Post-traumatic stress disorder (PTSD) is a severe psychiatric condition prevalent among combat veterans. Its diagnosis is challenging due to the heterogeneity of clinical presentations and the complex interplay of pathogenic factors. Objective: This study aimed to develop and validate a diagnostic algorithm for combat-related PTSD by integrating clinical data with a panel of biological markers associated with blood–brain barrier disruption (anti-GFAP and anti-NSE antibodies), HPA axis dysfunction (cortisol), and neuroinflammation (IL-6, IL-8). Methods: A total of 721 male participants were enrolled: 434 veterans with PTSD (F43.1), 147 combat veterans without PTSD, and 140 non-combat military controls. All participants underwent clinical and psychometric assessment (Likert scale, HADS). Serum levels of biomarkers were measured using ELISA. Statistical analysis included non-parametric tests, correlation analysis, and binary logistic regression with Wald’s method to build a predictive model. Results: The binary logistic regression model identified cortisol and IL-6 as the most significant predictors of PTSD. The final algorithm, based on a cortisol level below 199.8 nmol/L and an IL-6 level above 0.002438 pg/mL, correctly classified 78% of patients (AUC = 0.724, 95% CI [0.669, 0.779]). Furthermore, levels of IL-4, IL-8, and cortisol positively correlated with the severity of combat stress factors, independent of physical injuries. Conclusions: We developed a novel diagnostic algorithm for combat-related PTSD based on cortisol and IL-6 levels, demonstrating high accuracy. The correlation between neuroinflammatory markers and the severity of combat exposure suggests their role as primary indicators of stress response, highlighting their utility for early risk identification and targeted interventions.
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(This article belongs to the Section Environmental Neuroscience)
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Open AccessHypothesis
Multisensory Rhythmic Entrainment as a Mechanistic Framework for Modulating Prefrontal Network Stability in Focal Epilepsy
by
Ekaterina Andreevna Narodova
Brain Sci. 2025, 15(12), 1318; https://doi.org/10.3390/brainsci15121318 - 10 Dec 2025
Abstract
Epilepsy is increasingly conceptualized as a disorder of large-scale network instability, involving impairments in interhemispheric connectivity, prefrontal inhibitory control, and slow-frequency temporal processing. Rhythmic sensory stimulation—auditory, vibrotactile, or multisensory—can entrain neuronal oscillations and modulate attentional and sensorimotor networks, yet its mechanistic relevance to
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Epilepsy is increasingly conceptualized as a disorder of large-scale network instability, involving impairments in interhemispheric connectivity, prefrontal inhibitory control, and slow-frequency temporal processing. Rhythmic sensory stimulation—auditory, vibrotactile, or multisensory—can entrain neuronal oscillations and modulate attentional and sensorimotor networks, yet its mechanistic relevance to epileptic network physiology remains insufficiently explored. This conceptual and mechanistic article integrates empirical findings from entrainment research, prefrontal timing theories, multisensory integration, and network-based models of seizure dynamics and uses them to formulate a hypothesis-driven framework for multisensory exogenous rhythmic stimulation (ERS) in focal epilepsy. Rather than presenting a tested intervention, we propose a set of speculative mechanistic pathways through which low-frequency rhythmic cues might serve as an external temporal reference, engage fronto-parietal control systems, facilitate multisensory-driven sensorimotor coupling, and potentially modulate interhemispheric frontal coherence. These putative mechanisms are illustrated by exploratory neurophysiological observations, including a small pilot study reporting frontal coherence changes during mobile ERS exposure, but they have not yet been validated in controlled experimental settings. The framework does not imply therapeutic benefit; instead, it identifies theoretical pathways through which rhythmic sensory cues may transiently interact with epileptic networks. The proposed model is intended as a conceptual foundation for future neurophysiological validation, computational simulations, and early feasibility research in the emerging field of digital neuromodulation, rather than as evidence of clinical efficacy. This Hypothesis article formulates explicitly testable predictions regarding how multisensory ERS may transiently modulate candidate physiological markers of prefrontal network stability in focal epilepsy.
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(This article belongs to the Section Systems Neuroscience)
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Open AccessReview
Advancements and Applications of EEG in Gustatory Perception
by
Lingfeng Yang, Chengpeng Zhang, Wei Wu, Jing Xie and Zhaoyang Ding
Brain Sci. 2025, 15(12), 1317; https://doi.org/10.3390/brainsci15121317 - 10 Dec 2025
Abstract
Electroencephalography (EEG) is a powerful tool for investigating gustatory perception, offering high temporal resolution and non-invasive brain activity recording. This review highlights the ability of EEG to reveal the complex interactions between sensory input, emotional responses, and cognitive evaluation in the process of
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Electroencephalography (EEG) is a powerful tool for investigating gustatory perception, offering high temporal resolution and non-invasive brain activity recording. This review highlights the ability of EEG to reveal the complex interactions between sensory input, emotional responses, and cognitive evaluation in the process of taste perception. This review examines the physiological basis of taste, focusing on key brain regions and how environmental and psychological factors influence taste perception. It also discusses the methods and applications of EEG technology, including its principles, signal features, and measurement methods. Notably, EEG markers like event-related potentials (ERPs), frequency band power analysis, and brain network connectivity are essential for understanding the neural dynamics of taste processing. This review concludes with potential future research directions, including the integration of EEG with other neuroimaging techniques, cross-cultural studies on gustatory perception, and the use of EEG biomarkers in early neurological disease diagnosis.
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(This article belongs to the Section Neurotechnology and Neuroimaging)
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Open AccessArticle
A Longitudinal Observational Study to Monitor the Outpatient–Caregiver Dyad in a Rehabilitation Hospital: Sociodemographic Characteristics and the Impact of Cognitive and Functional Impairment
by
Daniela Mancini, Valeria Torlaschi, Marina Maffoni, Roberto Maestri, Pierluigi Chimento, Michelangelo Buonocore, Antonia Pierobon and Cira Fundarò
Brain Sci. 2025, 15(12), 1316; https://doi.org/10.3390/brainsci15121316 - 10 Dec 2025
Abstract
Background and objectives: This study examines how sociodemographic, clinical, and psychological factors within the patient–caregiver dyad affect caregiver burden and health-related quality of life (HRQoL) in cognitive impairment. By comparing baseline data with a 1-year follow-up, the research aims to identify key predictors
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Background and objectives: This study examines how sociodemographic, clinical, and psychological factors within the patient–caregiver dyad affect caregiver burden and health-related quality of life (HRQoL) in cognitive impairment. By comparing baseline data with a 1-year follow-up, the research aims to identify key predictors of caregiver burden and well-being. Methods: A longitudinal observational study was conducted in an Italian rehabilitation hospital, recruiting 132 outpatients and their caregivers at baseline, categorized as (a) Mild Cognitive Impairment (MCI, n = 33); (b) dementia (DEM, n = 58); (c) healthy subjects (No-CI, n = 41). One year after baseline assessment (T0), patients were contacted and invited for an in-person follow-up re-evaluation (T1). Most attrition was related to the COVID-19 pandemic. Statistical analyses included non-parametric tests for group comparisons and stepwise multiple linear regression to identify predictors of burden, adjusting for confounders (e.g., age, gender, education, employment, co-residence). Results: A total of 51 subjects (age: 80.0 ± 6.1) and 34 caregivers (age: 58.8 ± 15.9) were evaluated. Patients were balanced by gender (53% males); most were retired (96%), married (62.7%), and cared for by sons (47%) or wife–husband (47%). Caregivers (females: 85%) were married (68.3%) and active workers (46.4%). Over one year, 17 No-CI subjects developed MCI or DEM; 15 MCI patients progressed to DEM. Caregiver HRQoL negatively correlated with distress and burden in MCI and DEM groups. Patient cognitive status, functional abilities, neuropsychiatric symptoms, and gender predicted caregiver burden, emphasizing the interplay between clinical and demographic factors. Conclusions: It is essential to monitor psychosocial factors in both the patient and the caregiver to develop effective prevention and support strategies.
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(This article belongs to the Special Issue Dementia and Cognitive Decline in Aging)
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Open AccessArticle
Minimally Invasive Supraorbital vs. Traditional Pterional Approaches in Unruptured Aneurysm Surgery: Evaluating Risks and Results
by
Anna Brunner, Marlene Rainer, Uschi Pongratz, Klaus Leber, Máté Fehér, Alexander Micko and Stefan Wolfsberger
Brain Sci. 2025, 15(12), 1315; https://doi.org/10.3390/brainsci15121315 - 9 Dec 2025
Abstract
Background/Objectives: Intracranial aneurysms affect 3–5% of the population and are associated with high morbidity and mortality, particularly after rupture. Treatment options for unruptured aneurysms include microsurgical clipping, with the pterional and supraorbital approaches commonly employed. This study compares these two approaches regarding complications
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Background/Objectives: Intracranial aneurysms affect 3–5% of the population and are associated with high morbidity and mortality, particularly after rupture. Treatment options for unruptured aneurysms include microsurgical clipping, with the pterional and supraorbital approaches commonly employed. This study compares these two approaches regarding complications and outcomes. Methods: A retrospective analysis was conducted on 241 patients treated between 2004 and 2023 at the University Hospital of Graz. Patients underwent microsurgical clipping via the pterional (n = 170) or supraorbital (n = 71) approach, chosen according to aneurysm characteristics and surgeon preference. Data on demographics, aneurysm location and size, intraoperative complications, postoperative outcomes, and follow-up were evaluated. Results: The pterional approach was predominantly used for middle cerebral artery (MCA) aneurysms (79.2%), while the supraorbital approach was more frequently applied for internal carotid artery (ICA) and anterior communicating artery (ACOM) aneurysms. Aneurysms treated via the pterional approach were significantly larger (mean width 6.88 mm vs. 5.04 mm; p < 0.01). Severe intraoperative complications, including aneurysm rupture, were significantly more common in the supraorbital group (26.8% vs. 8.8%; p < 0.001). Postoperative hypo-/anosmia occurred more often after the supraorbital approach (8.5% vs. 1.8%; p = 0.013), while temporalis muscle atrophy (11.9% vs. 1.8%; p = 0.029) and chewing difficulties (19.5% vs. 1.8%; p = 0.002) were more frequent after the pterional approach. The supraorbital group had a shorter hospital stay (7.96 vs. 8.76 days; p = 0.001). No significant differences were found in 30-day mortality (p = 0.521). At one-year, functional outcomes assessed by the modified Rankin Scale showed no significant difference (p = 0.899). Complete aneurysm occlusion and recurrence rates were also comparable between groups. Conclusions: Both approaches provide effective treatment for unruptured aneurysms with favorable long-term outcomes. The pterional approach is associated with increased muscle-related complications, whereas the supraorbital approach carries higher risks of intraoperative complications and olfactory dysfunction. Tailoring the surgical approach based on patient and aneurysm characteristics remains essential.
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(This article belongs to the Special Issue Advances in the Diagnosis, Visualization and Treatment of Intracranial Aneurysms and Subarachnoid Hemorrhage)
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Open AccessEditorial
New Approaches in the Exploration of Parkinson’s Disease
by
Tommaso Ercoli, Francesco Loy, Carla Masala and Paolo Solla
Brain Sci. 2025, 15(12), 1314; https://doi.org/10.3390/brainsci15121314 - 9 Dec 2025
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and it is considered one of the major challenges in contemporary neuroscience [...]
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(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease)
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A Mathematical Model for the Variation of Cerebral Electrical Conductivity and the Amount of β-Amyloid Protein Values Due to Alzheimer’s Disease
by
Emmanouil Perakis and Panagiotis Vlamos
Brain Sci. 2025, 15(12), 1313; https://doi.org/10.3390/brainsci15121313 - 9 Dec 2025
Abstract
Background/Objectives: This study presents a time-dependent mathematical model that describes how progressive amyloid-β (Aβ) accumulation drives the gradual decline of cerebral electrical conductivity during Alzheimer’s disease (AD). Methods: The formulation captures the coupled evolution of molecular burden and electrophysiological function through a pair
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Background/Objectives: This study presents a time-dependent mathematical model that describes how progressive amyloid-β (Aβ) accumulation drives the gradual decline of cerebral electrical conductivity during Alzheimer’s disease (AD). Methods: The formulation captures the coupled evolution of molecular burden and electrophysiological function through a pair of interconnected dynamical processes, enabling a mechanistic link between early biochemical alterations and large-scale neural degradation. Results: Simulations reveal a characteristic pattern in which Aβ levels rise steadily toward a pathological plateau, while conductivity follows a delayed but persistent downward trajectory that stabilizes at an impaired state consistent with advanced neurodegeneration. The model reproduces key phenomena reported in experimental and clinical studies, including the slow, irreversible reduction in cortical conductivity and the strong inverse relationship between amyloid burden and electrophysiological integrity. Conclusions: Although intentionally minimal, the framework offers a tractable basis for interpreting disease progression and can be extended to incorporate additional pathological pathways such as tau aggregation, inflammatory responses, or spatial heterogeneity. By providing a compact yet biologically meaningful representation of the interplay between molecular pathology and electrical dysfunction, the model supports the development of computational biomarkers and contributes to a more integrated understanding of AD progression.
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(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)
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