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Brain Sci., Volume 16, Issue 7 (July 2026) – 112 articles

Cover Story (view full-size image): This narrative review summarizes the biological rationale, current clinical evidence, practical workflow, and limitations of nrTMS in neurorehabilitation, with particular attention to the distinction between conventional rTMS and neuronavigated protocols. Results: The strongest evidence for rTMS-based rehabilitation remains in post-stroke motor recovery, although most studies have used non-navigated protocols. In contrast, postoperative neuro-oncological rehabilitation represents a clinically relevant but still investigational context for nrTMS, as preoperative functional mapping, postoperative deficits, and early rehabilitation can be integrated within a patient-specific therapeutic pathway. View this paper
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19 pages, 336 KB  
Article
HbA1c and Cognitive Functioning Across Bipolar Disorder, Recurrent Major Depressive Disorder, and Schizophrenia: Findings from a Non-Diabetic Sample
by Ece Buyuksandalyaci Tunc, Serhat Tunc, Murat Ilhan Atagun and Samet Kose
Brain Sci. 2026, 16(7), 770; https://doi.org/10.3390/brainsci16070770 - 22 Jul 2026
Viewed by 612
Abstract
Objective: This study examined the association between glycemic status, indexed by HbA1c, and cognitive functioning in individuals with bipolar disorder (BD), recurrent major depressive disorder (rMDD), schizophrenia (SZ), and healthy controls (HCs). Methods: In this cross-sectional study, 215 participants (45 HCs, 64 BD, [...] Read more.
Objective: This study examined the association between glycemic status, indexed by HbA1c, and cognitive functioning in individuals with bipolar disorder (BD), recurrent major depressive disorder (rMDD), schizophrenia (SZ), and healthy controls (HCs). Methods: In this cross-sectional study, 215 participants (45 HCs, 64 BD, 62 rMDD, 44 SZ) were assessed. Cognitive performance was evaluated using a comprehensive neuropsychological battery measuring attention, processing speed, memory, executive functions, and social cognition. Sociodemographic characteristics, chlorpromazine-equivalent antipsychotic doses (CEDA), and metabolic variables (body mass index, waist circumference, lipid profile, fasting glucose, and HbA1c) were collected. Group differences, correlation analyses, and multiple regression models were performed. Results: All patient groups showed significantly poorer cognitive performance compared with HCs. HbA1c levels were highest in the SZ group; however, associations between HbA1c and cognitive performance were strongest in the BD group and less consistent in rMDD. In regression analyses, HbA1c was associated with cognitive performance in BD and HCs, with weaker effects in rMDD. CEDA was associated with HbA1c levels and partially attenuated the relationship between HbA1c and cognitive outcomes. Conclusions: HbA1c levels were associated with cognitive performance in non-diabetic individuals, particularly in BD and rMDD. These findings suggest that subclinical variation in glycemic regulation may be relevant to cognitive functioning in psychiatric disorders. Further longitudinal studies are needed to clarify the influence of metabolic factors and psychotropic medication on cognitive outcomes. Full article
(This article belongs to the Section Neuropsychiatry)
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20 pages, 3137 KB  
Article
EEG Markers as a Tool for the Individualization of Education and Optimization of Social Interventions for Children from Alcohol-Affected Families
by Małgorzata Chojak and Marta Czechowska-Bieluga
Brain Sci. 2026, 16(7), 769; https://doi.org/10.3390/brainsci16070769 - 22 Jul 2026
Viewed by 433
Abstract
Background: Children growing up in alcohol-affected families are exposed to chronic stress, adverse childhood experiences (ACEs), emotional insecurity, and environmental instability, all of which may influence neurodevelopmental processes. Numerous EEG markers have been proposed as indicators of attentional regulation, emotional functioning, and [...] Read more.
Background: Children growing up in alcohol-affected families are exposed to chronic stress, adverse childhood experiences (ACEs), emotional insecurity, and environmental instability, all of which may influence neurodevelopmental processes. Numerous EEG markers have been proposed as indicators of attentional regulation, emotional functioning, and stress responsivity; however, their relative diagnostic and practical value remains unclear. The aim of the present study was to verify whether commonly reported EEG markers remain valid indicators of neurofunctional difficulties in children from alcohol-affected families, to establish their hierarchy of importance, and to determine how identified neurofunctional profiles may inform the sequencing of educational interventions and the development of individualized support plans used by educators and social workers. Methods: The study included children aged 6–10 years from alcohol-affected families (n = 20) and a control group from non-dysfunctional family environments (n = 25). Resting-state EEG recordings were conducted under eyes-open and eyes-closed conditions, with analyses focused on the eyes-open condition. Quantitative EEG (qEEG) indices included global, frontal, prefrontal, and midline Theta–Beta Ratio (TBR), frontal alpha asymmetry (FAA), temporal beta stress and parietal beta2 tension. EEG preprocessing was performed using EEGLAB and included artifact rejection, filtering, epoch segmentation, and spectral power analysis. Group differences were analyzed using Welch’s t-tests with Benjamini–Hochberg correction for multiple comparisons. Results: The analyzed EEG markers differed in their ability to distinguish children from alcohol-affected families and controls. The strongest effects were observed for Theta–Beta Ratio (TBR) measures, particularly in frontal and prefrontal regions, indicating impairments in attention regulation, executive functioning, and self-control. Elevated temporal beta stress and parietal beta2 tension reflected increased physiological arousal and chronic stress. In contrast, frontal alpha asymmetry (FAA), commonly associated with depressive emotional processing, was not significant after correction for multiple comparisons. The obtained findings enabled the establishment of a hierarchy of neurofunctional markers, with attentional and executive-function indicators demonstrating greater importance than markers related to depressive symptomatology. Conclusions: The EEG profile of children from alcohol-affected families is characterized primarily by chronic stress, heightened physiological activation, and impaired attention regulation rather than by neurophysiological patterns associated with depression. The results suggest that educational difficulties in this group may stem mainly from deficits in attention control, inhibitory processes, and cognitive flexibility. Consequently, educational interventions should prioritize learning strategies, attentional training, and self-regulated learning skills. The identified hierarchy of EEG markers may also support the development of individualized educational plans and social-support programs, including participation in structured extracurricular activities and interventions aimed at strengthening executive and learning-related competencies. However, given the pilot nature of the present study and the relatively small sample size, these findings should be considered preliminary. Replication in larger, more diverse, and independent cohorts is necessary to confirm the stability, reliability, and generalizability of the identified neurofunctional profile and the proposed hierarchy of qEEG markers before they can be recommended for broader educational and social applications. Full article
(This article belongs to the Special Issue Neuroeducation: Bridging Cognitive Science and Classroom Practice)
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18 pages, 2723 KB  
Article
Herpesvirus-Associated Visual Impairment: Clinical Features, Etiological Spectrum, and Treatment Outcomes in Consecutive Patients from a Tertiary Neurological Clinic
by Lei Liu, Jingxiao Zhang, Qiuying Ma and Jiawei Wang
Brain Sci. 2026, 16(7), 768; https://doi.org/10.3390/brainsci16070768 - 22 Jul 2026
Viewed by 699
Abstract
[Background] Herpesvirus infections can induce diverse visual impairments with permanent sequelae, yet systematic data on their clinical spectrum and outcomes remain scarce. [Methods] We conducted a single-center retrospective cohort study at the Department of Neurology, Beijing Tongren Hospital, Capital Medical University. Thirteen consecutive [...] Read more.
[Background] Herpesvirus infections can induce diverse visual impairments with permanent sequelae, yet systematic data on their clinical spectrum and outcomes remain scarce. [Methods] We conducted a single-center retrospective cohort study at the Department of Neurology, Beijing Tongren Hospital, Capital Medical University. Thirteen consecutive patients (19 affected eyes) with herpesvirus-related visual impairment admitted between January 2016 and January 2025 were enrolled. Demographic data, clinical manifestations, etiological tests (polymerase chain reaction [PCR], metagenomic next-generation sequencing [mNGS], serology), neuroimaging, treatment regimens, and visual outcomes were analyzed. [Results] The cohort had a mean age of 50.4 years (range 31–66), with male predominance (84.6%, 11/13). Varicella zoster virus (VZV) was the leading pathogen (76.9%, 10/13), followed by herpes simplex virus type 1 (HSV-1), Epstein–Barr virus (EBV), and pseudorabies virus (PRV). Eight patients (61.5%) developed optic neuritis (ON) secondary to VZV infection, and five patients (38.5%) suffered from acute retinal necrosis (ARN), which was caused by VZV (n = 2), HSV-1 (n = 2), and PRV (n = 1). Bilateral involvement occurred in 46.2% (6/13) of patients. ARN was associated with the most severe visual loss. At the disease nadir, 46.2% of patients (6/13) presented with no light perception (NLP). Notably, five of these six NLP cases were diagnosed with ARN. Etiological confirmation was achieved in only 38.5% (5/13) of cases. mNGS of cerebrospinal and vitreous fluid, alongside aqueous humor PCR, are pivotal for diagnosing HSV-1/EBV mixed infections and rare PRV infection. All patients received antiviral therapy, 11 of whom (84.6%) were treated with intravenous antiviral agents. Glucocorticoids were administered as combination therapy to all patients. However, only one of eight VZV–ON eyes showed genuine visual improvement. In VZV–ARN, the initially involved eyes stayed NLP at final follow-up, while the fellow eyes recovered vision. Still, all non-VZV ARN patients had persistent bilateral NLP during follow-up. [Conclusions] Herpesvirus-associated visual impairment is dominated by VZV, manifests as ON or ARN, and carries a high risk of severe permanent vision loss—particularly in ARN. The emergence of zoonotic PRV underscores the need for heightened clinical vigilance. Diagnostic delays and insufficient interdisciplinary collaboration contribute substantially to poor outcomes. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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16 pages, 1581 KB  
Case Report
Long-Lasting Changes of Repeated Anodal Transcranial Direct Current Stimulation in Decreasing Chronic Pain in Patients with Multiple Sclerosis: A Case Series
by Renming Liu, Shapour Jaberzadeh, Mona Malekahmad, Murray Taverner, Jamie Young and Maryam Zoghi
Brain Sci. 2026, 16(7), 767; https://doi.org/10.3390/brainsci16070767 - 22 Jul 2026
Viewed by 536
Abstract
Background: Pain affects 50–75% of individuals with multiple sclerosis (MS) and is more common than in the general population. Chronic pain is difficult to manage and may involve motor cortical and sensorimotor network alterations. Anodal transcranial direct current stimulation (tDCS) over the primary [...] Read more.
Background: Pain affects 50–75% of individuals with multiple sclerosis (MS) and is more common than in the general population. Chronic pain is difficult to manage and may involve motor cortical and sensorimotor network alterations. Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been explored as a neuromodulatory approach, although its effects and mechanisms remain unclear. Objective: This case series describes longitudinal changes in pain and anxiety following repeated anodal tDCS over left M1 in six individuals with MS-related chronic pain and descriptively reports concurrent changes in transcranial magnetic stimulation (TMS)-derived neurophysiological measures. Methods: Six adults with MS and chronic pain (≥4/10) received 1 mA anodal tDCS over M1 (10 min stimulation, 25 min interval, 10 min stimulation) in two 5-day blocks separated by 2 weeks (10 sessions total), with usual care maintained. Pain and anxiety (0–10) were assessed before and after sessions and at follow-up. TMS assessed corticospinal excitability and intracortical inhibition and facilitation at baseline, post blocks, and at follow-up. Results: Marked inter-individual variability was observed in clinical and neurophysiological trajectories following repeated anodal tDCS. Response patterns included immediate improvement after stimulation blocks, delayed improvement after the second block, and transient rebound during the inter-block interval. TMS-derived measures showed heterogeneous changes, with no consistent correspondence with clinical outcomes. Conclusions: This case series describes variable changes in pain, anxiety, and neurophysiological measures following repeated anodal tDCS over M1 in MS-related chronic pain. The findings are observational and highlight inter-individual variability, supporting further controlled studies. Full article
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16 pages, 282 KB  
Review
Autism and Neurodegeneration: Distinct Disorders or a Shared Biological Continuum?
by Jorge Manzo and María Elena Hernández-Aguilar
Brain Sci. 2026, 16(7), 766; https://doi.org/10.3390/brainsci16070766 - 21 Jul 2026
Cited by 1 | Viewed by 886
Abstract
Background/Objectives: Autism spectrum disorder (ASD) is traditionally classified as a neurodevelopmental condition, whereas neurodegenerative diseases are defined by progressive neuronal decline in later life. This separation has shaped research and clinical practice, yet emerging evidence suggests potential biological overlap. This review aims to [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) is traditionally classified as a neurodevelopmental condition, whereas neurodegenerative diseases are defined by progressive neuronal decline in later life. This separation has shaped research and clinical practice, yet emerging evidence suggests potential biological overlap. This review aims to evaluate whether ASD and neurodegenerative disorders represent distinct entities or are linked through shared mechanisms operating across the lifespan. Methods: This narrative review synthesizes findings from genetic, molecular, cellular, circuit-level, and epidemiological studies examining ASD and major neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis. Emphasis is placed on identifying convergent pathways and evaluating evidence within a lifespan-oriented framework. Results: Across multiple levels of analysis, ASD and neurodegenerative diseases share partially overlapping biological mechanisms, including mitochondrial dysfunction, impaired proteostasis, neuroimmune alterations, and network-level instability. Genetic and molecular data reveal pleiotropic pathways influencing both early neurodevelopment and later neuronal resilience. Circuit-level studies highlight shared principles of network vulnerability, including cerebellar involvement and excitation–inhibition imbalance. Epidemiological data further indicate increased risk of dementia and parkinsonian features in autistic adults. These convergences suggest that early neurodevelopmental alterations may establish latent vulnerabilities that, under specific conditions, intersect with neurodegenerative processes later in life. Conclusions: ASD and neurodegenerative diseases are best understood as distinct clinical conditions that share partially overlapping biological substrates. Rather than implying a deterministic progression, the evidence supports a model of lifespan convergence in which timing, context, and individual susceptibility shape outcomes. This framework highlights the need for integrated research and clinical approaches that consider brain health as a continuous process from development through aging. Full article
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38 pages, 2643 KB  
Review
Cognitive Impairment Associated with Chemotherapy: Neuroimmunological Interactions, Gut–Brain Axis, and Therapeutic Approaches
by Beatriz Alejandra Llanes-Cervantes, José Alfonso Cruz-Ramos, María Esthela Barón-Cárdenas, Paola Montserrat Zepeda-Olmos, Sandra López-Verdín, Jennifer Mariana Vargas-López and Emmanuel de la Mora-Jiménez
Brain Sci. 2026, 16(7), 765; https://doi.org/10.3390/brainsci16070765 - 21 Jul 2026
Cited by 1 | Viewed by 2073
Abstract
Chemotherapy is a treatment designed to contain or eradicate neoplastic cells; however, patients may experience various treatment-related adverse effects. Chemotherapy-related cognitive impairment (CRCI), clinically referred to as “chemobrain,” is a frequent complication with a duration ranging from months to years, affecting between 17% [...] Read more.
Chemotherapy is a treatment designed to contain or eradicate neoplastic cells; however, patients may experience various treatment-related adverse effects. Chemotherapy-related cognitive impairment (CRCI), clinically referred to as “chemobrain,” is a frequent complication with a duration ranging from months to years, affecting between 17% and 70% of cancer patients. These cognitive deficits not only impair social, educational, and occupational functioning but may also impact survival outcomes, possibly by interfering with medication adherence and health-related behaviors. Emerging evidence has converged on an integrative cascade in which chemotherapy-induced systemic inflammation, intestinal dysbiosis, blood–brain barrier disruption, microglial/astroglial activation, and impaired hippocampal neurogenesis act in sequence rather than as independent pathways. Underlying pathophysiological mechanisms include neuroinflammation, reduced neurogenesis, loss of dendritic spines, oxidative stress, hormonal changes, epigenetic modifications, and mitochondrial dysfunction. In contrast, repair mechanisms involve complex glial responses, particularly those of astrocytes and microglia. Emerging studies suggest a link between changes in the microbiome and cognitive decline, demonstrating the importance of bidirectional communication in the gut–brain axis. Current research seeks to determine appropriate tests to identify chemobrain. Therefore, several biomarkers, such as GFAP, S100β, and isoprostanes, have been proposed to assess chemobrain, alongside screening tools such as MoCA, MMSE, and CAB-CF, to evaluate cognitive impairment and enable early detection. Pharmacological candidates—including lithium, fluoxetine, methylphenidate, modafinil, metformin, agomelatine, and melatonin—as well as nutritional and lifestyle interventions such as physical exercise, omega-3 fatty acids, curcumin, probiotics, and traditional Chinese medicine formulations—have been investigated, predominantly in animal models. These remain candidate, not validated, therapies; clinical evidence in CRCI populations is limited, heterogeneous, or absent, and well-powered randomized controlled trials are required before any recommendation can be issued. However, optimal strategies for symptom improvement remain unclear, as various approaches have yielded mixed outcomes. This review provides a comprehensive overview of chemobrain, focusing on its molecular mechanisms, interactions with the gut–brain axis, and potential therapeutic targets to improve the quality of life for cancer survivors. Full article
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12 pages, 1083 KB  
Article
Sex-Specific Cognitive Divergence in Parkinson’s Disease
by Julia Saltyte Benth, Gonzalo Sanchez Nido, Kenn Freddy Pedersen, Ole Bjørn Tysnes, Guido Werner Alves, Charalampos Tzoulis and Geir Olve Skeie
Brain Sci. 2026, 16(7), 764; https://doi.org/10.3390/brainsci16070764 - 21 Jul 2026
Viewed by 691
Abstract
Background: Sex differences in cognitive impairment in Parkinson’s disease (PD) have been reported, with several studies suggesting greater cognitive decline in males. However, evidence on long-term trajectories across specific cognitive domains is limited, as most prior work is cross-sectional. Aim: To investigate sex-specific [...] Read more.
Background: Sex differences in cognitive impairment in Parkinson’s disease (PD) have been reported, with several studies suggesting greater cognitive decline in males. However, evidence on long-term trajectories across specific cognitive domains is limited, as most prior work is cross-sectional. Aim: To investigate sex-specific longitudinal changes across multiple cognitive domains over 9 years in idiopathic PD, compared to age- and sex-matched controls. Methods: We analyzed data from the prospective ParkWest study, including n = 190 persons with PD (PwPs) and n = 202 controls. Regularly assessed cognitive domains included semantic fluency, processing speed, cognitive control, memory, and visuospatial ability. Linear mixed-effect models including a three-way interaction between time, disease status, and sex, to test whether sex-specific cognitive change in PD differed from that observed in controls, were estimated. Models were adjusted for age, years of education, baseline depression, and UPDRS part II. Results: Male PwPs showed faster decline than female PwPs in most cognitive measures, resulting in gradually increasing sex differences over 9 years. However, compared with controls, the differential sex-specific decline was statistically significant only for semantic fluency (p = 0.013) and processing speed (p = 0.027 and p = 0.035). These findings remained significant after covariate adjustment. Conclusions: PD was associated with increasing sex differences in semantic fluency and processing speed, likely driven by faster decline in males. Other domains did not show sex-specific divergence over time, suggesting that sex-specific vulnerabilities in cognitive trajectories are domain-specific rather than generalized among PwPs. Full article
(This article belongs to the Special Issue Advances in Parkinson’s Disease)
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16 pages, 1336 KB  
Article
Beyond Individual Features: Computational Analysis of Linguistic Coordination in Dementia Speech
by Vanessa Yoorhee and Gemma Moya-Galé
Brain Sci. 2026, 16(7), 763; https://doi.org/10.3390/brainsci16070763 - 20 Jul 2026
Viewed by 428
Abstract
Background/Objectives. In dementia, progressive changes in spoken language, including reduced lexical diversity, increased disfluency, and syntactic simplification, are well documented. Although computational approaches have demonstrated reliable group differences in individual linguistic features, less attention has been given to the potential coordination between linguistic [...] Read more.
Background/Objectives. In dementia, progressive changes in spoken language, including reduced lexical diversity, increased disfluency, and syntactic simplification, are well documented. Although computational approaches have demonstrated reliable group differences in individual linguistic features, less attention has been given to the potential coordination between linguistic features and discourse-level moderation of the features with group differences. Methods. Over five domains—syntactic, lexical, disfluency, output, and affective—nine linguistic features were extracted from 552 transcripts (309 dementia, 243 healthy controls) of individuals performing the Cookie Theft picture description task in the DementiaBank Pitt Corpus. The Mann–Whitney U test was used to examine group differences with rank-biserial correlation effect sizes. Fisher z-transformation tests were applied to compare within-group correlation to examine the moderation effect of discourse-pragmatic factors (self-references, hedging, and sentiment polarity) on different groups. Fisher z-transformation tests were used to compare inter-feature correlations between the two groups. All multiple comparisons were controlled using the Benjamini–Hochberg false discovery rate (FDR) procedure. Results. Out of the nine features, word complexity, repetition rate, MLU, and filler rate were significantly different between the group with dementia and healthy controls. Among them, word complexity and repetition rate showed the largest and most consistent effects. Self-referential language showed a stronger association with verbal output in the group with dementia, although the association was not significant when analyses were restricted to one visit per participant. Moreover, one inter-feature relationship (i.e., the positive correlation between short utterance ratio and word complexity) remained significant after FDR correction. This correlation was present only in healthy controls, suggesting that this preserved coordination may be disrupted in dementia. Conclusions. Dementia disrupts not only individual linguistic features but also the relationships between them. The preserved coordination between syntactic simplification and lexical elaboration was found to be absent in speakers with dementia. Inter-feature coordination may, therefore, be able to reveal group differences that individual feature analyses alone cannot detect. Full article
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18 pages, 1904 KB  
Perspective
Turns and Turn-Related Falls: Stepping on a Rotating Platform as a Potential Approach to Foster Adapted Muscular and Neural Plasticity in Fragile Persons and Patients with Motor Impairment
by Shashank Ghai and Marco Schieppati
Brain Sci. 2026, 16(7), 762; https://doi.org/10.3390/brainsci16070762 - 20 Jul 2026
Viewed by 555
Abstract
Falls remain the leading cause of injury-related death among older adults, with turning accident often producing the most severe consequences, such as hip fractures and a resulting decline in independence. Despite curved-path walking accounting for the majority of daily locomotion, most interventions insufficiently [...] Read more.
Falls remain the leading cause of injury-related death among older adults, with turning accident often producing the most severe consequences, such as hip fractures and a resulting decline in independence. Despite curved-path walking accounting for the majority of daily locomotion, most interventions insufficiently target the coordinated action of lower limb, pelvic and trunk muscles underlying safe turning. This leaves a large proportion of older adults and patients with motricity problems and movement disorders at heightened risk of life-altering injuries. Addressing this gap requires innovative strategies that proactively build on recent physiological research and improve turning strength and neuromuscular control of steering. Gait problems have often been addressed through the use of linear treadmills, which emphasise the symmetry and automaticity of walking but ignore the fact that more than half of daily locomotion involves deviations from the trajectory. In this perspective article, we review the differences between linear and curved walking. We also put forward the hypothesis that a turntable rotating parallel to the horizontal plane represents a potential solution. Such a device could allow individuals to step in place while the surface moves beneath them, simulating the natural rotation of legs, pelvis, and trunk involved in turning. The exercise is designed to train the muscle synergies and proprioceptive responses critical for turning, while minimising stress on vestibular systems, and enhancing task-specific neuroplasticity and proprioception. Full article
(This article belongs to the Special Issue Neural and Muscular Plasticity in Motor and Postural Control)
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25 pages, 489 KB  
Article
Satisfaction-Related Well-Being Among Working Young Adults and Their Parents: Core Self-Evaluations and Life Values in a Preregistered Cross-Sectional Study
by Radosław B. Walczak, Raluca Sassu, Hadar Nesher Shoshan and Maria Latusek-Mierzwa
Brain Sci. 2026, 16(7), 761; https://doi.org/10.3390/brainsci16070761 - 20 Jul 2026
Viewed by 423
Abstract
Background: Previous research has documented generational differences in life satisfaction and work-related attitudes, but less is known about how work and life satisfaction differ within parent–child dyads. This preregistered study examined work satisfaction, life satisfaction, core self-evaluations, personal values, and financial situation among [...] Read more.
Background: Previous research has documented generational differences in life satisfaction and work-related attitudes, but less is known about how work and life satisfaction differ within parent–child dyads. This preregistered study examined work satisfaction, life satisfaction, core self-evaluations, personal values, and financial situation among working young adults and their working parents in Poland. Methods: The study used a preregistered, cross-sectional, observational parent–child dyadic design. The final analytic sample consisted of 87 complete dyads, corresponding to 174 individual participants. Parent–child responses were linked using anonymised self-generated codes. Group differences in work satisfaction, life satisfaction, and core self-evaluations were tested using paired Yuen’s trimmed t-tests. Preregistered predictors of work satisfaction and life satisfaction were tested using linear mixed-effects models with dyads as a random intercept. Results: Parents reported higher work satisfaction and higher core self-evaluations than their young-adult children, whereas the expected group difference in life satisfaction was not supported. Core self-evaluations positively predicted work satisfaction, whereas the preregistered financial situation composite and achievement value did not. A supplementary component-level analysis showed heterogeneous associations among the individual financial indicators. Work satisfaction was positively associated with life satisfaction, whereas the preregistered Schwartz values were not significantly associated with life satisfaction. Conclusions: The findings suggest that parent–child differences in satisfaction-related outcomes are more visible in work satisfaction and core self-evaluations than in global life satisfaction. Core self-evaluations emerged as the most consistent psychological predictor of work satisfaction. The value-based hypotheses were not supported, although these null findings warrant caution because several brief PVQ scales had low reliability. Full article
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14 pages, 1048 KB  
Article
Fatigue and Cognitive Impairment in Patients with Kidney Failure Not Requiring Kidney Replacement Therapy and Patients Receiving Hemodialysis: A Cross-Sectional Study
by Piotr Olejnik, Gabriela Drzewiec, Jadwiga Rojek-Trębicka, Paweł Żebrowski, Jolanta Małyszko and Aleksandra Golenia
Brain Sci. 2026, 16(7), 760; https://doi.org/10.3390/brainsci16070760 - 20 Jul 2026
Viewed by 453
Abstract
Background: Cognitive impairment and fatigue are common in patients with advanced chronic kidney disease (CKD). However, whether these symptoms reflect kidney failure itself or factors associated with hemodialysis (HD) remains unclear. This study compared cognitive performance and fatigue between patients with CKD G5 [...] Read more.
Background: Cognitive impairment and fatigue are common in patients with advanced chronic kidney disease (CKD). However, whether these symptoms reflect kidney failure itself or factors associated with hemodialysis (HD) remains unclear. This study compared cognitive performance and fatigue between patients with CKD G5 not requiring kidney replacement therapy, referred to as CKD G5 not on dialysis (CKD G5 ND), and those receiving maintenance HD. Methods: In this cross-sectional, single-center study, 68 clinically stable patients with kidney failure were enrolled, including 27 patients with CKD G5 ND and 41 patients receiving HD. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) and fatigue via the Fatigue Assessment Scale (FAS). Results: Global cognitive performance did not differ significantly between patients receiving HD and those with CKD G5 ND, with median MoCA scores of 24.00 and 23.00, respectively. Cognitive impairment was frequent, affecting 61.0% of HD patients and 74.1% of those with CKD G5 ND. Fatigue severity was also comparably high, with significant fatigue in 51.2% and 44.4% of individuals, respectively. No association was observed between global cognitive performance and fatigue. Exploratory analyses showed that language performance was inversely associated with total and mental fatigue after false discovery rate correction. In the adjusted logistic regression, HD status was associated with lower odds of cognitive impairment; however, this finding should be interpreted cautiously, given the cross-sectional design, small sample size, and baseline clinical differences between groups. Conclusions: Cognitive impairment and fatigue were highly prevalent both in patients with CKD G5 ND and those receiving maintenance HD, with no significant between-group differences in global cognitive performance or fatigue severity scores. These findings suggest that neuropsychological vulnerability may be present in patients with kidney failure before dialysis initiation. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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13 pages, 17438 KB  
Article
Abnormal Ipsilesional Hemifields and Improvement Post-Biofeedback Training in Patients with Hemianopia Measured with the MAIA Microperimeter
by Jessica Cao, Ghaliah Nsour, Katrina Manas, Zainab Farooq, Samuel N. Markowitz and Monica Daibert-Nido
Brain Sci. 2026, 16(7), 759; https://doi.org/10.3390/brainsci16070759 - 20 Jul 2026
Viewed by 396
Abstract
Introduction: This study analyzes the ipsilesional hemifields in patients with hemianopia and biofeedback training (BT). Methods: Prospectively, BT stimulated the paracentral ipsilesional hemifields. BT was compared to a control group using C 10-2 program 68 points on the MAIA microperimetry (Centervue, [...] Read more.
Introduction: This study analyzes the ipsilesional hemifields in patients with hemianopia and biofeedback training (BT). Methods: Prospectively, BT stimulated the paracentral ipsilesional hemifields. BT was compared to a control group using C 10-2 program 68 points on the MAIA microperimetry (Centervue, Padova, Italy). Five weekly BT sessions of 20 min were delivered. A total of 34 subjects enrolled, with 28 in treatment, and six in control group. Outcomes: General retinal sensitivity (RS), average of the central two columns, the paracentral column of the blind hemifield, ipsilesional hemifield, and the whole ipsilesional and blind hemifields. Paired t-tests were used for statistical analysis. Results: Control and treatment groups were equal demographically. In the control group, no difference was found pre-and-post BT. Baseline RS on the ipsilesional hemifield was 21.4 ± 4.5, lower than the normal cut-off value of 25 dB (p < 0.001). BT improved RS from 14.0 ± 4.2 to 15.0 ± 4.8, p = 0.01, paracentral two columns, 16.3 ± 5.3 to 17.8 ± 5.6, p = 0.01, central column in ipsilesional hemifield, 20.7 ± 5.4 to 21.8 ± 4.8, p = 0.05, and ipsilesional hemifield, 21.42 ± 4.8 to 22.39 ± 4.24), p = 0.01. Conclusions: Ipsilesional hemifields were abnormal and BT improved RS, benefiting patients with hemianopia. Full article
(This article belongs to the Section Neurorehabilitation)
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27 pages, 1977 KB  
Review
Cerebellar Electrical Activity as a Marker for Predicting Brain Health and Disease: A Review
by Gordana Stojadinović, Ljiljana Martać, Srđan Kesić, Branka Petković and Jelena Podgorac Kojadinović
Brain Sci. 2026, 16(7), 758; https://doi.org/10.3390/brainsci16070758 - 19 Jul 2026
Viewed by 640
Abstract
The cerebellum is traditionally considered a structure responsible for motor control, but it is also involved in auditory perception, vocalization, speech, memory, emotional control, and social cognition. Due to its high intrinsic synaptic plasticity and complex connectivity with other brain regions, it is [...] Read more.
The cerebellum is traditionally considered a structure responsible for motor control, but it is also involved in auditory perception, vocalization, speech, memory, emotional control, and social cognition. Due to its high intrinsic synaptic plasticity and complex connectivity with other brain regions, it is of potential interest for monitoring adaptive responses under various physiological and pathological conditions to capture global brain dynamics. Nevertheless, the use of electrocerebellography (ECeG) to detect changes in cerebellar electrical activity is limited, and a systematic evaluation of ECeG data to inform future research directions is lacking. This review summarizes recent ECeG research to explore the contribution of this time-honored method to deciphering the cerebellum’s spatial and temporal dynamics in health and disease. ECeG studies from the past three decades examining the slow and fast adaptive responses of the cerebellum in different cerebellar layers during sleep, anesthesia, brain injury, epilepsy, neurodegenerative diseases, and neuropsychiatric disorders are compiled from the PubMed, Scopus, and Google Scholar databases and discussed accordingly. It can be concluded that, despite certain limitations, ECeG is a practical, valuable, and reliable technique for detecting and predicting the complex spatial and temporal features of cerebellar electrical activity. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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18 pages, 6605 KB  
Article
Low-Intensity Focused Ultrasound Alters Alzheimer’s Disease Pathology, In Vivo, as a Function of Ultrasound Dose and Age
by Alissa Phutirat, Kahte A. Culevski, Hannah Mach, Jamie Kwon, Henry Tan, Gabe Koh, Caren Marzban and Pierre D. Mourad
Brain Sci. 2026, 16(7), 757; https://doi.org/10.3390/brainsci16070757 - 18 Jul 2026
Viewed by 643
Abstract
Background/Objectives: Alzheimer’s Disease (AD) and vascular dementia contribute up to ~75% of dementia cases, as determined via autopsy. AD arises in part due to the buildup of aberrant proteins (amyloid beta (Aβ) and Tau); vascular dementia is caused by reduced cerebral blood flow. [...] Read more.
Background/Objectives: Alzheimer’s Disease (AD) and vascular dementia contribute up to ~75% of dementia cases, as determined via autopsy. AD arises in part due to the buildup of aberrant proteins (amyloid beta (Aβ) and Tau); vascular dementia is caused by reduced cerebral blood flow. Each dementia mechanisms damages brain. Bobola et al. found that their low-intensity focused ultrasound (FUS) protocol applied to the brains of the 5XFAD mouse model of AD reduced Aβ by 50% through activation of microglia. Eguchi et al. found that their own FUS protocol applied to the brains of the same mouse model reduced Aβ by 15% and increased cerebral blood flow by 50% through an increase in endothelial nitric oxide synthase (eNOS). Here, we sought to test a combined version of those two FUS protocols, expecting both a decrease in Aβ burden and an increase in eNOS. Methods: Using a diagnostic ultrasound probe, we applied our combined FUS protocol primarily to the left hippocampus of anesthetized 5XFAD mice, for an hour a day, for three days for younger mice and for five days for older mice. On day three or five, respectively, we harvested their brains and performed histological analysis to assess Aβ burden, microglial activation and their co-localization with Aβ, as well as the burden of eNOS within neuronal nuclei (here called intra-neuronal eNOS) and outside of neurons. Results: Relative to untreated mice, the treated younger mice had more activated microglia co-localized with Aβ and reduced Aβ burden for large plaques, as well as no change in each measure of eNOS. In contrast, the treated older AD mice had no change in activated microglia co-localized with Aβ, and no change in Aβ burden. However, relative to untreated older AD mice, FUS decreased total and extra-neuronal eNOS and increased intra-neuronal eNOS. Conclusions: The ability of our FUS protocol to reduce Aβ burden and alter the eNOS distribution depends critically upon the age of the AD mice (more Aβ plaques for a comparable number of microglia for older mice relative to younger mice) and duration of the treatment. The observed decrease in extra-neuronal eNOS distribution in older AD mice caused by FUS raises the concern that our protocol may increase ischemia, while the increase in intra-neuronal eNOS may counteract that effect via protection of synaptic function. These findings also identify two candidate therapeutic windows for our FUS treatment protocol, each requiring more research before translation to humans. One window is early intervention to maximize Aβ plaque removal via activation of microglia. The second is later intervention to protect synaptic function if it is possible to mitigate the potential ischemic risk caused by the differential effects of FUS on eNOS. Full article
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17 pages, 12685 KB  
Case Report
How Early Should I Refer My Patient? The Benefits of a Quick Ophthalmic Referral in Spinocerebellar Ataxias, a Case Series and Literature Review
by Andrea B. Fiscal-Carvajal, José L. De-León-Guerra, Cristian E. Salinas-Aguirre, Marisol Ibarra-Ramírez, Marissa L. Fernández-de-Luna, Ingrid E. Estrada-Bellmann, Joel Arenas-Estala, Luis D. Campos-Acevedo and Jibran Mohamed-Noriega
Brain Sci. 2026, 16(7), 756; https://doi.org/10.3390/brainsci16070756 - 17 Jul 2026
Viewed by 412
Abstract
Background: The spinocerebellar ataxias (SCA) are a group of multiple inherited disorders. The molecular diagnosis of the specific type of SCA is challenging due to the diversity of hereditary patterns and genetic anomalies. Certain key clinical features can help shorten the differential [...] Read more.
Background: The spinocerebellar ataxias (SCA) are a group of multiple inherited disorders. The molecular diagnosis of the specific type of SCA is challenging due to the diversity of hereditary patterns and genetic anomalies. Certain key clinical features can help shorten the differential diagnosis. Cases: At our center, we evaluated three patients presenting with gait disturbances. They were assessed by multiple hospital departments, and, due to suspected spinocerebellar ataxia, comprehensive genetic and ophthalmologic testing was performed, leading to diagnoses of SCA2, SCA7, and SCAR32. These cases highlight the importance of multidisciplinary evaluation for accurate diagnosis of complex neurogenetic disorders. All patients experienced prolonged diagnostic delays, requiring years of multiple consultations across different hospitals before reaching a definitive diagnosis. Literature Review: Among all published reports of patients with SCA, we consider that five distinct key clinical features can categorize many patients suffering from a possible SCA into different groups and reduce the potential differential diagnosis. Only two types of SCA presented macular anomalies, ten optic nerve involvements, one erythrokeratodermia, four hearing losses, and four dementias. Conclusions: Early referral to a multidisciplinary evaluation might help narrow the differential diagnosis of specific types of SCA, guiding the diagnostic work-up toward SCA1 and SCA7 in patients with macular involvement, or toward SCA1, SCA2, SCA3, SCA7, SCAR3, SCAR9, SCAR21, SCAR29, SCAR31, and SCAX3 in those with optic nerve involvement. Full article
(This article belongs to the Special Issue Molecular and Cellular Research in Neurodegenerative Diseases)
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25 pages, 358 KB  
Review
NTS Neural Subtypes and Satiety Pathways: taVNS as a Novel Neuromodulatory Intervention
by Hanyu Deng, Chen Xin, Haohan Zhu, Xinjiang Zhang, Lan Sun, Yanfeng Zheng and Peijing Rong
Brain Sci. 2026, 16(7), 755; https://doi.org/10.3390/brainsci16070755 - 17 Jul 2026
Viewed by 632
Abstract
The global obesity epidemic has become one of the most severe public health challenges of the 21st century, and existing treatment strategies have limitations such as poor long-term adherence, significant side effects, or high invasiveness. Dysregulation of feeding behavior is the core driver [...] Read more.
The global obesity epidemic has become one of the most severe public health challenges of the 21st century, and existing treatment strategies have limitations such as poor long-term adherence, significant side effects, or high invasiveness. Dysregulation of feeding behavior is the core driver of obesity, and its precise regulation depends on the complete transmission of gut–brain axis signals. The nucleus of the solitary tract (NTS), as the first central relay station for visceral afferent signals, is a key hub for the regulation of feeding homeostasis. This article reviews the peripheral signal transduction mechanisms of hunger and satiety, the core afferent pathway of the vagus nerve, and the functional heterogeneity of neuron subpopulations within the NTS, focusing on the anatomical basis, neuroimaging evidence, and preclinical and clinical research progress of transcutaneous auricular vagus nerve stimulation (taVNS) targeting the NTS to exert anti-obesity effects. Accumulating evidence suggests that taVNS may modulate the activity of satiety-promoting neurons and attenuate aberrant hyperactivity of TH+ catecholaminergic neurons in obesity via the auricular branch of the vagus nerve–NTS pathway, which may in turn bidirectionally suppress homeostatic and hedonic feeding, reduce energy intake, and ameliorate metabolic dysregulation. Current research still has key gaps such as unstandardized stimulation parameters, lack of large-sample long-term randomized controlled trials, and unclear interaction mechanisms between the NTS and higher brain regions. This article provides a theoretical basis for in-depth understanding of the feeding regulatory network of the NTS and the translational application of taVNS in obesity management. Full article
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16 pages, 532 KB  
Review
A Guide to Patients with Acute Transient Vestibular Symptoms in the Emergency Department
by Alexander A. Tarnutzer, Arlindo C. Lima Neto and Diego Kaski
Brain Sci. 2026, 16(7), 754; https://doi.org/10.3390/brainsci16070754 - 17 Jul 2026
Viewed by 1602
Abstract
Background: As many as two-thirds of acutely dizzy patients presenting to the emergency department report intermittent symptoms only, consistent with a transient acute vestibular syndrome (single episode lasting < 24 h) or an episodic vestibular syndrome (recurrent episodes, each lasting < 24 h). [...] Read more.
Background: As many as two-thirds of acutely dizzy patients presenting to the emergency department report intermittent symptoms only, consistent with a transient acute vestibular syndrome (single episode lasting < 24 h) or an episodic vestibular syndrome (recurrent episodes, each lasting < 24 h). A broad differential diagnosis, presentation outside the episode(s), and difficulties in describing the symptoms make the diagnostic workup of transient vestibular symptoms (TVS) challenging. Methods: This critical review provides an overview on the management of TVS, focusing on structured history-taking and bedside testing, but also reviewing the role of neuroimaging and eye movement recordings. Results: Asking about timing and triggers helps clarify the temporal evolution of symptoms (transient vs. persistent) and the circumstances of occurrence (spontaneous vs. triggered). Such structured history-taking narrows down the differential diagnosis and ensures appropriate bedside tests. On clinical examination, identifying focal neurologic signs, (subtle) ocular motor findings, and gait imbalance is essential. While positional testing should be applied in all patients with TVS, HINTS+ has not been validated in those patients without nystagmus or with transient (already resolved) symptoms. For neuroimaging, MRI with diffusion-weighted imaging is preferred, but early false-negative findings in up to 20% (to even 50% for small brainstem strokes) of cases must be considered. Quantitative eye movement recordings may be especially valuable in rural areas, supporting telemedicine consults. Conclusions: Special emphasis should be put on distinguishing vertebrobasilar transient ischemic attack from vestibular migraine and cardiac arrhythmia. In the case of triggered TVS, immediate and sustained response to liberation maneuvers strongly supports benign paroxysmal positional vertigo over vestibular migraine or structural central positional nystagmus. Treatment strategies in TVS strongly depend on the underlying cause, ranging from hyperacute stroke treatment to migraine prophylaxis to liberation maneuvers. Full article
(This article belongs to the Special Issue Controversies and Challenges in Vestibular Medicine)
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22 pages, 2952 KB  
Article
Phenotypic Diversity in Multiple Sclerosis Can Be Represented by Four Additive Symptom Modules
by Daniel B. Hier, Pavankumar Y. Srinivasula and Michael D. Carrithers
Brain Sci. 2026, 16(7), 753; https://doi.org/10.3390/brainsci16070753 - 16 Jul 2026
Viewed by 387
Abstract
Background: Multiple sclerosis (MS) lacks a single invariant phenotypic core. Patients accumulate heterogeneous combinations of sensory, motor, cognitive, and autonomic impairments over time, reflecting lesions that are disseminated in time and space. Standard scales such as the Expanded Disability Status Scale (EDSS) distribute [...] Read more.
Background: Multiple sclerosis (MS) lacks a single invariant phenotypic core. Patients accumulate heterogeneous combinations of sensory, motor, cognitive, and autonomic impairments over time, reflecting lesions that are disseminated in time and space. Standard scales such as the Expanded Disability Status Scale (EDSS) distribute disability across functional systems, but do not explicitly represent MS phenotype as a mixture of latent symptom modules. Methods: We analyzed 4617 de-identified neurology progress notes from 577 patients with MS at a single academic medical center. A large language model (GPT-5.2) categorized each note with respect to 17 non-mutually-exclusive neurological phenotype features, and note-level features were aggregated to patient-level binary vectors. Non-negative matrix factorization (NMF) was applied to generate three-, four-, and five-module solutions. For each rank, we computed approximate variance captured, relative reconstruction error, and module-level feature loadings. In the preferred four-module solution, we derived patient-level module percentages, identified highly dominant (≥55%) and archetypal (≥70%) module profiles, and quantified admixture using Shannon entropy and the effective number of modules. Results: Three-, four-, and five-module NMF solutions showed similar approximate variance captured (52.7–54.3%) and reconstruction error (0.47–0.53), but the four-module solution provided the clearest clinical interpretation. The four latent modules were sensory-visual-pain, ataxic-spastic-falls, cognitive-psychologic-fatigue, and autonomic-bladder-bowel, aligning closely with established functional systems in MS. Most patients exhibited admixed phenotypes, with module entropies ranging from 0 (single-module dominance) to 1.386 (equal mixture) and effective modules spanning approximately 1 to 4. Using pre-specified thresholds, 154 patients (26.6%) were highly dominant in a single module and 72 (12.5%) were archetypal; these purer phenotypes were most often in the sensory-visual-pain module. Conclusions: MS phenotypic diversity in routine clinical practice can be parsimoniously represented as mixtures of four latent symptom modules rather than as positions along a single severity axis. Most patients show substantial admixture of sensory, motor, cognitive, and autonomic involvement, but a minority exhibit relatively pure or strongly dominant module patterns. This modular representation provides an interpretable framework for quantifying MS phenotype and for generating testable hypotheses about MS subtypes whose biological relevance remains to be established. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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18 pages, 1285 KB  
Review
Neural Control of Mastication: Ion-Channel Mechanisms in the Brainstem Central Pattern Generator
by Hiroki Toyoda
Brain Sci. 2026, 16(7), 752; https://doi.org/10.3390/brainsci16070752 - 15 Jul 2026
Viewed by 1210
Abstract
Mastication is a fundamental rhythmic motor behavior controlled by a brainstem central pattern generator (CPG) located within the pontine and medullary reticular formations. Coordinated activation of jaw-opening and jaw-closing muscles is generated by this network and continuously refined through sensory feedback from periodontal [...] Read more.
Mastication is a fundamental rhythmic motor behavior controlled by a brainstem central pattern generator (CPG) located within the pontine and medullary reticular formations. Coordinated activation of jaw-opening and jaw-closing muscles is generated by this network and continuously refined through sensory feedback from periodontal mechanoreceptors and muscle spindles, together with descending inputs from the cortical masticatory area (CMA), basal ganglia, and cerebellum. Thus, mastication is regulated by distributed neural circuits rather than a single central locus. At the cellular level, the rhythmic activity of the masticatory CPG depends on the coordinated action of voltage-gated and ligand-gated ion channels. Recent electrophysiological and computational studies have identified candidate conductances that are proposed to underlie rhythm generation. Persistent sodium currents are proposed to facilitate burst initiation, whereas T-type calcium channels are thought to promote burst activation through post-inhibitory rebound. HCN channels may contribute to rhythmic timing, while calcium-activated potassium channels are thought to participate in burst termination. This review summarizes the hierarchical neural control of mastication and the biophysical mechanisms by which ion channels shape CPG rhythmogenesis. It also discusses the impact of channelopathies and neurodegenerative disorders on masticatory function, highlighting potential ion-channel-targeted therapeutic approaches for temporomandibular disorders, bruxism, and impaired mastication. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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31 pages, 637 KB  
Review
Radiomodulation—The Final Frontier of Radiosurgery?
by Fred C. Lam, Evan Chau, Yazhen Shi, Bryan Martinez, Amar Hamdan, Jay L. Gill, Nirmeen Zagzoog, Neeraj Kalra, Yusuke S. Hori, Michael B. Schneider, John Adler, Jr., David J. Park and Steven D. Chang
Brain Sci. 2026, 16(7), 751; https://doi.org/10.3390/brainsci16070751 - 15 Jul 2026
Viewed by 612
Abstract
Stereotactic radiosurgery (SRS) delivers high doses of focused ionizing radiation (IR) to a defined target while sparing surrounding tissues. The delivery of focused doses of IR has proven to be an effective modality for the treatment of brain tumors, cerebrovascular lesions, and primary [...] Read more.
Stereotactic radiosurgery (SRS) delivers high doses of focused ionizing radiation (IR) to a defined target while sparing surrounding tissues. The delivery of focused doses of IR has proven to be an effective modality for the treatment of brain tumors, cerebrovascular lesions, and primary neuropathic pain conditions. More recently, the emerging concept of “radiomodulation” to rewire neural circuitry through the delivery of focused IR to specific neural relay centers has emerged as an alternative way to treat neurological conditions, such as essential tremor, trigeminal neuralgia, and psychiatric illnesses. In this article, we performed a scoping review of the existing data supporting the ability of focused doses of ionizing radiation to achieve modulation of neural circuits for the treatment of neurological conditions. We review the current understanding of the neurophysiological mechanisms of radiomodulation, the gaps in knowledge limiting its widespread use for in-human applications and stress the unmet need for ongoing research to rigorously prove that radiomodulation may be the “final frontier” as a non-invasive, non-pharmacological, versatile, and tunable modality for the treatment of a multitude of neurological conditions. Full article
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28 pages, 1578 KB  
Review
Chemotherapy-Induced Brain Damage: Mechanisms and Insights from Rodent Models
by Milica Veljković, Tanja Džopalić, Pavle Ranđelović, Lidija Popović Dragonjić, Jelena Milenković and Ivan Ilić
Brain Sci. 2026, 16(7), 750; https://doi.org/10.3390/brainsci16070750 - 15 Jul 2026
Viewed by 580
Abstract
Background/Objectives: Chemotherapy-induced cognitive impairment, colloquially known as chemobrain, affects a substantial proportion of cancer patients. Preclinical rodent models help clarify underlying drug-specific neurotoxic effects, as well as histological, biochemical, molecular, and behavioral mechanisms. Methods: We conducted a narrative review of animal studies examining [...] Read more.
Background/Objectives: Chemotherapy-induced cognitive impairment, colloquially known as chemobrain, affects a substantial proportion of cancer patients. Preclinical rodent models help clarify underlying drug-specific neurotoxic effects, as well as histological, biochemical, molecular, and behavioral mechanisms. Methods: We conducted a narrative review of animal studies examining cognitive dysfunction following treatment with commonly used chemotherapeutic agents, including doxorubicin, cisplatin, cyclophosphamide, methotrexate, 5-fluorouracil, paclitaxel, and docetaxel. The review focused on behavioral and cognitive outcomes, and experimental parameters such as rodent models and dosing regimens. Results: Across studies, chemotherapeutic exposure has had a consistent negative effect on short-term and working memory, learning and other cognitive domains, with impairments being often mild and detectable even at doses not causing apparent systemic toxicity. Histological analyses revealed reduced neurogenesis, dendritic and myelin alterations, and glial activation, mainly in the hippocampus and prefrontal cortex. Biochemical and molecular changes included oxidative stress, pro-apoptotic signaling, inflammatory cytokine dysregulation, decreased neurotrophic support, and altered neurotransmitter dynamics. Age and sex influenced susceptibility, with juvenile or aged animals and females—particularly older females modeling breast cancer patients—showing greater deficits. Cumulative or repeated dosing exacerbated neurotoxicity, while single administrations produced milder, sometimes transient, impairments. Conclusions: Preclinical models provide compelling evidence that chemotherapeutic agents impair cognitive function via convergent mechanisms involving inflammation, oxidative stress, and synaptic dysregulation. These findings highlight the importance of considering age, sex, and treatment schedule in designing neuroprotective strategies and underscore the translational relevance of rodent models in understanding chemobrain. Full article
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21 pages, 3218 KB  
Review
From Sensation to Action: Neuroplasticity, Cognitive–Motor Training, and Emerging Biomarkers of Adaptation
by Carter Witbeck, Tony Montina and Gerlinde A. S. Metz
Brain Sci. 2026, 16(7), 749; https://doi.org/10.3390/brainsci16070749 - 15 Jul 2026
Cited by 1 | Viewed by 860
Abstract
Human interaction with the environment depends on the integration of sensory input, cognitive processing, and motor output within dynamic sensorimotor loops. These processes are supported by distributed neural circuits and shaped by learning, memory, and neuroplasticity across the lifespan. This review synthesizes current [...] Read more.
Human interaction with the environment depends on the integration of sensory input, cognitive processing, and motor output within dynamic sensorimotor loops. These processes are supported by distributed neural circuits and shaped by learning, memory, and neuroplasticity across the lifespan. This review synthesizes current understanding of the mechanisms underlying sensorimotor integration and highlights how experience-dependent plasticity supports functional recovery and performance optimization in both health and disease. Disruptions such as traumatic brain injury, neurodegenerative disease, and aging may frequently result in combined cognitive and motor impairments. Here, we review non-invasive interventions that leverage neuroplasticity, including physical activity, motor training, and cognitive training, with increasing emphasis on integrated cognitive–motor approaches. Emerging technologies such as virtual reality provide ecologically valid, immersive environments that simultaneously engage perception, cognition, and action, with the potential to enhance training outcomes. However, variability in effectiveness and limited evidence for far transfer remain key challenges. To address these limitations, we highlight the integration of immersive training with objective biological measures. In particular, proton nuclear magnetic resonance (1H NMR)-based metabolomics offers a promising, non-invasive approach to identify biomarkers of neuroplastic adaptation. The integration of robust biomarker tools may facilitate the development and assessment of effective precision cognitive–motor interventions to optimize rehabilitation approaches and help build resilience in vulnerable individuals. Full article
(This article belongs to the Special Issue Exploring Rehabilitation Strategies and Biomarkers for Brain Injury)
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16 pages, 741 KB  
Article
Mindfulness Development via Biofeedback for Anxiety in Hospitalized Patients: A Randomized Controlled Trial
by Anastasia V. Kotelnikova, Vera M. Ruzinova, Maria G. Kiseleva, Beatrice Volel and Anastasia A. Kukshina
Brain Sci. 2026, 16(7), 748; https://doi.org/10.3390/brainsci16070748 - 15 Jul 2026
Viewed by 554
Abstract
Background: Anxiety disorders are prevalent and debilitating. Given challenges in maintaining mindfulness at one-month remission, integrative approaches targeting anxiety and psychological resources (especially mindfulness) have gained interest. This study aimed to assess the effectiveness of adding biofeedback to the treatment of anxiety [...] Read more.
Background: Anxiety disorders are prevalent and debilitating. Given challenges in maintaining mindfulness at one-month remission, integrative approaches targeting anxiety and psychological resources (especially mindfulness) have gained interest. This study aimed to assess the effectiveness of adding biofeedback to the treatment of anxiety disorders. Methods: Inpatients with anxiety disorder (ICD10 F40/F41) were randomized to three groups: (1) biofeedback for enhancing mindfulness (BFB, n = 76); (2) medication therapy (MT, escitalopram 10 mg/day, n = 46); and (3) combined therapy (BFB + MT, CT, n = 66). Per-protocol analysis: 180 completers; ITT: all 188 randomized patients. The primary outcomes were changes in the Hamilton Anxiety Rating Scale (HAM-A) total score and the Five Facet Mindfulness Questionnaire total score, assessed at baseline, after 10 days of treatment, and at one-month follow-up. The HAM-A assessor was blinded to group allocation. Results: In the per-protocol analysis, the BFB and CT groups showed a significantly greater reduction in the HAM-A score than the MT group did. For example, post-treatment, the mean difference between BFB and MT groups was –6.30 points (95% CI: –9.12 to –3.48, p = 0.00046). The BFB and CT groups did not differ significantly. For mindfulness, the BFB and CT groups showed an increase, whereas the MT group showed a decrease (BFB vs. MT: mean difference 30.28 points, 95% CI: 23.54–37.02, p < 0.000001). Intention-to-treat (ITT) analysis (n = 188) confirmed the robustness of these findings. Conclusions: BFB appears to be a promising approach for reducing anxiety and fostering mindfulness skills; these findings suggest it may be worth exploring further as a potential component of comprehensive therapy for anxiety disorders. Clinical Trial Registration: ClinicalTrials.gov NCT07628153 (retrospectively registered). The trial was retrospectively registered, and the primary analysis was conducted on a per-protocol population. Full article
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13 pages, 235 KB  
Article
Navigating the Eloquent Brain: A Multicenter Study on the Safety and Efficacy of Symptomatic Cavernoma Resection
by Hojka Rowbottom, Tomaž Velnar, Janez Ravnik, Ninna Kozorog and Tomaž Šmigoc
Brain Sci. 2026, 16(7), 747; https://doi.org/10.3390/brainsci16070747 - 15 Jul 2026
Viewed by 467
Abstract
Background/Objectives: Surgical management of cerebral cavernous malformations (CCMs) within eloquent brain regions presents a high risk of neurological deficits. This study describes the clinical outcomes and technical feasibility of microsurgical resection for symptomatic eloquent CCMs, detailing the integration of advanced intraoperative adjuncts [...] Read more.
Background/Objectives: Surgical management of cerebral cavernous malformations (CCMs) within eloquent brain regions presents a high risk of neurological deficits. This study describes the clinical outcomes and technical feasibility of microsurgical resection for symptomatic eloquent CCMs, detailing the integration of advanced intraoperative adjuncts aimed at optimization of seizure control and functional preservation. Methods: We conducted a retrospective multicenter analysis of nine adult patients who underwent microsurgical resection for symptomatic eloquent CCMs between January 2021 and December 2025 across two tertiary centers in Slovenia. Intraoperative modalities included 100% neuronavigation, 55.6% intraoperative ultrasound, 77.8% intraoperative neuromonitoring (IONM) with motor and somatosensory evoked potentials, and 22.2% awake craniotomies. Results: Seizures were the primary clinical presentation in 77.8% of patients (66.7% medically refractory), and the overall hemorrhage rate was 66.7%. Gross total resection of the CCM was achieved in 100% of cases, with complete hemosiderin rim removal in 80% of applicable lesions. Early postoperative complications occurred in four patients, but at the maximum 48-month follow-up, 100% of the cohort achieved complete seizure control, and 44.4% successfully discontinued antiepileptic drugs. Long-term focal neurological deficits persisted in only two patients, while 77.8% were able to work following surgery. Conclusions: Microsurgical resection remains a well-established treatment modality for symptomatic CCMs. In this small, descriptive series of patients with lesions in functionally critical regions, high rates of gross total resection and favorable long-term seizure freedom were observed. These findings suggest that a multimodal approach combining anatomical neuronavigation with functional IONM may help minimize permanent morbidity, though larger cohorts are required to establish definitive efficacy. Full article
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22 pages, 10171 KB  
Article
A Novel Depression Recognition Network Based on Brain Functional Connectivity from Prefrontal Emotional State EEG
by Yubing Sun, Zijian Zhou, Jiaqi Sun, Wenjie Cui, Xinlei Hu, Yudan Lv and Guangda Liu
Brain Sci. 2026, 16(7), 746; https://doi.org/10.3390/brainsci16070746 - 14 Jul 2026
Viewed by 420
Abstract
Objective: Electroencephalogram (EEG) signals provide a noninvasive and objective method for detecting neural dysfunctions associated with depression. To address the limitations of limited sample sizes and inadequate modeling of spatiotemporal features, the study aims to develop an EEG-based depression recognition framework to capture [...] Read more.
Objective: Electroencephalogram (EEG) signals provide a noninvasive and objective method for detecting neural dysfunctions associated with depression. To address the limitations of limited sample sizes and inadequate modeling of spatiotemporal features, the study aims to develop an EEG-based depression recognition framework to capture dynamic patterns of neural activity related to depression. Methods: We propose DR-Net, a novel depression recognition framework integrating generative adversarial network (GAN), transition propagation graph convolution network (TPGCN), and transformer architectures. First, GAN-based data augmentation generates synthetic EEG samples that preserve the statistical properties of real data, improving data diversity and model generalization. Second, brain functional connectivity networks are constructed using the phase lag index, and the TPGCN models the dynamic propagation of information across channels, capturing the spatiotemporal evolution of brain network topologies beyond conventional static graph models. Concurrently, the transformer module employs self-attention to strengthen the modeling of long-range temporal dependencies. The framework also emphasizes the frontal lobe brain region, reducing input dimensionality while improving feature discriminability. Results: The proposed method achieved an accuracy of 98.7%, surpassing baseline and state-of-the-art methods, with no significant class bias. Validation on clinical datasets yielded an accuracy of 96.13%, demonstrating strong robustness and generalizability. Conclusions: By effectively modeling the spatiotemporal dynamics of EEG signals, DR-Net provides a reliable and generalizable approach to the objective diagnosis of depression and advances computational neurodiagnostic by integrating dynamic graph propagation, self-attention mechanisms, and data-efficient augmentation. These findings suggest that DR-Net may support future EEG-based clinical assessment of depression. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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16 pages, 278 KB  
Review
Consciousness in the Brain: An Integrative Review of Contemporary Theories
by Arosh S. Perera Molligoda Arachchige, Afanasy Svet and Maria Svet
Brain Sci. 2026, 16(7), 745; https://doi.org/10.3390/brainsci16070745 - 14 Jul 2026
Viewed by 2099
Abstract
Understanding consciousness remains one of the most significant challenges in neuroscience, philosophy, and cognitive science. Despite substantial advances in neuroimaging, electrophysiology, and computational modeling, a comprehensive account of the neural basis of conscious experience has yet to emerge. This review examines several leading [...] Read more.
Understanding consciousness remains one of the most significant challenges in neuroscience, philosophy, and cognitive science. Despite substantial advances in neuroimaging, electrophysiology, and computational modeling, a comprehensive account of the neural basis of conscious experience has yet to emerge. This review examines several leading contemporary theories of consciousness, including the Global Neuronal Workspace Theory (GNWT), Integrated Information Theory (IIT), Recurrent Processing Theory (RPT), Dendritic Integration Theory (DIT), Predictive Processing (PP), and the Memory Theory of Consciousness (MToC). The philosophical foundations, core theoretical claims, and empirical evidence supporting each framework are critically evaluated. Particular attention is given to how these theories address phenomenal consciousness—the subjective quality of experience—and access consciousness, i.e., the availability of information for cognitive control, report, and behavior. By comparing convergent and divergent predictions across theoretical perspectives, this review highlights key areas of agreement, ongoing debates, and unresolved questions in the field. The analysis suggests that consciousness is likely to involve multiple interacting neural mechanisms operating across different spatial and temporal scales, underscoring the need for continued interdisciplinary research to advance a more comprehensive understanding of conscious experience. Full article
(This article belongs to the Section Neuropsychology)
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20 pages, 893 KB  
Article
Brexpiprazole vs. Aripiprazole in Patients with Schizophrenia with or Without Comorbid Substance Use Disorder: A 12-Month Real-World Naturalistic Study of Efficacy
by Ginevra Lombardozzi, Georgios D. Kotzalidis, Giada Trovini, Emanuela Amici, Alessia Ceccherelli, Giuseppe Albanesi, Valeria Giovanetti, Giovanni Martinotti and Sergio De Filippis
Brain Sci. 2026, 16(7), 744; https://doi.org/10.3390/brainsci16070744 - 14 Jul 2026
Viewed by 1027
Abstract
Background: Schizophrenia with comorbid substance use disorder (SUD) is associated with greater clinical severity, poorer adherence, and worse functional outcomes. Third-generation antipsychotics, through partial dopamine agonism, may represent a useful strategy in this complex population. This study compared the long-term efficacy of [...] Read more.
Background: Schizophrenia with comorbid substance use disorder (SUD) is associated with greater clinical severity, poorer adherence, and worse functional outcomes. Third-generation antipsychotics, through partial dopamine agonism, may represent a useful strategy in this complex population. This study compared the long-term efficacy of brexpiprazole and aripiprazole in patients with schizophrenia, with or without comorbid SUD. Methods: Patients (N = 243) with DSM-5/DSM-5-TR schizophrenia orally received 4 mg/day brexpiprazole or 30 mg/day aripiprazole for 12 months in a real-world clinical setting. Psychopathology was assessed at baseline and after 1, 3, 6, and 12 months using the Brief Psychiatric Rating Scale (BPRS) and the Positive And Negative Syndrome Scale (PANSS). Analyses were performed on 217 completers, excluding 26 drop-outs. Outcomes were compared according to drug and presence/absence of comorbid SUD. Results: Both brexpiprazole and aripiprazole were associated with psychotic symptom and global psychopathology improvement over 12 months (p < 0.01). In patients without SUD, the two treatments showed comparable efficacy. Among patients with comorbid SUD, brexpiprazole showed greater improvement in BPRS and PANSS outcomes than aripiprazole (p < 0.01). Treatment response to aripiprazole, but not to brexpiprazole, was diminished by substance use. Brexpiprazole was associated with better tolerability and lower rates of subjective agitation-related discontinuation. Conclusions: Both dopamine partial agonists were effective in treating schizophrenia; however, brexpiprazole was superior in patients with comorbid SUD. Findings suggest that brexpiprazole may represent a promising therapeutic option in dual-disorder patients. Full article
(This article belongs to the Section Neuropsychiatry)
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18 pages, 2554 KB  
Article
MRI Markers of EDSS ≥ 3 in Relapsing–Remitting Multiple Sclerosis: An Assessment of Lesion Burden, Brain Volumetry, and IVIM-DWI Metrics
by Sami A. Alghamdi, Othman I. Alomair, Manal H. Alosaimi, Abdullah H. Abujamea, Salman Aljarallah, Nuha M. Alkhawajah and Yazeed I. Alashban
Brain Sci. 2026, 16(7), 743; https://doi.org/10.3390/brainsci16070743 - 14 Jul 2026
Viewed by 425
Abstract
Background/Objectives: Disability in relapsing–remitting multiple sclerosis (RRMS) reflects multiple pathological processes that may not be fully captured by individual MRI markers. Because an EDSS score ≥ 3 represents a clinically meaningful threshold of moderate-to-higher disability, this study evaluated the cross-sectional ability of brain [...] Read more.
Background/Objectives: Disability in relapsing–remitting multiple sclerosis (RRMS) reflects multiple pathological processes that may not be fully captured by individual MRI markers. Because an EDSS score ≥ 3 represents a clinically meaningful threshold of moderate-to-higher disability, this study evaluated the cross-sectional ability of brain volumetric measures and IVIM-DWI parameters to identify patients with RRMS who had EDSS ≥ 3. Methods: This retrospective cross-sectional study included 189 patients with RRMS who had complete EDSS, lesion count, IVIM-DWI, and brain volumetric MRI data. Patients were stratified into EDSS < 3 and EDSS ≥ 3 groups. Single-marker ROC analyses were performed for lesion count, IVIM-DWI parameters, absolute volumetric measures, and fractional volumetric measures. Combined ROC models were constructed to assess the discriminatory performance of integrating lesion burden, volumetric MRI, and IVIM-DWI metrics. Internal model stability was evaluated using 5-fold cross-validation. Results: Patients with EDSS ≥ 3 had higher lesion count, higher ADC and D values, lower gray matter, white matter, and brain parenchymal volumes, higher CSF volume, higher CSF fraction, and lower brain parenchymal fraction (BPF). In single-marker ROC analysis, BPF and CSF fraction showed the strongest discriminatory performance (AUC = 0.705), followed by lesion count (AUC = 0.696), whereas absolute BV showed minimal discriminatory value (AUC = 0.503). The core lesion count + BPF model achieved an AUC of 0.757 and a cross-validated AUC of 0.737. Adding perfusion fraction (f) produced the numerically highest cross-validated performance, with an AUC of 0.769 and a cross-validated AUC of 0.746, although the incremental improvement over lesion count + BPF was modest and not statistically significant. Conclusions: Fractional volumetric measures showed stronger discriminatory performance than absolute BV for EDSS ≥ 3 stratification in RRMS. The lesion count + BPF + f model achieved the highest cross-validated performance among the evaluated MRI models; however, overall discrimination was moderate, and the incremental improvement associated with f was not statistically significant. These exploratory findings require evaluation in larger longitudinal cohorts with external validation. Full article
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37 pages, 1502 KB  
Systematic Review
Sleep in Bipolar Disorder: A Systematic Review and Meta-Analysis of Case-Control Drug-Free Patients
by Giuseppe Barbato, Barbara Tondi and Dario Morra
Brain Sci. 2026, 16(7), 742; https://doi.org/10.3390/brainsci16070742 - 13 Jul 2026
Cited by 1 | Viewed by 572
Abstract
Background: A systematic review and meta-analysis of polysomnographic sleep parameters in bipolar disorder was conducted using articles identified through searches of major databases from inception to 5 May 2026. Methods: One hundred and seven studies were identified in the systematic review. [...] Read more.
Background: A systematic review and meta-analysis of polysomnographic sleep parameters in bipolar disorder was conducted using articles identified through searches of major databases from inception to 5 May 2026. Methods: One hundred and seven studies were identified in the systematic review. Forty-three case-control studies with 670 bipolar patients, 520 healthy controls and 280 patients with unipolar depression were eligible for the meta-analyses. Total sleep time, sleep onset latency, sleep efficiency, wake after sleep onset, REM time and percentage, REM latency, REM density, stage 1, 2, time and percentage, slow wave sleep (DELTA) time and percentage of drug-free patients with bipolar disorder were compared with case-control data of healthy controls and drug-free patients with unipolar depression. The primary outcome was the standard mean difference. Data were fitted with a random effects model. Publication bias assessment was checked by Egger’s regression and funnel plot asymmetry Results: Total sleep time and sleep efficiency were reduced in both manic and depressive drug-free bipolar patients compared with healthy controls. Delta sleep time and percentage were reduced only in the depressive patients, whereas the manic patients showed decreased stage 2 sleep time, reduced REM sleep time, shortened REM latency and increased REM density. Drug-free patients with unipolar depression showed reduced total sleep time and increased REM density compared with drug-free patients with bipolar depression. Drug-treated bipolar patients showed no differences compared with healthy controls, except for reduced % REM, increased REM latency and increased REM density. Conclusions: The results confirm the presence of sleep alterations in bipolar disorder. Although sleep duration is reduced in both manic and depressive patients, reduced delta sleep in depressive patients and increased activity/pressure of REM in manic patients appear to characterize the two phases of the illness. Altered monoaminergic activity during the depressive phase and increased cholinergic activity during the manic phase might possibly be linked to the sleep alterations also contributing to the mood changes and switch mechanisms. Full article
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23 pages, 1586 KB  
Review
The Endogenous Opioid System in Compulsive Eating
by Aneesha Janbandhu, Caden Leung, Evelyn Wu, Aidan Tom, Tobias D. Chang, Vinit Shah, Lauren Kim, Evan Robert Lauterborn and Kabirullah Lutfy
Brain Sci. 2026, 16(7), 741; https://doi.org/10.3390/brainsci16070741 - 13 Jul 2026
Viewed by 675
Abstract
Background/Objectives: The rates of obesity and binge-eating disorder (BED) have increased markedly over the last few decades. The onset of these conditions has been associated in part with the disruption of neural pathways that regulate food reward. Existing literature has implicated the endogenous [...] Read more.
Background/Objectives: The rates of obesity and binge-eating disorder (BED) have increased markedly over the last few decades. The onset of these conditions has been associated in part with the disruption of neural pathways that regulate food reward. Existing literature has implicated the endogenous opioid system as an important mediator of pleasure and reinforcing behaviors associated with food intake. While the relationship between opioids and food intake has been studied extensively, how dysregulated opioid signaling contributes to compulsive eating still remains unclear. Therefore, the aim of this review is to analyze the role of opioid peptides and receptors, and their interactions with dopamine in hedonic feeding. Methods: We conducted a narrative review of preclinical and clinical trials, incorporating studies that were relevant to opioid-mediated feeding and food reward. Results: β-endorphins appear to modulate the hedonic value of food, but their effects appear to be context-dependent. Enkephalins may influence motivational drive toward food, while nociceptin signaling has been linked to the preferential consumption of palatable foods under binge-like conditions. Consistent with these findings, NOP antagonism has been reported to reduce binge-like intake of a high-fat diet (HFD) without affecting homeostatic eating patterns. Lastly, chronic mu-opioid receptor (MOP) activation by palatable foods may induce neuroadaptive changes, including receptor desensitization, dopamine D2 receptor downregulation, and reward hypofunctionality, which overlap with mechanisms associated with substance use disorders. Conclusions: Altered MOP signaling may disrupt the hedonic and behavioral mechanisms that regulate feeding behavior. Pharmacological therapies targeting opioid and opioid-dopamine interactions may show promise for treating obesity and BED. However, additional research is still needed to clarify peptide-specific mechanisms, sex differences, and long-term neurobiological consequences associated with hedonic and compulsive eating. Full article
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