Brain Sciences

18 pages, 298 KiB

Open AccessReview

Memory Functions in Obsessive–Compulsive Disorder

by Riccardo Gurrieri, Matteo Gambini, Elena Pescini, Diletta Mastrogiacomo, Gerardo Russomanno and Donatella Marazziti

Brain Sci. 2025, 15(5), 492; https://doi.org/10.3390/brainsci15050492 - 7 May 2025

Abstract

Background/Objectives: Obsessive–compulsive disorder (OCD) is a complex psychiatric condition often associated with alterations in cognitive processes, including memory. Although memory dysfunction has been proposed as a contributing factor to the onset and maintenance of OCD symptoms, it remains debated whether these deficits reflect [...] Read more.

Background/Objectives: Obsessive–compulsive disorder (OCD) is a complex psychiatric condition often associated with alterations in cognitive processes, including memory. Although memory dysfunction has been proposed as a contributing factor to the onset and maintenance of OCD symptoms, it remains debated whether these deficits reflect genuine cognitive impairments or maladaptive metacognitive processes, such as pathological doubt and memory distrust. This review aims to synthesize current findings on memory functioning in OCD, focusing on distinct memory systems and the role of metacognition. Methods: A comprehensive literature search was conducted across five databases (PubMed, Scopus, Embase, PsycINFO, and Google Scholar), covering studies up to April 2025. Search terms included “Obsessive-compulsive disorder”; “OCD”; “Memory dysfunction”; “Episodic memory”; “Working memory impairment”; “Prospective memory deficits”; “Checking compulsions”; “Memory confidence”; “Cognitive biases”. Results: Short-term memory appears generally preserved in OCD. Working memory deficits are consistently reported, especially in the visuospatial domain, and they are associated with difficulties in updating and clearing irrelevant information. Episodic memory impairments are common and often linked to inefficient encoding strategies and heightened cognitive self-consciousness. Prospective memory is frequently compromised under neutral conditions. Individuals with checking symptoms tend to show intact objective memory performance, despite reporting low memory confidence, supporting the concept of memory distrust. Conclusions: Memory dysfunction in OCD is multifaceted, involving both cognitive and metacognitive alterations. The evidence supports a model in which executive dysfunctions and memory-related beliefs contribute to compulsive behaviors more than objective memory failure. These insights highlight the need for integrative assessment protocols and personalized interventions targeting both cognitive performance and metacognitive appraisals. Full article

(This article belongs to the Section Neuropsychiatry)

9 pages, 199 KiB

Open AccessArticle

Factors Associated with Initiation of Opioid Use in a US Department of Veterans Affairs Pain Clinic: A Retrospective Study

by Anderson Chen, Erin Pleasants, Justine Lazatin, Naim Mekdessi, Christopher J. Miller, Diana Higgins and James Levitt

Brain Sci. 2025, 15(5), 491; https://doi.org/10.3390/brainsci15050491 - 7 May 2025

Abstract

Background: Guidelines suggest that, in chronic non-cancer pain (CNCP) management, non-opioid modalities should be prioritized, as there are negative consequences related to opioid use. There is a dearth of literature elucidating the risk factors for initiating opioid use amongst veterans with CNCP. Methods: [...] Read more.

Background: Guidelines suggest that, in chronic non-cancer pain (CNCP) management, non-opioid modalities should be prioritized, as there are negative consequences related to opioid use. There is a dearth of literature elucidating the risk factors for initiating opioid use amongst veterans with CNCP. Methods: Chart review on 193 patients with a new referral at a local US Department of Veterans Affairs (VA) pain clinic. Patients were required to have CNCP and not be taking opioid medication at the time of referral. The review started on 1 January 2014 and covered the year following. Data were analyzed via stepwise multiple logistic regression using Statistical Analysis System (SAS) software (Version 9.4; SAS institute Inc., Cary, NC, USA). Results: A total of 37 veterans (19%) received a new opioid prescription in the year following initial encounters at the pain clinic for CNCP. A history of substance use was associated with lower odds of receiving an opioid prescription. In contrast, being employed was associated with higher odds of receiving an opioid prescription. Conclusions: Amongst veterans treated for CNCP in a VA pain clinic, a history of substance use and a presence of vocation within the past year prior to presentation are variables associated with the initiation of opioids. Future studies to further elucidate the predictors of opioid prescriptions for CNCP are warranted. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

12 pages, 254 KiB

Open AccessArticle

Beyond “Fire” and “Ashes”: The Influence of Trait Characteristics on the Response to Mood Stabilizers in Bipolar Disorders

by Alfonso Tortorella, Francesca Scopetta, Gianmarco Cinesi, Ilaria Baldini, Antonio Russo, Kety Amantini, Filippo De Giorgi and Giulia Menculini

Brain Sci. 2025, 15(5), 490; https://doi.org/10.3390/brainsci15050490 - 7 May 2025

Abstract

Background: The present study aimed to investigate the clinical correlates of treatment response to mood stabilizers in patients with bipolar disorder (BD), with a specific focus on trait-related characteristics such as impulsivity and affective temperaments. Methods: In- and outpatients diagnosed with BD were [...] Read more.

Background: The present study aimed to investigate the clinical correlates of treatment response to mood stabilizers in patients with bipolar disorder (BD), with a specific focus on trait-related characteristics such as impulsivity and affective temperaments. Methods: In- and outpatients diagnosed with BD were recruited at the Section of Psychiatry of the General Hospital/University of Perugia. Socio-demographic, clinical, and current psychopathological characteristics were collected. The treatment response was retrospectively assessed using the Alda Scale. Trait characteristics were evaluated through the Barratt Impulsiveness Scale (BIS-11) and the Brief Temperament Evaluation of Memphis, Pisa, and San Diego—Münster version (briefTEMPS-M). Bivariate analyses and a general linear model were employed to analyze the correlates of treatment response to mood stabilizers. Results: Among the investigated variables, trait impulsivity showed a significant negative association with treatment response. A similar effect was observed for depressive temperament, while other affective temperaments were not significantly associated with treatment outcomes. Patients with good treatment responses exhibited higher illness duration and lower severity of BD, higher prevalence of comorbid anxiety disorders, lower diurnal variation in depressive symptoms, and lower functional impairment in autonomy and occupational domains. The main limitations of this study were represented by the small sample size, the retrospective assessment of treatment response, and the inclusion of patients from a single center. Conclusions: The present findings suggest that impulsivity and depressive temperament should be investigated as potential predictors of poor response to mood stabilizers in BD. These trait dimensions, together with other clinical markers, may serve as useful targets for patient stratification and the development of personalized treatment strategies. Full article

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

3 pages, 146 KiB

Open AccessEditorial

Future Challenges for the Diagnosis and Management of Affective Disorders: From Preclinical Evidence to Clinical Trials

by Mario Luciano, Antonio Ventriglio and Andrea Fiorillo

Brain Sci. 2025, 15(5), 489; https://doi.org/10.3390/brainsci15050489 - 7 May 2025

Abstract

Affective Disorders (ADs) include a broad spectrum of clinical conditions, ranging from dysthymia and Major Depressive Disorder (MDD) to various forms of bipolar disorders (BD) and affective psychoses [...] Full article

(This article belongs to the Special Issue Future Challenges for the Diagnosis and Management of Affective Disorders: From Preclinical Evidence to Clinical Trials)

15 pages, 2381 KiB

Open AccessSystematic Review

Spontaneous Regression of Intracranial Aneurysms—Case Report and Systematic Review of the Literature

by Kristina Catalano, Lukas Andereggen, Gerrit A. Schubert, Serge Marbacher and Basil E. Grüter

Brain Sci. 2025, 15(5), 488; https://doi.org/10.3390/brainsci15050488 - 6 May 2025

Abstract

Background/Objectives: The natural course of intracranial aneurysms (IAs) remains unclear. Many of them remain stable over time and few experience patterns of growth. The spontaneous regression of IAs without any microsurgical or endovascular treatment is a very rare phenomenon. This paper reports [...] Read more.

Background/Objectives: The natural course of intracranial aneurysms (IAs) remains unclear. Many of them remain stable over time and few experience patterns of growth. The spontaneous regression of IAs without any microsurgical or endovascular treatment is a very rare phenomenon. This paper reports the case of a 56-year-old female who experienced spontaneous regression of her IA. Furthermore, it contains a systematic literature review to explore reported cases of spontaneous IA regression. Methods: The case of a 56-year old female patient who presented with an anterior communicating artery (ACom) IA that thrombosed spontaneously after 108 months follow-up is reported. Additionally, a systematic literature search was conducted using the Medline database to identify reported cases. Results: The IA showed spontaneous regression without any surgical or endovascular intervention. We identified 33 articles describing IAs with spontaneous regression. Reported reasons for spontaneous IA thrombosis included (1) anatomical factors like narrow aneurysmal necks; (2) coagulation pathway modifications, including antifibrinolytic activity that promotes thrombosis; and (3) hemodynamic changes such as altered blood flow dynamics and external vascular compression. These findings suggest that spontaneous regression, while rare and unpredictable, can be associated with distinct physiological and anatomical conditions. Conclusions: The spontaneous regression of IAs is an extremely rare phenomenon. It cannot reliably be predicted and may be associated with changes in the hemodynamic situation, specific anatomical constellations, or coagulation pathways. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

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4 pages, 154 KiB

Open AccessEditorial

Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness

by Yang Bai

Brain Sci. 2025, 15(5), 487; https://doi.org/10.3390/brainsci15050487 - 6 May 2025

Abstract

Disorders of consciousness (DOCs) are a dynamic and challenging field, presenting significant difficulties for clinicians and neurorehabilitation specialists due to the lack of reliable assessment methods and effective intervention strategies [...] Full article

(This article belongs to the Special Issue Opportunities and Challenges in the Diagnosis and Treatment of Disorders of Consciousness)

41 pages, 2878 KiB

Open AccessReview

Modeling Alzheimer’s Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling

by Anna M. Timofeeva, Kseniya S. Aulova and Georgy A. Nevinsky

Brain Sci. 2025, 15(5), 486; https://doi.org/10.3390/brainsci15050486 - 5 May 2025

Abstract

Alzheimer’s disease, a complex neurodegenerative disease, is characterized by the pathological aggregation of insoluble amyloid β and hyperphosphorylated tau. Multiple models of this disease have been employed to investigate the etiology, pathogenesis, and multifactorial aspects of Alzheimer’s disease and facilitate therapeutic development. Mammals, [...] Read more.

Alzheimer’s disease, a complex neurodegenerative disease, is characterized by the pathological aggregation of insoluble amyloid β and hyperphosphorylated tau. Multiple models of this disease have been employed to investigate the etiology, pathogenesis, and multifactorial aspects of Alzheimer’s disease and facilitate therapeutic development. Mammals, especially mice, are the most common models for studying the pathogenesis of this disease in vivo. To date, the scientific literature has documented more than 280 mouse models exhibiting diverse aspects of Alzheimer’s disease pathogenesis. Other mammalian species, including rats, pigs, and primates, have also been utilized as models. Selected aspects of Alzheimer’s disease have also been modeled in simpler model organisms, such as Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio. It is possible to model Alzheimer’s disease not only by creating genetically modified animal lines but also by inducing symptoms of this neurodegenerative disease. This review discusses the main methods of creating induced models, with a particular focus on modeling Alzheimer’s disease on cell cultures. Induced pluripotent stem cell (iPSC) technology has facilitated novel investigations into the mechanistic underpinnings of diverse diseases, including Alzheimer’s. Progress in culturing brain tissue allows for more personalized studies on how drugs affect the brain. Recent years have witnessed substantial advancements in intricate cellular system development, including spheroids, three-dimensional scaffolds, and microfluidic cultures. Microfluidic technologies have emerged as cutting-edge tools for studying intercellular interactions, the tissue microenvironment, and the role of the blood–brain barrier (BBB). Modern biology is experiencing a significant paradigm shift towards utilizing big data and omics technologies. Computational modeling represents a powerful methodology for researching a wide array of human diseases, including Alzheimer’s. Bioinformatic methodologies facilitate the analysis of extensive datasets generated via high-throughput experimentation. It is imperative to underscore the significance of integrating diverse modeling techniques in elucidating pathogenic mechanisms in their entirety. Full article

(This article belongs to the Special Issue Molecular and Neuroimaging Biomarkers in Alzheimer’s Disease and Frontotemporal Lobar Degeneration)

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27 pages, 997 KiB

Open AccessReview

The Role of Selected Flavonoids in Modulating Neuroinflammation in Alzheimer’s Disease: Mechanisms and Therapeutic Potential

by Joanna Kruszka, Jakub Martyński, Karolina Szewczyk-Golec, Alina Woźniak and Jarosław Nuszkiewicz

Brain Sci. 2025, 15(5), 485; https://doi.org/10.3390/brainsci15050485 - 5 May 2025

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-β (Aβ) deposition, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Growing evidence highlights neuroinflammation—driven by microglial activation and pro-inflammatory cytokine release—as a key contributor to AD pathogenesis and progression. In the [...] Read more.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-β (Aβ) deposition, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Growing evidence highlights neuroinflammation—driven by microglial activation and pro-inflammatory cytokine release—as a key contributor to AD pathogenesis and progression. In the absence of effective disease-modifying therapies, attention has turned to natural compounds with multi-target potential. Flavonoids, a diverse class of plant-derived polyphenols, have demonstrated neuroprotective properties through antioxidant activity, modulation of neuroinflammatory pathways, and interference with both Aβ aggregation and tau pathology. This narrative review provides an integrative overview of current findings on the mechanisms of action of key flavonoids—such as quercetin, luteolin, and apigenin—in both preclinical and clinical models. Emphasis is placed on their effects on microglial polarization, oxidative stress reduction, mitochondrial support, and synaptic function enhancement. Moreover, flavonoids show synergistic potential when combined with standard pharmacotherapies, such as acetylcholinesterase inhibitors, and may offer broader cognitive benefits in patients with mild cognitive impairment (MCI). Despite these promising findings, significant challenges persist, including poor bioavailability, inter-individual variability, and limited long-term clinical data. This review identifies critical gaps in knowledge and outlines future directions, including targeted drug delivery systems, biomarker-guided personalization, and long-duration trials. Flavonoids thus emerge not only as promising neuroprotective agents but also as complementary candidates in the development of future multi-modal strategies for AD treatment. Full article

(This article belongs to the Special Issue Chronic Non-Infectious Diseases with a High Impact on the Central Nervous System)

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14 pages, 257 KiB

Open AccessArticle

Depression and Anxiety Among Patients with Epilepsy: A Cross-Sectional Study in Saudi Arabia

by Mohammed A. Aljaffer, Ahmad H. Almadani, Ayedh H. Alghamdi, Anas A. Alalwan, Fay H. Albuqami, Khalid O. Altowaijri, Lujain A. Alkhalaf, Faisal A. Alazmi, Shahad F. Aljeri, Hadel H. Alhaluli and Bandar N. Aljafen

Brain Sci. 2025, 15(5), 484; https://doi.org/10.3390/brainsci15050484 - 5 May 2025

Abstract

Background: Epilepsy is a major neuropsychiatric disorder affecting many people worldwide, with depression and anxiety being common comorbidities that impact the quality of life (QoL). This study aims to examine depression and anxiety in epileptic patients at a tertiary care hospital, King Khalid [...] Read more.

Background: Epilepsy is a major neuropsychiatric disorder affecting many people worldwide, with depression and anxiety being common comorbidities that impact the quality of life (QoL). This study aims to examine depression and anxiety in epileptic patients at a tertiary care hospital, King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. It also aims to assess participants’ QoL and explore associated risk factors. Methods: This cross-sectional study enrolled 400 participants using a convenience sampling technique. The study tool consisted of a questionnaire, the Arabic version of the Hospital Anxiety and Depression Scale, and the Arabic version of the Quality of Life in Epilepsy Inventory. Results: The results revealed that 48.25% of the participants exhibited depression, and 39.75% exhibited anxiety. There was a statistically significant association between depression and educational level, employment status, history of psychiatric disorders, epilepsy duration, and all subscales of the Quality of Life in Epilepsy Inventory (QOLIE-31). There was also a statistically significant association between anxiety and educational level, employment status, history of psychiatric disorders, epilepsy duration, and all subscales of QOLIE-31. The mean overall QOLIE-31 score was 60.21 ± 20.19, with educational level and employment status, among other factors, being significantly associated with QOLIE-31. Conclusions: Depression and anxiety are prevalent among epileptic patients, requiring routine screening. Supporting education and employment among epileptic patients also appears to be crucial. Strategies to improve QoL among this population should be developed. Full article

(This article belongs to the Section Neuropsychiatry)

19 pages, 2116 KiB

Open AccessArticle

Right Parietal rTMS Induces Bidirectional Effects of Selective Attention upon Object Integration

by Markus Conci, Leonie Nowack, Paul C. J. Taylor, Kathrin Finke and Hermann J. Müller

Brain Sci. 2025, 15(5), 483; https://doi.org/10.3390/brainsci15050483 - 3 May 2025

Abstract

Background/Objectives: Part-to-whole object completion and search guidance by salient, integrated objects has been proposed to require attentional resources, as shown by studies of neglect patients suffering from right-parietal brain damage. The current study was performed to provide further causal evidence for the link [...] Read more.

Background/Objectives: Part-to-whole object completion and search guidance by salient, integrated objects has been proposed to require attentional resources, as shown by studies of neglect patients suffering from right-parietal brain damage. The current study was performed to provide further causal evidence for the link between attention and object integration. Methods: Healthy observers detected targets in the left and/or right hemifields, and these targets were in turn embedded in various Kanizsa-type configurations that systematically varied in the extent to which individual items could be integrated into a complete, whole object. Moreover, repetitive transcranial magnetic stimulation (rTMS) was applied over the right intraparietal sulcus (IPS) and compared to both active and passive baseline conditions. Results: The results showed that target detection was substantially facilitated when the to-be detected item(s) were fully embedded in a salient, grouped Kanizsa figure, either a unilateral triangle or a bilateral diamond. However, object groupings in one hemifield did not facilitate target detection to the same extent when there were bilateral targets, one inside the (triangle) grouping and the other outside of the grouped object. These results extend previous findings from neglect patients. Moreover, a subgroup of observers was found to be particularly sensitive to IPS stimulation, revealing neglect-like extinction behavior with the single-hemifield triangle groupings and bilateral targets. Conversely, a second subgroup showed the opposite effect, namely an overall, IPS-dependent improvement in performance. Conclusions: These explorative analyses show that the parietal cortex, in particular IPS, seems to modulate the processing of object groupings by up- and downregulating the deployment of attention to spatial regions were to-be-grouped items necessitate attentional resources for object completion. Full article

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

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12 pages, 1760 KiB

Open AccessArticle

Familiar Music Reduces Mind Wandering and Boosts Behavioral Performance During Lexical Semantic Processing

by Gavin M. Bidelman and Shi Feng

Brain Sci. 2025, 15(5), 482; https://doi.org/10.3390/brainsci15050482 - 2 May 2025

Abstract

Music has been shown to increase arousal and attention and even facilitate processing during non-musical tasks, including those related to speech and language functions. Mind wandering has been studied in many sustained attention tasks. Here, we investigated the intersection of these two phenomena: [...] Read more.

Music has been shown to increase arousal and attention and even facilitate processing during non-musical tasks, including those related to speech and language functions. Mind wandering has been studied in many sustained attention tasks. Here, we investigated the intersection of these two phenomena: the role of mind wandering while listening to familiar/unfamiliar musical excerpts, and its effects on concurrent linguistic processing. We hypothesized that familiar music would be less distracting than unfamiliar music, causing less mind wandering, and consequently benefit concurrent speech perception. Participants (N = 96 young adults) performed a lexical-semantic congruity task where they judged the relatedness of visually presented word pairs while listening to non-vocal classical music (familiar or unfamiliar orchestral pieces), or a non-music environmental sound clip (control) played in the background. Mind wandering episodes were probed intermittently during the task by explicitly asking listeners if their mind was wandering in that moment. The primary outcome was accuracy and reactions times measured during the lexical-semantic judgment task across the three background music conditions (familiar, unfamiliar, and control). We found that listening to familiar music, relative to unfamiliar music or environmental noise, was associated with faster lexical-semantic decisions and a lower incidence of mind wandering. Mind wandering frequency was similar when performing the task when listening to familiar music and control environmental sounds. We infer that familiar music increases task enjoyment, reduces mind wandering, and promotes more rapid lexical access during concurrent lexical processing, by modulating task-related attentional resources. The implications of using music as an aid during academic study and cognitive tasks are discussed. Full article

(This article belongs to the Section Behavioral Neuroscience)

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23 pages, 1558 KiB

Open AccessReview

Assistive Artificial Intelligence in Epilepsy and Its Impact on Epilepsy Care in Low- and Middle-Income Countries

by Nabin Koirala, Shishir Raj Adhikari, Mukesh Adhikari, Taruna Yadav, Abdul Rauf Anwar, Dumitru Ciolac, Bibhusan Shrestha, Ishan Adhikari, Bishesh Khanal and Muthuraman Muthuraman

Brain Sci. 2025, 15(5), 481; https://doi.org/10.3390/brainsci15050481 - 1 May 2025

Abstract

Epilepsy, one of the most common neurological diseases in the world, affects around 50 million people, with a notably disproportionate prevalence in individuals residing in low- and middle-income countries (LMICs). Alarmingly, over 80% of annual epilepsy-related fatalities occur within LMICs. The burden of [...] Read more.

Epilepsy, one of the most common neurological diseases in the world, affects around 50 million people, with a notably disproportionate prevalence in individuals residing in low- and middle-income countries (LMICs). Alarmingly, over 80% of annual epilepsy-related fatalities occur within LMICs. The burden of the disease assessed using Disability Adjusted Life Years (DALYs) shows that epilepsy accounts for about 13 million DALYs per year, with LMICs bearing most of this burden due to the disproportionately high diagnostic and treatment gaps. Furthermore, LMICs also endure a significant financial burden, with the cost of epilepsy reaching up to 0.5% of the Gross National Product (GNP) in some cases. Difficulties in the appropriate diagnosis and treatment are complicated by the lack of trained medical specialists. Therefore, in these conditions, adopting artificial intelligence (AI)-based solutions may improve epilepsy care in LMICs. In this theoretical and critical review, we focus on epilepsy and its management in LMICs, as well as on the employment of AI technologies to aid epilepsy care in LMICs. We begin with a general introduction of epilepsy and present basic diagnostic and treatment approaches. We then explore the socioeconomic impact, treatment gaps, and efforts made to mitigate these issues. Taking this step further, we examine recent AI-related developments and their potential as assistive tools in clinical application in LMICs, along with proposals for future directions. We conclude by suggesting the need for scalable, low-cost AI solutions that align with the local infrastructure, policy and community engagement to improve epilepsy care in LMICs. Full article

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

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18 pages, 6031 KiB

Open AccessArticle

Semaglutide and High-Intensity Interval Exercise Attenuate Cognitive Impairment in Type 2 Diabetic Mice via BDNF Modulation

by Sijie Lai, Zhenghong Kang, Jianting Sun, Ziyu Wang, Yanzi Xu, Sisi Xing, Mengying Feng, Yiyi Wang and Hua Liu

Brain Sci. 2025, 15(5), 480; https://doi.org/10.3390/brainsci15050480 - 1 May 2025

Abstract

Background/Objectives: Diabetes frequently leads to cognitive impairment, encompassing issues with memory and executive function, as well as depression and anxiety. This study examines the impact of high-intensity interval exercise (HIIE) alongside glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide on cognitive dysfunction associated [...] Read more.

Background/Objectives: Diabetes frequently leads to cognitive impairment, encompassing issues with memory and executive function, as well as depression and anxiety. This study examines the impact of high-intensity interval exercise (HIIE) alongside glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide on cognitive dysfunction associated with diabetes. Methods: Db/db mice were divided into a control group, semaglutide group, HIIE group, and semaglutide combined with HIIE group to study metabolic and neurobehavioral effects. Cognitive and behavioral tests, hippocampal morphology, and molecular analyses (APP, BDNF, Aβ, p-Tau, PKA, AMPK) were performed. HT22 cells under high glucose were treated with semaglutide, L-lactate, PKA inhibitor H89, and AMPK inhibitor Compound C to validate mechanisms. Results: Over 8 weeks, both HIIE and semaglutide improved neuronal morphology and cognitive performance while reducing depression in db/db mice. However, the current study observed no synergistic effects. Both therapies decreased Aβ and p-Tau protein levels and increased BDNF levels in the hippocampus, likely through the AMPK and PKA signaling pathways, respectively. In vitro, HT22 cells under high glucose conditions exhibited elevated APP and p-Tau expression and reduced BDNF levels, which could be altered by L-lactate and semaglutide. The AMPK inhibitor Compound C and the PKA inhibitor H89 attenuated the increase in BDNF levels induced by L-lactate and semaglutide, but their combination mitigated this inhibitory effect. This study suggests that while HIIE and semaglutide improve cognitive function and reduce depression via BDNF, their combined use did not show the anticipated synergistic benefits due to potential antagonism between the AMPK and PKA pathways. Conclusions: This has important implications for designing exercise prescriptions for cognitive impairment in diabetics. Full article

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

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20 pages, 1143 KiB

Open AccessReview

Perfecting Sensory Restoration and the Unmet Need for Personalized Medicine in Cochlear Implant Users: A Narrative Review

by Archana Podury, Brooke Barry, Karen C. Barrett and Nicole T. Jiam

Brain Sci. 2025, 15(5), 479; https://doi.org/10.3390/brainsci15050479 - 1 May 2025

Abstract

Hearing loss is one of the most common and undertreated medical conditions worldwide, with an estimated 466 million people (5% of the world’s population) reporting disabling hearing impairment. The implications are significant; untreated hearing loss increases the risk of depression, social isolation, unemployment, [...] Read more.

Hearing loss is one of the most common and undertreated medical conditions worldwide, with an estimated 466 million people (5% of the world’s population) reporting disabling hearing impairment. The implications are significant; untreated hearing loss increases the risk of depression, social isolation, unemployment, cognitive decline, and falls. Cochlear implants (CIs) are surgically implanted electrical devices that allow people with severe hearing loss to process sound. Over the past 50 years, CI development has made remarkable ground, such that most CI users have adequate speech perception in a silent environment. These language achievements, while significant milestones, fall short of perfect sensory restoration. Many of these limitations with complex sound perception are due to our one-size-fits-all approach towards CIs and speech-based metrics for evaluating implant performance. In the past decade, there has been exponential interest in improving CI-mediated music perception, as it serves as a key conduit to restoring normal hearing. The present literature demonstrates the need for a personalized approach towards cochlear implantation and management. Our proposed narrative review illustrates the limitations of CI-mediated sound processing and discusses ways in which precision medicine can be introduced into the ever-expanding hearing loss population. Full article

(This article belongs to the Special Issue Advances in Music, Language and Cognition: Sensitive Periods and Singing)

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10 pages, 596 KiB

Open AccessOpinion

Approach to Patients with Dysphagia: Clinical Insights

by Min-Su Kim

Brain Sci. 2025, 15(5), 478; https://doi.org/10.3390/brainsci15050478 - 30 Apr 2025

Abstract

Dysphagia is a commonly encountered condition in clinical practice, with a rising incidence reported particularly in South Korea. It can be broadly classified into oropharyngeal dysphagia and esophageal dysphagia, and distinguishing between the two is crucial for establishing rehabilitation treatment strategies. Oropharyngeal dysphagia [...] Read more.

Dysphagia is a commonly encountered condition in clinical practice, with a rising incidence reported particularly in South Korea. It can be broadly classified into oropharyngeal dysphagia and esophageal dysphagia, and distinguishing between the two is crucial for establishing rehabilitation treatment strategies. Oropharyngeal dysphagia frequently occurs in central nervous system diseases such as stroke, dementia, and Parkinson’s disease and has a significant impact on prognosis. Additionally, because there is a high risk of life-threatening aspiration pneumonia in patients complaining of dysphagia, an accurate diagnosis must be made during the early stages of the condition. Patients with oropharyngeal dysphagia may report difficulty initiating swallowing and may experience coughing, choking, nasopharyngeal reflux, aspiration, and a sensation of leftover food in the pharynx during swallowing. Patients with esophageal dysphagia may report a sensation of food getting stuck in the esophagus for a few seconds after the initiation of swallowing. Esophageal dysphagia should be characterized by analyzing whether the foods causing dysphagia are solid, liquid, or both, as well as by the progression of symptoms, whether they are progressive or intermittent; their severity; and associated symptoms such as weight loss, heartburn, or regurgitation. Video fluoroscopic swallowing study (VFSS), fiberoptic endoscopic evaluation of swallowing (FEES), and esophagogastroduodenoscopy (EGD) are invaluable in determining the causes, severity, and treatment strategies for dysphagia. Since swallowing disorders are significant factors influencing the course and prognosis regardless of the type of disease, clinicians should adopt a systematic approach to such disorders. Full article

(This article belongs to the Special Issue Deep Research into Stroke)

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17 pages, 643 KiB

Open AccessArticle

Cross-Cultural Biases of Emotion Perception in Music

by Marjorie G. Li, Kirk N. Olsen and William Forde Thompson

Brain Sci. 2025, 15(5), 477; https://doi.org/10.3390/brainsci15050477 - 29 Apr 2025

Abstract

Objectives: Emotion perception in music is shaped by cultural background, yet the extent of cultural biases remains unclear. This study investigated how Western listeners perceive emotion in music across cultures, focusing on the accuracy and intensity of emotion recognition and the musical features [...] Read more.

Objectives: Emotion perception in music is shaped by cultural background, yet the extent of cultural biases remains unclear. This study investigated how Western listeners perceive emotion in music across cultures, focusing on the accuracy and intensity of emotion recognition and the musical features that predict emotion perception. Methods: White-European (Western) listeners from the UK, USA, New Zealand, and Australia (N = 100) listened to 48 ten-second excerpts of Western classical and Chinese traditional bowed-string music that were validated by experts to convey happiness, sadness, agitation, and calmness. After each excerpt, participants rated the familiarity, enjoyment, and perceived intensity of the four emotions. Musical features were computationally extracted for regression analyses. Results: Western listeners experienced Western classical music as more familiar and enjoyable than Chinese music. Happiness and sadness were recognised more accurately in Western classical music, whereas agitation was more accurately identified in Chinese music. The perceived intensity of happiness and sadness was greater for Western classical music; conversely, the perceived intensity of agitation was greater for Chinese music. Furthermore, emotion perception was influenced by both culture-shared (e.g., timbre) and culture-specific (e.g., dynamics) musical features. Conclusions: Our findings reveal clear cultural biases in the way individuals perceive and classify music, highlighting how these biases are shaped by the interaction between cultural familiarity and the emotional and structural qualities of the music. We discuss the possibility that purposeful engagement with music from diverse cultural traditions—especially in educational and therapeutic settings—may cultivate intercultural empathy and an appreciation of the values and aesthetics of other cultures. Full article

(This article belongs to the Special Issue Advances in Emotion Processing and Cognitive Neuropsychology)

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16 pages, 3834 KiB

Open AccessArticle

Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study

by Daniela Amital, Raz Gross, Nadav Goldental, Eyal Fruchter, Haya Yaron-Wachtel, Aron Tendler, Yaki Stern, Lisa Deutsch, Jeffrey D. Voigt, Talma Hendler, Tal Harmelech, Neomi Singer and Haggai Sharon

Brain Sci. 2025, 15(5), 476; https://doi.org/10.3390/brainsci15050476 - 29 Apr 2025

Abstract

Background/Objectives: Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral striatum, in patients with MDD [...] Read more.

Background/Objectives: Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral striatum, in patients with MDD with anhedonia. This study aims to evaluate the safety and efficacy of a novel neurofeedback (NF) device (termed Prism) which incorporates the EEG–FRI-Pattern biomarker of the reward system (RS-EFP) for use in self-neuromodulation training (RS-EFP-NF) for alleviating depression in patients with MDD with anhedonia. Methods: A total of 49 adults (age range: M = 39.9 ± 11.03) with a DSM-5 diagnosis of MDD with anhedonia (per a SHAPS-C score ≥ 25) were screened for the administration of ten sessions of RS-EFP-NF twice a week on nonconsecutive days. Depression and anhedonia severity was assessed, respectively, by HDRS-17 and SHAPS-C at baseline, midway, and treatment end. Results: A total of 34 patients (77%) completed the protocol and were included in the analyses. No device-related adverse events were serious or required treatment. Depression symptoms were reduced at end of treatment as indicated by the HDRS-17, with a reduction of eight points on average (95% CI: −10.5 to −5.41, p < 0.0001), a clinical improvement rate of 78.47%, and a remission rate of 32.25%. Anhedonia, as indicated by the SHAPS-C score, was diminished, showing an average reduction of 6.3 points (95% CI: −8.51 to −4.14, p < 0.0001). Conclusions: Self-neuromodulation using RS-EFP-NF is a promising and safe treatment for MDD with anhedonia. The intervention demonstrates substantial clinical effects on both depression and anhedonia symptoms, with high patient acceptability and retention. Prism may address a critical mechanism-driven treatment gap for anhedonia that often persists despite conventional therapies. Larger controlled implementation, efficacy, and dosing studies are warranted. Full article

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

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3 pages, 132 KiB

Open AccessEditorial

Application of Nerve Stimulation: Current Status and Future Directions

by Hee Young Kim and Younbyoung Chae

Brain Sci. 2025, 15(5), 475; https://doi.org/10.3390/brainsci15050475 - 29 Apr 2025

Abstract

Neuromodulation is frequently used to modulate neuronal activity and influence brain function [...] Full article

(This article belongs to the Special Issue Application of Nerve Stimulation: Current Status and Future Directions)

40 pages, 5811 KiB

Open AccessReview

Metabolic Dysfunction and Dietary Interventions in Migraine Management: The Role of Insulin Resistance and Neuroinflammation—A Narrative and Scoping Review

by Cinzia Cavestro

Brain Sci. 2025, 15(5), 474; https://doi.org/10.3390/brainsci15050474 - 29 Apr 2025

Abstract

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, [...] Read more.

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets—now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions. Methods: A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on “MIGRAINE AND (neurogenic inflammation)” (2019–15 April 2025), followed by expanded searches from 1950 onward using terms such as “MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)”, and “MIGRAINE AND (diet, dietary, nutrition, nutritional)”. A specific search also targeted “(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)”. Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available. Results: Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization. Conclusions: The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes. Full article

(This article belongs to the Special Issue Advances in Neuroinflammation and Pain Medicine)

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