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Volume 15
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Brain Sci., Volume 15, Issue 5 (May 2025) – 94 articles

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16 pages, 4737 KiB  
Article
Co-Community Network Analysis Reveals Alterations in Brain Networks in Alzheimer’s Disease
by Xiaodong Wang, Zhaokai Zhang, Lingli Deng and Jiyang Dong
Brain Sci. 2025, 15(5), 517; https://doi.org/10.3390/brainsci15050517 (registering DOI) - 18 May 2025
Abstract
Background: Alzheimer’s disease (AD) is a common neurodegenerative disease. Functional magnetic resonance imaging (fMRI) can be used to measure the temporal correlation of blood-oxygen-level-dependent (BOLD) signals in the brain to assess the brain’s intrinsic connectivity and capture dynamic changes in the brain. [...] Read more.
Background: Alzheimer’s disease (AD) is a common neurodegenerative disease. Functional magnetic resonance imaging (fMRI) can be used to measure the temporal correlation of blood-oxygen-level-dependent (BOLD) signals in the brain to assess the brain’s intrinsic connectivity and capture dynamic changes in the brain. In this study, our research goal is to investigate how the brain network structure, as measured by resting-state fMRI, differs across distinct physiological states. Method: With the research goal of addressing the limitations of BOLD signal-based brain networks constructed using Pearson correlation coefficients, individual brain networks and community detection are used to study the brain networks based on co-community probability matrices (CCPMs). We used CCPMs and enrichment analysis to compare differences in brain network topological characteristics among three typical brain states. Result: The experimental results indicate that AD patients with increasing disease severity levels will experience the isolation of brain networks and alterations in the topological characteristics of brain networks, such as the Somatomotor Network (SMN), dorsal attention network (DAN), and Default Mode Network (DMN). Conclusion: This work suggests that using different data-driven methods based on CCPMs to study alterations in the topological characteristics of brain networks would provide better information complementarity, which can provide a novel analytical perspective for AD progression and a new direction for the extraction of neuro-biomarkers in the early diagnosis of AD. Full article
(This article belongs to the Special Issue Understanding the Functioning of Brain Networks in Health and Disease)
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24 pages, 1188 KiB  
Article
Impathy and Emotion Recognition: How Attachment Shapes Self- and Other-Focused Emotion Processing
by Dirk W. Eilert, Karin de Punder, Jeff Maerz, Johanna Dose, Manuela Gander, Philipp Mensah, Stefanie Neubrand, Josef Hinterhölzl and Anna Buchheim
Brain Sci. 2025, 15(5), 516; https://doi.org/10.3390/brainsci15050516 (registering DOI) - 18 May 2025
Abstract
Background/Objectives: Early attachment experiences and psychopathology both shape individuals’ emotion processing. However, the specific influence of adult attachment representations on self- (intrapersonal) and other-focused (interpersonal) emotion processing remains unclear, particularly in the context of personality disorders. This study examined how attachment representations (organized [...] Read more.
Background/Objectives: Early attachment experiences and psychopathology both shape individuals’ emotion processing. However, the specific influence of adult attachment representations on self- (intrapersonal) and other-focused (interpersonal) emotion processing remains unclear, particularly in the context of personality disorders. This study examined how attachment representations (organized vs. unresolved) modulate intrapersonal emotion perception (“impathy”) and interpersonal emotion recognition while accounting for personality pathology. Methods: Thirty-three adults (twenty-four patients with a personality disorder and nine healthy controls) were assessed for attachment representation using the Adult Attachment Projective Picture System (AAP). Emotion processing was measured via the Impathy Inventory and a facial emotion recognition task (READ-64). Group differences (organized vs. unresolved attachment; patients vs. controls) and correlations with the severity of unresolved attachment status were analyzed. Results: Patients with organized attachment representations did not differ from healthy controls in emotion recognition but showed significantly reduced impathy (M difference = −21.72, SE = 6.20, p = 0.002, 95% CI [−34.42, −9.01], d = −1.57). In contrast, patients with unresolved attachment exhibited impairments in both intrapersonal (M difference = −32.99, SE = 6.20, p < 0.001, 95% CI [−45.69, −20.29], d = −2.39) and interpersonal (M difference = −12.37, SE = 4.36, p = 0.008, 95% CI [−21.28, −3.46], d = −1.23) emotion processing compared to healthy controls. Furthermore, the severity of unresolved attachment status correlated with greater impairment in recognizing anger (r = −0.74, p = 0.004). Conclusions: An organized attachment representation may act as a protective factor, preserving interpersonal emotion recognition even in the presence of psychopathology. Conversely, an unresolved attachment constitutes an additional risk factor that exacerbates emotion processing impairments in the context of personality pathology. Attachment representation thus emerges as an active modulator of core emotion processes, with important implications for theory and targeted interventions in personality disorders. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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20 pages, 1350 KiB  
Review
Autobiographical Memory: A Scoping Meta-Review of Neuroimaging Data Enlightens the Inconsistencies Between Theory and Experimentation
by Edoardo Donarelli, Cristina Civilotti, Giulia Di Fini, Gabriella Gandino and Alessia Celeghin
Brain Sci. 2025, 15(5), 515; https://doi.org/10.3390/brainsci15050515 (registering DOI) - 18 May 2025
Abstract
Background/Objectives: Autobiographical memory (AM) is typically viewed in terms of comprising episodic (EAM) and semantic (SAM) components. Despite the emergence of numerous meta-analyses, the literature on these constructs remains fragmented. We aimed to summarize neural activations and to discuss the relations between constructs [...] Read more.
Background/Objectives: Autobiographical memory (AM) is typically viewed in terms of comprising episodic (EAM) and semantic (SAM) components. Despite the emergence of numerous meta-analyses, the literature on these constructs remains fragmented. We aimed to summarize neural activations and to discuss the relations between constructs based on theory and experimentation, while evaluating the consistency between literature sources and discussing the critical issues and challenges of current research. Methods: We conducted a scoping meta-review on AM, EAM, and SAM based on meta-analytic studies in five scientific databases (PubMed, Web of Science, Scopus, PsychInfo, and PsychArticles). No temporal or language limits were applied. Results: We included twelve meta-analyses on AM, EAM and SAM in healthy populations. The meta-analyses of AM and EAM actually investigated the same construct, leading to misinterpretation. The two available meta-analyses on SAM used two different operationalizations of the construct. Neural data about EAM were analyzed via mean rank classification, finding the most relevant areas in the posterior cingulate cortex, hippocampus, precuneus, temporo-parietal junction, angular gyrus, and medial prefrontal cortex. SAM was linked to the posterior and anterior cingulate cortexes, middle and inferior frontal gyri, thalamus, middle and superior temporal gyri, inferior frontal and fusiform gyri, and parahippocampal cortex. Conclusions: Variability in reported activation patterns persists, reflecting differences in methodology and assumptions. We propose the homogenization the notations of EAM and AM based on experimental practice. In this notation, AM does not have a separate experimental task nor activation pattern and may not indicate a separate construct but an array of its components. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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14 pages, 604 KiB  
Article
A Randomized Controlled Trial Comparing Subcutaneous Preservation of Bone Flaps with Cryogenic Preservation of Bone Flaps for Cranioplasty in Cases of Traumatic Brain Injury
by Rachith Sridhar, Anil Kumar, Harendra Kumar, Abdul Vakil Khan, Abdul Hakeem, Deepak Kumar, Anurag Kumar and Majid Anwer
Brain Sci. 2025, 15(5), 514; https://doi.org/10.3390/brainsci15050514 (registering DOI) - 17 May 2025
Abstract
Background and objectives: Decompressive craniectomy (DC) is a surgical procedure, useful for relieving the intracranial pressure following trauma. Following reduction in cerebral oedema, the bone is placed back to cover the defect. During the interim period, the bone flap may be preserved using [...] Read more.
Background and objectives: Decompressive craniectomy (DC) is a surgical procedure, useful for relieving the intracranial pressure following trauma. Following reduction in cerebral oedema, the bone is placed back to cover the defect. During the interim period, the bone flap may be preserved using cryopreservation or in subcutaneous tissue. This leads to a need to determine the benefits and risks involved in preservation of bone flap in a subcutaneous pocket or conventional freezer following decompressive craniectomy in traumatic brain injury. Materials and methods: An open randomized controlled trial was conducted at a level one trauma centre from July 2023 to December 2024. Simple randomization was performed in order to allocate patients into the subcutaneous preservation group and the cryogenic preservation group. Patients underwent cranioplasty after 3 months and were followed up post-operatively for complications and Glasgow Outcome Scale assessment. Results: The study initially recruited a total of 158 patients, out of which 104 patients remained eligible for the final analysis. The patients with cryopreserved flaps were found to have a higher rate of surgical site infection (31.3%) as compared to those with subcutaneously preserved flaps (5.6%), with the differences being statistically significant (p < 0.001). Among the 87 patients who had a poorer Glasgow Outcome Scale (GOS) score before the intervention, 55 (63.2%) patients had at least some improvement in GOS over a period of one month. Conclusion: The use of subcutaneous preservation of bone is more beneficial in resource-limited settings as compared to conventional freezer storage. Full article
(This article belongs to the Special Issue New Advances in Surgical Treatment of Brain Injury)
14 pages, 1322 KiB  
Article
Examination of Psychotropic Medication Use Following Outpatient Behavioral Assessment and Treatment
by Maria G. Valdovinos, Melissa Trites and Janelle Ausenhus
Brain Sci. 2025, 15(5), 513; https://doi.org/10.3390/brainsci15050513 (registering DOI) - 17 May 2025
Abstract
Background/Objectives: Psychotropic medications are often prescribed to treat challenging behavior in children with neurodevelopmental disorders. This study examined patterns of psychotropic medication use following outpatient behavioral assessment and treatment in children ages 2–16 years. Methods: Medication use at the time of behavioral assessments, [...] Read more.
Background/Objectives: Psychotropic medications are often prescribed to treat challenging behavior in children with neurodevelopmental disorders. This study examined patterns of psychotropic medication use following outpatient behavioral assessment and treatment in children ages 2–16 years. Methods: Medication use at the time of behavioral assessments, six months after the assessment, and a later follow-up time point (mean 25 months following the six-month time point, range 1 month to 41 months) were evaluated via a chart review. Alterations in psychotropic medication use were grouped into eight categories according to the type of medication change experienced. Care providers also completed a social validity survey rating their satisfaction with the assessment and interventions developed for their child. Results: This retrospective study revealed that children in this sample were more likely to experience starting a new medication and increases in the dose of psychotropic medication as time passed. Children were also less likely to remain on the same regimen of psychotropic medication as when they were first seen in the clinic. Additionally, although caregivers generally rated their experiences and outcomes with the behavioral clinic as favorable, additions and increases to psychotropic medication regimens still occurred. Conclusions: These findings are consistent with other reports of continued and increased prescribing of psychotropic medication across time in children with neurodevelopmental disorders, however, the results must be interpreted with caution given the small sample sizewhich limits generalizability of these findings. Additionally, the lack of follow-up with the patients in this sample made it difficult to correlate changes in challenging behavior with psychotropic medication prescribing. Full article
(This article belongs to the Special Issue Advances in Psychopharmacology in Neurodevelopmental Disorders (NDDs))
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17 pages, 855 KiB  
Article
The Influence of Transcranial Alternating Current Stimulation on the Excitability of the Unstimulated Contralateral Primary Motor Cortex
by Erik W. Wilkins, Richard J. Young, Ryder Davidson, Reese Krider, George Alhwayek, Jonathan A. Park, Armaan C. Parikh, Zachary A. Riley and Brach Poston
Brain Sci. 2025, 15(5), 512; https://doi.org/10.3390/brainsci15050512 (registering DOI) - 17 May 2025
Abstract
Objectives: Transcranial alternating current stimulation (tACS) can enhance primary motor cortex (M1) excitability and improve motor skill when delivered unilaterally to the dominant hemisphere. However, the impact of tACS on contralateral M1 excitability both during and after application has not been studied. The [...] Read more.
Objectives: Transcranial alternating current stimulation (tACS) can enhance primary motor cortex (M1) excitability and improve motor skill when delivered unilaterally to the dominant hemisphere. However, the impact of tACS on contralateral M1 excitability both during and after application has not been studied. The purpose of this study was to examine the effects of tACS delivered to the dominant left M1 on the excitability of the unstimulated contralateral non-dominant right M1. Methods: This study implemented a double-blind, randomized, SHAM-controlled, within-subjects, crossover experimental design. Eighteen young adults completed a tACS condition and a SHAM condition on two different days in counterbalanced order with a week washout period between days. Transcranial magnetic stimulation (TMS) was utilized to assess excitability of the contralateral right M1 while tACS was delivered to the left M1. TMS was administered in five test blocks (termed Pre, D5, D10, D15, and Post) relative to a 20 min application of tACS (70 Hz, 1 mA current strength). The Pre and Post TMS test blocks were conducted before and immediately after tACS was applied to the left M1, whereas the TMS test blocks performed during tACS were completed at time points starting at the 5, 10, and 15 min marks of the 20 min stimulation period. The primary dependent variable was the 1 mV motor evoked potential (MEP) amplitude. MEP data were analyzed with a 2 condition (tACS, SHAM) × 5 test (Pre, D5, D10, D15, Post) within-subjects ANOVA. Results: The main effect for condition (p = 0.704) and condition × test interaction (p = 0.349) were both non-statistically significant. There was a significant main effect for test (p = 0.003); however, post hoc analysis indicated that none of the pairwise comparisons were statistically significant. Conclusions: Overall, the findings indicate that tACS applied to the left M1 does not significantly modulate contralateral right M1 excitability during or immediately after stimulation, at least when utilizing the present tACS parameters. Full article
(This article belongs to the Special Issue New Insights into Movement Generation: Sensorimotor Processes)
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10 pages, 269 KiB  
Article
Interrater Reliability of the Occupational Therapy Anticipatory Awareness Test: A Performance-Based Cognitive Assessment
by Danielle Mahoney, Stephanie Alvarado and Rochelle Mendonca
Brain Sci. 2025, 15(5), 511; https://doi.org/10.3390/brainsci15050511 (registering DOI) - 16 May 2025
Abstract
Background: Functional cognitive impairments caused by acquired brain injury (ABI) negatively impact an individual’s daily functioning. Impaired self-awareness can pose obstacles to task execution and participation. Traditional assessment methods for self-awareness lack a functional approach, highlighting the need for performance-based assessments such as [...] Read more.
Background: Functional cognitive impairments caused by acquired brain injury (ABI) negatively impact an individual’s daily functioning. Impaired self-awareness can pose obstacles to task execution and participation. Traditional assessment methods for self-awareness lack a functional approach, highlighting the need for performance-based assessments such as the Occupational Therapy Anticipatory Awareness Test (OTAAT). The purpose of this study was to establish the interrater reliability of the OTAAT in adults with ABI. Methods: This was a two-phase study. Phase One involved the recruitment of three participants with ABI, who then underwent OTAAT administration within a setting of their choosing. OTAAT performances were recorded. In Phase Two, ten occupational therapists assessed the Phase One participants’ performances using the OTAAT. Phase Two’s raters’ outcomes were obtained by research personnel. These data were then collected and analyzed by research staff to measure interrater reliability using the Intraclass Correlation Coefficient (ICC) via IBM Statistical Package for the Social Sciences (SPSS) software. A two-way random effect, absolute agreement, multiple-rater/measurement ICC was adopted for this study. Results: Data analysis demonstrated strong interrater reliability for the OTAAT, demonstrating its consistency to measure self-awareness in individuals with ABI across different raters. Specifically, the ICC values indicated strong agreement among raters in their assessment of participants’ self-awareness performance using the OTAAT. Conclusion: The OTAAT has strong interrater reliability and holds promise as a valuable addition to neurorehabilitation practice. This study demonstrates the reliability of the OTAAT as a tool for assessing self-awareness in the ABI population. Full article
(This article belongs to the Special Issue The Impact of Stroke on Functional Cognition and Rehabilitation Approaches)
12 pages, 417 KiB  
Article
Superficial Neuromodulation in Dysautonomia in Women with Post-COVID-19 Condition: A Pilot Study
by Alberto Melián-Ortíz, Eduardo Zurdo-Sayalero, Sara Perpiñá-Martínez, Antonio Delgado-Lacosta, Carmen Jiménez-Antona, Josué Fernández-Carnero and Sofía Laguarta-Val
Brain Sci. 2025, 15(5), 510; https://doi.org/10.3390/brainsci15050510 (registering DOI) - 16 May 2025
Abstract
Post-COVID-19 condition involves persistent symptoms after acute infection, often linked to dysautonomia, which affects heart rate variability, pain perception, fatigue, and sleep. Superficial neuromodulation has been proposed as a treatment. Objective: To assess the effects of superficial neuromodulation on symptoms, sleep quality, [...] Read more.
Post-COVID-19 condition involves persistent symptoms after acute infection, often linked to dysautonomia, which affects heart rate variability, pain perception, fatigue, and sleep. Superficial neuromodulation has been proposed as a treatment. Objective: To assess the effects of superficial neuromodulation on symptoms, sleep quality, and autonomic function in post-COVID-19 condition patients. Methods: A pilot study was conducted based on a triple-blind randomized controlled trial methodology involving 16 female participants. The experimental group received neuromodulation, while the control group used a placebo device. The intervention spanned 15 sessions over two months. Primary outcomes included heart rate variability, pain threshold, cortisol levels, fatigue, sleep quality, and quality of life, analyzed using repeated-measures ANOVA. Results: Both groups improved over time. Heart rate variability (SDNN) increased in the experimental group (30.42 to 39.11 ms) but decreased in controls (31.88 to 28.73 ms) (p < 0.05). Pain threshold at C5–C6 improved in the experimental group (2.1 to 3.5 kg/cm2) but remained stable in controls (p = 0.032). Fatigue decreased significantly in both groups (p = 0.002). Sleep quality improved, with Pittsburgh Sleep Quality Index scores decreasing similarly in both groups. Cortisol levels increased, with a non-significant trend favoring controls. Conclusions: While improvements were seen, both groups benefited, suggesting a possible placebo effect. Superficial neuromodulation appears safe, but further studies with larger samples are needed to confirm efficacy. Full article
(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)
25 pages, 5709 KiB  
Article
EEG-Based Seizure Detection Using Dual-Branch CNN-ViT Network Integrating Phase and Power Spectrograms
by Zhuohan Wang, Yaoqi Hu, Qingyue Xin, Guanghao Jin, Yazhou Zhao, Weidong Zhou and Guoyang Liu
Brain Sci. 2025, 15(5), 509; https://doi.org/10.3390/brainsci15050509 (registering DOI) - 16 May 2025
Abstract
Background/Objectives: Epilepsy is a common neurological disorder with pathological mechanisms closely associated with the spatiotemporal dynamic characteristics of electroencephalogram (EEG) signals. Although significant progress has been made in epileptic seizure detection methods using time–frequency analysis, current research still faces challenges in terms of [...] Read more.
Background/Objectives: Epilepsy is a common neurological disorder with pathological mechanisms closely associated with the spatiotemporal dynamic characteristics of electroencephalogram (EEG) signals. Although significant progress has been made in epileptic seizure detection methods using time–frequency analysis, current research still faces challenges in terms of an insufficient utilization of phase information. Methods: In this study, we propose an effective epileptic seizure detection framework based on continuous wavelet transform (CWT) and a hybrid network consisting of convolutional neural network (CNN) and vision transformer (ViT). First, the raw EEG signals are processed by the CWT. Then, the phase spectrogram and power spectrogram of the EEG are generated, and they are sent into the designed CNN and ViT branches of the network to extract more discriminative EEG features. Finally, the features output from the two branches are fused and fed into the classification network to obtain the detection results. Results: Experimental results on the CHB-MIT public dataset and our SH-SDU clinical dataset show that the proposed framework achieves sensitivities of 98.09% and 89.02%, specificities of 98.21% and 95.46%, and average accuracies of 98.45% and 94.66%, respectively. Furthermore, we compared the spectral characteristics of CWT with other time–frequency transforms within the hybrid architecture, demonstrating the advantages of the CWT-based CNN-ViT architecture. Conclusions: These results highlight the outstanding epileptic seizure detection performance of the proposed framework and its significant clinical feasibility. Full article
(This article belongs to the Section Computational Neuroscience and Neuroinformatics)
16 pages, 588 KiB  
Study Protocol
The Effects of Endoscopic Third Ventriculostomy Versus Ventriculoperitoneal Shunt on Neuropsychological and Motor Performance in Patients with Idiopathic Normal Pressure Hydrocephalus—ENVENTOR-iNPH: Study Protocol
by Gianluca Scalia, Nicola Alberio, Pietro Trombatore, Mariangela Panebianco, Grazia Razza, Gianluca Galvano, Giovanni Federico Nicoletti and Francesca Graziano
Brain Sci. 2025, 15(5), 508; https://doi.org/10.3390/brainsci15050508 - 16 May 2025
Abstract
Background: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by cognitive decline, gait disturbances, and urinary incontinence. Surgical interventions such as ventriculoperitoneal shunt (VPS) and endoscopic third ventriculostomy (ETV) are the primary treatment options. While VPS is the standard of [...] Read more.
Background: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by cognitive decline, gait disturbances, and urinary incontinence. Surgical interventions such as ventriculoperitoneal shunt (VPS) and endoscopic third ventriculostomy (ETV) are the primary treatment options. While VPS is the standard of care, ETV offers a minimally invasive alternative with potentially fewer complications. However, comparative evidence regarding their impact on cognitive, motor, and structural outcomes remains limited. This study, titled ENVENTOR-iNPH (endoscopic ventriculostomy versus shunt on neuropsychological and motor performance in patients with iNPH), aims to address this gap through a rigorously designed comparative protocol. Methods: This protocol is designed as a multicenter, randomized, controlled trial (ENVENTOR-iNPH) to compare the effects of ETV and VPS in patients diagnosed with iNPH. The study will enroll 100 patients aged 60 years or older, randomly assigned to undergo ETV (n = 50) or VPS (n = 50). Preoperative and postoperative evaluations will include comprehensive cognitive and motor assessments, standardized quality-of-life instruments, and advanced neuroimaging techniques such as MRI with flowmetry and diffusion tensor imaging (DTI). Functional outcomes will also be evaluated using navigated transcranial magnetic stimulation (nTMS) and wearable motion analysis systems. The objective of this study is to compare the efficacy and safety of ETV versus VPS in restoring cognitive and motor performance in patients with iNPH. Results: Primary outcomes include cognitive and motor function improvements. Secondary endpoints are surgical complications, hospital stay duration, and changes in quality of life. Neuroimaging will assess changes in white matter integrity and cerebrospinal fluid dynamics, while nTMS will provide insights into neuroplasticity and motor pathway recovery. ETV is hypothesized to demonstrate clinical outcomes comparable or superior to VPS, particularly in terms of complication reduction and hospital recovery metrics. Conclusions: The ENVENTOR-iNPH protocol establishes the framework for a comprehensive, multicenter study comparing ETV and VPS in iNPH patients. The findings from this initial study will inform the design of larger-scale multicenter trials, guide clinical decision making, and potentially position ETV as a preferred treatment option for eligible patients. Full article
(This article belongs to the Special Issue Editorial Board Collection Series: Insight into Neurosurgery)
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52 pages, 1790 KiB  
Review
Emotion, Motivation, Reasoning, and How Their Brain Systems Are Related
by Edmund T. Rolls
Brain Sci. 2025, 15(5), 507; https://doi.org/10.3390/brainsci15050507 - 16 May 2025
Abstract
A unified theory of emotion and motivation is updated in which motivational states are states in which instrumental goal-directed actions are performed to obtain anticipated rewards or avoid punishers, and emotional states are states that are elicited when the (conditioned or unconditioned) instrumental [...] Read more.
A unified theory of emotion and motivation is updated in which motivational states are states in which instrumental goal-directed actions are performed to obtain anticipated rewards or avoid punishers, and emotional states are states that are elicited when the (conditioned or unconditioned) instrumental reward or punisher is or is not received. This advances our understanding of emotion and motivation, for the same set of genes and associated brain systems can define the primary or unlearned rewards and punishers such as a sweet taste or pain, and the brain systems that learn to expect rewards or punishers and that therefore produce motivational and emotional states. It is argued that instrumental actions under the control of the goal are important for emotion, because they require an intervening emotional state in which an action is learned or performed to obtain the goal, that is, the reward, or to avoid the punisher. The primate including human orbitofrontal cortex computes the reward value, and the anterior cingulate cortex is involved in learning the action to obtain the goal. In contrast, when the instrumental response is overlearned and becomes a habit with stimulus–response associations, emotional states may be less involved. In another route to output, the human orbitofrontal cortex has effective connectivity to the inferior frontal gyrus regions involved in language and provides a route for declarative reports about subjective emotional states to be produced. Reasoning brain systems provide alternative strategies to obtain rewards or avoid punishers and can provide different goals for action compared to emotional systems. Full article
(This article belongs to the Special Issue Defining Emotion: A Collection of Current Models)
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23 pages, 663 KiB  
Systematic Review
The Use of Griffiths III in the Appraisal of the Developmental Profile in Autism: A Systematic Search and Review
by Flavia Lecciso, Chiara Martis and Annalisa Levante
Brain Sci. 2025, 15(5), 506; https://doi.org/10.3390/brainsci15050506 - 15 May 2025
Viewed by 162
Abstract
Background: Griffiths III is a child-friendly and play-oriented direct gold-standard measure of a 0–6-year-old child’s developmental profile. It is a measure that helps practitioners in detecting the weaknesses in children who have an increased likelihood or a diagnosis of neurodevelopmental disorders, e.g., autism. [...] Read more.
Background: Griffiths III is a child-friendly and play-oriented direct gold-standard measure of a 0–6-year-old child’s developmental profile. It is a measure that helps practitioners in detecting the weaknesses in children who have an increased likelihood or a diagnosis of neurodevelopmental disorders, e.g., autism. Objectives: Following the PICO protocol, two research questions addressed the current systematic search and review (Prospero registration: CRD42024554286): What is(are) the main developmental domain(s) evaluated by Griffiths III impaired in autism? (RQ1); Using Griffiths III, what is(are) the main developmental domain(s) improved after an autism-specific early intervention? (RQ2). Methods: Six studies have been reviewed: three case–control studies, a case report study, and two studies examining the effectiveness of early autism-specific interventions. According to the study design, the methodological quality was evaluated using three standardised protocols: STROBE; JBI; CEC. Results: The results highlighted that the Language and Communication and Personal–Social–Emotional domains are the most impaired in autistic children and in those with an increased likelihood (RQ1). The results outlined that early target intervention enhanced the same domains (RQ2). Conclusions: In conclusion, the findings highlight the importance of screening not only for autism traits but also for impairments in language, communication, and socio-emotional skills. The future direction of the results is discussed. Full article
(This article belongs to the Section Developmental Neuroscience)
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31 pages, 1010 KiB  
Review
Cognitive Factors in Process Model Comprehension—A Systematic Literature Review
by Maximilian Möller, Michael Winter and Manfred Reichert
Brain Sci. 2025, 15(5), 505; https://doi.org/10.3390/brainsci15050505 - 15 May 2025
Viewed by 163
Abstract
Process models constitute essential tools in business process management and software engineering for representing and managing real-world business processes. Hence, the proper comprehension of these models is crucial for enabling an effective and efficient communication among stakeholders. While several studies have examined factors [...] Read more.
Process models constitute essential tools in business process management and software engineering for representing and managing real-world business processes. Hence, the proper comprehension of these models is crucial for enabling an effective and efficient communication among stakeholders. While several studies have examined factors affecting process model comprehension, such as the used modeling notation or process complexity, there is a lack of in-depth research on the cognitive processes important to comprehend process models deeper. This systematic literature review explores the cognitive mechanisms underlying process model comprehension by integrating insights from relevant disciplines such as cognitive neuroscience and psychology. Key areas of cognition include perception, attention, memory, language, problem solving, emotion, and metacognition. This review was conducted following the well-established Kitchenham methodology and included an extensive search in the following digital libraries: Web of Science, IEEE Xplore, ScienceDirect, ACM Digital Library, PubMed, and SpringerLink. By analyzing 47 studies, this literature review identifies gaps in current research, emphasizing the need for further investigation into these cognitive processes to improve model comprehensibility. Full article
(This article belongs to the Section Neuropsychology)
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17 pages, 923 KiB  
Article
Defective Awareness of Person-Recognition Disorders Through Face, Voice and Name in Right and Left Variants of Semantic Dementia: A Pilot Study
by Simona Luzzi, Oscar Prata and Guido Gainotti
Brain Sci. 2025, 15(5), 504; https://doi.org/10.3390/brainsci15050504 - 15 May 2025
Viewed by 183
Abstract
Background/Objectives: The aim of this investigation consisted of evaluating if the prevalence of anosognosia in right-brain-damaged patients is greater for tasks in which the right hemisphere plays a dominant role and if this prevalence is at least in part due to automatic [...] Read more.
Background/Objectives: The aim of this investigation consisted of evaluating if the prevalence of anosognosia in right-brain-damaged patients is greater for tasks in which the right hemisphere plays a dominant role and if this prevalence is at least in part due to automatic processing mechanisms typical of this hemisphere. Methods: We assessed defective awareness of person-recognition disorders in 14 patients with the right variant (rv-SD) and 15 with the left variant (lv-SD) of Semantic Dementia. A battery exploring person-recognition disorders through familiarity judgement of faces, voices and names was applied. In patients with pathological performance in one of these modalities, anosognosia was assessed comparing the patients’ subjective judgment to the objective result of their performance (objective evaluation) and to the subjective judgment given by an informed caregiver (external comparison). Results: In the comparison between subjective awareness and objective scores in the various person-recognition modalities, only anosognosia for face recognition disorders was significantly more frequent of in patients with rv-SD. When compared to their caregivers, subjects with rv-SD were significantly less aware than caregivers of their difficulties only on face recognition. On the contrary, patients with a lv-SD showed a greater (non-significant) trend to be unaware of their name recognition deficit. Conclusions: These data show that the prevalence of anosognosia in right-brain-damaged patients is greater for face recognition in which the right hemisphere plays a dominant role and that this prevalence is at least in part due to automatic processing mechanisms (evocation of familiarity feelings) typical of this hemisphere. Full article
(This article belongs to the Special Issue Anosognosia and the Determinants of Self-Awareness)
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17 pages, 575 KiB  
Article
The Mediating Role of Social Camouflaging on the Relationship Between Autistic Traits and Orthorexic Symptoms
by Barbara Carpita, Benedetta Nardi, Cristiana Pronestì, Gianluca Cerofolini, Matilde Filidei, Chiara Bonelli, Gabriele Massimetti, Ivan Mirko Cremone, Stefano Pini and Liliana Dell’Osso
Brain Sci. 2025, 15(5), 503; https://doi.org/10.3390/brainsci15050503 - 14 May 2025
Viewed by 142
Abstract
Background/Objectives: Recent lifestyle and dietary changes, driven by health awareness and ecological concerns, have led to the rise in numerous type of diets, which can promote well-being but may also contribute to Orthorexia Nervosa (ON), which have been suggested to be linked [...] Read more.
Background/Objectives: Recent lifestyle and dietary changes, driven by health awareness and ecological concerns, have led to the rise in numerous type of diets, which can promote well-being but may also contribute to Orthorexia Nervosa (ON), which have been suggested to be linked to autism spectrum disorder. This study aimed to explore the relationship between autistic traits, social camouflaging, and orthorexic tendencies in female university students, focusing on how these factors intersect with specific dietary habits. Methods: 554 female students were recruited via an online survey and assessed with the Adult Autism Subthreshold (AdAS) Spectrum, the Camouflaging Autistic Traits Questionnaire (CAT-Q), and the ORTO-R. Participants were categorized into four groups based on AdAS Spectrum and CAT-Q quartiles. Results: Vegans and vegetarians exhibited higher orthorexic tendencies and specific autistic traits. High scorers on the AdAS Spectrum and CAT-Q also showed higher ORTO-R scores, with both AdAS Spectrum and CAT-Q total scores, as well as certain domains, serving as significant positive predictors of higher ORTO-R scores. Notably, the AdAS Spectrum total score had a significant direct and indirect effect (through the CAT-Q) on the ORTO-R total score. Conclusions: The study found significant associations between autistic traits, social camouflaging behaviors, and orthorexic tendencies in female university students. These findings suggest that the strict dietary behaviors and rigid thinking characteristic of orthorexia may be influenced by underlying autistic features, highlighting the need for further research into the intersection of autism and eating disorders. Full article
(This article belongs to the Special Issue Advanced Clinical Diagnosis, Evaluation, and Treatment of Psychosis)
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17 pages, 488 KiB  
Systematic Review
Dysautonomia in Alzheimer’s Disease: A Systematic Review
by Marianna Papadopoulou, Maria-Ioanna Stefanou, Eleni Bakola, Christos Moschovos, Athanasia Athanasaki, Evdoxia Tsigkaropoulou, Ioannis Michopoulos, George P. Paraskevas, Rossetos Gournellis and Georgios Tsivgoulis
Brain Sci. 2025, 15(5), 502; https://doi.org/10.3390/brainsci15050502 - 14 May 2025
Viewed by 152
Abstract
Background: Alzheimer’s disease (AD) is the most common cause of dementia. In addition to cognitive decline, non-cognitive symptoms, including dysautonomia, have been reported, although these symptoms are rarely acknowledged by patients. Dysautonomia in AD is thought to arise from either cholinergic deficits [...] Read more.
Background: Alzheimer’s disease (AD) is the most common cause of dementia. In addition to cognitive decline, non-cognitive symptoms, including dysautonomia, have been reported, although these symptoms are rarely acknowledged by patients. Dysautonomia in AD is thought to arise from either cholinergic deficits or hypothalamic involvement. A wide range of tests has been used to investigate the role of the autonomic nervous system; however, the results have been inconsistent. Aim: To systematically review all published research investigating autonomic nervous system (ANS) involvement in patients with AD. A comprehensive literature search was conducted in December 2024 across the following databases: PubMed, Cochrane Library, ScienceDirect, and Scopus. Results: A total of 1422 records were identified, of which 30 studies fulfilled the inclusion criteria and were included in the review. Several autonomic tests were employed, with Heart Rate Variability (HRV) being the most frequently used. Other tests included assessments of orthostatic hypotension (OH), postprandial hypotension (PPH), sympathetic skin response (SSR), the tilt test, 123I-MIBG cardiac scintigraphy, norepinephrine (NE) measurements in serum and cerebrospinal fluid, and baroreflex sensitivity. In most studies, AD patients were compared to either healthy controls or patients with other types of dementia. Discussion: The primary finding of this review is that, although patients with AD rarely report dysautonomic symptoms, they frequently exhibit abnormal results on various autonomic tests. In some cases, these findings were sufficient to differentiate AD patients from healthy controls as well as from patients with Diffuse Lewy Body disease (DLB). The inconsistency in reporting symptoms, along with the variability in test results, suggests that autonomic dysfunction in AD may be under-recognized and warrants further investigation. Conclusions: The heterogeneity of the included studies limits the generalizability of the results. However, given the potential impact of dysautonomia on both quality of life and mortality, it is recommended that AD patients be systematically assessed for autonomic dysfunction. Even in the absence of overt symptoms, appropriate treatment should be considered where indicated to mitigate potential risks. Full article
(This article belongs to the Special Issue Aging-Related Changes in Memory and Cognition)
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16 pages, 3978 KiB  
Systematic Review
Impact of Flipped Classroom Instruction on Brain-Mediated Motor Skill Performance in University Students: A Systematic Review and Meta-Analysis
by Kerui Liu, Zikang Hao, Jiping Chen, Qingxu Wu, Wei Jin, Yang Pan and Xianliang Zhang
Brain Sci. 2025, 15(5), 501; https://doi.org/10.3390/brainsci15050501 - 14 May 2025
Viewed by 174
Abstract
Objective: This systematic review and meta-analysis evaluates how the flipped classroom model—considered as a neurocognitive training environment—affects cognitive–motor integration and brain-mediated motor skill performance in university students, providing scientific evidence for optimizing higher-education physical education pedagogy (a course related to physical literacy and [...] Read more.
Objective: This systematic review and meta-analysis evaluates how the flipped classroom model—considered as a neurocognitive training environment—affects cognitive–motor integration and brain-mediated motor skill performance in university students, providing scientific evidence for optimizing higher-education physical education pedagogy (a course related to physical literacy and the cultivation of physical and mental health, rather than a training program for professional physical education teachers). Methods: In order to compare the effects of flipped classroom and traditional teaching on the motor skill performance of university students, this study conducted a systematic review and meta-analysis according to PRISMA rules, whereby studies were screened according to specific inclusion criteria and data were extracted, assessed for quality, and then meta-analyzed to assess the effectiveness of the flipped classroom model in improving motor skill performance. Results: A total of 12 original randomized controlled trials (RCTs) were included in the study. The meta-analysis results indicated that the flipped classroom model significantly outperformed traditional teaching methods in improving university students’ motor skill scores (standardized mean difference (SMD) = 1.22, 95% CI = 0.64–1.79, p < 0.0001). Subgroup analysis showed significant effects in both general major students and sports science major students, with no significant difference between studies conducted in China and those conducted in non-China regions. Conclusions: The flipped classroom model demonstrates significant advantages over traditional PE teaching methods in improving motor skill performance. It enhances students’ skill acquisition and classroom engagement, showing promising potential for future implementation in university PE programs. Further research should explore the model’s applicability across different sports and student populations, as well as its long-term impact on skill retention and postgraduation sports participation. Full article
(This article belongs to the Special Issue Advances in the Relationship Among Brain, Physical Function, and Exercise Performance)
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65 pages, 3445 KiB  
Review
Exploring Virtual Reality-Based Reminiscence Therapy on Cognitive and Emotional Well-Being in People with Cognitive Impairments: A Scoping Review
by Susanna Pardini, Riccardo Calcagno, Anna Genovese, Elio Salvadori and Oscar Mayora Ibarra
Brain Sci. 2025, 15(5), 500; https://doi.org/10.3390/brainsci15050500 - 13 May 2025
Viewed by 279
Abstract
Background/Objectives: Virtual reality (VR) is increasingly being explored as a non-pharmacological therapy to enhance the well-being of people with cognitive impairment (PwCI). Studies suggest that VR-based interventions improve mood, reduce apathy, and enhance emotional engagement, making VR a valuable tool for cognitive and [...] Read more.
Background/Objectives: Virtual reality (VR) is increasingly being explored as a non-pharmacological therapy to enhance the well-being of people with cognitive impairment (PwCI). Studies suggest that VR-based interventions improve mood, reduce apathy, and enhance emotional engagement, making VR a valuable tool for cognitive and emotional support. This scoping review synthesizes evidence on VR-based reminiscence therapy (VRRT) for PwCI. It aims to map existing knowledge, highlight implementation challenges, and offer practical, technical design, and evidence-informed recommendations for clinical integration—building on prior reviews that have touched on these aspects, but placing a stronger and more structured emphasis on real-world applicability and translational insights. This review draws extensively on qualitative findings across the included studies to better capture contextual factors, user experiences, facilitator roles, and barriers to usability. Moreover, unlike previous research, we included only studies involving individuals—either directly or via proxies—with an age-related cognitive impairment, formally diagnosed by a qualified authority. Methods: A systematic search based on the PRISMA-ScR guideline identified 310 studies, of which 11 met the inclusion criteria. These studies assessed the effectiveness and feasibility of immersive VRRT. Research methodologies included longitudinal (n = 2), cross-sectional (n = 2), mixed-methods (n = 4), and randomized controlled trials (n = 3)—with most studies focusing on feasibility—with a cumulative sample size of approximately 287 participants. The quality of the included studies was generally moderate; common limitations included small sample sizes, short intervention periods, and limited control conditions. Results: The findings highlight VRRT’s potential to enhance engagement, emotional well-being, and cognitive function. However, usability challenges and technical limitations persist. While VR offers promising benefits, further research is needed to refine interventions, address personalization barriers, and assess long-term effects. Conclusions: This review underscores the importance of integrating VRRT into care programs and improving accessibility. Future research should enhance methodological rigor to ensure reliable outcomes and maximize VR’s impact on PwCI well-being. The scoping review protocol is registered a priori with the Center for Open Science (OSF) (registration type: OSF Preregistration, data registered: 15 November 2024, associated project: osf.io/r7jha, identifier: DOI 10.17605/OSF.IO/R7JHA). Full article
(This article belongs to the Section Neurodegenerative Diseases)
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19 pages, 667 KiB  
Review
Is There a Link Between Type 2 Diabetes Mellitus and Negative Symptoms in Schizophrenia? A Scoping Review
by István Bitter, Pál Czobor and László Tombor
Brain Sci. 2025, 15(5), 499; https://doi.org/10.3390/brainsci15050499 - 13 May 2025
Viewed by 185
Abstract
Background/Objectives: Type 2 diabetes mellitus (T2DM) and impaired glucose metabolism are more prevalent among patients with schizophrenia than in the general population. The incidence of T2DM is associated with lifestyle factors that are often influenced by the negative symptoms of schizophrenia; comorbid T2DM [...] Read more.
Background/Objectives: Type 2 diabetes mellitus (T2DM) and impaired glucose metabolism are more prevalent among patients with schizophrenia than in the general population. The incidence of T2DM is associated with lifestyle factors that are often influenced by the negative symptoms of schizophrenia; comorbid T2DM may contribute to the reduced life expectancy observed in patients with schizophrenia. The existing literature reveals a scarcity of data regarding the potential causal relationship between T2DM and negative symptoms. Methods: A scoping review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria, utilizing the PubMed database to identify clinical studies investigating the association between T2DM and the negative (but not cognitive) symptom domain of schizophrenia. Subsequently, the reference lists of these identified publications were searched. Results: Seventeen publications were included. There is evidence supporting the association between impaired glucose tolerance and increased negative symptoms in patients with first-episode psychosis, and several studies indicate that poorer glucose metabolic status correlates with more severe negative symptoms. Patients with T2DM and chronic schizophrenia, however, had milder negative symptom scores compared to those without diabetes, although this association was less pronounced than in early disease stages. Conclusions: There is insufficient confirmatory evidence regarding the potential causality of T2DM on the negative symptoms of schizophrenia. Further, preferably prospective studies are needed to explore the complex and potentially causal relationship between T2DM and negative symptoms of schizophrenia. If T2DM were found to have a causal relationship with negative symptoms or to exacerbate pre-existing symptoms, it could lead to significant changes in therapeutic approaches for schizophrenia. Full article
(This article belongs to the Special Issue Exploring Negative Symptoms of Schizophrenia: Where Do We Stand?)
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5 pages, 173 KiB  
Editorial
Amyotrophic Lateral Sclerosis: Recent Considerations for Diagnosis, Pathogenesis and Therapy
by Andrew Eisen
Brain Sci. 2025, 15(5), 498; https://doi.org/10.3390/brainsci15050498 - 13 May 2025
Viewed by 216
Abstract
Amyotrophic lateral sclerosis (ALS/MND) is considered a uniquely human complex neurodegenerative disorder, presenting with a variety of clinical phenotypes, which include frontotemporal dementia [...] Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis: Recent Considerations for Diagnosis, Pathogenesis and Therapy)
14 pages, 1204 KiB  
Article
Cognitive Control After ACL Reconstruction: A Cross-Sectional Study on Impaired Proactive Inhibition Compared to Healthy Controls
by Jesús Jiménez-Martínez, Alejandro Gutiérrez-Capote, Iker Madinabeitia, David Cárdenas and Francisco Alarcón
Brain Sci. 2025, 15(5), 497; https://doi.org/10.3390/brainsci15050497 - 12 May 2025
Viewed by 322
Abstract
Background/Objectives: Anterior cruciate ligament (ACL) injury is common in interaction sports and has severe physical and psychological consequences. Recent research suggests that neurocognitive factors, such as proactive inhibitory control, may influence injury risk. The present work compares the proactive inhibitory performance ability [...] Read more.
Background/Objectives: Anterior cruciate ligament (ACL) injury is common in interaction sports and has severe physical and psychological consequences. Recent research suggests that neurocognitive factors, such as proactive inhibitory control, may influence injury risk. The present work compares the proactive inhibitory performance ability of athletes with no ACL injury and ACL-rehabilitated athletes (ACLR). Methods: This study involved 60 athletes from interaction sports (30 with no history of ACL injury and 30 ACL rehabilitated athletes). During the experimental session, participants performed an executive go–no-go task to assess proactive inhibitory control. Results: The ACLR group exhibited higher adjusted-precision response times (p = 0.011), higher inhibitory failures response times (p < 0.001), poorer accuracy (p = 0.003), and higher commission error rate (p = 0.026) than the group of athletes with no history of ACL injury. Conclusions: Athletes rehabilitated from an ACL injury show inferior performance in proactive inhibitory control, evidenced by lower accuracy and higher reaction times than athletes without a history of injury. Consequently, physiotherapists and exercise professionals should consider cognition during ACL injury rehabilitation and physical retraining before returning to sporting activity. Full article
(This article belongs to the Special Issue Mind in Motion: Exploring Neuropsychophysiological Aspects of Sports Performance, Health and Physical Activity)
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17 pages, 2134 KiB  
Article
Comorbidity Between Hikikomori and Autistic Traits May Be Identified as a Phenotypical Presentation Characterized by Greater Severity
by Liliana Dell’Osso, Benedetta Nardi, Dario Muti, Chiara De Felice, Valeria Tognini, Francesca Parri, Federico Giovannoni, Filippo Del Grande, Chiara Bonelli, Gabriele Massimetti, Stefano Pini, Andrea Fiorillo and Barbara Carpita
Brain Sci. 2025, 15(5), 496; https://doi.org/10.3390/brainsci15050496 - 10 May 2025
Viewed by 425
Abstract
Objectives: Hikikomori is a condition characterized by extreme social withdrawal, functional impairment, and mental distress, which has gained increasing recognition worldwide. While it can be associated with comorbid psychiatric disorders, hikikomori shares similarities with autism spectrum, prompting investigations into their relationship. Given [...] Read more.
Objectives: Hikikomori is a condition characterized by extreme social withdrawal, functional impairment, and mental distress, which has gained increasing recognition worldwide. While it can be associated with comorbid psychiatric disorders, hikikomori shares similarities with autism spectrum, prompting investigations into their relationship. Given that hikikomori commonly manifests in early adulthood, this study aimed to explore the relationship between autistic features and hikikomori tendencies among university students. Methods: A total of 2037 university students were recruited via an online survey and assessed with the Adult Autism Subthreshold (AdAS) Spectrum and the Hikikomori Questionnaire (HQ-25). Participants were categorized into four groups: healthy controls (HCs), subjects with hikikomori tendencies (HKs), subjects with significant autistic traits (ATs), and subjects with both significant ATs and hikikomori tendencies (AT-HKs). Results: Results showed significant effects of both hikikomori presence and significant ATs on AdAS Spectrum and HQ-25 scores, while a significant effect of their interaction was detected on AdAS Spectrum scores. The AT-HK group consistently scored higher on both AdAS Spectrum and HQ-25 compared to other groups, with the AT and HK groups outperforming HCs in specific domains. HQ-25 Socialization and Isolation domains predicted higher AdAS Spectrum scores in hikikomori subjects, while various AdAS Spectrum domains served as predictors of HQ-25 scores in AT subjects. Conclusions: This study highlights a significant relationship between ATs and hikikomori tendencies in university students, suggesting that their comorbidity may represent a more severe phenotype, where each condition may exacerbate the other. Full article
(This article belongs to the Section Neuropsychiatry)
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26 pages, 710 KiB  
Systematic Review
The Role of Attachment in Refugees with Impaired Mental Health: A Systematic Review
by Thomas Egger, Anna Buchheim and Manuela Gander
Brain Sci. 2025, 15(5), 495; https://doi.org/10.3390/brainsci15050495 - 9 May 2025
Viewed by 336
Abstract
Although the relationship between attachment and mental health has been widely studied, no systematic review has focused specifically on refugee populations. Objectives: This systematic review examines associations between attachment patterns and psychological distress in refugees—a population at elevated risk for mental health disorders [...] Read more.
Although the relationship between attachment and mental health has been widely studied, no systematic review has focused specifically on refugee populations. Objectives: This systematic review examines associations between attachment patterns and psychological distress in refugees—a population at elevated risk for mental health disorders due to forced displacement and trauma. Methods: Following PRISMA guidelines. we searched PubMed, PsycINFO, and Web of Science (last search: 5 October 2024). Studies were included if they examined the relationship between attachment and psychological distress or disorders in refugees, presented empirical data, were peer-reviewed, were published from 2004 onward in English, and met quality criteria based on CASP and JBI checklists. Studies were excluded if they did not focus on refugees, lacked empirical data, did not assess both attachment and psychological distress, were not peer-reviewed, or consisted of grey literature. A narrative synthesis was conducted. Results: Of 2.951 records, 11 studies with 1.319 participants met inclusion criteria. Five studies examined adults, four children, and two adolescents. Insecure and unresolved attachment were consistently linked to higher psychological distress, particularly PTSD, especially in adults. In children, insecure attachment was associated with parental mental health problems and dysfunctional parenting, whereas secure attachment buffered the effects of parental PTSD. Discussion: Limitations include small sample sizes, cultural and linguistic complexity, inconsistent definitions of “refugee”, and varied assessment methods. Conclusions: Attachment insecurity is strongly associated with psychological distress in refugees, mirroring patterns in Western clinical populations. Findings support the integration of attachment-informed approaches into refugee mental health care. Funding: This review was funded by the Köhler Stiftung and registered in PROSPERO (CRD42024590759). Full article
(This article belongs to the Section Neuropsychology)
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25 pages, 333 KiB  
Review
AI-Driven Advances in Parkinson’s Disease Neurosurgery: Enhancing Patient Selection, Trial Efficiency, and Therapeutic Outcomes
by José E. Valerio, Guillermo de Jesús Aguirre Vera, Maria P. Fernandez Gomez, Jorge Zumaeta and Andrés M. Alvarez-Pinzon
Brain Sci. 2025, 15(5), 494; https://doi.org/10.3390/brainsci15050494 - 9 May 2025
Viewed by 458
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by motor and non-motor dysfunctions that severely compromise patients’ quality of life. While pharmacological treatments provide symptomatic relief in the early stages, advanced PD often requires neurosurgical interventions, such as deep brain stimulation (DBS) [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by motor and non-motor dysfunctions that severely compromise patients’ quality of life. While pharmacological treatments provide symptomatic relief in the early stages, advanced PD often requires neurosurgical interventions, such as deep brain stimulation (DBS) and focused ultrasound (FUS), for effective symptom management. A significant challenge in optimizing these therapeutic strategies is the early identification and recruitment of suitable candidates for clinical trials. This review explores the role of artificial intelligence (AI) in advancing neurosurgical and neuroscience interventions for PD, highlighting the ways in which AI-driven platforms are transforming clinical trial design and patient selection. Machine learning (ML) algorithms and big data analytics enable precise patient stratification, risk assessment, and outcome prediction, accelerating the development of novel therapeutic approaches. These innovations improve trial efficiency, broaden treatment options, and enhance patient outcomes. However, integrating AI into clinical trial frameworks presents challenges such as data standardization, regulatory hurdles, and the need for extensive validation. Addressing these obstacles will require collaboration among neurosurgeons, neuroscientists, AI specialists, and regulatory bodies to establish ethical and effective guidelines for AI-driven technologies in PD neurosurgical research. This paper emphasizes the transformative potential of AI and technological innovation in shaping the future of PD neurosurgery, ultimately enhancing therapeutic efficacy and patient care. Full article
13 pages, 1252 KiB  
Article
Effectiveness and Safety of CGRP-Targeted Therapies Combined with Lifestyle Modifications for Chronic Migraine in Korean Pediatric Patients: A Retrospective Study
by Ji-Hoon Na, Hayoon Jeon, Ji-Eun Shim, Hyunjoo Lee and Young-Mock Lee
Brain Sci. 2025, 15(5), 493; https://doi.org/10.3390/brainsci15050493 - 8 May 2025
Viewed by 373
Abstract
Background/Objectives: Pediatric chronic migraine (CM) is a debilitating condition with challenging management due to diagnostic complexities and a lack of evidence-based treatment. Calcitonin gene-related peptide (CGRP)-targeted therapies have transformed adult CM management, but their use in pediatric populations is underexplored. This study evaluated [...] Read more.
Background/Objectives: Pediatric chronic migraine (CM) is a debilitating condition with challenging management due to diagnostic complexities and a lack of evidence-based treatment. Calcitonin gene-related peptide (CGRP)-targeted therapies have transformed adult CM management, but their use in pediatric populations is underexplored. This study evaluated the safety and efficacy of CGRP-targeted therapies combined with structured lifestyle modifications in Korean pediatric patients with CM. Methods: This retrospective study examined 10 pediatric CM patients treated at Gangnam Severance Hospital from 2021 to 2024. Inclusion criteria were as follows: (1) Pediatric Migraine Disability Assessment Scale (PedMIDAS) score ≥ 30, (2) >2 failed preventive therapies, and (3) ≥8 migraine days per month. Patients received CGRP monoclonal antibodies or antagonists, alongside sleep, dietary, and exercise interventions. Changes in migraine burden, neuropsychological outcomes, and adherence to lifestyle interventions were assessed over 12 months. Results: Migraine frequency significantly decreased from a median of 26.5 to 14 days per month (p < 0.001); PedMIDAS scores declined from 58.5 to 48.0 (p = 0.037); and acute analgesic use was reduced from 14 to 5 days per month (p < 0.001). Adherence to lifestyle interventions improved significantly (p < 0.001). No serious adverse events were reported, and minor side effects, such as injection site pain and dizziness, were self-limiting. Conclusions: CGRP-targeted therapies, combined with structured lifestyle modifications, safely and effectively reduce migraine burden in pediatric CM patients. These therapies have facilitated sustainable improvements in management and support their integration into comprehensive pediatric CM care. This study highlights the importance of integrating pharmacologic and lifestyle-based approaches for holistic pediatric migraine management. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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18 pages, 298 KiB  
Review
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
Viewed by 392
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  
Article
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
Viewed by 215
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  
Article
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
Viewed by 195
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  
Editorial
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
Viewed by 366
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  
Systematic 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
Viewed by 250
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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