Brain Sciences

18 pages, 840 KB

Open AccessArticle

Effects of a Single Sub-Anesthetic Dose of Ketamine in Tobacco Use Disorder: An Active-Placebo, Randomized Crossover Study

by Nathan R. Luzum, Marcia H. McCall, Charlotte Talley Boyd, Heather Columbano, Edward Ip, Santiago Saldana, Alison H. Oliveto and Merideth Addicott

Brain Sci. 2026, 16(5), 496; https://doi.org/10.3390/brainsci16050496 (registering DOI) - 30 Apr 2026

Abstract

Background/Objectives: A sub-anesthetic dose of ketamine has shown promise in reducing craving, withdrawal symptoms, and use of drugs such as alcohol, cocaine, and opioids among individuals with substance use disorders. Ketamine’s therapeutic potential for tobacco use is unknown. Here, we investigated a single [...] Read more.

Background/Objectives: A sub-anesthetic dose of ketamine has shown promise in reducing craving, withdrawal symptoms, and use of drugs such as alcohol, cocaine, and opioids among individuals with substance use disorders. Ketamine’s therapeutic potential for tobacco use is unknown. Here, we investigated a single sub-anesthetic dose among adults with tobacco use disorder who were not interested in changing their smoking behavior. Methods: Utilizing a randomized, within-subject crossover, double-blinded, counter-balanced, midazolam-controlled design, participants (n = 18) received a 0.71 mg/kg infusion of ketamine and a 0.025 mg/kg infusion of midazolam (i.e., active placebo) at least two weeks apart. Participants were asked to abstain from smoking after the infusions until the post-infusion sessions, 1 day following infusion, where participants completed measures of smoking behavior, craving, and withdrawal symptoms. Participants continued to record their smoking behavior over the 7 days following infusion. Participants also completed a semi-structured qualitative interview regarding their experiences. Results: Compared to midazolam, ketamine infusion led to a non-significant reduction (p = 0.10, ƞ_p² = 0.153) in the number of cigarettes smoked during the requested abstinence period. Following this period, there were no significant differences in ad lib smoking. Ketamine showed no effect on craving or withdrawal symptoms. Participants reported more intense psychological experiences following ketamine infusion (p < 0.001, ƞ_p² = 0.830) and about half reported it felt easier to abstain from smoking after the ketamine infusion. Conclusions: While well tolerated, these findings suggest ketamine has little to no direct effect on quantitative measures of cigarette smoking, craving, or withdrawal. However, the qualitative measures suggest ketamine improves mood and reduces craving in some individuals for several days. Future studies should investigate whether ketamine can indirectly support smoking cessation among individuals with comorbid psychiatric indications for ketamine treatment. Full article

(This article belongs to the Special Issue Risks and Mechanisms in Addiction Neuroscience Informing Treatment)

20 pages, 783 KB

Open AccessReview

Parental ADHD as a Mechanistic Barrier to Behavioral Parent Training Implementation: An Intergenerational Framework for Addressing Childhood ADHD

by Lauren M. Friedman, Gabrielle Fabrikant-Abzug and Lindsay C. Chromik

Brain Sci. 2026, 16(5), 495; https://doi.org/10.3390/brainsci16050495 (registering DOI) - 30 Apr 2026

Abstract

Behavioral parent training (BPT) is a front-line psychosocial treatment for childhood ADHD, yet its real-world effectiveness is often constrained by parents’ ability to consistently implement learned strategies. Parental ADHD is a prevalent and mechanistically important factor shaping both parenting behavior and child treatment [...] Read more.

Behavioral parent training (BPT) is a front-line psychosocial treatment for childhood ADHD, yet its real-world effectiveness is often constrained by parents’ ability to consistently implement learned strategies. Parental ADHD is a prevalent and mechanistically important factor shaping both parenting behavior and child treatment response. Among parents with ADHD, deficits in executive functioning and emotion regulation, abilities essential for consistent and effective BPT implementation, often interfere with parents’ ability to apply learned strategies. Consequently, parental ADHD predicts reduced in-home skill use and attenuated child treatment gains, positioning it as a potentially critical, treatment-relevant risk factor. This narrative review synthesizes evidence on the intergenerational transmission of ADHD-related impairments, the impact of parental ADHD on parenting practices, and the role of parental ADHD as a moderator of BPT outcomes. We also examine existing approaches to addressing parental ADHD within the context of child BPT, including both pharmacological and psychosocial strategies, and evaluate their implications for parenting and child response. Building on this, we propose an intergenerational reconceptualization of psychosocial care for childhood ADHD in which parental functioning is routinely assessed and supported within BPT. Promising directions include integrating CBT-informed strategies to scaffold parents’ cognitive and regulatory processes, incorporating digital health tools that provide just-in-time guidance at the point of parenting performance, and tailoring BPT emphasis for families affected by multigenerational ADHD. Ultimately, embedding parent-focused supports within BPT may be essential for strengthening treatment impact, durability, and real-world effectiveness for many children and families. Full article

(This article belongs to the Special Issue Addressing ADHD in Children: Contemporary Treatment Strategies)

21 pages, 404 KB

Open AccessReview

Feeling Like a Woman: Interoception and the Objectified Body

by Tomi-Ann Roberts, James W. Pennebaker and Benita Jackson

Brain Sci. 2026, 16(5), 494; https://doi.org/10.3390/brainsci16050494 (registering DOI) - 30 Apr 2026

Abstract

Much of the interoception literature assumes that people can accurately detect their heart rate, stomach contractility, muscle tension, and other biological cues. This is not true. Instead, interoception is an active integrative psychological process where the feeling of one’s internal state emerges from [...] Read more.

Much of the interoception literature assumes that people can accurately detect their heart rate, stomach contractility, muscle tension, and other biological cues. This is not true. Instead, interoception is an active integrative psychological process where the feeling of one’s internal state emerges from physiological signals, contextual cues, and the social and cultural experiences of living in a body. Thinking of interoception this way shifts the focus from measuring accuracy at detecting biological signaling to studying lived experience. One such experience is the widespread objectification of women’s bodies. Living in a body that is chronically evaluated creates a particular form of self-consciousness. Here, we propose that self-objectification redirects attention toward the body, potentially reshaping both the allocation of attention to internal sensations and their interpretation and thereby offering a theoretical account of paradoxes in the interoception literature, such as women’s lower detection accuracy but higher symptom reporting, and mismatches between subjective and physiological reports of menopausal hot flashes. We consider implications for women’s health, including reproductive health, ACL injury risk, and chronic pain. Our framework suggests that “feeling like a woman” reflects an interoceptive experience shaped significantly by objectification, with important consequences for well-being. Full article

(This article belongs to the Special Issue Interoception and Women’s Health)

14 pages, 785 KB

Open AccessArticle

Association Between Freezing of Gait and Sleep Quality in People with Parkinson’s Disease

by Tracy Milane, Edoardo Bianchini, Lanfranco De Carolis, Antonio Suppa, Marco Salvetti, Clint Hansen, Massimo Marano, Domiziana Rinaldi and Nicolas Vuillerme

Brain Sci. 2026, 16(5), 493; https://doi.org/10.3390/brainsci16050493 - 30 Apr 2026

Abstract

Background/Objectives: Freezing of gait (FOG) and sleep disturbances are common in people with Parkinson’s disease (PwPD). A bidirectional association between them has been suggested, but quantitative evaluations are scarce. This study aimed to compare sleep disturbances in mild-to-moderate PwPD with (PD+FOG) and [...] Read more.

Background/Objectives: Freezing of gait (FOG) and sleep disturbances are common in people with Parkinson’s disease (PwPD). A bidirectional association between them has been suggested, but quantitative evaluations are scarce. This study aimed to compare sleep disturbances in mild-to-moderate PwPD with (PD+FOG) and without FOG (PD−FOG), and to assess the association between FOG severity and sleep parameters. Methods: Data from 54 PwPD with disease stage <4 and no severe cognitive decline were included (27 PD+FOG and 27 propensity score-matched for age, sex, and disease duration PD−FOG). Demographics and clinical variables were collected. Clinical assessment included the new freezing of gait questionnaire (NFOG-Q), Parkinson’s Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS) and Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Mann–Whitney U, Fisher’s exact and Spearman’s tests were used for group comparisons and correlations, respectively. Results: Significant differences were observed between PD+FOG and PD−FOG groups in MDS-UPDRS part II (p = 0.011) and part IV (p = 0.011), with higher scores in PD+FOG participants. No significant differences were found in PDSS-2 or ESS between the two groups. A significant moderate positive correlation was found between NFOG-Q score and PDSS-2 (ρ = 0.416; p = 0.044) in PD+FOG participants. Conclusions: FOG severity was positively associated with sleep disturbances within the PD+FOG group. However, no significant difference in sleep quality or excessive daytime sleepiness was found between PD+FOG and PD−FOG after propensity score matching. PD+FOG participants experienced more severe motor complications and greater impairment in daily activities compared to PD−FOG. Full article

(This article belongs to the Section Sleep and Circadian Neuroscience)

11 pages, 526 KB

Open AccessArticle

Firefighters’ Expertise in Locating Sounds

by Isabel Tissieres, Stephanie Clarke and Sonia Crottaz-Herbette

Brain Sci. 2026, 16(5), 492; https://doi.org/10.3390/brainsci16050492 - 30 Apr 2026

Abstract

Background: Firefighters search for survivors in low-visibility environments and have documented expertise in spatial orientation and wayfinding. No studies so far have investigated their ability to make use of auditory spatial cues. Methods: The performance of 41 professional firefighters and 24 control subjects [...] Read more.

Background: Firefighters search for survivors in low-visibility environments and have documented expertise in spatial orientation and wayfinding. No studies so far have investigated their ability to make use of auditory spatial cues. Methods: The performance of 41 professional firefighters and 24 control subjects to localise sounds played in a dark environment at 9 azimuthal positions was assessed using (i) meaningless single sounds and (ii) meaningful sounds presented with two simultaneous distractors. Localisation errors were analysed with a 3-way ANOVA Task × Position × Group. Results: The analysis yielded significant main effects of Task, Position and Group. The localisation errors tended to be smaller when localising meaningless single sounds (main effect Task), for items presented at central as compared to peripheral positions (main effect Position), and by firefighters rather than controls (main effect Group). The interactions Position × Group and Task × Position were significant; firefighters performed more accurately at peripheral positions than controls, and meaningless single sounds yielded fewer localisation errors at the periphery than meaningful sounds presented with distractors. Conclusions: Professional firefighters perform better than controls at explicit localisation of sounds, including in conditions where sound objects need to be segregated from distractors by spatial cues. These results suggest that firefighters have acquired expertise in the explicit and implicit use of auditory spatial cues. The proficiency of firefighters needs to be taken into consideration when planning and carrying out interventions. Full article

(This article belongs to the Special Issue Plasticity of Sensory Cortices: From Basic to Clinical Research)

21 pages, 8696 KB

Open AccessArticle

Homocysteine Drives Hippocampal Blood–Brain Barrier Disruption and Cognitive Decline Under Chronic Stress via DNA Hypomethylation of Cav1.2

by Mao-Yang Zhou, Jin-Shan Li, Zhao-Xin Sun, Jie Yin, Yun Zhao, Fang Xie, Xue Wang, Sheng-Hui Zhang, Zhao-Wei Sun and Ling-Jia Qian

Brain Sci. 2026, 16(5), 491; https://doi.org/10.3390/brainsci16050491 - 30 Apr 2026

Abstract

Background: Chronic stress is a major risk factor for cognitive decline and blood–brain barrier (BBB) disruption, yet the underlying molecular mechanisms remain elusive. This study aimed to investigate the specific role of the metabolic intermediate homocysteine (Hcy) in chronic stress-induced BBB dysfunction and [...] Read more.

Background: Chronic stress is a major risk factor for cognitive decline and blood–brain barrier (BBB) disruption, yet the underlying molecular mechanisms remain elusive. This study aimed to investigate the specific role of the metabolic intermediate homocysteine (Hcy) in chronic stress-induced BBB dysfunction and cognitive impairment. Methods: We utilized a male Sprague-Dawley rat model of chronic unpredictable mild stress (CUMS) and administered vitamin B complex to lower Hcy levels in vivo. Regional Hcy accumulation, BBB permeability, and cognitive behaviors were assessed. In vitro, primary rat brain microvascular endothelial cells (BMECs) were exposed to Hcy to evaluate barrier-forming function, transcriptomic alterations, DNA methylation patterns, Cav1.2 expression, and reactive oxygen species (ROS) production. Results: CUMS selectively induced BBB hyperpermeability and significant Hcy accumulation predominantly within the rat hippocampus, which correlated intimately with cognitive deficits. Lowering Hcy levels via vitamin B supplementation successfully restored hippocampal BBB integrity and alleviated cognitive impairment. In addition, elevated Hcy severely impaired the barrier function of BMECs. Mechanistically, Hcy reduced global DNA methylation in BMECs and specifically induced targeted DNA hypomethylation at the intro region of Cacna1c. This epigenetic shift caused the transcriptional derepression and overexpression of the Cav1.2 calcium channel. Upregulated Cav1.2 subsequently triggered a robust ROS burst, leading to tight junction degradation. Conclusions: Our findings unveil a novel metabolic–epigenetic axis where Hcy-driven Cacna1c hypomethylation directly disrupts BMECs function to dismantle the hippocampal BBB. Lowering Hcy or targeting this Hcy-Cav1.2 pathway establishes a promising therapeutic strategy for mitigating stress-related neurovascular damage and cognitive disorders. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

15 pages, 1683 KB

Open AccessArticle

Microsurgical Anatomy of the Posterior Commissure and Habenular Commissure in the Human Cadaveric Brain

by Aysegul Esen Aydin, Mehmet Emin Akdeniz and Orhun Mete Cevik

Brain Sci. 2026, 16(5), 490; https://doi.org/10.3390/brainsci16050490 - 30 Apr 2026

Abstract

Background/Objectives: The posterior commissure (PC) and habenular commissure (HC) are fine-caliber midline fiber bundles located within the epithalamic roof of the third ventricle. Their small size and deep anatomical position render them vulnerable during fiber dissection, and it is difficult to delineate reliably [...] Read more.

Background/Objectives: The posterior commissure (PC) and habenular commissure (HC) are fine-caliber midline fiber bundles located within the epithalamic roof of the third ventricle. Their small size and deep anatomical position render them vulnerable during fiber dissection, and it is difficult to delineate reliably with conventional diffusion MRI. To define a reproducible microsurgical strategy for three-dimensional exposure of the PC and HC, and to evaluate their tractographic representation using high-resolution diffusion template data. Methods: Four formalin-fixed adult cadaveric brains were prepared using a modified Klingler technique and underwent systematic microsurgical fiber dissection focused on preservation of the epithalamic roof and midline commissures. Diffusion MRI data from the Human Connectome Project (HCP-1065) were reconstructed in MNI space using q-space diffeomorphic reconstruction in DSI Studio to attempt deterministic tractographic reconstruction of the PC and HC. Results: In all specimens, the PC was identified as a compact transverse bundle superior to the rostral cerebral aqueduct within the inferior pineal lamina. The HC appeared as a thinner band superior to the pineal recess, interconnecting the bilateral habenular nuclei and separated from the PC by the hypothalamic sulcus. A midline-prioritized dissection sequence facilitated preservation of commissural continuity. Deterministic tractography reproduced adjacent peduncular trajectories but failed to consistently reconstruct discrete HC or PC streamlines. Conclusions: Cadaveric fiber dissection remains the most reliable method for studying the fine commissural anatomy of the epithalamus. A midline-first, roof-preserving strategy enhances visualization of the PC and HC and may have implications for posterior third ventricular surgery and stereotactic targeting. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

19 pages, 949 KB

Open AccessArticle

Perceptual Temporal Structure Supports Rhythm Learning and Enhances Theta Oscillations When Perception and Action Are Dissociated

by Xue Weng, Yang Lu, Xinyue Zhao, Haoran Jiang, Lin Li and Xiuyan Guo

Brain Sci. 2026, 16(5), 489; https://doi.org/10.3390/brainsci16050489 - 30 Apr 2026

Abstract

Background: Rhythmic knowledge enables the precise timing of actions in dynamic environments. Although rhythm learning has been extensively studied, it remains debated whether such learning arises primarily from the perceptual encoding of rhythmic inputs or from the repetitive execution of periodic actions. Methods: [...] Read more.

Background: Rhythmic knowledge enables the precise timing of actions in dynamic environments. Although rhythm learning has been extensively studied, it remains debated whether such learning arises primarily from the perceptual encoding of rhythmic inputs or from the repetitive execution of periodic actions. Methods: To address this question, we developed a temporal-rhythm serial reaction time (TR-SRT) paradigm that dissociates rhythmic structures in perceptual inputs from the timing of motor responses. Across three experiments, participants learned rhythms under visuomotor (Experiment 1, N = 27), visual-only (Experiment 2, N = 26), or motor-only (Experiment 3, N = 26) conditions while electroencephalography was recorded. Results: Behavioral learning slopes revealed robust rhythm learning in both the visuomotor and visual-only conditions, whereas no learning emerged when rhythmic structure was confined to motor timing alone. Post-learning awareness tests further indicated that the acquired rhythmic knowledge was predominantly implicit. Consistently, global (whole-brain) theta-band magnitude (4.8–5.2 Hz) was enhanced only in the conditions that supported rhythm learning. Conclusions: These findings indicate that rhythm learning depends primarily on perceptual temporal structure rather than the repetition of rhythmic actions and identify increased global theta oscillations as a neural signature of this perceptually driven and largely implicit learning process. Full article

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

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14 pages, 1165 KB

Open AccessArticle

An ERP Study of Modality-Specific Effects on Emotional Word Processing

by Yue Huang, Xiaogen Liao and Chuanbin Ni

Brain Sci. 2026, 16(5), 488; https://doi.org/10.3390/brainsci16050488 - 30 Apr 2026

Abstract

Background/Objectives: Sensory experiences and emotional information contribute to conceptual knowledge. Compared to exteroceptive modality (e.g., visual, auditory), interoceptive modality predominates in the representation of emotional concepts. However, few studies have examined the interoceptive modality-specific effects on emotional word processing. Additionally, questions remain about [...] Read more.

Background/Objectives: Sensory experiences and emotional information contribute to conceptual knowledge. Compared to exteroceptive modality (e.g., visual, auditory), interoceptive modality predominates in the representation of emotional concepts. However, few studies have examined the interoceptive modality-specific effects on emotional word processing. Additionally, questions remain about when emotional valence interacts with sensory experiences during the processing of emotional words, and to what extent these words are grounded in different sensory experiences. Methods: To address these gaps, the present ERP study investigated how sensory information (interoception and vision) influences emotional word processing in a lexical decision task. Results: Behavioral results showed significant differences between interoceptive and visual words, as well as between positive and negative valence. A trend toward an interaction between sensory modality and emotional valence was also observed. ERP results indicated that negative words elicited a more positive-going P2 than positive words. Significantly smaller N400 amplitudes were observed for interoceptive words than visual words in the positive condition. Negative visual words evoked enhanced LPC amplitudes compared with both negative interoceptive words and positive visual words. Conclusions: The present findings suggest a dynamic pattern of valence effects in emotional word processing, characterized by a negativity bias and a positivity bias at different stages. Furthermore, our findings highlight that interoception promotes the semantic retrieval and integration of emotional words. This study provides empirical support for the modality-specific hypothesis within the framework of interoceptive embodied cognition and offers novel implications for future research on emotional word processing. Full article

(This article belongs to the Section Neurolinguistics)

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46 pages, 1236 KB

Open AccessReview

Evolving Landscape of Glioblastoma Research: Integrating Therapeutic Advances and Diagnostic Frontiers

by Nirupama A. Sabnis, Luke C. Cooksey, Hareesh Jayakumar, Mariana Moguel Mendez, Ezek Mathew, Roland Max Petty, Amalendu Ranjan, Luis Colon-Perez, Rob Dickerman, Porunelloor A. Mathew and Bruce A. Bunnell

Brain Sci. 2026, 16(5), 487; https://doi.org/10.3390/brainsci16050487 - 30 Apr 2026

Abstract

Glioblastoma (GB) remains the most aggressive primary brain malignancy, with the Stupp regimen persisting as the standard of care for nearly two decades despite poor survival outcomes. This review was synthesized by extensively reviewing and analyzing the literature from PubMed, Scopus, and Web [...] Read more.

Glioblastoma (GB) remains the most aggressive primary brain malignancy, with the Stupp regimen persisting as the standard of care for nearly two decades despite poor survival outcomes. This review was synthesized by extensively reviewing and analyzing the literature from PubMed, Scopus, and Web of Science to evaluate the emerging promising therapeutic and diagnostic strategies for combating GB. Results indicate significant progress in molecularly targeted therapies, biomimetic nanocarriers, and advanced radiotherapy. While immunotherapeutic approaches, such as checkpoint inhibitors and vaccines, show variable clinical success, the integration of bioinformatics and machine learning has significantly enhanced treatment response prediction. Furthermore, advances in radiomics and molecular imaging have improved the differentiation between true tumor progression and pseudoprogression, potentially reducing invasive diagnostic requirements. Additionally, other emerging and investigational adjuvant therapeutic approaches have shown promise. We conclude that, while multimodal strategies integrating molecular and computational approaches offer a path toward personalized GB management, significant barriers—namely tumor heterogeneity and the blood–brain barrier—persist. Future research must prioritize precision-based combinatorial models to successfully translate these preclinical advancements into improved clinical outcomes for patients. Full article

(This article belongs to the Topic Advances in High Grade Glioma Research)

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9 pages, 1016 KB

Open AccessArticle

Infarct Laterality Patterns in Relation to A1 Segment Hypoplasia/Aplasia According to Etiological Subtype

by Junpei Nagasawa, Tatsuhiro Yokoyama, Ryuichi Okamoto, Junya Ebina, Mari Shibukawa, Takehisa Hirayama and Osamu Kano

Brain Sci. 2026, 16(5), 486; https://doi.org/10.3390/brainsci16050486 - 30 Apr 2026

Abstract

Background: The Circle of Willis (CoW) is a key collateral pathway that enables communication between the anterior and posterior cerebral circulations. However, anatomical variations in the A1 segment of the anterior cerebral artery, such as hypoplasia or aplasia, can alter hemodynamics and may [...] Read more.

Background: The Circle of Willis (CoW) is a key collateral pathway that enables communication between the anterior and posterior cerebral circulations. However, anatomical variations in the A1 segment of the anterior cerebral artery, such as hypoplasia or aplasia, can alter hemodynamics and may compromise this collateral function. While incomplete CoW configurations have been linked to aneurysm formation and altered patterns of hemorrhage, their role in the distribution of cerebral infarctions remains controversial. We aimed to explore the association between A1 segment hypoplasia/aplasia and infarct laterality across different etiological subtypes. Methods: We retrospectively analyzed patients with unilateral anterior circulation infarction admitted between April 2017 and March 2023. The CoW was assessed by magnetic resonance angiography (MRA). A1 segment hypoplasia was defined as a segment diameter <1 mm, and A1 aplasia was defined as non-visualization on MRA. The side with hypoplasia or aplasia was defined as the minor side, and the contralateral side as dominant. We assessed whether infarction occurred on the minor or dominant side. Results: Among 198 patients with unilateral anterior circulation infarction classified as lacunar, cardioembolic stroke (CES), or embolic stroke of undetermined source (ESUS), 30% had A1 hypoplasia or aplasia, with similar prevalence across subtypes. Infarcts occurred on the A1 dominant side in 53% of lacunar, 55% of ESUS, and 75% of CES cases. Although this difference did not reach statistical significance (p = 0.43), it should be interpreted with caution given the limited sample size. Conclusions: The rates of A1 hypoplasia and aplasia were similar across stroke types. No statistically significant association was identified. The findings remain inconclusive given the limited sample size. These results should be considered exploratory and hypothesis-generating. Full article

(This article belongs to the Section Neurorehabilitation)

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22 pages, 2042 KB

Open AccessReview

Lysophospholipids in Synucleinopathies: A Conceptual Framework Linking Proteostasis and Neuroinflammatory Signaling

by Tamotsu Tsukahara, Hisao Haniu and Yoshikazu Matsuda

Brain Sci. 2026, 16(5), 485; https://doi.org/10.3390/brainsci16050485 - 30 Apr 2026

Abstract

Synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies, are characterized by progressive α-synuclein (α-Syn) aggregation accompanied by chronic neuroinflammatory changes. However, the mechanistic relationship between disrupted proteostasis and inflammatory signaling remains incompletely defined and may vary across disease stages and clinical subtypes. [...] Read more.

Synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies, are characterized by progressive α-synuclein (α-Syn) aggregation accompanied by chronic neuroinflammatory changes. However, the mechanistic relationship between disrupted proteostasis and inflammatory signaling remains incompletely defined and may vary across disease stages and clinical subtypes. Lysophospholipids (LPLs) are bioactive lipids derived from membrane phospholipids that participate in diverse cellular processes. These functions are primarily mediated through G protein-coupled receptor (GPCR) signaling, but may also involve direct effects on membrane organization and biophysical properties. In addition to receptor-mediated pathways, the surrounding lipid environment may influence protein behavior, although its role in neurodegenerative processes remains to be fully elucidated. Within this framework, LPLs can be considered not only as signaling molecules but also as modulators of the cellular environment in which proteostasis and inflammatory responses occur. In this review, we adopt a lipid-centered perspective in which LPLs occupy an interface between lipid signaling, protein aggregation, and neuroinflammation. Rather than acting as a single initiating factor, altered lipid metabolism is likely to contribute through multiple interconnected pathways. Although current evidence is largely derived from preclinical studies, it supports a role for lipid-related mechanisms, particularly in early stages of synucleinopathy. Full article

(This article belongs to the Special Issue New Approaches to Prevent Neuropsychiatric Disorders Through the Control of Neuroinflammation)

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13 pages, 4314 KB

Open AccessReview

Combined Striatal Dopaminergic and Cardiac Sympathetic Imaging in Parkinson’s Disease

by Louis Versweyveld, Greet Vanderlinden, Wim Vandenberghe, Aline Delva and Koen Van Laere

Brain Sci. 2026, 16(5), 484; https://doi.org/10.3390/brainsci16050484 - 30 Apr 2026

Abstract

Background/Objectives: Imaging of both cardiac sympathetic denervation and nigrostriatal dopaminergic degeneration can support the diagnosis of Parkinson’s disease (PD). However, their temporal relationship and combined diagnostic value remain unclear. This review addresses (1) whether nigrostriatal degeneration and cardiac sympathetic denervation are correlated in [...] Read more.

Background/Objectives: Imaging of both cardiac sympathetic denervation and nigrostriatal dopaminergic degeneration can support the diagnosis of Parkinson’s disease (PD). However, their temporal relationship and combined diagnostic value remain unclear. This review addresses (1) whether nigrostriatal degeneration and cardiac sympathetic denervation are correlated in PD and (2) the comparative and combined diagnostic accuracy of striatal dopaminergic and cardiac sympathetic imaging in PD. Methods: We searched PubMed (October 2025) for studies assessing both a striatal dopaminergic and a cardiac sympathetic imaging biomarker in the same PD cohort, supplemented by citation chaining. Diagnostic accuracy studies were evaluated using QUADAS-2. Results: Nineteen studies met the inclusion criteria. Ten studies examined within-subject associations; six reported significant correlations ranging from weak to strong (ρ ~0.2–0.8). Two studies observed a significant correlation for the akinetic-rigid subtype but not for the tremor-dominant subtype of PD. Ten studies compared diagnostic accuracies, five of which used pre-defined thresholds and consistently found higher sensitivity for [¹²³I]FP-CIT SPECT (78–100%) compared to [¹²³I]MIBG scintigraphy (65–82%), but higher specificity for [¹²³I]MIBG (range 75–100%) than for [¹²³I]FP-CIT (range 11–73%). Adding [¹²³I]MIBG scintigraphy to [¹²³I]FP-CIT SPECT generally increased specificity but had inconsistent effects on overall accuracy. QUADAS-2 revealed substantial risks of patient selection bias, data-driven thresholds, and limited blinding. Conclusions: Reported correlations between nigrostriatal dopaminergic degeneration and cardiac sympathetic denervation in PD are inconsistent, likely reflecting both methodological heterogeneity and real variation between phenotypes. There may be a stronger correlation in the akinetic-rigid phenotype. Dopaminergic imaging is more sensitive in early PD, while cardiac sympathetic imaging is more specific for differentiating PD from atypical Parkinsonian syndromes. However, study designs greatly restrict the generalizability of reported diagnostic accuracies. Full article

(This article belongs to the Special Issue The Role of Multimodal Imaging in Assessing the Biology and Staging of Neurodegenerative Disorders)

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14 pages, 335 KB

Open AccessReview

Mindfulness Practice and Increases in Gray Matter Density, Gray Matter Volume, and Cortical Thickness: A Scoping Review

by Colin Rafter, Erika McCarthy, Curt Stilp and Jason Brumitt

Brain Sci. 2026, 16(5), 483; https://doi.org/10.3390/brainsci16050483 - 30 Apr 2026

Abstract

Background/Objectives: Mindfulness-based interventions (MBIs) have been linked to psychological and cognitive benefits, yet evidence for their impact on brain structure remains sparse. Neuroimaging suggests MBIs may alter gray matter volume (GMV), density (GMD), and cortical thickness (CT). The purpose of this scoping [...] Read more.

Background/Objectives: Mindfulness-based interventions (MBIs) have been linked to psychological and cognitive benefits, yet evidence for their impact on brain structure remains sparse. Neuroimaging suggests MBIs may alter gray matter volume (GMV), density (GMD), and cortical thickness (CT). The purpose of this scoping review was to investigate structural neuroplasticity following MBIs. Methods: Following PRISMA-ScR guidelines, databases were searched for studies published between 2010 and 2023 that used structural MRI to assess structural brain changes in subjects after receiving MBIs. Nine studies met inclusion criteria, including five randomized controlled trials. Results: Mindfulness interventions ranged from 10 h of training to long-term practice spanning decades. Structural changes were most consistently observed in the insula, prefrontal cortex, hippocampus, posterior cingulate, and temporoparietal junction, regions tied to interoception, executive control, and self-referential processing. The greatest structural changes were reported in studies implementing multi-month interventions or long-term meditative practice. Conclusions: MBIs are associated with structural brain changes across a limited and heterogeneous body of literature, but current evidence is insufficient to draw firm conclusions regarding causality or consistency of effect. Larger, diverse, and more methodologically rigorous trials with extended follow-up are needed to clarify the durability and significance of observed changes. Full article

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17 pages, 246 KB

Open AccessArticle

Healthcare Professionals’ Perceptions of the Palliative Care Needs of Patients with Severe Brain Injury and Their Caregivers: A Qualitative Study

by Flavia Primosa, Serena Cazzato, Lucia Gotri, Romano Marchini, Orejeta Diamanti, Laura Iacorossi and Andreina Saba

Brain Sci. 2026, 16(5), 482; https://doi.org/10.3390/brainsci16050482 - 30 Apr 2026

Abstract

Background/Objectives: Severe brain injuries generate complex, long-term needs requiring intensive physical, cognitive and relational care. These conditions also profoundly affect families, who often experience emotional distress, uncertainty and a heavy caregiving burden. Although neuro-palliative care is increasingly recognised, the early integration of [...] Read more.

Background/Objectives: Severe brain injuries generate complex, long-term needs requiring intensive physical, cognitive and relational care. These conditions also profoundly affect families, who often experience emotional distress, uncertainty and a heavy caregiving burden. Although neuro-palliative care is increasingly recognised, the early integration of palliative care for this population remains limited. This study aimed to explore healthcare professionals’ perceptions of the palliative care needs of patients with severe brain injuries and their caregivers and to identify factors that hinder or facilitate early palliative care implementation in specialised settings. Methods: An interpretive qualitative study was conducted using Reflexive Thematic Analysis. Fifteen semi-structured narrative interviews were carried out with healthcare professionals working in specialised hospital units in Northern Italy. Data were analysed inductively through an iterative and reflexive process following Braun and Clarke’s six phases. Methodological rigour and transparency were ensured using the COREQ checklist. Results: Five themes were identified: (1) intensive, individualised patient care needs with complex communication issues; (2) palliative needs centred on dignity, quality of life and early integrated management; (3) caregivers’ involvement and expectation-related difficulties; (4) continuous or anticipatory grief requiring structured psychological support; (5) facilitators and barriers influencing care pathways. Conclusions: Healthcare professionals identify intertwined and evolving palliative care needs in both patients with severe brain injuries and their families. The findings highlight the perceived importance of early, integrated and multidisciplinary neuro-palliative care models focused on dignity, symptom relief and sustained emotional support. Full article

(This article belongs to the Special Issue Palliative Care for Patients with Severe Neurological Impairment)

17 pages, 300 KB

Open AccessArticle

Communicating in Palliative Care for Neurodegenerative Diseases: A Qualitative Study on Professional–Family Interactions

by Barbara Rizzi, Maria Chiara Gandini, Andreina Saba, Giada Lonati and Angela Recchia

Brain Sci. 2026, 16(5), 481; https://doi.org/10.3390/brainsci16050481 - 29 Apr 2026

Abstract

Background/Objectives: In Palliative Care (PC), the communication is an essential aspect of care becoming particularly significant at the end-of-life. In neurodegenerative diseases, communication involves additional complexity due to prolonged disease trajectories, early cognitive decline, and frequent loss of decision-making capacity. The aim [...] Read more.

Background/Objectives: In Palliative Care (PC), the communication is an essential aspect of care becoming particularly significant at the end-of-life. In neurodegenerative diseases, communication involves additional complexity due to prolonged disease trajectories, early cognitive decline, and frequent loss of decision-making capacity. The aim of this study was to explore PC healthcare professionals’ experiences with communication process and relational dynamics involving families of patients with advanced and terminal neurogenerative disease. Methods: The study design was qualitative, using semi-structured interviews and reflexive thematic analysis. Participants were healthcare professionals directly involved in communication with the family. Results: Twenty PC professionals were interviewed, generating 792 coded excerpts. Four themes emerged: (1) Navigating PC in neurodegenerative diseases, highlighting shift from oncology-centred palliative models toward neuropalliative care, with distinctive relational challenges; (2) Navigating conversations between professionals and families, describing multidisciplinary communication, core clinical and emotional topics, and goal-oriented decision-making in contexts of impaired patient capacity; (3) Facing challenges in health care professional–family communication, including conspiracy of silence, absence of Advance Treatment Directives (ATD) or Shared Care Planning (SCP), and limited collaboration with neurologists; and (4) Envisioning methods for improvement, emphasizing the need for disease-specific competencies, advanced relational skills, interprofessional coordination, and support for professionals’ emotional wellbeing. Conclusions: Communication in neurodegenerative palliative care is an ongoing relational and interpretative process requiring professionals to mediate uncertainty, surrogate decision-making, and caregiver burden. Strengthening disease-specific communication skills, early integrated PC, and structured interprofessional collaboration may enhance shared decision-making, caregiver support, and care continuity. Full article

(This article belongs to the Special Issue Palliative Care for Patients with Severe Neurological Impairment)

16 pages, 407 KB

Open AccessSystematic Review

Efficacy of Non-Invasive Brain Stimulation in Improving Working Memory in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Systematic Review

by Wilson Alexander Zambrano Vélez, Johanna Lilibeth Alcívar Ponce, Walter Gonzalo Bailón Bailón, Harol Marcial Castillo del Valle and Rocisela Adriana Baquerizo Quirumbay

Brain Sci. 2026, 16(5), 480; https://doi.org/10.3390/brainsci16050480 - 29 Apr 2026

Abstract

Background/Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with working memory deficits linked to frontoparietal alterations. Non-invasive brain stimulation (NIBS) is a potential intervention to modulate neuroplasticity and improve this executive function. In this study, we aimed to evaluate the clinical efficacy of non-invasive [...] Read more.

Background/Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with working memory deficits linked to frontoparietal alterations. Non-invasive brain stimulation (NIBS) is a potential intervention to modulate neuroplasticity and improve this executive function. In this study, we aimed to evaluate the clinical efficacy of non-invasive brain stimulation techniques (tDCS/rTMS) for strengthening working memory in children and adolescents with ADHD. Methods: This systematic review adhered to the PRISMA 2020 guidelines, with a search of Scopus and Web of Science conducted to identify relevant studies published between 2011 and 2026. Eligibility criteria, defined a priori, included original empirical studies (RCTs and quasi-experimental designs) focusing on pediatric populations (≤18 years) diagnosed with ADHD. Eligible interventions involved tDCS or rTMS with explicit working memory outcomes. Only peer-reviewed articles published in English or Spanish were included. Reviews, case reports, and studies exclusive to adults were excluded. Data on application parameters, durability, and safety were extracted for narrative synthesis. Results: Six studies met the criteria. Both tDCS and rTMS targeting the left dorsolateral prefrontal cortex showed improvements in working memory, particularly in executive components measured using digit span backward and N-back tasks. High-frequency rTMS (10 Hz) with repeated sessions showed more consistent effects, while tDCS showed modest and variable improvements. Evidence regarding long-term effects was limited. Both techniques were well-tolerated, with mild and transient adverse events. Conclusions: NIBS shows promise as a complementary intervention to improve working memory in pediatric ADHD; however, current evidence is limited. Larger, standardized, longitudinal trials are required to confirm its efficacy and clinical utility. Full article

(This article belongs to the Topic Advancing Neuroscience and Brain Sciences: Insights from the 5th International Electronic Conference on Brain Sciences & 1st International Electronic Conference on Neurosciences (IECBS-IECNS 2026))

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13 pages, 824 KB

Open AccessArticle

Event Source Modulates the Valence Focus of Optimism Bias: Evidence from Behavior and ERPs

by Chunsheng Wang, Baojing Zhang and Jun Ren

Brain Sci. 2026, 16(5), 479; https://doi.org/10.3390/brainsci16050479 - 29 Apr 2026

Abstract

Background: Optimism bias is the tendency to expect more positive and fewer negative events for themselves versus for others. However, it remains unclear whether the valence focus of this bias depends on how events unfold (i.e., through autonomous choice vs. external imposition). This [...] Read more.

Background: Optimism bias is the tendency to expect more positive and fewer negative events for themselves versus for others. However, it remains unclear whether the valence focus of this bias depends on how events unfold (i.e., through autonomous choice vs. external imposition). This study used behavioral and ERP measures to investigate how the event source modulates the valence focus of optimism bias. Methods: Thirty participants completed a 2 (event source: autonomous choice vs. external imposition) × 2 (valence: positive events vs. negative events) × 2 (target: self vs. other) task while an EEG was recorded. The late positive potential (LPP) was analyzed as a neural index of self-relevance. Results: Behaviorally, autonomous choice preserved optimism bias for positive events (self > other, p = 0.023), whereas external imposition induced it for negative events (self < other, p = 0.006). Under autonomous choice, the LPP mirrored this pattern (enhanced for self-positive events, p = 0.038). Under external imposition, the LPP showed only a valence-general self-bias (main effect of target, p = 0.014). Conclusions: These preliminary findings suggest that event sources may influence the valence focus of optimism bias. Under autonomous choice, the bias is positive-focused. Under external imposition, it shifts to negative-focused. This dissociation between behavioral and neural patterns is consistent with dual patterns in optimism bias expression, though further research is needed. Full article

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

12 pages, 3224 KB

Open AccessArticle

Serum MAP1A as a Potential Biomarker for Autism Spectrum Disorder

by Jiwon Jeong, Seung Hyeon Lee and Dongsun Park

Brain Sci. 2026, 16(5), 478; https://doi.org/10.3390/brainsci16050478 - 29 Apr 2026

Abstract

Background/Objectives: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition currently diagnosed through subjective behavioral assessments. Objective blood-based biomarkers are needed to enable earlier and more accurate identification. In this study, we aimed to identify synapse-related biomarkers associated with ASD and evaluate [...] Read more.

Background/Objectives: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition currently diagnosed through subjective behavioral assessments. Objective blood-based biomarkers are needed to enable earlier and more accurate identification. In this study, we aimed to identify synapse-related biomarkers associated with ASD and evaluate their potential as serum-based indicators. Methods: RNA sequencing was performed on the cerebellum, hippocampus, and cerebral cortex of a valproic acid-induced rat model of ASD to identify differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were conducted to explore associated pathways. Synapse-related hub genes were selected by comparison with the SFARI autism gene database, and the serum expression of candidate proteins was assessed using Western blotting. Results: A total of 692, 813, and 1059 DEGs were identified in the cerebellum, hippocampus, and cortex, respectively. Enrichment analyses highlighted dendrite development, postsynaptic density, and glutamatergic synapse pathways as significantly affected. Six synaptic hub genes were prioritized, among which serum MAP1A expression was significantly elevated in the ASD rats. Conclusions: These findings suggest that serum MAP1A may represent a potential biomarker reflecting synaptic abnormalities in ASD. Further validation in human cohorts and integration into a multi-marker framework are warranted to account for the heterogeneity of ASD. Full article

(This article belongs to the Topic Autism: Molecular Bases, Diagnosis and Therapies, 3rd Volume)

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