Brain Sciences

24 pages, 1145 KB

Open AccessEditor’s ChoiceReview

Biochemical Pathways of Neuroplasticity in Sport Skill Acquisition: From Neuroscience to Coaching Practice

by Patrizia Proia, Alessandro Sclafani, Andrea Pagliaro, Anna Alioto, Alessia Boatta, Sara Baldassano, Giuseppe Messina, Erika Loi, Cristina Cortis, Armando Sangiorgio and Alessandra Amato

Brain Sci. 2026, 16(7), 694; https://doi.org/10.3390/brainsci16070694 - 30 Jun 2026

Viewed by 2185

Abstract

Background/Aim: Motor skill acquisition is the foundation of athletic performance, from the novice learning a new technique to the elite athlete executing complex movements automatically under pressure. Although classical models have defined the neural substrates of motor control—the cerebellum for error correction, the [...] Read more.

Background/Aim: Motor skill acquisition is the foundation of athletic performance, from the novice learning a new technique to the elite athlete executing complex movements automatically under pressure. Although classical models have defined the neural substrates of motor control—the cerebellum for error correction, the basal ganglia for action selection, and the primary motor cortex (M1) for execution—emerging evidence suggests that motor learning is the result of the dynamic interaction of multiple parallel processes rather than a linear hierarchy. This narrative review integrates classical neuroanatomical knowledge with contemporary findings on multisite plasticity, with a particular focus on sport-specific adaptations. Methods: We examined three core learning mechanisms operating in parallel: error-based learning (cerebellar-dependent, driven by sensory prediction errors), reinforcement learning (striatal-dependent, driven by reward prediction errors and dopamine), and use-dependent learning (cortical-dependent, driven by mere repetition). We also summarize the biochemical pathways supporting these learning processes, including glutamatergic LTP-like cortical plasticity, cerebellar mGluR1–PKC–LTD signaling, dopaminergic corticostriatal plasticity, BDNF–TrkB-dependent neurotrophic mechanisms, growth-factor signaling, and exercise-induced muscle–brain communication. Results: We then propose a spatiotemporal model in which the relative contribution of each network shifts dynamically across the three stages of skill acquisition, from the early cognitive/strategic phase to the late automatic phase characteristic of elite performance. At the molecular level, these stage-dependent adaptations are supported by synaptic strengthening and weakening mechanisms, reward-dependent dopamine signaling, neurotrophic and growth-factor-mediated remodeling, and peripheral metabolic/myokine signals that modulate brain plasticity during training and recovery. Special attention is given to contextual and sport-specific adaptations, using the paradigmatic example of elite swimmers who demonstrate enhanced short-interval intracortical inhibition (SICI) selectively in the aquatic environment, reflecting long-term sport-induced neuroplasticity. Conclusions: Understanding these dynamic network mechanisms has direct implications for coaching, training periodization, and the development of targeted neuromodulatory interventions to accelerate skill acquisition and optimize athletic performance. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

► Show Figures

Figure 1

42 pages, 1370 KB

Open AccessEditor’s ChoiceSystematic Review

The Dual Facets of Emotion Perception in Adult Attachment Representations: A Systematic Review on Impathy and Empathy

by Dirk W. Eilert, Philipp Mensah and Anna Buchheim

Brain Sci. 2026, 16(6), 651; https://doi.org/10.3390/brainsci16060651 - 19 Jun 2026

Viewed by 2107

Abstract

Background/Objectives: Emotion processing has increasingly been conceptualized as a transdiagnostic mechanism underlying psychological adaptation and psychopathology. From an attachment perspective, individual differences in emotion perception may be rooted in internal working models shaped by early relationships. This systematic review synthesized the literature on [...] Read more.

Background/Objectives: Emotion processing has increasingly been conceptualized as a transdiagnostic mechanism underlying psychological adaptation and psychopathology. From an attachment perspective, individual differences in emotion perception may be rooted in internal working models shaped by early relationships. This systematic review synthesized the literature on the relationship between adult attachment representations and intrapersonal emotion perception (Impathy) and interpersonal emotion perception (Empathy). Methods: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was conducted on 9 February 2026, in PsycINFO, PsycArticles, and PubMed. Studies were included if they investigated adolescents or adults, assessed attachment representations using narrative-based measures (Adult Attachment Interview (AAI) or Adult Attachment Projective Picture System (AAP)), and examined intrapersonal and/or interpersonal emotion perception. Findings were synthesized narratively, and a random-effects meta-analysis examined the association between attachment security and reflective functioning. Results: Thirty-eight studies, including 2736 participants, met the inclusion criteria. Across studies, attachment representations were systematically associated with intrapersonal and interpersonal emotion perception. The strongest evidence emerged for reflective functioning, the Impathy dimensions Perceiving and Understanding, and cognitive-empathic processes. Secure attachment representations were consistently associated with higher reflective functioning and more adaptive emotion perception, whereas insecure and especially unresolved attachment representations were linked to impairments in emotional self-awareness, alexithymia-related processes, differentiated emotional understanding, and cognitive-empathic processing. The meta-analysis showed a large positive association between secure attachment representations and reflective functioning (k = 8; r = 0.64, 95% CI [0.50, 0.74]). Conclusions: Attachment representations appear systematically associated with the perceptual foundations of emotion processing. Intrapersonal and interpersonal emotion perception may therefore represent attachment-sensitive processes relevant to psychological adaptation, psychopathology, caregiving, and therapeutic change. Full article

(This article belongs to the Topic The Relationship Between Bodily, Autonomic, and Communicative Behaviors and the Experiential and Cognitive Aspects of Emotion)

► Show Figures

Graphical abstract

27 pages, 2771 KB

Open AccessEditor’s ChoiceReview

Neuroinflammatory Mechanisms in Depression: From Biomarkers to Anti-Inflammatory Therapy

by Sixian Li, Qixian Wang, Junhua Li and Qi Luo

Brain Sci. 2026, 16(6), 632; https://doi.org/10.3390/brainsci16060632 - 12 Jun 2026

Cited by 1 | Viewed by 1663

Abstract

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric disorder with a high prevalence. Neuroinflammation may define biologically distinct patient subgroups with different mechanisms, clinical phenotypes, and treatment responses. This narrative review integrates current evidence around three linked questions: how neuroinflammatory processes [...] Read more.

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric disorder with a high prevalence. Neuroinflammation may define biologically distinct patient subgroups with different mechanisms, clinical phenotypes, and treatment responses. This narrative review integrates current evidence around three linked questions: how neuroinflammatory processes contribute to depression, how biomarkers can identify clinically relevant inflammatory phenotypes, and how these findings can inform anti-inflammatory treatment strategies. The major mechanisms discussed include microglial activation and neuroimmune signaling, hypothalamic–pituitary–adrenal axis dysregulation and glucocorticoid receptor resistance, kynurenine pathway alterations, and cytokine-driven impairment of neurogenesis and synaptic plasticity. These pathways interact with stress responses, neurotransmitter systems, and neuronal function, while their expression may vary according to sex, age, hormonal status, disease stage, and treatment exposure. These interconnected pathways may contribute to depressive symptoms by disrupting neurotransmitter systems and impairing neural plasticity. In addition, this review discusses several candidate biomarkers, including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and transforming growth factor-β1 (TGF-β), which may support patient stratification, treatment prediction, and assessment of target engagement. Clinical trials of anti-inflammatory agents have shown inconsistent and generally modest effects in unselected MDD populations. By integrating mechanistic evidence with biomarker-guided therapeutic implications, this review aims to clarify how neuroinflammatory research may inform more precise and individualized treatment strategies for depression. Full article

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

► Show Figures

Figure 1

17 pages, 503 KB

Open AccessEditor’s ChoiceArticle

Differences in Spatial Cognition and Motor–Cognitive Integration by Side of Onset in People with Parkinson’s Disease

by Ejew Beyla Kim, Morgan Brianna Patrick, Liang Ni, J. Lucas McKay and Madeleine Eve Hackney

Brain Sci. 2026, 16(6), 619; https://doi.org/10.3390/brainsci16060619 - 10 Jun 2026

Viewed by 1185

Abstract

Background: Spatial cognition, a skill paramount to survival, is impaired in Parkinson’s disease (PD) but has been little researched. Spatial cognition is utilized during motor–cognitive integration, which impacts daily functioning and quality of life in PD. As PD is a unilateral-onset condition, spatial–cognitive [...] Read more.

Background: Spatial cognition, a skill paramount to survival, is impaired in Parkinson’s disease (PD) but has been little researched. Spatial cognition is utilized during motor–cognitive integration, which impacts daily functioning and quality of life in PD. As PD is a unilateral-onset condition, spatial–cognitive and motor–cognitive ability may differ by side of onset. Spatial cognition is suggested to be modulated by the right hemisphere; thus, we hypothesize to observe worse spatial and motor–cognitive performance by people with left-onset PD (LOPD) than right-onset PD (ROPD). Methods: 216 participants with PD were recruited (LOPD = 107; M = 62; mean age = 69.80 ± 8.5). Spatial outcomes were collected via the body position spatial task (BPST), Reverse Corsi Blocks, and visuospatial items of the Montreal Cognitive Assessment (MoCA); motor–cognitive outcomes were collected by a Trails test, a Four Square Step Test (FSST), and a Timed Up and Go test. An independent t-test and the Mann–Whitney U test compared outcome variables between onset groups. Results: No significant differences were found between onset groups. Exploratory subgroup analyses revealed differences. Significantly worse performance by LOPD in single- and dual-task TUG was found within people with bilateral symptoms and postural instability (Hoehn & Yahr stage, >2; LOPD, N = 33; single, p = 0.001; dual, p = 0.021) and worse performance in single-task TUG in people with MoCA < 18 (LOPD, N = 5; single, p = 0.036) and people with freezing of gait (FOGQ, >0; LOPD, N = 14, p = 0.048). Significantly larger DTC by LOPD was found within frequent freezers (FOGQ, >3; LOPD, N = 9; p = 0.003). Conclusions: LOPD may tend to perform worse in motor–cognitive tasks among subgroups of those with more severe symptoms, i.e., those at later stages of disease. These findings may have implications for prognoses of those with LOPD versus ROPD and suggest that those with LOPD may have worse long-term outcomes in spatial cognition and motor–cognitive integration. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

► Show Figures

Figure 1

17 pages, 4347 KB

Open AccessEditor’s ChoiceArticle

A Low-Cost Modular Multi-Region Electrode for Distributed Network Recording and Brain State Decoding

by Bo-Yu Wang, Yu Chen, Bin Wang, Wen Xie, Jia-Yi Zeng, Yi-Zheng Wang and Chun-Kui Zhang

Brain Sci. 2026, 16(6), 606; https://doi.org/10.3390/brainsci16060606 - 1 Jun 2026

Viewed by 1555

Abstract

Background: Precise decoding of brain states is essential for closed-loop neuromodulation, but current electrodes and recording strategies are inadequate. Multi-region recording offers network-level advantages over single-region approaches, yet remains underdeveloped due to the lack of low-cost, flexible multi-region electrodes and standardized workflows. Methods: [...] Read more.

Background: Precise decoding of brain states is essential for closed-loop neuromodulation, but current electrodes and recording strategies are inadequate. Multi-region recording offers network-level advantages over single-region approaches, yet remains underdeveloped due to the lack of low-cost, flexible multi-region electrodes and standardized workflows. Methods: We developed a low-cost, modular, silica capillary tube-based 16-channel electrode for multi-region local field potential (LFP) recording in small animals, along with an integrated workflow for spectral analysis, functional connectivity assessment, and machine learning-based brain state decoding. Results: Our electrode design enables flexible customization of target regions and low-cost (~19.43 USD/unit) assembly without specialized equipment. In vivo validation in rats targeting eight emotional network nuclei achieved 79.2% implantation accuracy, with stable LFP recordings maintained for over 3 months. In a reserpine-induced depression model, spectral analysis revealed state-specific oscillatory changes including reduced alpha power in the infralimbic cortex. Inter-regional functional connectivity analysis further captured drug-induced network-level synchronization changes. We also developed a machine learning pipeline with random forest classifier that achieved ~96.4% accuracy in decoding brain states from the multi-region signals. Conclusions: This modular multi-region electrode provides a practical, adaptable, and low-cost platform for long-term distributed network recording, supporting quantitative LFP analysis, functional connectivity assessment, and high-accuracy brain state decoding, laying a technical foundation for preclinical closed-loop neuromodulation research. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

► Show Figures

Figure 1

20 pages, 368 KB

Open AccessEditor’s ChoiceReview

Review of Emotion Regulation Psychosocial Interventions for Children and Adolescents with ADHD

by Rosanna Breaux, Charity Majusiak, Annah R. Cash, Stephanie N. Pham and Michelle Le

Brain Sci. 2026, 16(6), 560; https://doi.org/10.3390/brainsci16060560 - 25 May 2026

Viewed by 2671

Abstract

Emotion dysregulation (ED), emotional responses that impair goal-directed behavior, have been argued to be a core characteristic of attention-deficit/hyperactivity disorder (ADHD), and are associated with functional impairment beyond the core symptoms of ADHD. Additionally, deficits in emotion regulation (ER), the ability to increase, [...] Read more.

Emotion dysregulation (ED), emotional responses that impair goal-directed behavior, have been argued to be a core characteristic of attention-deficit/hyperactivity disorder (ADHD), and are associated with functional impairment beyond the core symptoms of ADHD. Additionally, deficits in emotion regulation (ER), the ability to increase, decrease, or maintain the intensity, duration, and trajectory of emotions are common among children and adolescents with ADHD. Despite this, treatment efforts to improve such ER abilities and to decrease ED in youths with ADHD have been limited, particularly during the adolescent developmental period. Clinical knowledge was used to inform PsycInfo and Google Scholar searches to identify the relevant literature. This narrative review discusses transdiagnostic interventions (cognitive behavioral therapy, the Unified Protocol for Children/Adolescents, dialectical behavior therapy, acceptance and commitment therapy, and mindfulness-based interventions) that can be used to target ER in ADHD, and interventions for youths with ADHD that either have been found to improve ER outcomes or that directly target ER/ED for youths with ADHD and their families. We end our review by highlighting the gaps and limitations in the existing literature prior to drawing conclusions and making recommendations for future research in this important area. Full article

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

39 pages, 812 KB

Open AccessEditor’s ChoiceSystematic Review

Noninvasive Brain Stimulation Techniques and Their Efficacy in Treating Cognition and Memory in Mild Cognitive Impairment and Alzheimer’s Disease—A Systematic Review

by Hector P. Valverde, Benjamin J. Clark, Jeremy Hogeveen and Vincent P. Clark

Brain Sci. 2026, 16(5), 527; https://doi.org/10.3390/brainsci16050527 - 15 May 2026

Viewed by 1801

Abstract

Background/Objectives: The growing aging population is susceptible to cognitive and memory impairment, most commonly due to Alzheimer’s disease, with no cures currently available. Noninvasive brain stimulation (NIBS) techniques may serve to improve cognition and delay catastrophic memory loss. Methods: A systematic review of [...] Read more.

Background/Objectives: The growing aging population is susceptible to cognitive and memory impairment, most commonly due to Alzheimer’s disease, with no cures currently available. Noninvasive brain stimulation (NIBS) techniques may serve to improve cognition and delay catastrophic memory loss. Methods: A systematic review of NIBS research on cognitive impairment was carried out using PubMed, with additional backward citation searching. A total of 81 studies using NIBS were included. Conclusions: The reviewed studies show that NIBS holds promise in improving memory deficits in patients with cognitive impairment. While the longevity of benefits from transcranial electrical stimulation appears limited, its short-term effects may provide benefits when used consistently. Transcranial magnetic stimulation appears to provide longer-lasting benefits. Transcranial focused ultrasound stimulation may also provide further benefits through more precise targeting of deeper brain structures compared to other NIBS techniques. Together, these results suggest that NIBS shows promise for the treatment of symptoms related to cognitive and memory impairment, and may help to alleviate some of the growing issues associated with the increasing level of Alzheimer’s disease in an aging population. Full article

(This article belongs to the Special Issue Advanced Applications of Non-Invasive Stimulation for Therapeutics)

► Show Figures

Figure 1

21 pages, 865 KB

Open AccessEditor’s ChoiceReview

When the Clock Shifts: A Comprehensive Review of Daylight-Saving Time (DST), Circadian Disruption, and Neuropsychological Risk in Chronic Mental Illness

by Liahm Blank, Joshua Khorsandi, Elizabeth England-Kennedy, Srikanta Banerjee, Karen Kopera-Frye, Roberto Sagaribay, Jagdish Khubchandani and Kavita Batra

Brain Sci. 2026, 16(5), 522; https://doi.org/10.3390/brainsci16050522 - 14 May 2026

Viewed by 2056

Abstract

Daylight Saving Time (DST) creates abrupt, externally imposed circadian disruptions that can impair sleep regulation, hormonal balance, cognitive performance, and emotional stability. Although these effects are known in the general population, individuals with chronic mental illness, whose circadian systems are often intrinsically dysregulated, [...] Read more.

Daylight Saving Time (DST) creates abrupt, externally imposed circadian disruptions that can impair sleep regulation, hormonal balance, cognitive performance, and emotional stability. Although these effects are known in the general population, individuals with chronic mental illness, whose circadian systems are often intrinsically dysregulated, may face increased neuropsychological consequences. This comprehensive review synthesizes evidence from chronobiology, psychiatry, neuroscience, and population health to examine how DST-related circadian misalignment impacts cognitive functioning, mood regulation, suicidality risk, and symptom exacerbation across psychological disorders such as depression, anxiety disorders, bipolar disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and psychotic disorders. Following the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines, a search of PubMed, PsycINFO, Scopus, and Google Scholar was conducted to identify studies published from 2000–2026 examining DST, circadian rhythm disruption, neuropsychological outcomes, and chronic mental illness. Empirical, theoretical, and mechanistic studies were included to ensure comprehensive synthesis. Across conditions, DST, particularly spring forward transitions, is associated with increased sleep disturbance, impaired executive functioning, reduced attention and working memory, heightened emotional reactivity, increased depressive symptoms, elevated risk of manic episodes, and short-term increases in suicidality. Neurobiological mechanisms include altered melatonin secretion, cortisol dysregulation, Hypothalamus Pituitary Axis (HPA-axis) activation, and clock-gene desynchrony. DST may function as a modifiable negative environmental influence capable of affecting neuropsychological functioning in vulnerable populations. These findings underscore the need for clinical awareness, preventive strategies, and policy reconsiderations, including calls to eliminate seasonal time changes. Standardizing DST-related research outcomes and expanding longitudinal, multi-site studies will be essential for advancing this emerging field. Full article

(This article belongs to the Section Neuropsychology)

► Show Figures

Figure 1

14 pages, 1073 KB

Open AccessEditor’s ChoiceArticle

Submaximal Unilateral Arm Cycling Produces Transient but Not Sustained Changes in Corticospinal Excitability in the Homologous Muscles of the Non-Exercised Limb

by Hiwa Rahmani, Hamid Amoozi, Ibrahim Saif Allah Ahmed Refai and Kevin E. Power

Brain Sci. 2026, 16(5), 514; https://doi.org/10.3390/brainsci16050514 - 12 May 2026

Viewed by 1809

Abstract

Purpose: This study investigated whether an acute bout of submaximal unilateral arm cycling elicits sustained changes in corticospinal excitability (CSE) and short-interval intracortical inhibition (SICI) in the homologous muscles of the non-exercised, resting limb. A secondary aim was to determine whether prior exercise [...] Read more.

Purpose: This study investigated whether an acute bout of submaximal unilateral arm cycling elicits sustained changes in corticospinal excitability (CSE) and short-interval intracortical inhibition (SICI) in the homologous muscles of the non-exercised, resting limb. A secondary aim was to determine whether prior exercise induces a preconditioning effect on subsequent motor output. Methods: Transcranial magnetic stimulation was used to assess motor evoked potential (MEP) amplitude (single-pulse) and SICI (paired-pulse) in the resting non-dominant flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles of healthy participants. Measures were obtained at rest, during a 10 min bout of unilateral arm cycling (30 W, 60 rpm), and throughout a 20 min recovery period. To assess potential preconditioning effects, measurements were repeated during a second 2 min cycling bout following a 20 min recovery. Rest and exercise conditions were analyzed separately due to differences in stimulation intensity (RMT vs. AMT). Results: Unilateral arm cycling did not produce sustained changes in CSE or SICI in the resting limb when both arms were at rest. Furthermore, unilateral arm cycling followed by a 20 min recovery period did not result in a preconditioning effect, as CSE in the resting limb was not enhanced during a subsequent unilateral arm cycling bout. Conclusions: Submaximal unilateral arm cycling induces a transient, state-dependent increase in CSE to the non-exercised limb without altering SICI. The absence of SICI modulation suggests that this facilitation is not mediated by GABA_A-dependent intracortical mechanisms, and may instead reflect modulation arising from spinal and interlimb locomotor circuitry. The lack of sustained post-exercise effects indicates that low-intensity arm cycling does not induce a plasticity-permissive cortical state, highlighting a distinction between transient, movement-dependent facilitation and longer-lasting exercise-induced neuroplasticity. Full article

(This article belongs to the Special Issue Brain Plasticity and Motor Control—3rd Edition)

► Show Figures

Figure 1

21 pages, 308 KB

Open AccessEditor’s ChoiceReview

Schizophrenic Consciousness in the Light of the Phenomenological Epoché: A Foundational Map for Psychiatry

by Giovanni Stanghellini

Brain Sci. 2026, 16(5), 498; https://doi.org/10.3390/brainsci16050498 - 1 May 2026

Viewed by 1856

Abstract

This review explores the hypothesis that schizophrenic symptoms may be understood not as isolated deficits, but as interconnected manifestations of a structural reorganization of consciousness. The premises of this work are grounded in a comparative matrix that suggests an underlying “consanguinity” between the [...] Read more.

This review explores the hypothesis that schizophrenic symptoms may be understood not as isolated deficits, but as interconnected manifestations of a structural reorganization of consciousness. The premises of this work are grounded in a comparative matrix that suggests an underlying “consanguinity” between the philosopher’s voluntary epoché—the suspension of the natural attitude performed to study the inner workings of consciousness—and the involuntary “unworlding” passively experienced in schizophrenia. By exploring this shared ontological ground, the text suggests how specific phenomenological shifts, such as the collapse of the “vital drive,” may manifest as clinical markers; this process may eventually lead to an involuntary “transcendental reduction” where the mind’s internal machinery becomes an object of forced awareness. Building on these premises, the review tentatively outlines several key achievements. It addresses the substrate-subjectivity gap by linking biological sensory-binding failures to the onset of involuntary hyper-reflexivity. Regarding structural loss and gain of function, it suggests that the psychotic transition involves a simultaneous erosion of common-sense coherence and an intensified receptivity to unfiltered perceptual fragments, which may trigger a search for metaphysical meanings. In terms of a therapeutic synthesis, it proposes exploring the conversion of “artless decentering” into a manageable, strategic distance through mindfulness and person-centered position-taking. Finally, it discusses a potential nosographic evolution, advocating for future diagnostic classifications that prioritize the experiencing self and qualitative insights to support a more translational and empathetic approach to psychiatry. Full article

(This article belongs to the Section Neuropsychiatry)

13 pages, 456 KB

Open AccessEditor’s ChoiceReview

Regenerative Medicine Strategies for Spinal Cord Injury: Advances in Stem Cell Therapy

by Ahmed I. Anwar, Alaa Abd-Elsayed and Alan D. Kaye

Brain Sci. 2026, 16(5), 461; https://doi.org/10.3390/brainsci16050461 - 25 Apr 2026

Cited by 2 | Viewed by 4209

Abstract

Spinal cord injuries disrupt the motor, sensory, and autonomic functions routinely carried out by the spinal cord, with injury progressing from primary mechanical damage from the initial trauma to a secondary phase driven by inflammation and cellular cascades. This disruption significantly impacts the [...] Read more.

Spinal cord injuries disrupt the motor, sensory, and autonomic functions routinely carried out by the spinal cord, with injury progressing from primary mechanical damage from the initial trauma to a secondary phase driven by inflammation and cellular cascades. This disruption significantly impacts the patient’s ability to perform basic physiological and voluntary functions seen in a normal spinal cord, which often results in long-term disability and dependence on supportive care. Stem cell therapies, including mesenchymal stem cells, neural stem cells, and induced pluripotent stem cells, have been investigated as potential regenerative approaches that may promote repair through neuroprotection, remyelination, and axonal regeneration. Preclinical studies have demonstrated encouraging results in motor and sensory recovery following injury; however, clinical evidence remains limited and variable. Some studies report improvements in motor and sensory function post-injury, with improvements in bladder and bowel management, tissue repair, and other functions. Overall, the outcomes vary based on cell type, delivery method, and the stage of spinal cord injury. The key challenges of stem cell therapy include safety concerns and the limited number of small-scale studies currently available. Additionally, understanding the variability in therapeutic outcomes and identifying optimal treatment conditions are critical steps toward advancing stem cell therapies in spinal cord injury repair. This review aims to characterize and summarize the stem cell approach to the treatment of spinal cord injuries, while also critically highlighting the limitations of current preclinical and clinical evidence, as well as the importance of continued investigation into the long-term and functional recovery processes and possibilities, as well as the patient’s quality of life following treatment with stem cells for spinal cord injury. Full article

(This article belongs to the Special Issue Spinal Cord Injury: Biomarkers, Neuroimaging and Therapeutic Approaches)

► Show Figures

Figure 1

25 pages, 545 KB

Open AccessEditor’s ChoiceArticle

LearningRx Cognitive Training for Workplace Self-Efficacy in Adults with Post-COVID-19 Brain Fog: A Mixed-Methods Pilot Study

by Amy Lawson Moore, Edward J. Jedlicka, James C. Patterson and Christina R. Ledbetter

Brain Sci. 2026, 16(4), 410; https://doi.org/10.3390/brainsci16040410 - 11 Apr 2026

Viewed by 3078

Abstract

Background/Objectives: Cognitive dysfunction, or “brain fog”, following COVID-19 viral infection is strongly associated with diminished work capacity which disproportionality affects working-age adults. This study examined an existing method of cognitive rehabilitation training applied to adults struggling with workplace functioning and self-efficacy due to [...] Read more.

Background/Objectives: Cognitive dysfunction, or “brain fog”, following COVID-19 viral infection is strongly associated with diminished work capacity which disproportionality affects working-age adults. This study examined an existing method of cognitive rehabilitation training applied to adults struggling with workplace functioning and self-efficacy due to post-COVID-19 brain fog. Methods: Nine adults with post-COVID-19 cognitive dysfunction participated in this single arm pilot trial of a severity-adaptive cognitive training program. The participants completed 45–90 h of clinician-delivered cognitive training exercises delivered remotely in 60- to 90-min sessions, two or three times per week. The primary outcome measure was overall workplace self-efficacy with subskills of perceived workplace functioning, perception of cognitive functioning, and perception of home functioning assessed through pre and post surveys and qualitative interviews. The secondary outcome was cognitive function operationalized by an IQ score administered before and after the intervention. Results: The participants achieved significant improvements in workplace self-efficacy and cognition following cognitive training. The main qualitative themes of self-reported improvements were in executive function, health and energy, daily living activities, productivity, and socioemotional functioning. A cross-case synthesis of pre-intervention struggles, and post-intervention improvements revealed subthemes at work or school in cognitive processing and comprehension, memory, executive function, fatigue, emotional distress, confidence in work or academics, and work/academic performance impairment. As a group, the mean gain in IQ score was 10.5 points. Conclusions: This study adds to the growing body of literature examining the possibility of using cognitive rehabilitation for post-COVID-19 cognitive dysfunction impacting workplace self-efficacy and work functioning. Full article

(This article belongs to the Special Issue Cognitive Training in Health and Disease)

► Show Figures

Figure 1

16 pages, 778 KB

Open AccessEditor’s ChoiceSystematic Review

Surgical Versus Conservative Management for Carpal Tunnel Syndrome: An Updated Systematic Review of Randomised Trials

by Sara Masiero, Pasquale Arcuri, Paolo Boccolari, Elena Zorzi, Alessandro Vio, Tracy Fairplay, Davide Zanin, Fabio Vita, Danilo Donati and Roberto Tedeschi

Brain Sci. 2026, 16(4), 399; https://doi.org/10.3390/brainsci16040399 - 8 Apr 2026

Viewed by 2845

Abstract

Background: Carpal tunnel syndrome (CTS) is one of the most common entrapment neuropathies. While surgical decompression is widely considered the definitive treatment, conservative options remain clinically relevant, particularly for symptom relief and functional recovery in the short term. Objectives: To update the evidence [...] Read more.

Background: Carpal tunnel syndrome (CTS) is one of the most common entrapment neuropathies. While surgical decompression is widely considered the definitive treatment, conservative options remain clinically relevant, particularly for symptom relief and functional recovery in the short term. Objectives: To update the evidence comparing surgical versus non-surgical interventions for CTS, assessing pain, function, and clinical recovery. Design: Systematic review of randomised controlled trials (RCTs). Data Sources and Methods: Six databases (CENTRAL, MEDLINE, Embase, Cochrane Neuromuscular Register, ClinicalTrials.gov, and WHO ICTRP) were searched for RCTs published between November 2022 and January 2025. Risk of bias was assessed with RoB 2.0 and certainty of evidence with GRADE. Due to clinical heterogeneity, a narrative synthesis was performed. Results: Four RCTs (n = 1158) were included. Corticosteroid injection and percutaneous electrical nerve stimulation (PENS) appeared to provide faster symptom relief than surgery at short-term follow-up. However, surgery was associated with a higher probability of sustained recovery at 12–18 months (RR 1.36; 95% CI 1.19–1.56). Evidence for PENS was limited to one female-only trial, which restricts generalisability. Certainty of evidence was moderate for long-term outcomes and low for short-term results and safety. Conclusions: The available evidence suggests that surgery may offer more durable long-term recovery, whereas corticosteroids and PENS may be useful for short-term symptom relief. These findings should be interpreted with caution given the limited number of trials and the risk of bias in most included studies. Treatment choice should align with patient goals and recovery timelines. Registration: PROSPERO (CRD420250650789). Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

► Show Figures

Figure 1

17 pages, 578 KB

Open AccessEditor’s ChoiceReview

Dopamine and Acetylcholine in the Striatum: Circuit Interactions and Behavioral Control in Substance Use Disorders

by Oyku Dinckol, Noah H. Wenger, Aryanna Copling, Bhumiben P. Patel and Munir Gunes Kutlu

Brain Sci. 2026, 16(4), 397; https://doi.org/10.3390/brainsci16040397 - 7 Apr 2026

Cited by 1 | Viewed by 3189

Abstract

Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by persistent drug seeking and impaired behavioral control. Dopaminergic signaling has long been recognized as a central regulator of reinforcement learning, motivation, and habit formation. Addictive substances profoundly alter dopamine transmission through multiple [...] Read more.

Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by persistent drug seeking and impaired behavioral control. Dopaminergic signaling has long been recognized as a central regulator of reinforcement learning, motivation, and habit formation. Addictive substances profoundly alter dopamine transmission through multiple mechanisms. These drug-induced changes contribute to the initiation, escalation, and persistence of addictive behaviors. In addition to dopamine, the cholinergic system has emerged as an important modulator of striatal circuit function. Acetylcholine and its receptors interact extensively with dopaminergic pathways, shaping striatal signaling dynamics and influencing learning and action selection, with particularly strong relevance for nicotine dependence. In this review, we discuss how striatal dopamine and acetylcholine contribute to learning, habit formation, and addiction-related behaviors, as well as how these systems interact at the circuit level. By integrating these findings, we propose a framework for understanding how dopamine–acetylcholine interactions may influence behavioral regulation relevant to substance use disorders. Full article

(This article belongs to the Special Issue Advances in Dopamine and Cognition)

► Show Figures

Figure 1

12 pages, 1163 KB

Open AccessEditor’s ChoiceArticle

Signal Detection of Depression and Suicidality Associated with Finasteride and Dutasteride: Updated Pharmacovigilance Evidence and Recommendations for Comprehensive Psychiatric Assessment

by Stefania Chiappini, John Martin Corkery, Amira Guirguis, Alessio Mosca, Mya Murray, Davide Arillotta, Luigi Dattoli, Giovanni Martinotti, Stefania Bonaccorso, Fabrizio Schifano and Nicolò Schifano

Brain Sci. 2026, 16(4), 394; https://doi.org/10.3390/brainsci16040394 - 4 Apr 2026

Cited by 1 | Viewed by 4728

Abstract

Background/Objectives: Finasteride and dutasteride are 5α-reductase inhibitors that block the conversion of testosterone to dihydrotestosterone, reducing androgenic stimulation of tissues such as the prostate and hair follicles. Used mainly for benign prostatic hyperplasia and androgenic alopecia, finasteride selectively inhibits type-2 5α-reductase isoenzyme, [...] Read more.

Background/Objectives: Finasteride and dutasteride are 5α-reductase inhibitors that block the conversion of testosterone to dihydrotestosterone, reducing androgenic stimulation of tissues such as the prostate and hair follicles. Used mainly for benign prostatic hyperplasia and androgenic alopecia, finasteride selectively inhibits type-2 5α-reductase isoenzyme, while dutasteride inhibits both type-1 and type-2. Although sexual adverse effects like erectile dysfunction are well-documented, emerging evidence suggests possible neuropsychiatric reactions—including depression, suicidal ideation, and cognitive decline—potentially linked to reduced neurosteroid synthesis, such as that of allopregnanolone. Causality cannot be inferred from spontaneous reporting data. This study aimed to assess pharmacovigilance signals for psychopathological disorders associated with finasteride and dutasteride in the FAERS database. Methods: Cleaned FAERS data referring to years up to 2025 after deduplication were analyzed, excluding non-serious cases and those without the drug as the sole suspect (MedDra 29.0). Reporting Odds Ratios (RORs) with 95% CIs were calculated to compare psychiatric reactions between finasteride and dutasteride. Python 3.11 was used to screen and summarize relevant cases, accounting for differences in total case numbers. Results: This pharmacovigilance study analyzed FAERS data to assess the neuropsychiatric and sexual adverse reactions associated with finasteride and dutasteride. Depression, anxiety, suicidality, and libido-related issues were reported more frequently for finasteride, especially in younger men using low-dose therapy for alopecia. Potential mechanisms include reduced neurosteroid synthesis, androgen/sex-hormone axis disruption, altered hippocampal neurogenesis, and dopaminergic changes. Conclusions: A baseline psychiatric assessment and the regular monitoring of mood, sexual function, and suicidal ideation are recommended. Limitations include under-reporting, reporting bias, and a lack of incidence data. The findings underscore the need for ongoing surveillance and controlled studies to clarify the clinical significance of these signals. Full article

(This article belongs to the Special Issue From Circuits to Symptoms: Advances in Psychiatry and Brain Science)

► Show Figures

Figure 1

33 pages, 1379 KB

Open AccessEditor’s ChoiceReview

Quantum-Inspired and Non-Classical Approaches to Consciousness: Models, Evidence and Constraints

by Oscar Arias-Carrión, Emmanuel Ortega-Robles and Elías Manjarrez

Brain Sci. 2026, 16(4), 386; https://doi.org/10.3390/brainsci16040386 - 31 Mar 2026

Cited by 1 | Viewed by 3694

Abstract

Consciousness presents a structural puzzle: a unified, context-sensitive, globally integrated mode of experience emerging from distributed neural dynamics. While classical neuroscience has mapped synaptic, oscillatory, and network-level mechanisms with increasing precision, debate persists as to whether classical formalisms fully capture the integrative and [...] Read more.

Consciousness presents a structural puzzle: a unified, context-sensitive, globally integrated mode of experience emerging from distributed neural dynamics. While classical neuroscience has mapped synaptic, oscillatory, and network-level mechanisms with increasing precision, debate persists as to whether classical formalisms fully capture the integrative and contextual features of conscious processing. This review examines whether quantum principles offer explanatory leverage in two distinct senses: as formal mathematical frameworks for modeling contextual cognition, and as mechanistic hypotheses proposing biologically instantiated non-classical states. We surveyed empirical and theoretical developments spanning zero-quantum-coherence in MRI signals, entanglement-structured learning paradigms, quantum-inspired computational models, and proposed neural substrates, including microtubules, nuclear spins, and photonic architectures. Although certain findings have been interpreted as consistent with a non-classical structure, no study to date has demonstrated entanglement, long-lived coherence, or collapse dynamics in neural tissue under operational criteria comparable to those used in controlled quantum systems. Replication remains limited, biological entanglement witnesses are not yet established, and nonlinear classical dynamics can reproduce many putative quantum signatures. Accordingly, the decisive question is not whether the brain is quantum, but whether its dynamics exceed the explanatory reach of rigorously defined classical models. Progress hinges on replication, adversarial scrutiny, and operational criteria precise enough to discriminate genuine non-classical correlations from classical complexity. Whether quantum mechanisms ultimately prove necessary or refined classical models remain sufficient, this inquiry compels a deeper understanding of integration, contextuality, and the physical constraints shaping conscious experience. Full article

► Show Figures

Graphical abstract

22 pages, 360 KB

Open AccessEditor’s ChoiceReview

Psilocybin in Neuropsychiatric Disorders: Seeking Valuable Evidence in History, Pure Science, Clinical Trials and Real-World Data (RWD)

by Piotr Skalski, Katarzyna Pękacka-Falkowska, Agnieszka Pluto-Prądzyńska and Michał K. Owecki

Brain Sci. 2026, 16(4), 358; https://doi.org/10.3390/brainsci16040358 - 26 Mar 2026

Viewed by 3962

Abstract

Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)—the current gold standard in evidence-based medicine—may not adequately [...] Read more.

Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)—the current gold standard in evidence-based medicine—may not adequately capture the therapeutic complexity of psilocybin, which depends not only on pharmacological action but also on contextual, psychological, and interpersonal factors. This critical narrative review aimed to evaluate the adequacy of existing clinical research frameworks for assessing psilocybin’s therapeutic potential and to explore alternative methodologies that may better reflect real-world clinical conditions. Methods: Using the Web of Science Core Collection database, we identified and analysed the ten most cited clinical studies on psilocybin published between 2015 and 2025 inclusive. Additional literature was included through reference cross-checking, systematic reviews, meta-analyses, and interdisciplinary sources covering neurobiology, history, and real-world evidence (RWE). The review synthesizes clinical outcomes, methodological constraints, and epistemic considerations relevant to psychedelic-assisted therapy. Results: Evidence from highly cited trials demonstrates rapid and sustained antidepressant and anxiolytic effects of psilocybin, with notable benefits also observed in addiction treatment. However, significant methodological limitations were identified, including selection bias, challenges in placebo design and blinding, small sample sizes, and the underrepresentation of diverse populations. Psilocybin outcomes were strongly influenced by subjective experience and contextual factors such as set and setting. Emerging RWE studies revealed heterogeneous patterns of response and provided insights unattainable through RCTs alone. Conclusions: Psilocybin shows considerable therapeutic promise, but current RCT methodologies capture only part of its clinical effects. Comprehensive evaluation will require larger and more diverse clinical trials, long-term follow-up, standardized psychotherapeutic protocols, and the integration of RWE to reflect real-world practice. Psychedelic-assisted therapy should be conceptualized as a complex intervention that combines pharmacological and psychotherapeutic components. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

14 pages, 463 KB

Open AccessEditor’s ChoiceReview

The Relevance of Heart Rate Variability for Hypnotherapy and Psychotherapy

by Donald Moss

Brain Sci. 2026, 16(4), 352; https://doi.org/10.3390/brainsci16040352 - 25 Mar 2026

Viewed by 4452

Abstract

This review examines what constitutes heart rate variability (HRV), the relationship between HRV and the autonomic nervous system, and the physiology driving HRV. HRV is correlated with vagal nerve activity and parasympathetic nervous activation. Higher HRV is correlated with youth, active lifestyle, adaptive [...] Read more.

This review examines what constitutes heart rate variability (HRV), the relationship between HRV and the autonomic nervous system, and the physiology driving HRV. HRV is correlated with vagal nerve activity and parasympathetic nervous activation. Higher HRV is correlated with youth, active lifestyle, adaptive capacity, and good health. Next, the review examines the medical significance of HRV, especially the correlation between lower HRV and the presence of medical and psychological disorders. In general, HRV serves as a biomarker for health and disease, an index of autonomic nervous system dysregulation, an index of prefrontal cortical functionality, and a marker for psychopathology across diagnoses. Higher HRV is associated with several characteristics associated with successful psychotherapy and hypnotherapy: social engagement, compassion, emotional regulation, and cognitive flexibility. Given this association, somatic regulation should be regarded as integral to treatment alongside psychotherapy and hypnosis. Understanding HRV can enable the psychotherapist and hypnotherapist to optimize treatment. In effect, the therapist can harness the power of the brain and nervous system to better prepare the patient for therapy and to enhance the process of therapy. This review encourages therapists to utilize several strategies and interventions to increase patients’ HRV levels prior to and during therapy. The review will be most applicable for those hypnotherapists who integrate hypnosis into counseling and psychotherapy. The review describes the process by which HRV biofeedback training guides the individual to voluntarily increase HRV. It also identifies a number of lifestyle parameters and self-care practices (including self-hypnosis) that increase HRV. Encouraging lifestyle and self-care practices to increase HRV can support a greater response to hypnotherapy and psychotherapy. With additional training, hypnotherapists can integrate HRV biofeedback into a hypnosis practice. Further, several simple interventions already within the scope of most hypnosis practitioners can be utilized to enhance HRV at the beginning of a hypnotherapy process, and again during the process of therapy. Full article

(This article belongs to the Special Issue Hypnotherapy: From Basic Research to Clinical Practice)

► Show Figures

Graphical abstract

10 pages, 773 KB

Open AccessEditor’s ChoiceArticle

Inducing Lucid Dreaming Based on a Contemplative Practice of Compassion

by Daniel J. Morris, Susana G. Torres-Platas, Karen R. Konkoly, John Hirschle, Lodoe Sangpo, Thabkhe, Tenzin Legden, Lobsang Pelmo, Tenzin Pasang, Marcia Grabowecky, Robin Nusslock and Ken A. Paller

Brain Sci. 2026, 16(3), 315; https://doi.org/10.3390/brainsci16030315 - 16 Mar 2026

Cited by 2 | Viewed by 3281

Abstract

Background/Objectives: Lucid dreaming—dreaming with the awareness that one is dreaming—has been explored from many perspectives, including those of cognitive neuroscience and various ancient cultural traditions. Lucid dreaming appears within the Tibetan-Buddhist literature together with dream yoga, a set of contemplative practices aimed at [...] Read more.

Background/Objectives: Lucid dreaming—dreaming with the awareness that one is dreaming—has been explored from many perspectives, including those of cognitive neuroscience and various ancient cultural traditions. Lucid dreaming appears within the Tibetan-Buddhist literature together with dream yoga, a set of contemplative practices aimed at cultivating lucidity during dreams along with other qualities such as visual imagination, somatic awareness, and cognitive flexibility. These practices include deity visualization, which is the practice of bringing to mind a detailed image of a being whose qualities the practitioner wishes to cultivate. We examined whether it is possible to induce a lucid dream of Chenrezig, the ultimate embodiment of compassion in a Tibetan-Buddhist context. Methods: Five participants slept in the sleep laboratory for 7 overnight sessions with polysomnographic recording and auditory reminders to visualize Chenrezig during REM sleep. Results: Lucid dreams were reported by two participants. A frequent lucid dreamer with no prior Tibetan-Buddhist training experienced a lucid dream that included a visualization of Chenrezig following auditory cueing during REM sleep. A monastic participant with no prior history of lucid dreaming reported their first-ever lucid dream on the night following their laboratory session. Conclusions: This exploratory study illustrates, via collaborative research including monastic scholars trained in neuroscience, that dream content can be intentionally shaped using an approach that integrates contemplative visualization practices with modern techniques of dream engineering. Full article

(This article belongs to the Special Issue Lucid Dreaming and Psychophysiological Correlates of States of Consciousness)

► Show Figures

Figure 1

24 pages, 5034 KB

Open AccessEditor’s ChoiceReview

Multiscale Mechanisms of Exercise-Induced Neuroplasticity: From Molecular Pathways to Network Dynamics and Behavioral Adaptation

by Xue Wang, Jun Zhang, Xiaoyu Wang, Shuren Wang, Yidan Zhang, Yupeng Yang, Xuchang Zhou, Chang Liu, Junjie Liu and Mi Zheng

Brain Sci. 2026, 16(3), 294; https://doi.org/10.3390/brainsci16030294 - 6 Mar 2026

Cited by 2 | Viewed by 3482

Abstract

Exercise as a non-pharmacological measure is important to increase the brain plasticity hence improving cognitive performance as well as mental health. This narrative review describes in depth the hierarchical multiscale processes of neuroplasticity to exercise, including the presence of neurotrophic factor regulation, cellular [...] Read more.

Exercise as a non-pharmacological measure is important to increase the brain plasticity hence improving cognitive performance as well as mental health. This narrative review describes in depth the hierarchical multiscale processes of neuroplasticity to exercise, including the presence of neurotrophic factor regulation, cellular metabolic adaptations and neurotransmitter remodeling, up to the structure and functional reorganization of brain networks as seen through neuroimaging, and concluding with adaptive cognitive and behavioral outcomes. We further investigate the role of personal variations in genetic time and social environments in moderating the neuroplasticity of exercise. Furthermore, the review identifies the importance of combining multimodal visualization methods with computational models in generating accurate workout prescriptions and their potential of translation into clinical and educational practice. Lastly, the research problems and “grand challenges” are addressed, with a focus on the importance of exercise as a pleiotropic behavior-intervention and its general implications to the area of promoting brain health. Full article

(This article belongs to the Special Issue Physical Activity Across the Lifespan: Mechanisms, Interventions and Cognitive Function)

► Show Figures

Figure 1

13 pages, 886 KB

Open AccessEditor’s ChoiceReview

Transcranial Photobiomodulation for Spasticity in Pediatric Cerebral Palsy: A Scoping Review of Neurodevelopmental Considerations, Treatment Protocols, Functional Outcomes, and Methodological Gaps

by Amalio Jiménez, Frederick R. Carrick and Monèm Jemni

Brain Sci. 2026, 16(3), 272; https://doi.org/10.3390/brainsci16030272 - 28 Feb 2026

Viewed by 2854

Abstract

Background: Spasticity, affecting over 80% of children with cerebral palsy (CP), is a major source of disability. Transcranial photobiomodulation (tPBM) is a promising non-invasive neuromodulatory intervention, but evidence for its use in pediatric CP spasticity is fragmented and limited. Objective: This scoping review [...] Read more.

Background: Spasticity, affecting over 80% of children with cerebral palsy (CP), is a major source of disability. Transcranial photobiomodulation (tPBM) is a promising non-invasive neuromodulatory intervention, but evidence for its use in pediatric CP spasticity is fragmented and limited. Objective: This scoping review aimed to systematically map the literature to characterize neurodevelopmental considerations, treatment protocols, functional outcomes, and methodological gaps related to tPBM for spasticity in pediatric CP. Methods: The review followed the PRISMA extension for Scoping Reviews (PRISMA-ScR). A systematic search was performed across eight databases from January 2000 to September 2025. The PCC framework guided inclusion of studies involving children/adolescents (0–18 years) with CP and spasticity, investigating PBM with a primary focus on transcranial application. Results: From 345 records, only five primary studies (total n = 45 children) met the inclusion criteria. The evidence base is severely limited and heterogeneous, with only two of the five studies applying tPBM. A profound lack of protocol standardization was identified, with frequent reports that are internally inconsistent or contain physically implausible dosimetry reporting. Methodological quality was pre-preliminary, with no sham-controlled or adequately blinded trials. Although all studies reported reductions in spasticity and/or motor improvements, the high risk of bias prevents attribution of the effects to tPBM. Conclusions: The evidence supporting tPBM for spasticity in pediatric CP is in a pre-preliminary stage, defined by a critically small number of studies, a pervasive lack of methodological rigor, and an absence of pediatric-specific safety protocols. The field requires an immediate pivot to foundational, sham-controlled, double-blind trials with standardized dosimetry before tPBM can be considered anything other than an unproven experimental intervention. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

► Show Figures

Figure 1

22 pages, 349 KB

Open AccessEditor’s ChoiceReview

The Effect of Traumatic Brain Injury on the Gastrointestinal System: A Comprehensive Review

by Ruhi K. Shah, Justin J. Lin, Tejaswi Makkapati, Arielle A. Berkowitz and Brian D. Greenwald

Brain Sci. 2026, 16(3), 254; https://doi.org/10.3390/brainsci16030254 - 25 Feb 2026

Cited by 2 | Viewed by 4060

Abstract

Background/Objectives: Traumatic brain injury (TBI) is a significant public health concern resulting in physical, cognitive, and behavioral impairments. Emerging evidence highlights a bidirectional relationship between brain injury and gut health, known as the brain–gut axis. This paper provides a comprehensive review of current [...] Read more.

Background/Objectives: Traumatic brain injury (TBI) is a significant public health concern resulting in physical, cognitive, and behavioral impairments. Emerging evidence highlights a bidirectional relationship between brain injury and gut health, known as the brain–gut axis. This paper provides a comprehensive review of current literature exploring the relationship between TBI and various gastrointestinal (GI) pathologies, examining how brain injuries contribute to GI dysfunction and how gut health influences neurorecovery. Methods: A comprehensive search of peer-reviewed articles was conducted between March and June 2025 using databases including PubMed, Scopus, and Cochrane. Studies from 2010 onwards involving human subjects were screened. Search terms included combinations of “traumatic brain injury,” “TBI,” and “[gastrointestinal pathology].” Data regarding study design, population, GI outcomes, and proposed mechanisms were analyzed. Results: TBI triggers secondary injury cascades, including neuroinflammation, dysautonomia, and gut microbiome dysbiosis. The review identifies a wide spectrum of TBI-associated GI disorders, including dysphagia, esophageal disorders, gastric disorders, and intestinal disorders. Bowel dysfunction, manifesting as constipation or incontinence, is prevalent due to neurogenic factors and cognitive impairments. Additionally, metabolic dysregulation following TBI leads to malnutrition, hyperglycemia, and hypoglycemia, all of which impact morbidity. Conclusions: The GI system is integrally connected to TBI recovery through immune modulation and nutrient absorption. Dysfunction within the brain–gut axis, specifically altered motility, permeability, and inflammation, contributes to secondary brain injury and impedes neurological outcomes. Clinical assessment of GI dysfunction should be integrated into routine TBI care. Therapeutic strategies, including early enteral nutrition, are essential to optimize recovery and reduce systemic inflammation. Full article

(This article belongs to the Section Neurorehabilitation)

21 pages, 600 KB

Open AccessEditor’s ChoiceArticle

The Role of the Different Components of Attention on Observational Learning in Early Primary School Children: New Insights and Educational Implications

by Francesca Foti, Valentina Lucia La Rosa, Luca Pullano, Tiziana Iaquinta and Elena Commodari

Brain Sci. 2026, 16(2), 237; https://doi.org/10.3390/brainsci16020237 - 19 Feb 2026

Cited by 5 | Viewed by 2200

Abstract

Background/Objectives: Observational learning enables children to acquire new skills by observing others’ actions. Attention is widely recognized as a key supporting process and consists of multiple components that develop substantially during the early school years. Empirical evidence on the association between specific components [...] Read more.

Background/Objectives: Observational learning enables children to acquire new skills by observing others’ actions. Attention is widely recognized as a key supporting process and consists of multiple components that develop substantially during the early school years. Empirical evidence on the association between specific components of attention and observational learning remains limited. Therefore, this study examined the relationship between the main components of attention and observational learning among early primary school children. Methods: Sixty-eight children, aged 6–8, completed a computerized battery assessing the main components of attention (reaction times, simple and related to a choice; focused attention; short-term span of attention; divided and alternating attention) and an observational learning task where children observed an actor detecting a hidden spatial sequence and then reproduced it across detection phase (DP), exercise phase (EP), and automatization phase (AP). Correlational and regression analyses were conducted, controlling for age and gender. Results: Visual and visual–spatial focused attention emerged as significant predictors of performance during DP and EP, with higher levels of focused attention associated with fewer errors and repetitions. Choice reaction time showed phase-specific associations with error rates during early learning phases, whereas age was primarily related to performance during the AP. Conclusions: Observational learning in early primary school relies on specific components of attention rather than on attention as a unitary construct. Visual and visual–spatial focused attention plays a central role during the acquisition and consolidation of observed sequences, with implications for understanding learning from models and for educational practices based on demonstration. Full article

(This article belongs to the Section Developmental Neuroscience)

► Show Figures

Figure 1

18 pages, 401 KB

Open AccessEditor’s ChoiceReview

Neuropsychiatric Phenotype and Treatment Challenges in 47,XYY Syndrome: A Narrative Review with a Case Series of Adolescents

by Maria Giulia D’Acunto, Chiara Bosetti, Deianira Rinaldi, Marika Ricci, Stefano Berloffa, Gabriele Masi and Maria Mucci

Brain Sci. 2026, 16(2), 232; https://doi.org/10.3390/brainsci16020232 - 15 Feb 2026

Viewed by 4546

Abstract

Background: 47,XYY syndrome is a relatively common sex chromosome aneuploidy that remains largely underdiagnosed. While its somatic phenotype is often mild, growing evidence indicates a substantial burden of neurodevelopmental and psychiatric morbidity. However, the characterization of the neuropsychiatric phenotype across development, particularly during [...] Read more.

Background: 47,XYY syndrome is a relatively common sex chromosome aneuploidy that remains largely underdiagnosed. While its somatic phenotype is often mild, growing evidence indicates a substantial burden of neurodevelopmental and psychiatric morbidity. However, the characterization of the neuropsychiatric phenotype across development, particularly during adolescence, and the associated treatment challenges remain incomplete. Objectives: To provide a comprehensive narrative review of the neuropsychiatric phenotype of 47,XYY syndrome and to illustrate clinical complexity and treatment response through a case series of adolescents. Methods: A narrative review of the literature was conducted focusing on genetics, neurodevelopmental and psychiatric features, neuroimaging and neurophysiology findings, clinical course, and management strategies in 47,XYY syndrome. This review is complemented by a case series of adolescents with confirmed 47,XYY karyotype, evaluated for developmental history, psychiatric comorbidity and response to pharmacological and non-pharmacological interventions. Results: The literature consistently describes increased risks of language impairment, executive dysfunction, ADHD, autism spectrum traits, and emotional and behavioral dysregulation in males with 47,XYY syndrome. Psychiatric vulnerability appears to increase during adolescence and adulthood, with elevated rates of mood, psychotic, and substance use disorders. The presented cases illustrate a convergent clinical trajectory marked by early developmental delays, progressive behavioral dysregulation in adolescence and limited or inconsistent response to multiple classes of psychotropic medications, suggesting a pattern of pharmacoresistance in a subset of patients. Conclusions: 47,XYY syndrome is associated with a distinct and heterogeneous neuropsychiatric phenotype that extends beyond early neurodevelopmental disorders. Early diagnosis alone may be insufficient to prevent severe psychiatric outcomes, highlighting the need for long-term monitoring and integrated, multidisciplinary management. Further research is required to identify early predictors of high-risk trajectories and to optimize treatment strategies for this population. Full article

(This article belongs to the Special Issue Rethinking Neurodevelopmental Disorders: Beyond One-Size-Fits-All)

► Show Figures

Figure 1

25 pages, 6229 KB

Open AccessEditor’s ChoiceReview

Acute Disseminated Encephalomyelitis (ADEM): Current View into Etiopathogenesis and Clinical Features

by Klara Ferenc, Piotr Semik and Justyna Paprocka

Brain Sci. 2026, 16(2), 201; https://doi.org/10.3390/brainsci16020201 - 9 Feb 2026

Cited by 4 | Viewed by 10026

Abstract

Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system (CNS) that predominantly affects children and young adults. ADEM typically follows an infectious or, less commonly, immunization-related trigger, and despite decades of clinical observation, its etiopathogenesis remains only [...] Read more.

Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system (CNS) that predominantly affects children and young adults. ADEM typically follows an infectious or, less commonly, immunization-related trigger, and despite decades of clinical observation, its etiopathogenesis remains only partially understood. Clinically, the diagnosis of ADEM continues to pose significant challenges due to the absence of disease-specific biomarkers and its clinical and radiological overlap with other acquired demyelinating syndromes. This narrative review aims to summarize and critically discuss current knowledge on ADEM, with particular emphasis on its etiopathogenesis and clinical characteristics, highlighting the potential implications of recent research for clinical practice and management of this disease. Particular emphasis is placed on post-infectious immune mechanisms, including molecular mimicry, blood–brain barrier (BBB) disruption, loss of immune tolerance, and neuroinflammatory cascades. A wide spectrum of infectious triggers—viral, bacterial, parasitic—as well as post-vaccination, post-transplantation, paraneoplastic, metabolic, and host-related genetic factors are discussed in the context of immune dysregulation leading to CNS demyelination. We also highlight characteristic clinical and neuroimaging features that may aid in differentiating ADEM from other demyelinating syndromes, while acknowledging current diagnostic limitations. The integration of recent advances in ADEM immunopathogenesis with established clinical and radiological insights underscores the complexity of this disorder and highlights the evolving nature of current concepts regarding its diagnosis and clinical heterogeneity. Full article

(This article belongs to the Special Issue Advances in Immune-Mediated Disorders of the Nervous System in Childhood)

► Show Figures

Figure 1

17 pages, 2652 KB

Open AccessEditor’s ChoiceSystematic Review

Inconsistency in the Association Between Proton Pump Inhibitor Use and Dementia Risk: An Updated Meta-Analysis

by Tzu-Rong Peng, Hung-Hong Lin, Li-Jou Yang and Ta-Wei Wu

Brain Sci. 2026, 16(2), 159; https://doi.org/10.3390/brainsci16020159 - 29 Jan 2026

Cited by 1 | Viewed by 3606

Abstract

Background: Proton pump inhibitors (PPIs) are commonly used to manage acid-related gastrointestinal conditions. Nevertheless, growing attention has been paid to their long-term safety, especially their possible link to dementia and Alzheimer’s disease (AD). Prior research has yielded inconsistent findings, underscoring the need for [...] Read more.

Background: Proton pump inhibitors (PPIs) are commonly used to manage acid-related gastrointestinal conditions. Nevertheless, growing attention has been paid to their long-term safety, especially their possible link to dementia and Alzheimer’s disease (AD). Prior research has yielded inconsistent findings, underscoring the need for a comprehensive and current evaluation. Methods: A systematic search was conducted across PubMed, Embase (Ovid), and the Cochrane Library to identify relevant publications up to May 28, 2025, without language restrictions. Two investigators independently extracted study information and evaluated methodological quality as well as potential sources of bias. Eligible studies were observational in design and investigated the association between proton pump inhibitor (PPI) exposure and the risk of developing dementia compared with non-use. For the quantitative synthesis, pooled risk ratios (RRs) and corresponding confidence intervals were generated using a random-effects approach. Study Results: Eighteen studies, encompassing more than 6.3 million participants, met the inclusion criteria. The pooled estimate showed no statistically significant association between PPI use and overall dementia risk (RR = 1.14, 95% CI 0.98–1.33; I² = 99%). However, significant heterogeneity and variable risk of bias—particularly due to confounding, exposure misclassification, and immortal time bias—limit certainty in these findings. Subgroup analyses revealed significantly elevated risks among individuals aged ≥65 years (RR = 1.21, 95% CI 1.01–1.46) and in studies from Asia (RR = 1.31, 95% CI 1.12–1.52) and Europe (RR = 1.32, 95% CI 1.10–1.59), suggesting possible population- or context-specific vulnerability. Conclusions: Our findings reveal a lack of consistent evidence supporting a link between PPI use and dementia risk, primarily due to significant heterogeneity among existing studies. While no robust overall association was demonstrated, significant subgroup signals in older adults and specific regions suggest that clinical uncertainty remains. Rather than indicating a direct causal risk, these results underscore the importance of prescribing stewardship. Clinicians should focus on appropriate prescribing, ensuring long-term PPI therapy is reserved for patients with a clear therapeutic justification and utilized for the shortest effective duration. Full article

(This article belongs to the Section Neurodegenerative Diseases)

► Show Figures

Figure 1

22 pages, 432 KB

Open AccessEditor’s ChoiceReview

Sensory Deprivation and the Brain: Neurobiological Mechanisms, Psychological Effects, and Clinical Implications

by Donatella Marazziti, Gerardo Russomanno, Matteo Gambini, Francesca Rita Digiuseppe, Enrico Fazio and Riccardo Gurrieri

Brain Sci. 2026, 16(2), 122; https://doi.org/10.3390/brainsci16020122 - 23 Jan 2026

Cited by 1 | Viewed by 6973

Abstract

Background/Objectives: Sensory deprivation, defined as a reduction or absence of external sensory input across one or more modalities, has long been investigated in extreme and experimental settings. More recently, its relevance has expanded to clinical contexts and environmental conditions. The present narrative review [...] Read more.

Background/Objectives: Sensory deprivation, defined as a reduction or absence of external sensory input across one or more modalities, has long been investigated in extreme and experimental settings. More recently, its relevance has expanded to clinical contexts and environmental conditions. The present narrative review aims to synthesize current evidence on the neurobiological mechanisms, psychological effects, and clinical implications of sensory deprivation, with particular attention to its dual role as both a risk factor and, under controlled conditions, a potential therapeutic tool. Methods: A narrative literature search was conducted using PubMed, Scopus, and PsycINFO, covering studies published up to August 2025. Search terms included sensory deprivation, neuroplasticity, neurotransmitters, HPA axis, neuro-inflammation, circadian rhythms, psychopathology, extreme environments, and spaceflight. Preclinical and clinical studies examining biological, cognitive, and psychological consequences of reduced sensory stimulation were included. Data were synthesized thematically without quantitative meta-analysis. Results: Evidence indicates that sensory deprivation induces widespread neurobiological adaptations involving neurotransmitter systems (particularly dopaminergic pathways), dysregulation of the hypothalamic–pituitary–adrenal axis, neuroimmune activation, circadian rhythm disruption, and structural and functional brain changes, notably affecting the hippocampus. These alterations are associated with increased vulnerability to depression, anxiety, hallucinations, dissociative symptoms, and cognitive impairment. Duration, voluntariness, and individual differences (e.g., baseline vulnerability/resilience, trait anxiety, and prior psychiatric history) critically modulate outcomes. However, short-term and voluntary sensory restriction, such as Floatation-REST, may promote relaxation and emotional regulation under specific conditions. Conclusions: Sensory deprivation exerts complex, context-dependent effects on brain function and mental health. Duration, individual vulnerability, and voluntariness critically modulate outcomes. Understanding these mechanisms is increasingly relevant for clinical practice and for developing preventive strategies in extreme environments, including future long-duration space missions. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

22 pages, 1120 KB

Open AccessEditor’s ChoiceReview

Beyond Cognitive Load Theory: Why Learning Needs More than Memory Management

by Andrew Sortwell, Evgenia Gkintoni, Jesús Díaz-García, Peter Ellerton, Ricardo Ferraz and Gregory Hine

Brain Sci. 2026, 16(1), 109; https://doi.org/10.3390/brainsci16010109 - 19 Jan 2026

Cited by 19 | Viewed by 7007

Abstract

Background: The role of cognitive load theory (CLT) in understanding effective pedagogy has received increased attention in the fields of education and psychology in recent years. A considerable amount of literature has been published on the CLT construct as foundational guidance for instructional [...] Read more.

Background: The role of cognitive load theory (CLT) in understanding effective pedagogy has received increased attention in the fields of education and psychology in recent years. A considerable amount of literature has been published on the CLT construct as foundational guidance for instructional design by focusing on managing cognitive load in working memory to enhance learning outcomes. However, recent neuroscientific findings and practical critiques suggest that CLT’s emphasis on content-focused instruction and cognitive efficiency may overlook the complexity of human learning. Methods: This conceptual paper synthesises evidence from cognitive science, developmental psychology, neuroscience, health sciences and educational research to examine the scope conditions and limitations of CLT when applied as a general framework for K–12 learning. One of the major theoretical issues identified is the lack of consideration for the broad set of interpersonal and self-management skills, creating potential limitations for real-world educational contexts, where social-emotional and self-regulatory abilities are as crucial as cognitive competencies. Results: As a result of the critique, this paper introduces the Neurodevelopmental Informed Holistic Learning and Development Framework as a neuroscience-informed construct that integrates cognitive, emotional, and interpersonal dimensions essential for effective learning. Conclusions: In recognising the limitations of CLT, the paper offers practitioners contemporary, neurodevelopmentally informed insights that extend beyond cognitive efficiency alone and better reflect the multidimensional nature of real-world learning. Full article

(This article belongs to the Special Issue Neuroeducation: Bridging Cognitive Science and Classroom Practice)

► Show Figures

Graphical abstract

37 pages, 1276 KB

Open AccessEditor’s ChoiceReview

Versatility of Transcranial Magnetic Stimulation: A Review of Diagnostic and Therapeutic Applications

by Massimo Pascuzzi, Nika Naeini, Adam Dorich, Marco D’Angelo, Jiwon Kim, Jean-Francois Nankoo, Naaz Desai and Robert Chen

Brain Sci. 2026, 16(1), 101; https://doi.org/10.3390/brainsci16010101 - 17 Jan 2026

Cited by 3 | Viewed by 3900

Abstract

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight [...] Read more.

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight into neurophysiological dysfunctions and the therapeutic modulation of abnormal cortical excitability. This review examines key TMS outcome measures, including motor thresholds (MT), input–output (I/O) curves, cortical silent periods (CSP), and paired-pulse paradigms such as short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), intracortical facilitation (ICF), long interval cortical inhibition (LICI), interhemispheric inhibition (IHI), and short-latency afferent inhibition (SAI). These biomarkers reflect underlying neurotransmitter systems and can aid in differentiating neurological conditions. Diagnostic applications of TMS are explored in Parkinson’s disease (PD), dystonia, essential tremor (ET), Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Each condition displays characteristic neurophysiological profiles, highlighting the potential for TMS-derived biomarkers in early or differential diagnosis. Therapeutically, repetitive TMS (rTMS) has shown promise in modulating cortical circuits and improving motor and cognitive symptoms. High- and low-frequency stimulation protocols have demonstrated efficacy in PD, dystonia, ET, AD, and MCI, targeting the specific cortical regions implicated in each disorder. Moreover, the successful application of TMS in differentiating and treating AD and MCI underscores its clinical utility and translational potential across all neurodegenerative conditions. As research advances, increased attention and investment in TMS could facilitate similar diagnostic and therapeutic breakthroughs for other neurological disorders that currently lack robust tools for early detection and effective intervention. Moreover, this review also aims to underscore the importance of maintaining standardized TMS protocols. By highlighting inconsistencies and variability in outcomes across studies, we emphasize that careful methodological design is critical for ensuring the reproducibility, comparability, and reliable interpretation of TMS findings. In summary, this review emphasizes the value of TMS as a distinctive, non-invasive approach to probing brain function and highlights its considerable promise as both a diagnostic and therapeutic modality in neurology—roles that are often considered separately. Full article

(This article belongs to the Special Issue Application of Transcranial Magnetic Stimulation (TMS) in Motor Control and Learning)

► Show Figures

Figure 1

11 pages, 409 KB

Open AccessEditor’s ChoiceArticle

Detecting Dementia Using Lexical Analysis: Terry Pratchett’s Discworld Tells a More Personal Story

by Melody Pattison, Ahmet Begde and Thomas D. W. Wilcockson

Brain Sci. 2026, 16(1), 94; https://doi.org/10.3390/brainsci16010094 - 16 Jan 2026

Viewed by 13577

Abstract

Background/Objectives: Dementia, characterised by cognitive decline, significantly impacts language abilities. While the risk of dementia increases with age, it often manifests years before clinical diagnosis. Identifying early warning signs is crucial for timely intervention. Previous research has demonstrated that changes in language, [...] Read more.

Background/Objectives: Dementia, characterised by cognitive decline, significantly impacts language abilities. While the risk of dementia increases with age, it often manifests years before clinical diagnosis. Identifying early warning signs is crucial for timely intervention. Previous research has demonstrated that changes in language, such as reduced vocabulary diversity and simpler sentence structures, may be observed in individuals with dementia. This study investigates the potential of linguistic analysis to detect early signs of cognitive decline by examining the writing of Sir Terry Pratchett, a renowned author diagnosed with Posterior Cortical Atrophy (PCA), typically a form of dementia caused by Alzheimer’s disease. Methods: This study analysed 33 Discworld novels by Terry Pratchett, comparing linguistic features before and after a potential turning point identified through analysis of adjective type-token ratios (TTR). Results: A significant decrease in lexical diversity (TTR) was observed for nouns and adjectives in later works. Total wordcount increased, while lexical diversity decreased, suggesting a shift towards simpler language. This shift coincided with a decrease in adjective TTR below a defined threshold, occurring approximately ten years before Pratchett’s formal diagnosis. Conclusions: These findings suggest that subtle changes in linguistic patterns, such as decreased lexical diversity, may precede clinical diagnosis of dementia by a considerable margin. This research highlights the potential of linguistic analysis as a valuable tool for early detection of cognitive decline. Further research is needed to validate these findings in larger cohorts and explore the specific linguistic markers associated with different types of dementia. Full article

(This article belongs to the Special Issue Advances in Speech and Language Research for Cognitive Well-Being in Aging)

► Show Figures

Figure 1

21 pages, 2074 KB

Open AccessEditor’s ChoiceReview

Neurobiophilia

by Mohamed Hesham Khalil and Koen Steemers

Brain Sci. 2026, 16(1), 85; https://doi.org/10.3390/brainsci16010085 - 9 Jan 2026

Cited by 3 | Viewed by 3264

Abstract

Despite unprecedented disconnection from nature and increased urbanisation, the brain still shows an affinity for nature. However, biophilia lacks a neuroscience foundation despite growing evidence of how the brain changes in response to the contrasting influences of urban and natural environments. To address [...] Read more.

Despite unprecedented disconnection from nature and increased urbanisation, the brain still shows an affinity for nature. However, biophilia lacks a neuroscience foundation despite growing evidence of how the brain changes in response to the contrasting influences of urban and natural environments. To address this timely gap, this paper establishes Neurobiophilia through four objectives. First, it identifies seven neuro-needs (7NNs) and establishes their hierarchical order and interconnected outcomes. Second, it maps how natural environments fulfil each of the brain’s 7NNs. Third, it explores whether climate change is turning nature into a harmful environment for the brain, specifically with respect to temperature extremes. Fourth, it examines how built environments vary in their enrichment with respect to the 7NNs. This paper highlights critical environmental enrichment challenges in natural environments caused by climate change and in built environments. The novel Neurobiophilia framework established herein identifies these gaps and provides recommendations to achieve neurosustainability through environmental enrichment that sustains adaptive brain responses throughout the lifespan. Full article

(This article belongs to the Section Environmental Neuroscience)

► Show Figures

Figure 1

21 pages, 2580 KB

Open AccessEditor’s ChoiceArticle

Effects of Video Game Type on Cognitive Performance and Brain Functional Connectivity: A Longitudinal EEG Study

by Jingqing Lu, Ruifang Cui, Lijun Jiang, Chenyu Mu, Weiyi Ma, Diankun Gong and Dezhong Yao

Brain Sci. 2026, 16(1), 24; https://doi.org/10.3390/brainsci16010024 - 25 Dec 2025

Cited by 9 | Viewed by 14709

Abstract

Background: Previous research has shown that video gaming experience is associated with changes in cognitive and perceptual functions as well as neural structure and function. However, how the different types of video games differentially influence cognitive function and neuroplasticity remains unclear. Methods [...] Read more.

Background: Previous research has shown that video gaming experience is associated with changes in cognitive and perceptual functions as well as neural structure and function. However, how the different types of video games differentially influence cognitive function and neuroplasticity remains unclear. Methods: In this 30-week longitudinal study, participants were randomly assigned to an action video game group or a strategy card game group. Behavioral assessments and resting-state electroencephalography (EEG) recordings were administered at six time points to evaluate changes in attention, working memory, executive function, and their neural correlates. Results: Both groups showed significant improvements in multiple cognitive tasks, but the underlying neural mechanisms differed. The action video game group showed greater increases in low-frequency EEG relative power (delta and theta bands) and more pronounced decreases in alpha-band functional connectivity at the 10-week follow-up after the end of training. Conclusions: These findings suggest that different types of video games improve cognition through distinct neuroplasticity pathways, with action games effective in optimizing neural efficiency and producing sustained effects. This study provides new insights into the cognitive and neural mechanisms of game-based enhancements and offers implications for the design of targeted digital cognitive interventions. Full article

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

► Show Figures

Figure 1

39 pages, 3412 KB

Open AccessEditor’s ChoiceReview

Alpha-Synuclein Neurobiology in Parkinson’s Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives

by Jamir Pitton Rissardo, Andrew McGarry, Yiwen Shi, Ana Leticia Fornari Caprara and George T. Kannarkat

Brain Sci. 2025, 15(12), 1260; https://doi.org/10.3390/brainsci15121260 - 25 Nov 2025

Cited by 22 | Viewed by 9832

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the presence of intracellular α-synuclein (αSyn) aggregates known as Lewy bodies (LB). αSyn, a presynaptic protein, is believed to play a crucial [...] Read more.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the presence of intracellular α-synuclein (αSyn) aggregates known as Lewy bodies (LB). αSyn, a presynaptic protein, is believed to play a crucial role in synaptic function, neurotransmitter release, and neuronal plasticity. However, its misfolding and aggregation are thought to be central to PD pathogenesis. This review provides a comprehensive analysis of αSyn’s role in PD, exploring its normal physiological functions, pathological mechanisms, and therapeutic potential. The pathological transformation of αSyn involves structural alterations that promote oligomerization and fibrillization, leading to toxic gain-of-function effects. These aggregates disrupt cellular homeostasis through mechanisms including mitochondrial dysfunction, oxidative stress, lysosomal impairment, and endoplasmic reticulum stress. Furthermore, pathogenic αSyn is thought to exacerbate neurodegeneration via prion-like spread along interconnected neuronal circuits. Emerging evidence highlights the frequent co-occurrence of other proteinopathies, such as tau and amyloid-β, which may synergistically accelerate disease progression. Targeting αSyn has emerged as a potential therapeutic strategy. Approaches such as immunotherapy, small-molecule inhibitors, gene silencing, and modulation of protein degradation pathways (e.g., autophagy and proteasomal systems) are actively being explored. Additionally, lifestyle-based interventions, particularly exercise, have shown neuroprotective effects, potentially mediated by irisin—a myokine implicated in protein clearance and synaptic resilience—underscoring the importance of multimodal strategies in PD management. Full article

(This article belongs to the Section Neurodegenerative Diseases)

► Show Figures

Figure 1

17 pages, 1139 KB

Open AccessEditor’s ChoiceReview

The Influence of Music on Mental Health Through Neuroplasticity: Mechanisms, Clinical Implications, and Contextual Perspectives

by Yoshihiro Noda and Takahiro Noda

Brain Sci. 2025, 15(11), 1248; https://doi.org/10.3390/brainsci15111248 - 20 Nov 2025

Cited by 10 | Viewed by 11746

Abstract

Music is a near-universal anthropological and sensory phenomenon that engages distributed brain networks and peripheral physiological systems to shape emotion, cognition, sociality, and bodily regulation. Evidence from electrophysiology, neuroimaging, endocrinology, randomized controlled trials, and longitudinal training studies indicates that both receptive and active [...] Read more.

Music is a near-universal anthropological and sensory phenomenon that engages distributed brain networks and peripheral physiological systems to shape emotion, cognition, sociality, and bodily regulation. Evidence from electrophysiology, neuroimaging, endocrinology, randomized controlled trials, and longitudinal training studies indicates that both receptive and active musical experiences produce experience-dependent neural and systemic adaptations. These include entrainment of neural oscillations, modulation of predictive and reward signaling, autonomic and neuroendocrine changes, and long-term structural connectivity alterations that support affect regulation, cognition, social functioning, motor control, sleep, and resilience to neuropsychiatric illness. This narrative review integrates mechanistic domains with clinical outcomes across major conditions, such as depression, anxiety, schizophrenia, dementia, and selected neurodevelopmental disorders, by mapping acoustic and procedural parameters onto plausible biological pathways. We summarize how tempo, beat regularity, timbre and spectral content, predictability, active versus passive engagement, social context, dose, and timing influence neural entrainment, synaptic and network plasticity, reward and prediction-error dynamics, autonomic balance, and immune/endocrine mediators. For each condition, we synthesize randomized and observational findings and explicitly link observed improvements to mechanistic pathways. We identify methodological limitations, including heterogeneous interventions, small and biased samples, sparse longitudinal imaging and standardized physiological endpoints, and inconsistent acoustic reporting, and translate these into recommendations for translational trials: harmonized acoustic reporting, pre-specified mechanistic endpoints (neuroimaging, autonomic, neuroendocrine, immune markers), adequately powered randomized designs with active controls, and long-term follow-up. Contextual moderators including music education, socioeconomic and cultural factors, sport, sleep, and ritual practices are emphasized as critical determinants of implementation and effectiveness. Full article

(This article belongs to the Special Issue Modulating Brain Network Dynamics Through Training: Impacts on Perception, Cognition, and Action in Health and Disorder)

► Show Figures

Figure 1

18 pages, 895 KB

Open AccessEditor’s ChoiceReview

Physical Activity and Its Effects on Executive Functions and Brain Outcomes in Children: A Narrative Review

by Eduardo Guzmán-Muñoz, Yeny Concha-Cisternas, Emilio Jofré-Saldía, Antonio Castillo-Paredes, Iván Molina-Márquez and Rodrigo Yáñez-Sepúlveda

Brain Sci. 2025, 15(11), 1238; https://doi.org/10.3390/brainsci15111238 - 18 Nov 2025

Cited by 20 | Viewed by 7081

Abstract

Background/Objectives: Executive functions—including inhibitory control, working memory, and cognitive flexibility—are fundamental for children’s learning and development. Physical activity is recognized as a key factor that enhances these functions through neurobiological and structural brain adaptations. This narrative review aims to synthesize current evidence on [...] Read more.

Background/Objectives: Executive functions—including inhibitory control, working memory, and cognitive flexibility—are fundamental for children’s learning and development. Physical activity is recognized as a key factor that enhances these functions through neurobiological and structural brain adaptations. This narrative review aims to synthesize current evidence on the relationship between physical activity, executive functions, and brain outcomes in children. Methods: A narrative review was conducted using systematic evidence search across PubMed, Scopus, and Web of Science until August 2025. Search terms encompassed physical activity, executive functions, and brain mechanisms. Eligible studies included randomized controlled trials, longitudinal and cross-sectional studies, systematic reviews, and meta-analyses that examined executive function domains and brain-related outcomes in children, with or without neurodevelopmental disorders. Results: The evidence reviewed highlights that acute physical activity improves inhibitory control, working memory, and cognitive flexibility, primarily through enhanced neurotransmission and cerebral oxygenation. Chronic interventions promote structural and functional brain adaptations, including improved white matter integrity and increased network efficiency. Benefits are observed in both neurotypical children and those with ADHD, with inhibitory control emerging as the most responsive domain. However, findings are moderated by intervention type, intensity, and duration, with heterogeneity across protocols. Conclusions: Physical activity is a promising strategy to support the development of executive and brain functions in childhood, with implications for education and clinical practice. Despite consistent short- and long-term benefits, further research is required to establish optimal prescriptions and evaluate sustained real-world impacts, particularly in children with neurodevelopmental disorders. Full article

(This article belongs to the Special Issue Advances in the Relationship Among Brain, Physical Function, and Exercise Performance)

► Show Figures

Figure 1

17 pages, 1328 KB

Open AccessEditor’s ChoiceArticle

Relationships Between Sleep Quality, Anxiety and Depression in University Students: Stable Trends over Time and a Pronounced Concern for Sleep Initiation

by Jonathan P. Whitehead and Caroline L. Horton

Brain Sci. 2025, 15(11), 1142; https://doi.org/10.3390/brainsci15111142 - 24 Oct 2025

Cited by 7 | Viewed by 8147

Abstract

Background/Objectives: Relationships between sleep quality, anxiety and depression are well-documented across the lifespan. Here we investigated relationships between sleep, mental health and markers of obesity and cardiovascular health in Higher Education students (young adults, 18–28 years) using repeated cross-sectional sampling. Methods: [...] Read more.

Background/Objectives: Relationships between sleep quality, anxiety and depression are well-documented across the lifespan. Here we investigated relationships between sleep, mental health and markers of obesity and cardiovascular health in Higher Education students (young adults, 18–28 years) using repeated cross-sectional sampling. Methods: Students (n = 486) participated at one of four timepoints across 2020–2023. The PSQI (sleep quality), GAD7 (anxiety) and PHQ8 (depression) were completed online. Measurements of obesity (Body Mass Index (BMI), body fat percent (BF%) and waist–hip ratio (WHR)) and cardiovascular function (heart rate (HR), diastolic and systolic blood pressure (DP and SP)) were determined. Changes over time, differences between sexes, and correlations between parameters were examined. Results: All measures were stable over the 4-year period. GAD7 (p < 0.0001) and PHQ8 (p = 0.0014) scores were significantly higher in females than males. There were significant, moderate to strong correlations between PSQI, GAD7 and PHQ8 scores for both sexes (r = 0.34–0.71). Only 18.1% of females and 23% of males reported both good quality sleep and no or low levels of anxiety and depression. Significant sex-specific differences were observed across markers of obesity and cardiovascular function (for BF%, WHR, HR and SP—all p ≤ 0.01), which showed weak to moderate correlations with sleep and mental health. Impaired sleep latency (C2) was identified as a potential key contributing factor. Conclusions: These observations provide evidence of multiple established, interlinked chronic challenges affecting sleep, mental and physical health in students. Identification of a key role for impaired sleep latency provides a foundation for targeted intervention, focusing upon improving sleep initiation, to improve mental health outcomes. Full article

(This article belongs to the Special Issue Relationships Between Disordered Sleep and Mental Health)

► Show Figures

Figure 1

32 pages, 1492 KB

Open AccessEditor’s ChoiceReview

Quantitative MRI in Neuroimaging: A Review of Techniques, Biomarkers, and Emerging Clinical Applications

by Gaspare Saltarelli, Giovanni Di Cerbo, Antonio Innocenzi, Claudia De Felici, Alessandra Splendiani and Ernesto Di Cesare

Brain Sci. 2025, 15(10), 1088; https://doi.org/10.3390/brainsci15101088 - 8 Oct 2025

Cited by 16 | Viewed by 8538

Abstract

Quantitative magnetic resonance imaging (qMRI) denotes MRI methods that estimate physical tissue parameters in units, rather than relative signal. Typical readouts include T1/T2 relaxation (ms; or R1/R2 in s⁻¹), proton density (%), diffusion metrics (e.g., ADC in mm²/s, FA), [...] Read more.

Quantitative magnetic resonance imaging (qMRI) denotes MRI methods that estimate physical tissue parameters in units, rather than relative signal. Typical readouts include T1/T2 relaxation (ms; or R1/R2 in s⁻¹), proton density (%), diffusion metrics (e.g., ADC in mm²/s, FA), magnetic susceptibility (χ, ppm), perfusion (e.g., CBF in mL/100 g/min; rCBV; K^trans), and regional brain volumes (cm³; cortical thickness). This review synthesizes brain qMRI across T1/T2 relaxometry, myelin/MT (MWF, MTR/MTsat/qMT), diffusion (DWI/DTI/DKI/IVIM), susceptibility imaging (SWI/QSM), perfusion (DSC/DCE/ASL), and volumetry using a unified framework: physics and signal model, acquisition and key parameters, outputs and units, validation/repeatability, clinical applications, limitations, and future directions. Our scope is the adult brain in neurodegenerative, neuro-inflammatory, neuro-oncologic, and cerebrovascular disease. Representative utilities include tracking demyelination and repair (T1, MWF/MTsat), grading and therapy monitoring in gliomas (rCBV, K^trans), penumbra and tissue-at-risk assessment (DWI/DKI/ASL), iron-related pathology (QSM), and early dementia diagnosis with normative volumetry. Persistent barriers to routine adoption are protocol standardization, vendor-neutral post-processing/QA, phantom-based and multicenter repeatability, and clinically validated cut-offs. We highlight consensus efforts and AI-assisted pipelines, and outline opportunities for multiparametric integration of complementary qMRI biomarkers. As methodological convergence and clinical validation mature, qMRI is poised to complement conventional MRI as a cornerstone of precision neuroimaging. Full article

(This article belongs to the Special Issue Application of MRI in Brain Diseases)

► Show Figures

Figure 1

12 pages, 565 KB

Open AccessEditor’s ChoiceArticle

Rethinking Melatonin Dosing: Safety and Efficacy at Higher-than-Usual Levels in Aged Patients with Sleep Disturbances and Comorbidities

by Stella M. Valiensi, Vanesa A. Vera, Agustín L. Folgueira, Sofía Caporale, Marcela Ponce de León, Isis Pino Fernández, Daniel E. Vigo and Daniel P. Cardinali

Brain Sci. 2025, 15(10), 1040; https://doi.org/10.3390/brainsci15101040 - 25 Sep 2025

Cited by 6 | Viewed by 17495

Abstract

Background. Although melatonin is widely used in Sleep Medicine for its chronobiological action, its potent antioxidant and mitochondrial regulatory effects, as well as its immunomodulatory and anti-inflammatory functions, make it of interest as a cytoprotective agent in several chronic pathologies. These actions [...] Read more.

Background. Although melatonin is widely used in Sleep Medicine for its chronobiological action, its potent antioxidant and mitochondrial regulatory effects, as well as its immunomodulatory and anti-inflammatory functions, make it of interest as a cytoprotective agent in several chronic pathologies. These actions are evident at doses higher than those used for sleep disorders. Even at high doses, melatonin’s adverse effects are few, mild, and self-limited or resolve quickly after discontinuation of treatment. Based on its safety profile, we treated melatonin for sleep disorders in the presence of comorbidities with doses ≥ 40 mg daily. Methods. This was a retrospective mixed observational analytical design comprising a retrospective uncontrolled cohort analysis and a cross-sectional study. Eighty-one patients (57 female) with sleep disorders ranging in age from 55 to 98 years (mean 74.4 years) were treated with melatonin 40 to 200 mg daily (mean 72.7 mg) were examined. Fifty-six percent of patients received treatment for more than 4 years. The control group for the cross-sectional analysis included 81 patients over 52 years of age, matched by age and sex and not receiving melatonin but having sleep disorders within the same period. Results. A significant decrease was observed in arterial hypertension, ischemic heart disease and diabetes mellitus after melatonin administration. Analysis of clinical laboratory variables indicated no changes in the treated group versus the untreated group, except for a lower alkaline phosphatase concentration in patients who received melatonin. Conclusions. These findings suggest a beneficial effect of cytoprotective doses of melatonin on the cardiovascular and metabolic profile in an aged population. Full article

(This article belongs to the Special Issue Advances in Global Sleep and Circadian Health)

► Show Figures

Figure 1

18 pages, 711 KB

Open AccessEditor’s ChoiceReview

Exploring Imagined Movement for Brain–Computer Interface Control: An fNIRS and EEG Review

by Robert Finnis, Adeel Mehmood, Henning Holle and Jamshed Iqbal

Brain Sci. 2025, 15(9), 1013; https://doi.org/10.3390/brainsci15091013 - 19 Sep 2025

Cited by 16 | Viewed by 5856

Abstract

Brain–Computer Interfaces (BCIs) offer a non-invasive pathway for restoring motor function, particularly for individuals with limb loss. This review explored the effectiveness of Electroencephalography (EEG) and function Near-Infrared Spectroscopy (fNIRS) in decoding Motor Imagery (MI) movements for both offline and online BCI systems. [...] Read more.

Brain–Computer Interfaces (BCIs) offer a non-invasive pathway for restoring motor function, particularly for individuals with limb loss. This review explored the effectiveness of Electroencephalography (EEG) and function Near-Infrared Spectroscopy (fNIRS) in decoding Motor Imagery (MI) movements for both offline and online BCI systems. EEG has been the dominant non-invasive neuroimaging modality due to its high temporal resolution and accessibility; however, it is limited by high susceptibility to electrical noise and motion artifacts, particularly in real-world settings. fNIRS offers improved robustness to electrical and motion noise, making it increasingly viable in prosthetic control tasks; however, it has an inherent physiological delay. The review categorizes experimental approaches based on modality, paradigm, and study type, highlighting the methods used for signal acquisition, feature extraction, and classification. Results show that while offline studies achieve higher classification accuracy due to fewer time constraints and richer data processing, recent advancements in machine learning—particularly deep learning—have improved the feasibility of online MI decoding. Hybrid EEG–fNIRS systems further enhance performance by combining the temporal precision of EEG with the spatial specificity of fNIRS. Overall, the review finds that predicting online imagined movement is feasible, though still less reliable than motor execution, and continued improvements in neuroimaging integration and classification methods are essential for real-world BCI applications. Broader dissemination of recent advancements in MI-based BCI research is expected to stimulate further interdisciplinary collaboration among roboticists, neuroscientists, and clinicians, accelerating progress toward practical and transformative neuroprosthetic technologies. Full article

(This article belongs to the Special Issue Exploring the Neurobiology of the Sensory-Motor System)

► Show Figures

Figure 1

19 pages, 1875 KB

Open AccessEditor’s ChoiceArticle

Boosting Working Memory in ADHD: Adaptive Dual N-Back Training Enhances WAIS-IV Performance, but Yields Mixed Corsi Outcomes

by Alessandra Lintas, Michel Bader and Alessandro E. P. Villa

Brain Sci. 2025, 15(9), 998; https://doi.org/10.3390/brainsci15090998 - 16 Sep 2025

Cited by 2 | Viewed by 20951

Abstract

Background/Objectives: This study investigates the efficacy of working memory training (WMT) using the dual N-back (DNB) task on cognitive performance in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: Over the course of at least 18 daily sessions conducted within one month, 106 participants [...] Read more.

Background/Objectives: This study investigates the efficacy of working memory training (WMT) using the dual N-back (DNB) task on cognitive performance in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: Over the course of at least 18 daily sessions conducted within one month, 106 participants (33 non-medicated ADHD, 42 medicated ADHD, and 45 controls) were randomly assigned to either a fixed dual 1-back (FD1B) training condition or an adaptive DNB condition, wherein the N-back level increased following successful completion of each trial block. Cognitive performance was assessed pre- and post-intervention using the Wechsler Adult Intelligence Scale–Fourth Edition (WAIS-IV) Working Memory Index (WMI) and the Corsi Block-Tapping Task. Results: A mixed-design ANOVA revealed significant improvements in DNB performance across all groups, with the adaptive training condition producing larger gains (e.g., a 204.6% improvement in controls, Cohen’s

d = 1.85

). WAIS-IV WMI scores—particularly the Digit Span Backward subtest—also improved significantly post-training, with greater effect sizes in the adaptive condition (

d = 0.46

) than in FD1B (

d = 0.27

). Corsi performance showed very modest gains, showing a surprising tendency to be more associated with the FD1B condition than the adaptive condition. Control participants outperformed the medicated ADHD group on WAIS-IV subtests, although no significant differences emerged between medicated and non-medicated ADHD participants. Correlational analyses indicated task-specific training effects, with adaptive training enhancing associations between DNB and Corsi performance in both controls (

r = 0.60

) and medicated ADHD participants (

r = 0.51

). Conclusions: This study demonstrates that dual N-back training improves verbal working memory in young adults with ADHD, specifically in a sample without psychiatric comorbidities. Transfer benefit to visuospatial domains appears limited and may not generalize to adolescents, older adults, or individuals with complex clinical profiles. The results underscore the importance of tailoring training protocols to maximize cognitive outcomes across different domains. Full article

(This article belongs to the Section Neurorehabilitation)

► Show Figures

Figure 1

20 pages, 1125 KB

Open AccessEditor’s ChoiceReview

Beyond Hot Flashes: The Role of Estrogen Receptors in Menopausal Mental Health and Cognitive Decline

by Jung Min Cho, Jihye Lee, Eun-Mi Ahn and Jaehoon Bae

Brain Sci. 2025, 15(9), 1003; https://doi.org/10.3390/brainsci15091003 - 16 Sep 2025

Cited by 25 | Viewed by 15237

Abstract

Menopause is a natural phase in a woman’s life marked by the cessation of menstruation, typically accompanied by hormonal fluctuations that have significant impacts on physical and mental health. While much attention has been given to the physical symptoms of menopause, such as [...] Read more.

Menopause is a natural phase in a woman’s life marked by the cessation of menstruation, typically accompanied by hormonal fluctuations that have significant impacts on physical and mental health. While much attention has been given to the physical symptoms of menopause, such as hot flashes and osteoporosis, the neurocognitive consequences of hormonal fluctuations during the menopausal transition and the subsequent sustained estrogen loss after menopause have received less focus. Estrogen receptors (ERs), specifically ERα and ERβ, play a critical role in maintaining brain health, influencing mood, memory, and cognition. This review explores the connection between estrogen receptor signaling and mental health during menopause, focusing on mood disorders such as depression and anxiety, as well as cognitive decline and dementia. We discuss the molecular mechanisms by which ERs modulate brain function, including their effects on neuroplasticity, neurotransmitter systems, and gene expression. The review also examines current clinical approaches to managing menopausal cognitive and mental health issues, including hormone replacement therapy and selective ER modulators, while emphasizing the need for further research into alternative therapies and individualized treatments. The importance of estrogen receptors in the menopausal brain and their potential as therapeutic targets is critically evaluated, aiming to shed light on this often-overlooked aspect of menopause and aging. Full article

(This article belongs to the Section Neuropsychology)

► Show Figures

Graphical abstract

20 pages, 1600 KB

Open AccessEditor’s ChoiceReview

Acute Vertigo, Dizziness and Imbalance in the Emergency Department—Beyond Stroke and Acute Unilateral Vestibulopathy—A Narrative Review

by Sun-Uk Lee, Jonathan A. Edlow and Alexander A. Tarnutzer

Brain Sci. 2025, 15(9), 995; https://doi.org/10.3390/brainsci15090995 - 15 Sep 2025

Cited by 9 | Viewed by 14007

Abstract

New-onset vertigo, dizziness and gait imbalance are amongst the most common symptoms presenting to the emergency department, accounting for 2.1–4.4% of all patients. The broad spectrum of underlying causes in these patients cuts across many specialties, which often results in diagnostic challenges. For [...] Read more.

New-onset vertigo, dizziness and gait imbalance are amongst the most common symptoms presenting to the emergency department, accounting for 2.1–4.4% of all patients. The broad spectrum of underlying causes in these patients cuts across many specialties, which often results in diagnostic challenges. For patients meeting the diagnostic criteria for acute vestibular syndrome (AVS, i.e., presenting with acute-onset prolonged vertigo/dizziness with accompanying gait imbalance, motion intolerance, nausea/vomiting, with or without nystagmus), the typical differential diagnosis is vertebrobasilar stroke and acute unilateral vestibulopathy. However, other disorders may also present with AVS. These include non-neurological causes such as drug side-effects or intoxication, electrolyte disturbances, cardiac disease, severe anemia, carbon monoxide poisoning, endocrine disorders and others. Other non-stroke neurological disorders may also present with AVS or episodic vertigo/dizziness, including demyelinating CNS diseases, posterior fossa mass lesions, acute thiamine deficiency and vestibular migraine. Furthermore, acute physiological abnormalities (e.g., hypotension, fever, severe anemia) may unmask previous vestibular impairments that had been well-compensated. Here, we review the diagnostic approach to patients with acute-onset dizziness in the emergency room and discuss the most important differential diagnoses beyond stroke and acute unilateral vestibulopathy. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

► Show Figures

Figure 1

33 pages, 1073 KB

Open AccessEditor’s ChoiceReview

Sleep Disorders in Children with Autism Spectrum Disorder: Developmental Impact and Intervention Strategies

by Maria Ludovica Albertini, Giulia Spoto, Graziana Ceraolo, Maria Flavia Fichera, Carla Consoli, Antonio Gennaro Nicotera and Gabriella Di Rosa

Brain Sci. 2025, 15(9), 983; https://doi.org/10.3390/brainsci15090983 - 13 Sep 2025

Cited by 14 | Viewed by 14096

Abstract

Sleep disorders are highly prevalent in children with Autism Spectrum Disorder (ASD), profoundly impacting their neurodevelopment and daily functioning. Alterations in sleep architecture and regulatory mechanisms contribute to difficulties with sleep onset, maintenance, and overall sleep quality. Sensory processing differences, commonly observed in [...] Read more.

Sleep disorders are highly prevalent in children with Autism Spectrum Disorder (ASD), profoundly impacting their neurodevelopment and daily functioning. Alterations in sleep architecture and regulatory mechanisms contribute to difficulties with sleep onset, maintenance, and overall sleep quality. Sensory processing differences, commonly observed in ASD, may further exacerbate these disturbances by affecting arousal regulation and environmental responsiveness during sleep. Given the fundamental role of sleep in brain maturation, its disruption negatively impacts synaptic plasticity and neurological development, particularly during critical periods. These sleep-related alterations can influence cognitive and behavioral outcomes and may serve as early indicators of ASD, highlighting their potential value in early diagnosis and intervention. Understanding the neurobiological mechanisms linking sleep and ASD is essential for developing targeted therapeutic strategies. Ongoing research increasingly focuses on pharmacological, nutraceutical, and behavioral interventions aimed at mitigating sleep disorders and their cascading effects on neurodevelopment. Optimizing these therapeutic approaches through a multidisciplinary lens is crucial for enhancing clinical outcomes and improving overall quality of life in children with ASD. Full article

(This article belongs to the Special Issue Unraveling Autism: Neurobiological Mechanisms and Emerging Therapeutic Advances)

► Show Figures

Figure 1

14 pages, 2352 KB

Open AccessEditor’s ChoiceReview

A Comprehensive Overview of Subacute Combined Degeneration: MRI Diagnostic Challenges and Treatment Pathways

by Caterina Bernetti, Laura Cea, Andrea Buoso, Federico Greco, Mariagrazia Rossi, Fabio Pilato, Rosalinda Calandrelli, Gianfranco Di Gennaro, Vincenzo Di Lazzaro, Bruno Beomonte Zobel and Carlo Augusto Mallio

Brain Sci. 2025, 15(9), 972; https://doi.org/10.3390/brainsci15090972 - 10 Sep 2025

Cited by 7 | Viewed by 17227

Abstract

Subacute combined degeneration (SCD) is a neurological disorder primarily caused by vitamin B12 deficiency. This condition leads to progressive demyelination and axonal damage, predominantly affecting the dorsal and lateral columns of the spinal cord. This review provides a comprehensive overview of SCD, detailing [...] Read more.

Subacute combined degeneration (SCD) is a neurological disorder primarily caused by vitamin B12 deficiency. This condition leads to progressive demyelination and axonal damage, predominantly affecting the dorsal and lateral columns of the spinal cord. This review provides a comprehensive overview of SCD, detailing its complex etiology, pathophysiology, and clinical presentation. We highlight the critical role of magnetic resonance imaging (MRI) in the diagnostic process, discussing both the characteristic spinal cord findings and the more subtle intracranial abnormalities. Furthermore, we address the diagnostic challenges presented by conditions that mimic SCD in MRI, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). We conclude by outlining current treatment pathways and identifying key areas for future research, including the use of advanced neuroimaging techniques and the potential for new therapeutic approaches. This updated synthesis aims to provide a clear framework for clinicians and researchers to better understand and manage SCD. Full article

(This article belongs to the Special Issue Application of MRI in Brain Diseases)

► Show Figures

Figure 1

22 pages, 734 KB

Open AccessEditor’s ChoiceReview

Brain Nuclei in the Regulation of Sexual Behavior, Peripheral Nerves Related to Reproduction, and Their Alterations in Neurodegenerative Diseases: A Brief Review

by María de la Paz Palacios-Arellano, Jessica Natalia Landa-García, Edson David García-Martínez, Jorge Manzo-Denes, Gonzalo Emiliano Aranda-Abreu, Fausto Rojas-Durán, Deissy Herrera-Covarrubias, María Rebeca Toledo-Cárdenas, Genaro Alfonso Coria-Ávila, Jorge Manuel Suárez-Medellín, César Antonio Pérez-Estudillo and María Elena Hernández-Aguilar

Brain Sci. 2025, 15(9), 942; https://doi.org/10.3390/brainsci15090942 - 29 Aug 2025

Cited by 2 | Viewed by 9977

Abstract

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. [...] Read more.

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study. Full article

(This article belongs to the Special Issue From Brain Circuits to Behavior: A Neuroendocrine Perspective)

► Show Figures

Figure 1

14 pages, 964 KB

Open AccessEditor’s ChoiceReview

Optic Pathway Glioma: Current Treatment Approaches and Ongoing Clinical Trials

by Osama Elzaafarany, Sarah Elhomosany, Alexandra Rincones, Vincent Dlugi and Sepideh Mokhtari

Brain Sci. 2025, 15(8), 894; https://doi.org/10.3390/brainsci15080894 - 21 Aug 2025

Cited by 3 | Viewed by 14052

Abstract

Optic pathway glioma (OPG) is a rare pediatric low-grade glioma, frequently associated with neurofibromatosis type 1 (NF–1), that presents unique therapeutic challenges due to its anatomical location and its potential to impair vision, endocrine function, and developmental trajectories. Current clinical management prioritizes a [...] Read more.

Optic pathway glioma (OPG) is a rare pediatric low-grade glioma, frequently associated with neurofibromatosis type 1 (NF–1), that presents unique therapeutic challenges due to its anatomical location and its potential to impair vision, endocrine function, and developmental trajectories. Current clinical management prioritizes a multidisciplinary, patient-specific approach aimed at tumor control while preserving long-term quality of life. Strategies vary based on clinical presentation, ranging from observation in asymptomatic cases to chemotherapy for progressive or symptomatic tumors. Surgical and radiation options are limited due to potential risks and complications. In recent years, advances in molecular characterization have guided the development of targeted therapies, particularly MEK inhibitors, which demonstrate encouraging efficacy and reduced toxicity profiles. In parallel, investigational therapies including immunotherapy and precision medicine-based approaches are under clinical evaluation. This review provides a synthesis of current standard practices, emerging targeted treatments, and ongoing clinical trials, drawing on relevant literature and expert consensus to inform clinicians and families about available therapeutic options. Literature discussed in this review was identified through a non-systematic search of published articles, clinical trial registries, and authoritative guidelines, with selection based on relevance, clinical significance, and contribution to understanding current and emerging management strategies for OPG. Full article

(This article belongs to the Section Neuroglia)

► Show Figures

Figure 1

19 pages, 1162 KB

Open AccessEditor’s ChoiceArticle

Beyond the Scars: An Analysis of Adverse Childhood Experiences and the Interconnections Between Emotion Dysregulation, Dissociation, and Trauma in Patients with Borderline Personality Disorder

by Luciana Ciringione, Enrico Perinelli, Francesco Mancini and Elena Prunetti

Brain Sci. 2025, 15(8), 889; https://doi.org/10.3390/brainsci15080889 - 20 Aug 2025

Cited by 6 | Viewed by 9139

Abstract

Background/Objectives: Borderline Personality Disorder (BPD) frequently overlaps with trauma-related conditions, particularly PTSD and Complex PTSD (cPTSD). Adverse Childhood Experiences (ACEs)—especially emotional and sexual abuse—are considered key factors in the development of emotion dysregulation and dissociation. This study investigates the impact of different [...] Read more.

Background/Objectives: Borderline Personality Disorder (BPD) frequently overlaps with trauma-related conditions, particularly PTSD and Complex PTSD (cPTSD). Adverse Childhood Experiences (ACEs)—especially emotional and sexual abuse—are considered key factors in the development of emotion dysregulation and dissociation. This study investigates the impact of different ACE dimensions on borderline symptomatology, emotion dysregulation, and dissociative symptoms. Methods: Eighty-three BPD patients were assessed using standardized self-report questionnaires: CTQ-SF (ACEs), DERS (emotion dysregulation), DES (dissociation), BSL-23 (borderline symptoms), and PDS-3 (post-traumatic symptoms). Analyses included bivariate correlations, Structural Equation Modeling (SEM), and Exploratory Graph Analysis (EGA). Results: Emotional abuse significantly predicted borderline symptoms, while sexual abuse predicted dissociation. Emotion dysregulation was strongly associated with both borderline and dissociative symptoms, emerging as a central node in the symptom network. EGA confirmed the clustering of dissociative symptoms with sexual abuse and the centrality of emotion dysregulation across domains. Conclusions: Findings support the role of specific ACEs in shaping the clinical expression of BPD. Emotion dysregulation acts as a key transdiagnostic factor linking trauma history to borderline and dissociative features. These results underscore the importance of trauma-informed assessments and interventions, such as DBT and DBT-PTSD, tailored to individual ACE profiles. Full article

(This article belongs to the Special Issue Traumatic Stress and Dissociative Disorder)

► Show Figures

Figure 1

18 pages, 4617 KB

Open AccessEditor’s ChoiceSystematic Review

The Relationship Between Physical Activity and Depression in College Students: A Systematic Review and Meta-Analysis

by Xiaorui Huang, Zhuying Chen, Ze Xu, Xiaojie Liu, Yuanyuan Lv and Laikang Yu

Brain Sci. 2025, 15(8), 875; https://doi.org/10.3390/brainsci15080875 - 18 Aug 2025

Cited by 13 | Viewed by 9455

Abstract

Objectives: Depression is a significant and growing global concern with substantial societal impact. College students, being particularly vulnerable to depression, necessitate exploration of physical activity (PA) as a potential mitigating factor. This study aims to examine the relationship between PA and depression [...] Read more.

Objectives: Depression is a significant and growing global concern with substantial societal impact. College students, being particularly vulnerable to depression, necessitate exploration of physical activity (PA) as a potential mitigating factor. This study aims to examine the relationship between PA and depression in college students. Methods: Studies were identified through systematic searches of PubMed, Embase, Cochrane, Scopus, and Web of Science. The Pearson correlation coefficient was utilized to assess the PA–depression relationship. Heterogeneity was evaluated, and subgroup analyses were performed. Sensitivity analysis via the leave-one-out method was conducted. Quality assessment was assessed using the Joanna Briggs Institute literature quality assessment approach, resulting in the inclusion of 38 high-quality, low-risk studies. Results: A significant negative correlation between PA and depression was found (r = −0.238; 95% CI, −0.307 to −0.173; p < 0.001). Subgroup analyses revealed notable PA–depression correlations post-COVID-19 (r = −0.324; 95% CI, −0.493 to −0.132; p < 0.001), in developing countries (r = −0.202; 95% CI, −0.213 to −0.191; p < 0.001), and in physical education majors (r = −0.390; 95% CI, −0.589 to −0.147; p < 0.001). Moderate PA levels were associated with reduced depression (r = −0.428; 95% CI, −0.708 to −0.031; p = 0.035). Conclusions: This systematic review and meta-analysis suggests that PA is significantly and negatively associated with depression and plays a crucial role in alleviating depression in college students. Various influences, including the pandemic, national development level, student major, and PA intensity, moderate this relationship. Post-pandemic, developing countries, physical education majors, and moderate PA intensity emerged as optimal factors for enhancing the depression-alleviating effects of PA. Full article

(This article belongs to the Special Issue Unraveling the Role of Physical Activity in Brain, Cognition, and Mental Health)

► Show Figures

Figure 1

18 pages, 2650 KB

Open AccessEditor’s ChoiceArticle

The Effectiveness of an Exercise Program Based on Motor Learning Principles for the Correction of the Forward Head Posture: A Randomized Controlled Trial

by Stephani Argyrou, Pavlos Kitixis, Zacharias Dimitriadis, Anna Christakou, Nikolaos Strimpakos, George Paras, Maria Tsioutsoumaka and Eleni Kapreli

Brain Sci. 2025, 15(8), 873; https://doi.org/10.3390/brainsci15080873 - 15 Aug 2025

Cited by 6 | Viewed by 11133

Abstract

Background/Objectives: The aim of this study was to examine the effectiveness of an exercise program based on principles of motor learning with cognitive elements (such as attention) in the correction of Forward Head Posture (FHP). Methods: A total of 55 university students [...] Read more.

Background/Objectives: The aim of this study was to examine the effectiveness of an exercise program based on principles of motor learning with cognitive elements (such as attention) in the correction of Forward Head Posture (FHP). Methods: A total of 55 university students from the University of Thessaly, aged between 18 and 25 years, participated in this study. Volunteers found to have a craniovertebral angle <50° were randomly divided into two groups: the intervention group IG (n = 27) and the control group CG (n = 28). The IG followed a treatment protocol consisting of three 30–45-min sessions per week for four weeks, a total of twelve sessions, while the control group received the same content instructions and group sessions upon completion. Results: After the four-week intervention period, significant improvements were observed in both static and dynamic craniovertebral angle measurements (p < 0.05) when comparing the IG to the CG. Additionally, there was a notable increase in the endurance of the deep neck flexors (p < 0.05), even though the intervention for the IG did not include specific strength exercises. Furthermore, participants with FHP were able to transfer (B–C) motor skills (p < 0.01) acquired during static position tasks to a similar but dynamically untrained task. They also retained (B–D) improvements in posture and strength during the two-week detraining period (p < 0.01), indicating sustained motor learning effects. Conclusions: The exercise intervention was successful at decreasing FHP in subjects, sustaining the results for a two-week period. This study supports the effectiveness of postural training by a program based on motor learning principles. New rehabilitation strategies based on motor control and motor learning could be introduced into physiotherapy practice to increase effectiveness. Full article

(This article belongs to the Special Issue Neuromuscular Diseases and Musculoskeletal Disorders)

► Show Figures

Figure 1

22 pages, 1071 KB

Open AccessEditor’s ChoiceReview

The Interplay of Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation in Autism Spectrum Disorder: Behavioral Implications and Therapeutic Strategies

by Ansab Akhtar and SK Batin Rahaman

Brain Sci. 2025, 15(8), 853; https://doi.org/10.3390/brainsci15080853 - 11 Aug 2025

Cited by 12 | Viewed by 8704

Abstract

Autism spectrum disorder (ASD) deals with several symptoms, including language and speech impairment and developmental delays. The main brain regions affected could be the prefrontal cortex (PFC) or the temporal lobe. The detrimental features could include oxidative stress, mitochondrial dysfunction, and neuroinflammation. Most [...] Read more.

Autism spectrum disorder (ASD) deals with several symptoms, including language and speech impairment and developmental delays. The main brain regions affected could be the prefrontal cortex (PFC) or the temporal lobe. The detrimental features could include oxidative stress, mitochondrial dysfunction, and neuroinflammation. Most often, these phenomena are interrelated and can lead to one another, creating a vicious cycle. They also influence the regulation of certain genes involved in the pathogenesis of ASD or related behavior. In the brain regions prone to these detrimental features, a cascade of free radicals, inflammatory cytokines, and mitochondrial energy disruptions is initiated. These actions during the prenatal or developmental stage of the child potentially lead to ASD symptomatic features, such as social isolation, communication difficulty, speech and language impairment, cognitive dysfunction, and intellectual disability. The more recent theories, including genetics, epigenetics, and the gut–brain axis, have been demonstrated to play a greater role in ASD pathology, often being associated with the more common ones as mentioned above. We also introduced some of the neurological disorders possessing shared genetic and behavioral traits with ASD. Many genes playing a role in ASD-like features and their potential targeted drugs were explained briefly. However, there are limited therapeutic options, and molecular pathways related to this disorder are less explored. Currently, researchers and therapists are racing to uncover a concrete remedy. This review also provides a brief outline of potential antioxidant, mitochondrial, and anti-inflammatory therapies. We finally included some novel strategies to diagnose and manage autistic pathology and symptoms. Full article

(This article belongs to the Special Issue Role of Inflammation, Oxidative Stress, and Metabolic Dysfunction in Neurodevelopmental and Neurodegenerative Diseases: Pharmacological Targets and Therapeutic Interventions)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI